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Sample records for mouse aged kidney

  1. Experimental investigation of mouse kidney aging with SR PCI technology

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    Yifeng, P.; Zehua, Z.; Guohao, D.; Tiqiao, X.; Hongjie, X.; Peiping, Z.

    2013-08-01

    Objective. Basing on the coherence character of the Synchrotron radiation (SR), the mouse kidney study is performed using the propagation-based phase-contrast imaging (PCI) technology which as one approach of the phase contrasts imaging (PCI). The aim of this paper was to visualize the kidney at different ages and evaluate the latent value of aging mechanism with SR phase contrast imaging technology. Methods. The experiments were performed at the BL13W1 line of the SSRF (the Shanghai synchrotron radiation facility), the samples were soaked in 10% formalin solution, the mouse kidneys at different ages were imaged on the shelf in the propagation-based phase-contrast imaging setup and captured with CCD. The captured images were analyzed and compared. Results. When the distance is 50 cm between the samples and imaging plate, good contrast and high resolution were obtained in the propagation-based phase-contrast imaging (PCI), as such renal capsule revealed well, and the resolution reach to 30 micron; there is significant difference in the shape and vessels structures among the mouse kidneys at different age. Conclusion. The PCI is good for the applying of main light element organization imaging, the difference in shape and vessels structure between the young and old mouse kidney maybe indicated at some extent with the propagation-based phase-contrast imaging technology.

  2. Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age

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    Roeder, Sebastian S.; Stefanska, Ania; Eng, Diana G.; Kaverina, Natalya; Sunseri, Maria W.; McNicholas, Bairbre A.; Rabinovitch, Peter; Engel, Felix B.; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W.

    2015-01-01

    Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. PMID:26017974

  3. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

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    Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  4. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    International Nuclear Information System (INIS)

    Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

    2015-01-01

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

  5. Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age.

    Science.gov (United States)

    Roeder, Sebastian S; Stefanska, Ania; Eng, Diana G; Kaverina, Natalya; Sunseri, Maria W; McNicholas, Bairbre A; Rabinovitch, Peter; Engel, Felix B; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W; Shankland, Stuart J

    2015-07-15

    Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. Copyright © 2015 the American Physiological Society.

  6. Developmental immunolocalization of the Klotho protein in mouse kidney epithelial cells

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    J.H. Song

    2014-01-01

    Full Text Available A defect in Klotho gene expression in the mouse results in a syndrome that resembles rapid human aging. In this study, we investigated the detailed distribution and the time of the first appearance of Klotho in developing and adult mouse kidney. Kidneys from 16-(F16, 18-(F18 and 20-day-old (F20 fetuses, 1- (P1, 4- (P4, 7- (P7, 14- (P14, and 21-day-old (P21 pups and adults were processed for immunohistochemistry and immunoblot analyses. In the developing mouse kidney, Klotho immunoreactivity was initially observed in a few cells of the connecting tubules (CNT of 18-day-old fetus (F and in the medullary collecting duct (MCD and distal nephron of the F16 developing kidney. In F20, Klotho immunoreactivity was increased in CNT and additionally observed in the outer portion of MCD and tip of the renal papilla. During the first 3 weeks after birth, Klotho-positive cells gradually disappeared from the MCD due to apoptosis, but remained in the CNT and cortical collecting ducts (CCD. In the adult mouse, the Klotho protein was expressed only in a few cells of the CNT and CCD in cortical area. Also, Klotho immunoreactivity was observed in the aquaporin 2-positive CNT, CCD, and NaCl co-transporter-positive distal convoluted tubule (DCT cells and type B and nonA-nonB intercalated cells of CNT, DCT, and CCD. Collectively, our data indicate that immunolocalization of Klotho is closely correlated with proliferation in the intercalated cells of CNT and CCD from aging, and may be involved in the regulation of tubular proliferation.

  7. Protective Effects of Hydrogen Sulfide in the Ageing Kidney.

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    Hou, Cui-Lan; Wang, Ming-Jie; Sun, Chen; Huang, Yong; Jin, Sheng; Mu, Xue-Pan; Chen, Ying; Zhu, Yi-Chun

    2016-01-01

    Aims . The study aimed to examine whether hydrogen sulfide (H 2 S) generation changed in the kidney of the ageing mouse and its relationship with impaired kidney function. Results . H 2 S levels in the plasma, urine, and kidney decreased significantly in ageing mice. The expression of two known H 2 S-producing enzymes in kidney, cystathionine γ -lyase (CSE) and cystathionine- β -synthase (CBS), decreased significantly during ageing. Chronic H 2 S donor (NaHS, 50  μ mol/kg/day, 10 weeks) treatment could alleviate oxidative stress levels and renal tubular interstitial collagen deposition. These protective effects may relate to transcription factor Nrf2 activation and antioxidant proteins such as HO-1, SIRT1, SOD1, and SOD2 expression upregulation in the ageing kidney after NaHS treatment. Furthermore, the expression of H 2 S-producing enzymes changed with exogenous H 2 S administration and contributed to elevated H 2 S levels in the ageing kidney. Conclusions . Endogenous hydrogen sulfide production in the ageing kidney is insufficient. Exogenous H 2 S can partially rescue ageing-related kidney dysfunction by reducing oxidative stress, decreasing collagen deposition, and enhancing Nrf2 nuclear translocation. Recovery of endogenous hydrogen sulfide production may also contribute to the beneficial effects of NaHS treatment.

  8. Trb2, a mouse homolog of tribbles, is dispensable for kidney and mouse development

    International Nuclear Information System (INIS)

    Takasato, Minoru; Kobayashi, Chiyoko; Okabayashi, Koji; Kiyonari, Hiroshi; Oshima, Naoko; Asashima, Makoto; Nishinakamura, Ryuichi

    2008-01-01

    Glomeruli comprise an important filtering apparatus in the kidney and are derived from the metanephric mesenchyme. A nuclear protein, Sall1, is expressed in this mesenchyme, and we previously reported that Trb2, a mouse homolog of Drosophila tribbles, is expressed in the mesenchyme-derived tissues of the kidney by microarray analyses using Sall1-GFP knock-in mice. In the present report, we detected Trb2 expression in a variety of organs during gestation, including the kidneys, mesonephros, testes, heart, eyes, thymus, blood vessels, muscle, bones, tongue, spinal cord, and ganglions. In the developing kidney, Trb2 signals were detected in podocytes and the prospective mesangium of the glomeruli, as well as in ureteric bud tips. However, Trb2 mutant mice did not display any apparent phenotypes and no proteinuria was observed, indicating normal glomerular functions. These results suggest that Trb2 plays minimal roles during kidney and mouse development

  9. Conserved and Divergent Features of Human and Mouse Kidney Organogenesis.

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    Lindström, Nils O; McMahon, Jill A; Guo, Jinjin; Tran, Tracy; Guo, Qiuyu; Rutledge, Elisabeth; Parvez, Riana K; Saribekyan, Gohar; Schuler, Robert E; Liao, Christopher; Kim, Albert D; Abdelhalim, Ahmed; Ruffins, Seth W; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; Kesselman, Carl; McMahon, Andrew P

    2018-03-01

    Human kidney function is underpinned by approximately 1,000,000 nephrons, although the number varies substantially, and low nephron number is linked to disease. Human kidney development initiates around 4 weeks of gestation and ends around 34-37 weeks of gestation. Over this period, a reiterative inductive process establishes the nephron complement. Studies have provided insightful anatomic descriptions of human kidney development, but the limited histologic views are not readily accessible to a broad audience. In this first paper in a series providing comprehensive insight into human kidney formation, we examined human kidney development in 135 anonymously donated human kidney specimens. We documented kidney development at a macroscopic and cellular level through histologic analysis, RNA in situ hybridization, immunofluorescence studies, and transcriptional profiling, contrasting human development (4-23 weeks) with mouse development at selected stages (embryonic day 15.5 and postnatal day 2). The high-resolution histologic interactive atlas of human kidney organogenesis generated can be viewed at the GUDMAP database (www.gudmap.org) together with three-dimensional reconstructions of key components of the data herein. At the anatomic level, human and mouse kidney development differ in timing, scale, and global features such as lobe formation and progenitor niche organization. The data also highlight differences in molecular and cellular features, including the expression and cellular distribution of anchor gene markers used to identify key cell types in mouse kidney studies. These data will facilitate and inform in vitro efforts to generate human kidney structures and comparative functional analyses across mammalian species. Copyright © 2018 by the American Society of Nephrology.

  10. Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis.

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    Davisson, Muriel T; Cook, Susan A; Akeson, Ellen C; Liu, Don; Heffner, Caleb; Gudis, Polyxeni; Fairfield, Heather; Murray, Stephen A

    2015-06-15

    Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis. Copyright © 2015 the American Physiological Society.

  11. Nuclear hormone receptor expression in mouse kidney and renal cell lines.

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    Daisuke Ogawa

    Full Text Available Nuclear hormone receptors (NHRs are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN, the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m, and cell lines of mesangial (MES13, podocyte (MPC, proximal tubular epithelial (mProx24 and collecting duct (mIMCD3 origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77, nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN.

  12. The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.

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    Lehman, J M [University of Alabama, Birmingham; Michaud III, Edward J [ORNL; Schoeb, T [University of Alabama, Birmingham; Aydin Son, Yesim [University of Tennessee, Knoxville (UTK); Miller, M [University of Alabama, Birmingham; Yoder, Bradley [University of Alabama, Birmingham

    2008-08-01

    The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can be analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.

  13. The Aging Kidney: Increased Susceptibility to Nephrotoxicity

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    Wang, Xinhui; Bonventre, Joseph V.; Parrish, Alan R.

    2014-01-01

    Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI). Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair. PMID:25257519

  14. The use of urinary and kidney SILAM proteomics to monitor kidney response to high dose morpholino oligonucleotides in the mdx mouse

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    Aiping Zhang

    2015-01-01

    Full Text Available Phosphorodiamidate morpholino oligonucleotides (PMO are used as a promising exon-skipping gene therapy for Duchenne muscular dystrophy (DMD. One potential complication of high dose PMO therapy is its transient accumulation in the kidneys. Therefore new urinary biomarkers are needed to monitor this treatment. Here, we carried out a pilot proteomic profiling study using stable isotope labeling in mammals (SILAM strategy to identify new biomarkers to monitor the effect of PMO on the kidneys of the dystrophin deficient mouse model for DMD (mdx-23. We first assessed the baseline renal status of the mdx-23 mouse compared to the wild type (C57BL10 mouse, and then followed the renal outcome of mdx-23 mouse treated with a single high dose intravenous PMO injection (800 mg/kg. Surprisingly, untreated mdx-23 mice showed evidence of renal injury at baseline, which was manifested by albuminuria, increased urine output, and changes in established urinary biomarker of acute kidney injury (AKI. The PMO treatment induced further transient renal injury, which peaked at 7 days, and returned to almost the baseline status at 30 days post-treatment. In the kidney, the SILAM approach followed by western blot validation identified changes in Meprin A subunit alpha at day 2, then returned to normal levels at days 7 and 30 after PMO injection. In the urine, SILAM approach identified an increase in Clusterin and γ-glutamyl transpeptidase 1 as potential candidates to monitor the transient renal accumulation of PMO. These results, which were confirmed by Western blots or ELISA, demonstrate the value of the SILAM approach to identify new candidate biomarkers of renal injury in mdx-23 mice treated with high dose PMO.

  15. The aging kidney revisited: a systematic review.

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    Bolignano, Davide; Mattace-Raso, Francesco; Sijbrands, Eric J G; Zoccali, Carmine

    2014-03-01

    As for the whole human body, the kidney undergoes age-related changes which translate in an inexorable and progressive decline in renal function. Renal aging is a multifactorial process where gender, race and genetic background and several key-mediators such as chronic inflammation, oxidative stress, the renin-angiotensin-aldosterone (RAAS) system, impairment in kidney repair capacities and background cardiovascular disease play a significant role. Features of the aging kidney include macroscopic and microscopic changes and important functional adaptations, none of which is pathognomonic of aging. The assessment of renal function in the framework of aging is problematic and the question whether renal aging should be considered as a physiological or pathological process remains a much debated issue. Although promising dietary and pharmacological approaches have been tested to retard aging processes or renal function decline in the elderly, proper lifestyle modifications, as those applicable to the general population, currently represent the most plausible approach to maintain kidney health. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Optical Coherence Tomography of the Aging Kidney.

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    Andrews, Peter M; Wang, Hsing-Wen; Guo, Hengchang; Anderson, Erik; Falola, Reuben; Chen, Yu

    2016-12-01

    The aging kidney exhibits a progressive decline in renal function with characteristic histopathologic changes and is a risk factor for renal transplant. However, the degree to which the kidney exhibits this decline depends on several factors that vary from one individual to the next. Optical coherence tomography is an evolving noninvasive imaging technology that has recently been used to evaluate acute tubular necrosis of living-human donor kidneys before their transplant. With the increasing use of kidneys from older individuals, it is important to determine whether optical coherence tomography also can distinguish the histopathology associated with aging. In this investigation, we used Munich-Wistar rats to evaluate the ability of optical coherence tomography to detect histopathologic changes associated with aging. Optical coherence tomography observations were correlated with renal function and conventional light microscopic evaluation of these same kidneys. With the onset of severe proteinuria at 10 to 12 months of age, optical coherence tomography revealed tubular necrosis/atrophy, interstitial fibrosis, tubular dilation, and glomerulosclerosis. With a further deterioration in kidney function at 16 to 18 months of age (as indicated by rising creatinine levels), optical coherence tomography revealed more extensive interstitial fibrosis and tubular atrophy, increased tubular dilation with cyst formation and more sclerotic glomeruli. The foregoing observations suggest that optical coherence tomography can be used to detect the histopathology of progressive nephropathy associated with aging.

  17. Developing better mouse models to study cisplatin-induced kidney injury.

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    Sharp, Cierra N; Siskind, Leah J

    2017-10-01

    Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury. Copyright © 2017 the American Physiological Society.

  18. A transcriptional profile of aging in the human kidney.

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    Graham E J Rodwell

    2004-12-01

    Full Text Available In this study, we found 985 genes that change expression in the cortex and the medulla of the kidney with age. Some of the genes whose transcripts increase in abundance with age are known to be specifically expressed in immune cells, suggesting that immune surveillance or inflammation increases with age. The age-regulated genes show a similar aging profile in the cortex and the medulla, suggesting a common underlying mechanism for aging. Expression profiles of these age-regulated genes mark not only age, but also the relative health and physiology of the kidney in older individuals. Finally, the set of aging-regulated kidney genes suggests specific mechanisms and pathways that may play a role in kidney degeneration with age.

  19. The renin-angiotensin system and aging in the kidney.

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    Yoon, Hye Eun; Choi, Bum Soon

    2014-05-01

    Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and functional changes in the aging kidney and age-related renal injury, and describes the underlying mechanisms of RAS-related renal aging. An improved understanding of the renal aging process may lead to better individualized care of the elderly and improved renal survival in age-related diseases.

  20. Thioacetamide-induced changes in the body weight, kidney weight and the total nucleic acids content of kidney of mouse

    International Nuclear Information System (INIS)

    Shakoori, Abdul Rauf; Ashraf, Fauzia.

    1976-01-01

    Effects of thioacetamide (TAA) on the body weight, kidney weight and the total nucleic acids content of kidney of mouse were studied. TAA 1% and 2% solutions were injected intraperitoneally, twice with an interval of 24 hours in two different batches of male mice. In this way one batch received a total dose of 100 mg TAA/Kg body wt. while the other got a total dose of 200 mg TAA/Kg. Both the body as well as kidney weights decrease after TAA treatment. A total dose of 200 mg/Kg is a stronger inhibitor of growth as compared with that of 100 mg/Kg. The nucleic acids content show an increase after the drug treatment. The ribonucleic acid content of kidney increased from an average value of 4.30+0.14 mg/g kidney to 4.60+-0.22 mg/g kidney after 1% TAA treatment. The increase in 2% TAA treated mice is slightly more prominent. The deoxyribonucleic acid (DNA) content of kidney are likewise affected. After an initial increase in 1% TAA-treated animals, the DNA content gradually fall down to normal control values. Administration of 2% TAA solution causes an average increase of 21% i.e. from 1.93+-0.19 mg/g kidney wt to 2.26+-0.23 mg/g kidney wt. The size of cell, nucleus and nucleolus also increased after drug treatment, which mainly occurred during the first 24 hours of the post-treatment period

  1. Aging changes in the kidneys and bladder

    Science.gov (United States)

    ... affect kidney function. COMMON PROBLEMS Aging increases the risk of kidney and bladder problems such as: Bladder control issues, such as leakage or urinary incontinence (not being able to hold your urine), or ...

  2. The renin-angiotensin system and aging in the kidney

    OpenAIRE

    Yoon, Hye Eun; Choi, Bum Soon

    2014-01-01

    Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and function...

  3. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    International Nuclear Information System (INIS)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

    2016-01-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

  4. Kidney growth in 717 healthy children aged 0-18 months

    DEFF Research Database (Denmark)

    Schmidt, Ida M; Main, Katharina M; Damgaard, Ida N

    2004-01-01

    Kidney size is an important parameter in the evaluation of children with renal disease. However, reference materials for kidney size in healthy children have been limited beyond the neonatal period. We performed a longitudinal cohort study of 717 healthy children born at term with normal birth...... weight. Kidney size and shape were determined by ultrasonography and related to gender, age, and body size (weight, length, body surface area, skinfold thickness) at 0, 3, and 18 months of age. Gender-differentiated reference charts were established. Boys had significantly larger kidney volumes than...... girls ( Page. The best single predictor of gender-differentiated kidney volume was weight. Relative kidney volume changed with increasing age and height in a two-phase pattern: an initial...

  5. Restoration of Haemoglobin Level Using Hydrodynamic Gene Therapy with Erythropoietin Does Not Alleviate the Disease Progression in an Anaemic Mouse Model for TGFβ1-Induced Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Pedersen, Lea Hougaard; Wogensen, Lise; Marcussen, N.

    2015-01-01

    . The experiment is conducted by hydrodynamic gene transfer of a plasmid encoding murine Epo in a transgenic mouse model that overexpresses TGF-β1 locally in the kidneys. This model develops anaemia due to chronic kidney disease characterised by thickening of the glomerular basement membrane, deposition...... of mesangial matrix and mild interstitial fibrosis. A group of age matched wildtype littermates are treated accordingly. After a single hydrodynamic administration of plasmid DNA containing murine EPO gene, sustained high haemoglobin levels are observed in both transgenic and wildtype mice from 7.5 ± 0.6 mmol...... treatment in this model of chronic kidney disease normalises haemoglobin levels but has no effect on kidney fibrosis or function....

  6. Effects of hydro-alcoholic extract of Vitex agnus-castus fruit on kidney of D-galactose-induced aging model in female mice.

    Science.gov (United States)

    Oroojan, A A; Ahangarpour, A; Khorsandi, L; Najimi, S A

    2016-01-01

    The aim of the present study was to evaluate the effect of a hydro-alcoholic extract of Vitex agnus-castus (VAC) fruit on blood urea nitrogen (BUN), creatinine (Cr) and, kidney histology of a female mouse model of D-galactose induced aging. In this experimental study, 72 NMRI mice were divided into 6 groups: control, VAC, D-galactose, D-galactose+VAC, aging, and aging+VAC. D-galactose was injected for 45 days and, VAC extract administered in the last 7 days, twice a day. Serum BUN and Cr levels were not significantly changed in the D-galactose and natural aged animals in comparison to control group. Histological changes such as nuclear pyknosis, proximal cell swelling, infiltration of inflammatory cells, tubular dilatation and, vasodilatation were observed in both D-galactose and natural aged mice. Further, glomerules diameter was decreased in them. Administration of VAC could attenuate the histological alterations. These results indicate that VAC may have beneficial effects on aging and aging related kidney disease.

  7. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

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    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States); Uehara, Takeki; Kato, Yuki [Laboratory of Veterinary Pathology, Osaka Prefecture University, Osaka (Japan); Kono, Hiroshi [First Department of Surgery, University of Yamanashi, Yamanashi (Japan); Bataller, Ramon [Division of Gastroenterology & Hepatology, Department of Medicine, University of North Carolina, Chapel Hill, NC (United States); Rusyn, Ivan, E-mail: irusyn@tamu.edu [Department of Veterinary Integrative Biosciences, Texas A& M University, College Station, TX (United States)

    2016-11-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.

  8. Gender-dependent effects of aging on the kidney

    Directory of Open Access Journals (Sweden)

    A.L. Gava

    2011-09-01

    Full Text Available It is well known that the kidney plays an important role in the development of cardiovascular diseases such as hypertension. The normal aging process leads to changes in kidney morphology, hemodynamics and function, which increase the incidence of cardiovascular events in the elderly population. These disturbances are influenced by several factors, including gender. In general, females are protected by the effects of estrogens on the cardiorenal system. Several studies have demonstrated the beneficial effects of estrogens on renal function in the elderly; however, the relationships between androgens and kidney health during one’s lifetime are not well understood. Sex steroids have many complex actions, and the decline in their levels during aging clearly influences kidney function, decreases the renal reserve and facilitates the development of cardiovascular disorders. Therefore, in this review, we discuss the cellular, biochemical, and molecular mechanisms by which sex hormones may influence renal function during the aging process.

  9. Mitochondrial autophagy involving renal injury and aging is modulated by caloric intake in aged rat kidneys.

    Science.gov (United States)

    Cui, Jing; Shi, Suozhu; Sun, Xuefeng; Cai, Guangyan; Cui, Shaoyuan; Hong, Quan; Chen, Xiangmei; Bai, Xue-Yuan

    2013-01-01

    A high-calorie (HC) diet induces renal injury and promotes aging, and calorie restriction (CR) may ameliorate these responses. However, the effects of long-term HC and CR on renal damage and aging have been not fully determined. Autophagy plays a crucial role in removing protein aggregates and damaged organelles to maintain intracellular homeostasis and function. The role of autophagy in HC-induced renal damage is unknown. We evaluated the expression of LC3/Atg8 as a marker of the autophagosome; p62/SQSTM1; polyubiquitin aggregates as markers of autophagy flux; Ambra1, PINK1, Parkin and Bnip3 as markers of mitophagy; 8-hydroxydeoxyguanosine (8-OHdG) as a marker of DNA oxidative damage; and p16 as a marker of organ aging by western blot and immunohistochemical staining in the kidneys of 24-month-old Fischer 344 rats. We also observed mitochondrial structure and autolysosomes by transmission electron microscopy. Expression of the autophagosome formation marker LC3/Atg8 and markers of mitochondrial autophagy (mitophagy) were markedly decreased in the kidneys of the HC group, and markedly increased in CR kidneys. p62/SQSTM1 and polyubiquitin aggregates increased in HC kidneys, and decreased in CR kidneys. Transmission electron microscopy demonstrated that HC kidneys showed severe abnormal mitochondrial morphology with fewer autolysosomes, while CR kidneys exhibited normal mitochondrial morphology with numerous autolysosomes. The level of 8-hydroxydeoxyguanosine was increased in HC kidneys and decreased in CR kidneys. Markers of aging, such as p16 and senescence-associated-galactosidase, were increased significantly in the HC group and decreased significantly in the CR group. The study firstly suggests that HC diet inhibits renal autophagy and aggravates renal oxidative damage and aging, while CR enhances renal autophagy and ameliorates oxidative damage and aging in the kidneys.

  10. Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

    Science.gov (United States)

    Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

    2014-01-01

    Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

  11. Increased susceptibility to structural acute kidney injury in a mouse model of presymptomatic cardiomyopathy.

    Science.gov (United States)

    Pleasant, LaTawnya; Ma, Qing; Devarajan, Mahima; Parameswaran, Priyanka; Drake, Keri; Siroky, Brian; Shay-Winkler, Kritton; Robbins, Jeffrey; Devarajan, Prasad

    2017-09-01

    The early events that signal renal dysfunction in presymptomatic heart failure are unclear. We tested the hypothesis that functional and mechanistic changes occur in the kidney that precede the development of symptomatic heart failure. We employed a transgenic mouse model with cardiomyocyte-specific overexpression of mutant α-B-crystallin that develops slowly progressive cardiomyopathy. Presymptomatic transgenic mice displayed an increase in serum creatinine (1.17 ± 0.34 vs. wild type 0.65 ± 0.16 mg/dl, P kidneys exhibited a twofold upregulation of the Ren1 gene, marked overexpression of renin protein in the tubules, and a worsened response to ischemia-reperfusion injury based on serum creatinine (2.77 ± 0.66 in transgenic mice vs. 2.01 ± 0.58 mg/dl in wild type, P kidney that occur in early presymptomatic heart failure, which increase the susceptibility to subsequent acute kidney injury. Copyright © 2017 the American Physiological Society.

  12. Effects of hydro-alcoholic extract of Vitex agnus-castus fruit on kidney of D-galactose-induced aging model in female mice

    OpenAIRE

    Oroojan, A. A.; Ahangarpour, A.; Khorsandi, L.; Najimi, S. A.

    2016-01-01

    The aim of the present study was to evaluate the effect of a hydro-alcoholic extract of Vitex agnus-castus (VAC) fruit on blood urea nitrogen (BUN), creatinine (Cr) and, kidney histology of a female mouse model of D-galactose induced aging. In this experimental study, 72 NMRI mice were divided into 6 groups: control, VAC, D-galactose, D-galactose+VAC, aging, and aging+VAC. D-galactose was injected for 45 days and, VAC extract administered in the last 7 days, twice a day. Serum BUN and Cr leve...

  13. Conditional ablation of glycogen synthase kinase 3β in postnatal mouse kidney.

    Science.gov (United States)

    Ge, Yan; Si, Jin; Tian, Li; Zhuang, Shougang; Dworkin, Lance D; Gong, Rujun

    2011-01-01

    Glycogen synthase kinase (GSK)3 is a ubiquitously expressed serine/threonine kinase existing in two isoforms, namely GSK3α and GSK3β. Aside from the long-recognized role in insulin signal transduction and glycogen biosynthesis, GSK3β has been recently coined as a master control molecule in nuclear factor-κB activation and inflammatory kidney injury. Nevertheless, previous studies are less conclusive because they relied greatly on small molecule inhibitors, which lack selectivity and barely distinguish between the GSK3 isoforms. In addition, early embryonic lethality after global knockout of GSK3β precludes interrogation of the biological role of GSK3β in the adult kidney. To circumvent these issues, the Cre/loxP system was used to generate a conditional knockout mouse model in which the GSK3β gene was specifically deleted in kidney cortical tubules at postnatal mature stage. Kidney-specific ablation of GSK3β resulted in a phenotype no different from control littermates. Knockout mice (KO) were viable and exhibited normal development and normal kidney physiology in terms of kidney function, urine albumin excretion, and urine-concentrating ability. It is noteworthy that apart from normal glomerular and tubulointerstitial morphology, the kidneys from KO demonstrated more glycogen accumulation in the renal cortical tubules as assessed by both periodic acid-Schiff staining for light microscopy and direct biochemical assay, consistent with an elevated glycogen synthetic activity as evidenced by diminished inhibitory phosphorylation of glycogen synthase that occurred subsequent to GSK3β ablation. This finding was further validated by electron microscopic observations of increased deposition of glycogen particles in the renal tubules of KO, suggesting that GSK3α could not fully compensate for the loss of GSK3β in regulating glycogen metabolism in the kidney. Collectively, our study suggests that kidney-specific ablation of GSK3β barely affects kidney function

  14. Graft function assessment in mouse models of single- and dual- kidney transplantation.

    Science.gov (United States)

    Wang, Lei; Wang, Ximing; Jiang, Shan; Wei, Jin; Buggs, Jacentha; Fu, Liying; Zhang, Jie; Liu, Ruisheng

    2018-05-23

    Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild type recipients or vise verse. Dual kidney transplantation (DKT) provides a more physiological environment for recipients than single kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher GFR than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 µl/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease.

  15. Echotomographic characteristics of kidney in different age groups of our population

    Directory of Open Access Journals (Sweden)

    Gašić Miloš

    2015-01-01

    Full Text Available Introduction: Aging is a continuous process, which leaves its mark on all tissues, organs and organ systems. The aging process causes a number of functional and morphological and structural changes in the kidneys. Objective: The aim of our study was to analyze echotomographic changes in the size of the renal parenchyma and renal sinus during the aging process. Method: The study was conducted on 62 subjects in the service of the radiological diagnostics of CHC Dr Dragisa Mišović in Belgrade. All subjects included in this study were neither anamnestically nor echotomographically positive for any of kidney diseases. Subjects were assorted in three age groups. Group I (20-39 years - 21 subjects, group II (40-59 years - 21 subjects, and group III (60-79 years - 20 subjects. Results: During aging process dimensions of the renal parenchyma decrease. Dimensions of the renal parenchyma exhibit statistically significant difference (p<0.05 between the first and third age group for both kidneys, but difference between the first and second age group is significant only for the right kidney (p<0,05. Dimensions (length and width, of the renal sinuses tend to increase during the aging process, with difference between the first and third age group that is statistically significant for both kidneys (p<0.05. Difference in width of the sinuses for both kidneys is statistically significant only between the second and third age group. Conclusion: During aging process size of the renal sinus increases at the expense of renal parenchyma, and parenchyma-pyelon index decreases.

  16. Aging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease.

    Science.gov (United States)

    Glassock, Richard J; Rule, Andrew D

    2016-01-01

    The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD. © 2016 S. Karger AG, Basel.

  17. A roadmap for the genetic analysis of renal aging.

    Science.gov (United States)

    Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

    2015-10-01

    Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression. © 2015 The Authors. Aging Cell published by the Anatomical Society and John

  18. Altered lipid metabolism in the aging kidney identified by three layered omic analysis.

    Science.gov (United States)

    Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E

    2016-03-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease.

  19. A roadmap for the genetic analysis of renal aging

    Science.gov (United States)

    Noordmans, Gerda A; Hillebrands, Jan-Luuk; van Goor, Harry; Korstanje, Ron

    2015-01-01

    Several studies show evidence for the genetic basis of renal disease, which renders some individuals more prone than others to accelerated renal aging. Studying the genetics of renal aging can help us to identify genes involved in this process and to unravel the underlying pathways. First, this opinion article will give an overview of the phenotypes that can be observed in age-related kidney disease. Accurate phenotyping is essential in performing genetic analysis. For kidney aging, this could include both functional and structural changes. Subsequently, this article reviews the studies that report on candidate genes associated with renal aging in humans and mice. Several loci or candidate genes have been found associated with kidney disease, but identification of the specific genetic variants involved has proven to be difficult. CUBN, UMOD, and SHROOM3 were identified by human GWAS as being associated with albuminuria, kidney function, and chronic kidney disease (CKD). These are promising examples of genes that could be involved in renal aging, and were further mechanistically evaluated in animal models. Eventually, we will provide approaches for performing genetic analysis. We should leverage the power of mouse models, as testing in humans is limited. Mouse and other animal models can be used to explain the underlying biological mechanisms of genes and loci identified by human GWAS. Furthermore, mouse models can be used to identify genetic variants associated with age-associated histological changes, of which Far2, Wisp2, and Esrrg are examples. A new outbred mouse population with high genetic diversity will facilitate the identification of genes associated with renal aging by enabling high-resolution genetic mapping while also allowing the control of environmental factors, and by enabling access to renal tissues at specific time points for histology, proteomics, and gene expression. PMID:26219736

  20. Proteomic study on gender differences in aging kidney of mice

    Directory of Open Access Journals (Sweden)

    Cristobal Susana

    2009-04-01

    Full Text Available Abstract Background This study aims to analyze sex differences in mice aging kidney. We applied a proteomic technique based on subfractionation, and liquid chromatography coupled with 2-DE. Samples from male and female CD1-Swiss outbred mice from 28 weeks, 52 weeks, and 76 weeks were analysed by 2-DE, and selected proteins were identified by matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS. Results This proteomic analysis detected age-related changes in protein expression in 55 protein-spots, corresponding to 22 spots in males and 33 spots in females. We found a protein expression signature (PES of aging composed by 8 spots, common for both genders. The identified proteins indicated increases in oxidative and proteolytic proteins and decreases in glycolytic proteins, and antioxidant enzymes. Conclusion Our results provide insights into the gender differences associated to the decline of kidney function in aging. Thus, we show that proteomics can provide valuable information on age-related changes in expression levels of proteins and related modifications. This pilot study is still far from providing candidates for aging-biomarkers. However, we suggest that the analysis of these proteins could suggest mechanisms of cellular aging in kidney, and improve the kidney selection for transplantation.

  1. Reduction in podocyte SIRT1 accelerates kidney injury in aging mice.

    Science.gov (United States)

    Chuang, Peter Y; Cai, Weijing; Li, Xuezhu; Fang, Lu; Xu, Jin; Yacoub, Rabi; He, John Cijiang; Lee, Kyung

    2017-09-01

    Both the incidence and prevalence of chronic kidney disease are increasing in the elderly population. Although aging is known to induce kidney injury, the underlying molecular mechanisms remain unclear. Sirtuin 1 (Sirt1), a longevity gene, is known to protect kidney cell injury from various cellular stresses. In previous studies, we showed that the podocyte-specific loss of Sirt1 aggravates diabetic kidney injury. However, the role of Sirt1 in aging-induced podocyte injury is not known. Therefore, in this study we sought to determine the effects of podocyte-specific reduction of Sirt1 in age-induced kidney injury. We employed the inducible podocyte-specific Sirt1 knockdown mice that express shRNA against Sirt1 (Pod-Sirt1 RNAi ) and control mice that express shRNA for luciferase (Pod-Luci RNAi ). We found that reduction of podocyte Sirt1 led to aggravated aging-induced glomerulosclerosis and albuminuria. In addition, urinary level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, was markedly increased in aged Pod-Sirt1 RNAi mice compared with aged Pod-Luci RNAi mice. Although podocyte-specific markers decreased in aged mice compared with the young controls, the decrease was further exacerbated in aged Pod-Sirt1 RNAi compared with Pod-Luci RNAi mice. Interestingly, expression of cellular senescence markers was significantly higher in the glomeruli of Pod-Sirt1 RNAi mice than Pod-Luci RNAi mice, suggesting that cellular senescence may contribute to podocyte loss in aging kidneys. Finally, we confirmed that Pod-Sirt1 RNAi glomeruli were associated with reduced activation of the transcription factors peroxisome proliferator-activated receptor (PPAR)-α coactivador-1 (PGC1α)/PPARγ, forkhead box O (FOXO)3, FOXO4, and p65 NF-κB, through SIRT1-mediated deacetylation. Together, our data suggest that SIRT1 may be a potential therapeutic target to treat patients with aging-related kidney disease.

  2. The Kidney in Aging: Physiological Changes and Pathological Implications.

    Science.gov (United States)

    Sobamowo, H; Prabhakar, S S

    2017-01-01

    Aging is associated with progressive decline in renal function along with concurrent morphological changes that ultimately lead to glomerulosclerosis. The mechanisms leading to such changes in the kidney with age as well as the basis of controversies that surround the physiological basis vs pathological nature of aging kidney are the focus of this in-depth review. In addition, the renal functional defects of acid-base homeostasis and electrolyte disturbances in elderly and the physiological basis of such disorders are also discussed. © 2017 Elsevier Inc. All rights reserved.

  3. The Expression Changes of Inflammasomes in the Aging Rat Kidneys.

    Science.gov (United States)

    Song, Fei; Ma, Yuxiang; Bai, Xue-Yuan; Chen, Xiangmei

    2016-06-01

    The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Inflammasomes are important components of innate immune system in the body. However, the function of inflammasomes and their underlying mechanisms in renal aging remain unclear. In this study, for the first time, we systematically investigated the role of the inflammasomes and the inflammatory responses activated by inflammasomes during kidney aging. We found that during kidney aging, the expression levels of the molecules associated with the activation of inflammasomes, including toll-like receptor-4 and interleukin-1 receptor (IL-1R), were significantly increased; their downstream signaling pathway molecule interleukin-1 receptor-associated kinase-4 (IRAK4) was markedly activated (Phospho-IRAK4 was obviously increased); the nuclear factor-κB (NF-κB) signaling pathway was activated (the activated NF-κB pathway molecules Phospho-IKKβ, Phospho-IκBα, and Phospho-NF-κBp65 were significantly elevated); the levels of the inflammasome components NOD-like receptor P3 (NLRP3), NLRC4, and pro-caspase-1 were prominently upregulated; and the proinflammatory cytokines IL-1β and IL-18 were notably increased in the kidneys of 24-month-old (elderly group) rats. These results showed that inflammasomes are markedly activated during the renal aging process and might induce inflamm-aging by promoting the maturation and secretion of the proinflammatory cytokines IL-1β and IL-18. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Fast glomerular quantification of whole ex vivo mouse kidneys using Magnetic Resonance Imaging at 9.4 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Chacon-Caldera, Jorge; Kraemer, Philipp; Schad, Lothar R. [Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Geraci, Stefania; Gretz, Norbert [Heidelberg Univ., Mannheim (Germany). Medical Research Centre; Cullen-McEwen, Luise; Bertram, John F. [Monash Univ., Melbourne, VIC (Australia). Development and Stem Cells Program and Dept. of Anatomy and Developmental Biology

    2016-05-01

    A method to measure total glomerular number (N{sub glom}) in whole mouse kidneys using MRI is presented. The method relies on efficient acquisition times. A 9.4 T preclinical MRI system with a surface cryogenic coil and a 3D gradient echo sequence were used to image nine whole ex vivo BALB/c mouse kidneys labelled with cationized-ferritin (CF). A novel method to segment the glomeruli was developed. The quantification of glomeruli was achieved by identifying and fitting the probability distribution of glomeruli thus reducing variations due to noise. For validation, N{sub glom} of the same kidneys were also obtained using the gold standard: design-based stereology. Excellent agreement was found between the MRI and stereological measurements of N{sub glom}, with values differing by less than 4%: (mean ± SD) MRI = 15 606 ± 1 178; stereology = 16 273 ± 1 523. Using a robust segmentation method and a reliable quantification method, it was possible to acquire N{sub glom} with a scanning time of 33 minutes and 20 seconds. This was more than 8 times faster than previously presented MRI-based methods. Thus, an efficient approach to measure N{sub glom} ex vivo in health and disease is provided.

  5. Analysed cap mesenchyme track data from live imaging of mouse kidney development

    Directory of Open Access Journals (Sweden)

    James G. Lefevre

    2016-12-01

    Full Text Available This article provides detailed information on manually tracked cap mesenchyme cells from timelapse imaging of multiple ex vivo embryonic mouse kidneys. Cells were imaged for up to 18 h at 15 or 20 min intervals, and multiple cell divisions were tracked. Positional data is supplemented with a range of information including the relative location of the closest ureteric tip and a correction for drift due to bulk movement and tip growth. A subset of tracks were annotated to indicate the presence of processes attached to the ureteric epithelium. The calculations used for drift correction are described, as are the main methods used in the analysis of this data for the purpose of describing cap cell motility. The outcomes of this analysis are discussed in “Cap mesenchyme cell swarming during kidney development is influenced by attraction, repulsion, and adhesion to the ureteric tip” (A.N. Combes, J.G. Lefevre, S. Wilson, N.A. Hamilton, M.H. Little, 2016 [1].

  6. Structural and Functional Changes in Human Kidneys with Healthy Aging.

    Science.gov (United States)

    Hommos, Musab S; Glassock, Richard J; Rule, Andrew D

    2017-10-01

    Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFRage-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria. Copyright © 2017 by the American Society of Nephrology.

  7. Emerging role of autophagy in kidney function, diseases and aging

    Science.gov (United States)

    Huber, Tobias B.; Edelstein, Charles L.; Hartleben, Björn; Inoki, Ken; Jiang, Man; Koya, Daisuke; Kume, Shinji; Lieberthal, Wilfred; Pallet, Nicolas; Quiroga, Alejandro; Ravichandran, Kameswaran; Susztak, Katalin; Yoshida, Sei; Dong, Zheng

    2012-01-01

    Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy. PMID:22692002

  8. Flavocoxid, a Natural Antioxidant, Protects Mouse Kidney from Cadmium-Induced Toxicity

    Directory of Open Access Journals (Sweden)

    Antonio Micali

    2018-01-01

    Full Text Available Background. Cadmium (Cd, a diffused environmental pollutant, has adverse effects on urinary apparatus. The role of flavocoxid, a natural flavonoid with antioxidant activity, on the morphological and biochemical changes induced in vivo by Cd in mice kidney was evaluated. Methods. C57 BL/6J mice received 0.9% NaCl alone, flavocoxid (20 mg/kg/day i.p. alone, Cd chloride (CdCl2 (2 mg/kg/day i.p. alone, or CdCl2 plus flavocoxid (2 mg/kg/day i.p. plus 20 mg/kg/day i.p. for 14 days. The kidneys were processed for biochemical, structural, ultrastructural, and morphometric evaluation. Results. Cd treatment alone significantly increased urea nitrogen and creatinine, iNOS, MMP-9, and pERK 1/2 expression and protein carbonyl; reduced GSH, GR, and GPx; and induced structural and ultrastructural changes in the glomeruli and in the tubular epithelium. After 14 days of treatment, flavocoxid administration reduced urea nitrogen and creatinine, iNOS, MMP-9, and pERK 1/2 expression and protein carbonyl; increased GSH, GR, and GPx; and showed an evident preservation of the glomerular and tubular structure and ultrastructure. Conclusions. A protective role of flavocoxid against Cd-induced oxidative damages in mouse kidney was demonstrated for the first time. Flavocoxid may have a promising antioxidant role against environmental Cd harmful effects on glomerular and tubular lesions.

  9. The role of long-term label-retaining cells in the regeneration of adult mouse kidney after ischemia/reperfusion injury.

    Science.gov (United States)

    Liu, Xiangchun; Liu, Haiying; Sun, Lina; Chen, Zhixin; Nie, Huibin; Sun, Aili; Liu, Gang; Guan, Guangju

    2016-04-30

    Label-retaining cells (LRCs) have been recognized as rare stem and progenitor-like cells, but their complex biological features in renal repair at the cellular level have never been reported. This study was conducted to evaluate whether LRCs in kidney are indeed renal stem/progenitor cells and to delineate their potential role in kidney regeneration. We utilized a long-term pulse chase of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in C57BL/6J mice to identify renal LRCs. We tracked the precise morphological characteristics and locations of BrdU(+)LRCs by both immunohistochemistry and immunofluorescence. To examine whether these BrdU(+)LRCs contribute to the repair of acute kidney injury, we analyzed biological characteristics of BrdU(+)LRCs in mice after ischemia/reperfusion (I/R) injury. The findings revealed that the nuclei of BrdU(+) LRCs exhibited different morphological characteristics in normal adult kidneys, including nuclei in pairs or scattered, fragmented or intact, strongly or weakly positive. Only 24.3 ± 1.5 % of BrdU(+) LRCs co-expressed with Ki67 and 9.1 ± 1.4 % of BrdU(+) LRCs were positive for TUNEL following renal I/R injury. Interestingly, we found that newly regenerated cells formed a niche-like structure and LRCs in pairs tended to locate in this structure, but the number of those LRCs was very low. We found a few scattered LRCs co-expressed Lotus tetragonolobus agglutinin (LTA) in the early phase of injury, suggesting differentiation of those LRCs in mouse kidney. Our findings suggest that LRCs are not a simple type of slow-cycling cells in adult kidneys, indicating a limited role of these cells in the regeneration of I/R injured kidney. Thus, LRCs cannot reliably be considered stem/progenitor cells in the regeneration of adult mouse kidney. When researchers use this technique to study the cellular basis of renal repair, these complex features of renal LRCs and the purity of real stem cells among renal LRCs should be considered.

  10. Young for young! Mandatory age-matched exchange of paediatric kidneys.

    Science.gov (United States)

    Pape, Lars; Ehrich, Jochen H H; Offner, Gisela

    2007-04-01

    Some allocation systems include a mandatory donation of paediatric kidneys to children, others do not. Both approaches have medical and organisational advantages and disadvantages for adults and children. This article discusses why "young for young" is the best allocation system for children. Primary age-matched kidney allocation to children is one important factor leading to: (1) higher long-term glomerular filtration rates (GFRs) and graft survival and, thereby, to lesser need for dialysis; (2) better psychosocial rehabilitation, growth and development of children and, last but not least, (3) likely increase of the donor pool. As a consequence, health care costs will be reduced for children with end-stage renal failure. The chance of adults receiving an adequate kidney would be only minimally reduced by this policy. Therefore, we recommend an age-matched allocation programme giving children with end- stage kidney diseases a better prognosis.

  11. Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Zhang, Zhongtao; Johnson, Gail; Cooper, Arthur JL; Feola, Julianne; Bank, Alexander; Shein, Jonathan; Ruotsalainen, Heli; Pihlajaniemi, Taina; Goligorsky, Michael S

    2016-01-01

    Endostatin (EST), an anti-angiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild type mice, aging kidneys exhibited a 2–4 fold increase in TG2 paralleled by increased cross-linked extracellular matrix proteins and fibrosis. Mice transgenic to express EST showed renal fibrosis at a young age. One month delivery of EST via minipumps to young mice showed increased renal fibrosis that became more robust when superimposed on folic acid-induced nephropathy. Upregulated TG2 and impaired renal function were apparent with EST delivery combined with folic acid-induced nephropathy. Subcapsular injection of TG2 and/or EST into kidneys of young mice not only induced interstitial fibrosis, but also increased the proportion of senescent cells. Thus, kidney fibrosis in aging may represent a natural outcome of upregulated EST and TG2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, EST and TG2. PMID:27165830

  12. Sexual dimorphism in development of kidney damage in aging Fischer-344 rats.

    Science.gov (United States)

    Sasser, Jennifer M; Akinsiku, Oladele; Moningka, Natasha C; Jerzewski, Katie; Baylis, Chris; LeBlanc, Amanda J; Kang, Lori S; Sindler, Amy L; Muller-Delp, Judy M

    2012-08-01

    Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide. Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys. We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress. There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability. The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3

  13. Tick-Tock Chimes the Kidney Clock – from Biology of Renal Ageing to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Joshua Rowland

    2018-01-01

    Full Text Available Ageing of the kidney is a multi-dimensional process that occurs simultaneously at the molecular, cellular, histological, anatomical and physiological level. Nephron number and renal cortical volume decline, renal tubules become atrophic and glomeruli become sclerotic with age. These structural changes are accompanied by a decline in glomerular filtration rate, decreased sodium reabsorption and potassium excretion, reduced urinary concentrating capacity and alterations in the endocrine activity of the kidney. However, the pace of progression of these changes is not identical in everyone - individuals of the same age and seemingly similar clinical profile often exhibit stark differences in the age-related decline in renal health. Thus, chronological age poorly reflects the time-dependent changes that occur in the kidney. An ideal measure of renal vitality is biological kidney age – a measure of the age-related changes in physiological function. Replacing chronological age with biological age could provide numerous clinical benefits including improved prognostic accuracy in renal transplantation, better stratification of risk and identification of those who are on a fast trajectory to an age-related drop in kidney health.

  14. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

    Directory of Open Access Journals (Sweden)

    Indira Pokkunuri

    2016-01-01

    Full Text Available We examined the effects and mechanism of grape powder- (GP- mediated improvement, if any, on aging kidney function. Adult (3-month and aged (21-month Fischer 344 rats were treated without (controls and with GP (1.5% in drinking water and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1, which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions.

  15. Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

    Science.gov (United States)

    Musso, Carlos G; Oreopoulos, Dimitrios G

    2011-01-01

    In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

  16. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L.; Youssef, S. A.; de Bruin, A.

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of geroscience,

  17. Pathology of Mouse Models of Accelerated Aging

    NARCIS (Netherlands)

    Harkema, L; Youssef, S A; de Bruin, A

    2016-01-01

    Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience,"

  18. Magnolia Extract (BL153 Ameliorates Kidney Damage in a High Fat Diet-Induced Obesity Mouse Model

    Directory of Open Access Journals (Sweden)

    Wenpeng Cui

    2013-01-01

    Full Text Available Accumulating evidence demonstrated that obesity is a risk factor for renal structural and functional changes, leading to the end-stage renal disease which imposes a heavy economic burden on the community. However, no effective therapeutic method for obesity-associated kidney disease is available. In the present study, we explored the therapeutic potential of a magnolia extract (BL153 for treating obesity-associated kidney damage in a high fat diet- (HFD- induced mouse model. The results showed that inflammation markers (tumor necrosis factor-α and plasminogen activator inhibitor-1 and oxidative stress markers (3-nitrotyrosine and 4-hydroxy-2-nonenal were all significantly increased in the kidney of HFD-fed mice compared to mice fed with a low fat diet (LFD. Additionally, proteinuria and renal structure changes in HFD-fed mice were much more severe than that in LFD-fed mice. However, all these alterations were attenuated by BL153 treatment, accompanied by upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α and hexokinase II (HK II expression in the kidney. The present study indicates that BL153 administration may be a novel approach for renoprotection in obese individuals by antiinflammation and anti-oxidative stress most likely via upregulation of PGC-1α and HK II signal in the kidney.

  19. Acellular Mouse Kidney ECM can be Used as a Three-Dimensional Substrate to Test the Differentiation Potential of Embryonic Stem Cell Derived Renal Progenitors.

    Science.gov (United States)

    Sambi, Manpreet; Chow, Theresa; Whiteley, Jennifer; Li, Mira; Chua, Shawn; Raileanu, Vanessa; Rogers, Ian M

    2017-08-01

    The development of strategies for tissue regeneration and bio-artificial organ development is based on our understanding of embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities of gastrulation and organogenesis, coupled with cell selection regimens to isolate the cells of choice. This strategy is impeded by the lack of optimal in vitro culture systems since traditional culture systems do not allow for the three-dimensional interaction between cells and the extracellular matrix. While artificial three-dimensional scaffolds are available, using the natural extracellular matrix scaffold is advantageous because it has a distinct architecture that is difficult to replicate. The adult extracellular matrix is predicted to mediate signaling related to tissue repair not embryogenesis but existing similarities between the two argues that the extracellular matrix will influence the differentiation of stem and progenitor cells. Previous studies using undifferentiated embryonic stem cells grown directly on acellular kidney ECM demonstrated that the acellular kidney supported cell growth but limited differentiation occurred. Using mouse kidney extracellular matrix and mouse embryonic stem cells we report that the extracellular matrix can support the development of kidney structures if the stem cells are first differentiated to kidney progenitor cells before being applied to the acellular organ.

  20. Molecular events in matrix protein metabolism in the aging kidney

    Science.gov (United States)

    Sataranatarajan, Kavithalakshmi; Feliers, Denis; Mariappan, Meenalakshmi M.; Lee, Hak Joo; Lee, Myung Ja; Day, Robert T.; Yalamanchili, Hima Bindu; Choudhury, Goutam G.; Barnes, Jeffrey L.; Van Remmen, Holly; Richardson, Arlan; Kasinath, Balakuntalam S.

    2018-01-01

    Summary We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied in youth, middle age, and old age. Albuminuria and serum cystatin C level (an index of glomerular filtration) increased with aging. Renal hypertrophy was evident in middle-aged and old mice and was associated with glomerulomegaly and increase in mesangial fraction occupied by extracellular matrix. Content of collagen types I and III and fibronectin was increased with aging; increment in their mRNA varied with the phase of aging. The content of ZEB1 and ZEB2, collagen type I transcription inhibitors, and their binding to the collagen type Iα2 promoter by ChIP assay also showed age-phase-specific changes. Lack of increase in mRNA and data from polysome assay suggested decreased degradation as a potential mechanism for kidney collagen type I accumulation in the middle-aged mice. These changes occurred with increment in TGFβ mRNA and protein and activation of its SMAD3 pathway; SMAD3 binding to the collagen type Iα2 promoter was also increased. TGFβ-regulated microRNAs (miRs) exhibited selective regulation. The renal cortical content of miR-21 and miR-200c, but not miR-192, miR-200a, or miR-200b, was increased with aging. Increased miR-21 and miR-200c contents were associated with reduced expression of their targets, Sprouty-1 and ZEB2, respectively. These data show that aging is associated with complex molecular events in the kidney that are already evident in the middle age and progress to old age. Agephase-specific regulation of matrix protein synthesis occurs and involves matrix protein-specific transcriptional and post-transcriptional mechanisms. PMID:23020145

  1. A study on the ultrastructure of the mouse kidney tissues affected by lead (Pb)

    International Nuclear Information System (INIS)

    Yoo, Chang Kyu; Choe, Rim Soon

    1986-01-01

    This study was made to investigate the ultrastructural changes of the male mouse(ICR strain) kidney tissue affected by lead(Pb). Pb, as a form of Pb(CH 3 COO) 2 was injected within the peritoneal cavity at the time interval of 24 hrs, 48 hrs and 72 hrs from injection time. In the meantime, electron microscopy was used to investigate the histologic changes occured in control animals, experimental animals. In kidney cells of experimental animals, changes of the nuclear chromatin were little, but cristae of mitochondria presented in cytoplasm was impaired, vacuolation was risen, thoseby many vacuole was formed. Especially, in the case of 5 mg/kg and 10 mg/kg Pb concentration, mitochondrial presented in cytoplasm was considerably deformed. While, with 20 mg/kg of Pb(CH 3 C00) 2 , it was observed that normal structure was presented in the nucleus electrodensity in cytoplasm was decreased mostly, but mitochondrial deform was slightly decreased. (Author)

  2. [Is there an age limit for cadaveric kidney donors currently?].

    Science.gov (United States)

    Cofán Pujol, F; Oppenheimer Salinas, F; Talbot-Wright, R; Carretero González, P

    1996-12-01

    The insufficient number of kidney transplants has gradually raised the age limit to the cadaver kidney donor. The use of grafts harvested from older donors has been debated due to the existing structural and functional changes that might influence renal function and long-term graft survival. The foregoing aspects are discussed herein. The anatomical, histological and functional changes in the kidney associated with ageing are analyzed. The clinical experience with renal grafts from older donors before and after cyclosporine became available are reviewed. The ethical issues on whether grafts from very old donors should be used and who should receive these grafts are discussed. The use of grafts from donors over 60 years old had no significant short and medium term differences in comparison with younger donors in terms of graft survival, although a higher incidence of acute tubular necrosis and poor renal function have been observed. There are no conclusive studies on the long-term effects on graft survival when kidneys from donors aged over 65 are utilized. In our experience, the results achieved with grafts from donors over 70 has been unsatisfactory. The guidelines utilized in the selection of grafts derived from older donors are presented. Grafts from donors aged 60 to 70 may be utilized in renal transplantation following precise selection criteria. Graft survival has been satisfactory, although a higher incidence of acute tubular necrosis and higher creatinine levels have been observed. We do not advocate the use of grafts from donors over 70, except in very exceptional cases. Long-term multicenter studies on grafts from very old donors and trials using alternative immunosuppressor modalities that might permit optimal use of these grafts are warranted.

  3. Endostatin and transglutaminase 2 are involved in fibrosis of the aging kidney.

    Science.gov (United States)

    Lin, Chi Hua Sarah; Chen, Jun; Zhang, Zhongtao; Johnson, Gail V W; Cooper, Arthur J L; Feola, Julianne; Bank, Alexander; Shein, Jonathan; Ruotsalainen, Heli J; Pihlajaniemi, Taina A; Goligorsky, Michael S

    2016-06-01

    Endostatin (EST), an antiangiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild-type mice, aging kidneys exhibited a 2- to 4-fold increase in TG2 paralleled by increased cross-linked extracellular matrix proteins and fibrosis. Mice transgenic to express EST showed renal fibrosis at a young age. One-month delivery of EST via minipumps to young mice showed increased renal fibrosis that became more robust when superimposed on folic acid-induced nephropathy. Upregulated TG2 and impaired renal function were apparent with EST delivery combined with folic acid-induced nephropathy. Subcapsular injection of TG2 and/or EST into kidneys of young mice not only induced interstitial fibrosis, but also increased the proportion of senescent cells. Thus, kidney fibrosis in aging may represent a natural outcome of upregulated EST and TG2, but more likely it appears to be a result of cumulative stresses occurring on the background of synergistically acting geronic (aging) proteins, EST and TG2. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  4. Radioprotection by dipyridamole in the aging mouse. Effects on lipid peroxidation in mouse liver, spleen and brain after whole-body X-ray irradiation

    International Nuclear Information System (INIS)

    Seino, Noritaka

    1995-01-01

    To investigate the radioprotective effect of dipyridamole in the aging mouse, the lipid peroxide content in aging mouse liver, spleen and brain irradiated by X-ray were measured both before and after injection of dipyridamole. The lipid peroxide content increased with aging from 2 months old to 16 months old in the mouse liver, spleen and brain. The content of lipid peroxide in the liver and spleen of the aging mouse was significantly increased in 7 days after whole-body irradiation with 8 Gy, but was unchanged in the brain. Dipyridamole, given before irradiation, significantly inhibited the increase of lipid peroxide after irradiation. These results suggest that dipyridamole may have radioprotective effects on aging mouse liver and spleen as well as on young mouse, and that inhibition of lipid peroxidation is a possible factor in the radioprotective effect of dipyridamole. (author)

  5. Aging Selectively Modulates Vitamin C Transporter Expression Patterns in the Kidney.

    Science.gov (United States)

    Forman, Katherine; Martínez, Fernando; Cifuentes, Manuel; Bertinat, Romina; Salazar, Katterine; Nualart, Francisco

    2017-09-01

    In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR, and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. J. Cell. Physiol. 232: 2418-2426, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Age-related changes of MAO-A and -B distribution in human and mouse brain.

    Science.gov (United States)

    Mahy, N; Andrés, N; Andrade, C; Saura, J

    2000-01-01

    Age-related changes of MAO-A and -B were studied in human and BL/C57 mouse brain areas (substantia nigra, putamen and cerebellum). [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. MAO-A binding was higher in mouse, whereas MAO-B binding was higher in human. With aging, mouse MAO-A was significantly reduced between 4 and 8 weeks and remained unchanged until 19 months followed by a slight increase between 19 and 25 months. In contrast, no clear variation was observed in humans between the age of 17-93 years. In most of the structures studied a clear age-related increase in MAO-B was observed beginning in mouse brain at 4 weeks, whereas in human tissue this increase started at the age of 50-60 years. These results show marked differences in the levels and variations of mouse and human MAO-A and -B associated with aging and should be taken into account when extrapolating experimental data from mouse to human.

  7. Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease.

    Science.gov (United States)

    Chen, Yumay; Chiang, Huai-Chin; Litchfield, Patricia; Pena, Michelle; Juang, Charity; Riley, Daniel J

    2014-07-17

    Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD. We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman's space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths. Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron.

  8. How age affects pointing with mouse and touchpad

    DEFF Research Database (Denmark)

    Hertzum, Morten; Hornbæk, Kasper

    2010-01-01

    pointing with mouse and touchpad. The goal is to provide an integrated analysis of (a) how these three age groups differ in pointing performance, (b) how these differences are affected by the two pointing devices, and (c) how the submovement structure of cursor trajectories may explain performance...... neither more nor less errors than young and adult participants. All three age groups were slower and made more errors with the touchpad than the mouse, but the touchpad slowed down elderly participants more than young participants, who in turn were slowed down more than adult participants. Adult......Effects of age on pointing performance have become increasingly important as computers have become extensively used by still larger parts of the population. This study empirically investigates young (12-14 years), adult (25-33 years), and elderly (61-69 years) participants' performance when...

  9. Local CD34-positive capillaries decrease in mouse models of kidney disease associating with the severity of glomerular and tubulointerstitial lesions.

    Science.gov (United States)

    Masum, Md Abdul; Ichii, Osamu; Elewa, Yaser Hosny Ali; Nakamura, Teppei; Kon, Yasuhiro

    2017-09-04

    The renal vasculature plays important roles in both homeostasis and pathology. In this study, we examined pathological changes in the renal microvascular in mouse models of kidney diseases. Glomerular lesions (GLs) in autoimmune disease-prone male BXSB/MpJ-Yaa (Yaa) mice and tubulointerstitial lesions (TILs) in male C57BL/6 mice subjected to unilateral ureteral obstruction (UUO) for 7 days were studied. Collected kidneys were examined using histopathological techniques. A nonparametric Mann-Whitney U test (P < 0.05) was performed to compare healthy controls and the experimental mice. The Kruskal-Wallis test was used to compare three or more groups, and multiple comparisons were performed using Scheffe's method when significant differences were observed (P < 0.05). Yaa mice developed severe autoimmune glomerulonephritis, and the number of CD34 + glomerular capillaries decreased significantly in GLs compared to that in control mice. However, UUO-treated mice showed severe TILs only, and CD34 + tubulointerstitial capillaries were decreased significantly in TILs with the progression of tubulointerstitial fibrosis compared to those in untreated control kidneys. Infiltrations of B-cells, T-cells, and macrophages increased significantly in the respective lesions of both disease models (P < 0.05). In observations of vascular corrosion casts by scanning electron microscopy and of microfil rubber-perfused thick kidney sections by fluorescence microscopy, segmental absences of capillaries were observed in the GLs and TILs of Yaa and UUO-treated mice, respectively. Further, transmission electron microscopy revealed capillary endothelial injury in the respective lesions of both models. The numbers of CD34 + glomerular and tubulointerstitial capillaries were negatively correlated with all examined parameters in GLs (P < 0.05) and TILs (P < 0.01), respectively. From the analysis of mouse models, we identified inverse pathological correlations between the number of

  10. Digital three-dimensional reconstruction and ultrastructure of the mouse proximal tubule

    DEFF Research Database (Denmark)

    Zhai, X.Y.; Birn, H.; Jensen, K.B.

    2003-01-01

    . In the medullary rays, these are arranged in layers outside the clusters of more superficial tubules. In contrast to rat and human kidney, no major segmental variation in the ultrastructure of the proximal tubule was identified, and no parameters enabled definition of distinct segments in this strain of mice......, detailed analyses of normal mouse kidney structure and organization are lacking. This study describes the 3D organization and ultrastructural, segmental variation of the mouse kidney proximal tubule. A total of 160 proximal tubules in three C57/BL/6J mouse kidneys were analyzed on 800 serial sections from...

  11. Cux1 promotes cell proliferation and polycystic kidney disease progression in an ADPKD mouse model.

    Science.gov (United States)

    Porath, Binu; Livingston, Safia; Andres, Erica L; Petrie, Alexandra M; Wright, Joshua C; Woo, Anna E; Carlton, Carol G; Baybutt, Richard; Vanden Heuvel, Gregory B

    2017-10-01

    Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic hereditary disorders in humans characterized by fluid-filled cysts, primarily in the kidneys. Cux1, a cell cycle regulatory gene highly expressed during kidney development, is elevated in the cyst-lining cells of Pkd1 mutant mice, and in human ADPKD cells. However, forced expression of Cux1 is insufficient to induce cystic disease in transgenic mice or to induce rapid cyst formation after cilia disruption in the kidneys of adult mice. Here we report a double mutant mouse model that has a conditional deletion of the Pkd1 gene in the renal collecting ducts together with a targeted mutation in the Cux1 gene (Pkd1 CD ;Cux1 tm2Ejn ). While kidneys isolated from newborn Pkd1 CD mice exhibit cortical and medullary cysts, kidneys isolated from newborn Pkd1 CD ;Cux1 tm2Ejn-/- mice did not show any cysts. Because Cux1 tm2Ejn-/- are perinatal lethal, we evaluated Pkd1 CD mice that were heterozygote for the Cux1 mutation. Similar to the newborn Pkd1 CD ;Cux1 tm2Ejn-/- mice, newborn Pkd1 CD ;Cux1 tm2Ejn+/- mice did not show any cysts. Comparison of Pkd1 CD and Pkd1 CD ;Cux1 tm2Ejn+/- mice at later stages of development showed a reduction in the severity of PKD in the Pkd1 CD ;Cux1 tm2Ejn+/- mice. Moreover, we observed an increase in expression of the cyclin kinase inhibitor p27, a target of Cux1 repression, in the rescued collecting ducts. Taken together, our results suggest that Cux1 expression in PKD is not directly involved in cystogenesis but promotes cell proliferation required for expansion of existing cysts, primarily by repression of p27. Copyright © 2017 the American Physiological Society.

  12. Kidney development in the first year of life in small-for-gestational-age preterm infants

    International Nuclear Information System (INIS)

    Hotoura, Efthalia; Giapros, Vasilios; Drougia, Aikaterini; Argyropoulou, Maria; Papadopoulou, Frederica; Nikolopoulos, Panayiotis; Andronikou, Styliani

    2005-01-01

    Small-for-gestational-age (SGA) infants have been reported to have a significantly reduced number of nephrons that could be a risk factor for development of hypertension later in life. To evaluate kidney size prospectively in relation to other anthropometric parameters during the first year of life in SGA babies. The babies in the study were 31-36 weeks' gestational age (GA) at birth and were matched with control preterm infants of similar GA, but appropriate for gestational age (AGA). The SGA infants were further classified as symmetrical and asymmetrical according to the anthropometric parameters. The total number of measurements in symmetrical SGA preterm infants was 324, in asymmetrical SGA preterm infants 295, and in AGA infants 536. In symmetrical SGA preterm infants (31-36 weeks' GA) mean kidney length (± SD) of 56±4 mm was significantly different from the controls (58.9±4.6 mm) up to 6 months' chronological age (P < 0.05). In the asymmetrical SGA preterm infants, mean kidney length (45.3±4.0 mm) was significantly different from the controls (48.2±4.4 mm) up to 40 weeks' corrected age. At 1 year chronological age, all preterm infants (symmetrical and asymmetrical SGA and AGA) had similar mean kidney length (61.6±4.6, 62.8±4.3, and 62.3±4.0 mm, respectively). The ratio of kidney length to crown-to-heel length was similar in all preterm groups. Kidney length in preterm SGA infants (symmetrical and asymmetrical) follows closely the other auxological parameters during the first year of life. (orig.)

  13. Formation of DNA adducts in mouse tissues after 1-nitropyrene administration

    International Nuclear Information System (INIS)

    Mitchell, C.E.

    1986-01-01

    DNA adducts were isolated and characterized in mouse lung, liver and kidney after intratracheal instillation of [ 3 H]-1-nitropyrene (1-NP). HPLC analysis of the enzymatically digested DNA indicated the presence of multiple DNA adducts in mouse lung, liver and kidney. These results indicate that DNA adducts of 1-NP are formed in mouse lung, liver and kidney after intratracheal instillation of 1-NP; the HPLC profiles of the multiple adducts suggests that adducts may be formed via metabolic pathways that involve both nitroreduction and ring-oxidation. 6 references, 1 figure

  14. Influence of age, irradiation and humanization on NSG mouse phenotypes

    Directory of Open Access Journals (Sweden)

    Jaclyn S. Knibbe-Hollinger

    2015-10-01

    Full Text Available Humanized mice are frequently utilized in bench to bedside therapeutic tests to combat human infectious, cancerous and degenerative diseases. For the fields of hematology-oncology, regenerative medicine, and infectious diseases, the immune deficient mice have been used commonly in basic research efforts. Obstacles in true translational efforts abound, as the relationship between mouse and human cells in disease pathogenesis and therapeutic studies requires lengthy investigations. The interplay between human immunity and mouse biology proves ever more complicated when aging, irradiation, and human immune reconstitution are considered. All can affect a range of biochemical and behavioral functions. To such ends, we show age- and irradiation-dependent influences for the development of macrocytic hyper chromic anemia, myelodysplasia, blood protein reductions and body composition changes. Humanization contributes to hematologic abnormalities. Home cage behavior revealed day and dark cycle locomotion also influenced by human cell reconstitutions. Significant age-related day-to-day variability in movement, feeding and drinking behaviors were observed. We posit that this data serves to enable researchers to better design translational studies in this rapidly emerging field of mouse humanization.

  15. Of mice and men: divergence of gene expression patterns in kidney.

    Directory of Open Access Journals (Sweden)

    Lydie Cheval

    Full Text Available Since the development of methods for homologous gene recombination, mouse models have played a central role in research in renal pathophysiology. However, many published and unpublished results show that mice with genetic changes mimicking human pathogenic mutations do not display the human phenotype. These functional differences may stem from differences in gene expression between mouse and human kidneys. However, large scale comparison of gene expression networks revealed conservation of gene expression among a large panel of human and mouse tissues including kidneys. Because renal functions result from the spatial integration of elementary processes originating in the glomerulus and the successive segments constituting the nephron, we hypothesized that differences in gene expression profiles along the human and mouse nephron might account for different behaviors. Analysis of SAGE libraries generated from the glomerulus and seven anatomically defined nephron segments from human and mouse kidneys allowed us to identify 4644 pairs of gene orthologs expressed in either one or both species. Quantitative analysis shows that many transcripts are present at different levels in the two species. It also shows poor conservation of gene expression profiles, with less than 10% of the 4644 gene orthologs displaying a higher conservation of expression profiles than the neutral expectation (p<0.05. Accordingly, hierarchical clustering reveals a higher degree of conservation of gene expression patterns between functionally unrelated kidney structures within a given species than between cognate structures from the two species. Similar findings were obtained for sub-groups of genes with either kidney-specific or housekeeping functions. Conservation of gene expression at the scale of the whole organ and divergence at the level of its constituting sub-structures likely account for the fact that although kidneys assume the same global function in the two species

  16. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Aging-related renal injury and inflammation are associated with downregulation of Klotho and induction of RIG-I/NF-κB signaling pathway in senescence-accelerated mice.

    Science.gov (United States)

    Zeng, Yi; Wang, Ping-Han; Zhang, Mao; Du, Jun-Rong

    2016-02-01

    The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury. Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury. Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls. The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.

  18. Correlation and clinical significance between glomerular filtration rate and age in living-related kidney donors

    International Nuclear Information System (INIS)

    Zhao Xiuyi; Shao Yahui; Wang Yanming; Zhang Aimin; Hao Junwen; Tian Jun; Sun Ben; Han Jiankui

    2010-01-01

    Objective: To quantitatively investigate the effect of age on the glomerular filtration rate (GFR) in living-related kidney donors. to analyze the clinical value and the dependence of GFR on age and to provide an objective basis for the selection of the living kidney donor. Methods: One hundred and sixty-one living-related kidney donors were divided into four age groups, namely 20-29 years (n=52), 30-39 years (n=44), 40-49 years (n=38) and ≥50 years (n=27). On the other hand, the total donors were divided into the groups older than 55 years (n=24) and younger than 55 years (n=137). To quantify GFR in all the subjects using the 99 Tc m -diethylenetriamine pentaacetic acid ( 99 Tc m -DTPA) renography according to standard procedure and to evaluate the effects of age on renal function. Results: The total GFR in living-related kidney donors was calculated as (89.55±12.87) ml·min -1 ·(1.73 m 2 ) -1 . The GFR in the first to the four age groups were (88.27±12.29) ml·min -1 ·(1.73 m 2 ) -1 , (91.85±14.51) ml·min -1 ·(1.73 m 2 ) -1 , (98.25±11.26) ml·min -1 ·(1.73 m 2 ) -1 and (88.24±13.20) ml·min -1 ·(1.73 m 2 ) -1 . The difference of GFR were not significant between the four age groups (F=2.09, P=0.10). The GFR in the donors older than 55 years and younger than 55 years were (88.57±13.14) ml·min -1 ·(1.73 m 2 ) -1 and (89.44±10.34) ml·min -1 ·(1.73 m 2 ) -1 , there no significant difference in GFR between the two groups (F=1.31, P=0.25). When relating GFR to age in all the living-related kidney donors, there was no significant correlation (r=-0.033, P=0.69). No serious complications occurred after living kidney transplantation, serum creatinine values and blood urea nitrogen recovered to the normal levels in a short period, hepatic and renal functions were normal. Conclusion: This study indicated that the GFR values were not correlated with the change of age in living-related kidney donors, and the results were helpful for the selection of living

  19. A low molecular weight urinary proteome profile of human kidney aging

    OpenAIRE

    Zürbig, Petra; Decramer, Stéphane; Dakna, Mohammed; Jantos, Justyna; Good, David M.; Coon, Joshua J.; Bandin, Flavio; Mischak, Harald; Bascands, Jean-Loup; Schanstra, Joost P

    2009-01-01

    Aging induces morphological changes of the kidney and reduces renal function. We analyzed the low molecular weight urinary proteome of 324 healthy individuals from 2-73 years of age to gain insight on renal aging in humans. We observed age-related modification of secretion of 325 out of 5000 urinary peptides. The majority of these changes was associated with renal development before and during puberty, while 49 peptides were related to aging in adults. Of these 49 peptides, the majority were ...

  20. Acute response of mouse kidney clonogens to fractionated irradiation in situ and then assayed in primary culture

    International Nuclear Information System (INIS)

    Yeemin Jen; Hendry, J.H.

    1991-01-01

    The radiosensitivity of mouse kidney cells after in situ single-dose, 2, 8, and 16 fraction X-irradiations was measured in primary culture using a clonogenic assay. The assay was made 12 h after single doses or 12 h after the last dose of the multifraction regimens. When analysed using the linear-quadratic model, as predicted the individual α components for all the different fractionation schedules were not significantly different, and the changes in the β values were consistent with those expected on the basis of the reciprocal fraction numbers. When all four data sets were integrated to derive a common α/β ratio, the result was 4.4±1.3 (1SE) Gy, or 2.8±0.9 Gy (a better fit) if the single-dose data set was excluded. These values fall into the range reported for kidney using assays of tissue function at long times after irradiation. (author)

  1. Aging has small effects on initial ischemic acute kidney injury development despite changing intrarenal immunologic micromilieu in mice.

    Science.gov (United States)

    Jang, Hye Ryoun; Park, Ji Hyeon; Kwon, Ghee Young; Park, Jae Berm; Lee, Jung Eun; Kim, Dae Joong; Kim, Yoon-Goo; Kim, Sung Joo; Oh, Ha Young; Huh, Wooseong

    2016-02-15

    Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required. Copyright © 2016 the American Physiological Society.

  2. Kidney Problems

    Science.gov (United States)

    ... our e-newsletter! Aging & Health A to Z Kidney Problems Basic Facts & Information The kidneys are two ... kidney (renal) diseases are called nephrologists . What are Kidney Diseases? For about one-third of older people, ...

  3. The Inflammatory Transcription Factors NFκB, STAT1 and STAT3 Drive Age-Associated Transcriptional Changes in the Human Kidney

    Science.gov (United States)

    O’Brown, Zach K.; Van Nostrand, Eric L.; Higgins, John P.; Kim, Stuart K.

    2015-01-01

    Human kidney function declines with age, accompanied by stereotyped changes in gene expression and histopathology, but the mechanisms underlying these changes are largely unknown. To identify potential regulators of kidney aging, we compared age-associated transcriptional changes in the human kidney with genome-wide maps of transcription factor occupancy from ChIP-seq datasets in human cells. The strongest candidates were the inflammation-associated transcription factors NFκB, STAT1 and STAT3, the activities of which increase with age in epithelial compartments of the renal cortex. Stimulation of renal tubular epithelial cells with the inflammatory cytokines IL-6 (a STAT3 activator), IFNγ (a STAT1 activator), or TNFα (an NFκB activator) recapitulated age-associated gene expression changes. We show that common DNA variants in RELA and NFKB1, the two genes encoding subunits of the NFκB transcription factor, associate with kidney function and chronic kidney disease in gene association studies, providing the first evidence that genetic variation in NFκB contributes to renal aging phenotypes. Our results suggest that NFκB, STAT1 and STAT3 underlie transcriptional changes and chronic inflammation in the aging human kidney. PMID:26678048

  4. Changes of mitochondrial ultrastructure and function during ageing in mice and Drosophila.

    Science.gov (United States)

    Brandt, Tobias; Mourier, Arnaud; Tain, Luke S; Partridge, Linda; Larsson, Nils-Göran; Kühlbrandt, Werner

    2017-07-12

    Ageing is a progressive decline of intrinsic physiological functions. We examined the impact of ageing on the ultrastructure and function of mitochondria in mouse and fruit flies ( Drosophila melanogaster ) by electron cryo-tomography and respirometry. We discovered distinct age-related changes in both model organisms. Mitochondrial function and ultrastructure are maintained in mouse heart, whereas subpopulations of mitochondria from mouse liver show age-related changes in membrane morphology. Subpopulations of mitochondria from young and old mouse kidney resemble those described for apoptosis. In aged flies, respiratory activity is compromised and the production of peroxide radicals is increased. In about 50% of mitochondria from old flies, the inner membrane organization breaks down. This establishes a clear link between inner membrane architecture and functional decline. Mitochondria were affected by ageing to very different extents, depending on the organism and possibly on the degree to which tissues within the same organism are protected against mitochondrial damage.

  5. 2C.07: INVOLVEMENT OF THE RENIN-ANGIOTENSIN SYSTEM IN A PREMATURE AGING MOUSE MODEL.

    Science.gov (United States)

    Van Thiel, B S; Ridwan, Y; Garrelds, I M; Vermeij, M; Groningen, M C Clahsen-Van; Danser, A H J; Essers, J; Van Der Pluijm, I

    2015-06-01

    Changes in the renin-angiotensin system (RAS), known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. Here we characterized the RAS and kidney pathology in mice with genomic instability due to a defective nucleotide excision repair gene (Ercc1d/- mice). These mice display premature features of aging, including vascular dysfunction. Studies were performed in male and female Ercc1d/- mice and their wild type controls (Ercc1+/+) at the age of 12 or 18 weeks before and after treatment with losartan. The renin-activatable near-infrared fluorescent probe ReninSense 680™ was applied in vivo to allow non-invasive imaging of renin activity. Plasma renin concentrations (PRC) were additionally measured ex vivo by quantifying Ang I generation in the presence of excess angiotensinogen. Kidneys were harvested and examined for markers of aging, and albumin was determined in urine. Kidneys of 12-week old Ercc1d/- mice showed signs of aging, including tubular anisokaryosis, cell-senescence and increased apoptosis. This was even more pronounced at the age of 18 weeks. Yet, urinary albumin was normal at 12 weeks. The ReninSense 680™ probe showed increased intrarenal renin activity in Ercc1d/- mice versus Ercc1+/+ mice, both at 12 and 18 weeks of age, while PRC in these mice tended to be lower compared to Ercc1+/+ mice. Renin was higher in male than female mice, both in the kidney and in plasma, and losartan increased kidney and plasma renin in both Ercc1d/- and Ercc1+/+ mice. Rapidly aging Ercc1d/- mice display an activated intrarenal RAS, as evidenced by the increased fluorescence detected with the ReninSense 680™ probe. This increased RAS activity may contribute to the disturbed kidney pathology in these mice. The increased intrarenal activity detected with the ReninSense 680™ probe in male vs. female mice, as well as after losartan treatment, are in full agreement with the literature, and

  6. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Picq

    Full Text Available The mouse lemur (Microcebus murinus is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12 and aged (n = 8 adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination.

  7. Age-related changes in liver, kidney, and spleen stiffness in healthy children measured with acoustic radiation force impulse imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mi-Jung, E-mail: mjl1213@yuhs.ac [Department of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Yonsei University, College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kim, Myung-Joon, E-mail: mjkim@yuhs.ac [Department of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Yonsei University, College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Han, Kyung Hwa, E-mail: khhan@yuhs.ac [Biostatistics Collaboration Unit, Yonsei University, College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yoon, Choon Sik, E-mail: yooncs58@yuhs.ac [Department of Radiology, Gangnam Severance Hospital, Yonsei University, College of Medicine, 211 Unjoo-ro, Gangnam-gu, Seoul (Korea, Republic of)

    2013-06-15

    Objectives: To evaluate the feasibility and age-related changes of shear wave velocity (SWV) in normal livers, kidneys, and spleens of children using acoustic radiation force impulse (ARFI) imaging. Materials and methods: Healthy pediatric volunteers prospectively underwent abdominal ultrasonography and ARFI. The subjects were divided into three groups according to age: group 1: <5 years old; group 2: 5–10 years old; and group 3: >10 years old. The SWV was measured using a 4–9 MHz linear probe for group 1 and a 1–4 MHz convex probe for groups 2 and 3. Three valid SWV measurements were acquired for each organ. Results: Two hundred and two children (92 male, 110 female) with an average age of 8.1 years (±4.7) were included in this study and had a successful measurement rate of 97% (196/202). The mean SWVs were 1.12 m/s for the liver, 2.19 m/s for the right kidney, 2.33 m/s for the left kidney, and 2.25 m/s for the spleen. The SWVs for the right and left kidneys, and the spleen showed age-related changes in all children (p < 0.001). And the SWVs for the kidneys increased with age in group 1, and those for the liver changed with age in group 3. Conclusions: ARFI measurements are feasible for solid abdominal organs in children using high or low frequency probes. The mean ARFI SWV for the kidneys increased according to age in children less than 5 years of age and in the liver, it changed with age in children over 10.

  8. Cytochrome P450-2E1 is involved in aging-related kidney damage in mice through increased nitroxidative stress.

    Science.gov (United States)

    Abdelmegeed, Mohamed A; Choi, Youngshim; Ha, Seung-Kwoon; Song, Byoung-Joon

    2017-11-01

    The aim of this study was to investigate the role of cytochrome P450-2E1 (CYP2E1) in aging-dependent kidney damage since it is poorly understood. Young (7 weeks) and aged female (16-17 months old) wild-type (WT) and Cyp2e1-null mice were used. Kidney histology showed that aged WT mice exhibited typical signs of kidney aging such as cell vacuolation, inflammatory cell infiltration, cellular apoptosis, glomerulonephropathy, and fibrosis, along with significantly elevated levels of renal TNF-α and serum creatinine than all other groups. Furthermore, the highest levels of renal hydrogen peroxide, protein carbonylation and nitration were observed in aged WT mice. These increases in the aged WT mice were accompanied by increased levels of iNOS and mitochondrial nitroxidative stress through altered amounts and activities of the mitochondrial complex proteins and significantly reduced levels of the antioxidant glutathione (GSH). In contrast, the aged Cyp2e1-null mice exhibited significantly higher antioxidant capacity with elevated heme oxygenase-1 and catalase activities compared to all other groups, while maintaining normal GSH levels with significantly less mitochondrial nitroxidative stress compared to the aged WT mice. Thus, CYP2E1 is important in causing aging-related kidney damage most likely through increasing nitroxidative stress and that CYP2E1 could be a potential target in preventing aging-related kidney diseases. Published by Elsevier Ltd.

  9. Anatomic and physiologic changes of the aging kidney.

    Science.gov (United States)

    Karam, Zeina; Tuazon, Jennifer

    2013-08-01

    Aging is associated with structural and functional changes in the kidney. Structural changes include glomerulosclerosis, thickening of the basement membrane, increase in mesangial matrix, tubulointerstitial fibrosis and arteriosclerosis. Glomerular filtration rate is maintained until the fourth decade of life, after which it declines. Parallel reductions in renal blood flow occur with redistribution of blood flow from the cortex to the medulla. Other functional changes include an increase in glomerular basement permeability and decreased ability to dilute or concentrate urine. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Time- and dose rate-related effects of internal 177Lu exposure on gene expression in mouse kidney tissue

    International Nuclear Information System (INIS)

    Schüler, Emil; Rudqvist, Nils; Parris, Toshima Z.; Langen, Britta; Spetz, Johan; Helou, Khalil; Forssell-Aronsson, Eva

    2014-01-01

    Introduction: The kidneys are the dose-limiting organs in some radionuclide therapy regimens. However, the biological impact of internal exposure from radionuclides is still not fully understood. The aim of this study was to examine the effects of dose rate and time after i.v. injection of 177 LuCl 3 on changes in transcriptional patterns in mouse kidney tissue. Methods: To investigate the effect of dose rate, female Balb/c nude mice were i.v. injected with 11, 5.6, 1.6, 0.8, 0.30, and 0 MBq of 177 LuCl 3 , and killed at 3, 6, 24, 48, 168, and 24 hours after injection, respectively. Furthermore, the effect of time after onset of exposure was analysed using mice injected with 0.26, 2.4, and 8.2 MBq of 177 LuCl 3 , and killed at 45, 90, and 140 days after injection. Global transcription patterns of irradiated kidney cortex and medulla were assessed and enriched biological processes were determined from the regulated gene sets using Gene Ontology terms. Results: The average dose rates investigated were 1.6, 0.84, 0.23, 0.11 and 0.028 mGy/min, with an absorbed dose of 0.3 Gy. At 45, 90 and 140 days, the absorbed doses were estimated to 0.3, 3, and 10 Gy. In general, the number of differentially regulated transcripts increased with time after injection, and decreased with absorbed dose for both kidney cortex and medulla. Differentially regulated transcripts were predominantly involved in metabolic and stress response-related processes dependent on dose rate, as well as transcripts associated with metabolic and cellular integrity at later time points. Conclusion: The observed transcriptional response in kidney tissue was diverse due to difference in absorbed dose, dose rate and time after exposure. Nevertheless, several transcripts were significantly regulated in all groups despite differences in exposure parameters, which may indicate potential biomarkers for exposure of kidney tissue

  11. Evaluation of the Normal Fetal Kidney Length and Its Correlation with Gestational Age

    OpenAIRE

    Farrokh Seilanian Toosi; Hossein Rezaie-Delui

    2013-01-01

    A true estimation of gestational age (GA) plays an important role in quality maternity care and scheduling the labor date. This study aimed to evaluate the normal fetal kidney length (KL) and its correlation with GA. A cross-sectional study on 92 pregnant women between 8th and 10th week of gestation with normal singleton pregnancy underwent standard ultrasound fetal biometry and kidney length measurement. univariate and multivariate linear regression analysis was used to create a predictive e...

  12. The mouse as a model organism in aging research: usefulness, pitfalls and possibilities.

    Science.gov (United States)

    Vanhooren, Valerie; Libert, Claude

    2013-01-01

    The mouse has become the favorite mammalian model. Among the many reasons for this privileged position of mice is their genetic proximity to humans, the possibilities of genetically manipulating their genomes and the availability of many tools, mutants and inbred strains. Also in the field of aging, mice have become very robust and reliable research tools. Since laboratory mice have a life expectancy of only a few years, genetic approaches and other strategies for intervening in aging can be tested by examining their effects on life span and aging parameters during the relatively short period of, for example, a PhD project. Moreover, experiments on mice with an extended life span as well as on mice demonstrating signs of (segmental) premature aging, together with genetic mapping strategies, have provided novel insights into the fundamental processes that drive aging. Finally, the results of studies on caloric restriction and pharmacological anti-aging treatments in mice have a high degree of relevance to humans. In this paper, we review a number of recent genetic mapping studies that have yielded novel insights into the aging process. We discuss the value of the mouse as a model for testing interventions in aging, such as caloric restriction, and we critically discuss mouse strains with an extended or a shortened life span as models of aging. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Apparent diffusion coefficient measurements of bilateral kidneys at 3 T MRI: Effects of age, gender, and laterality in healthy adults

    International Nuclear Information System (INIS)

    Suo, S.-T.; Cao, M.-Q.; Ding, Y.-Z.; Yao, Q.-Y.; Wu, G.-Y.; Xu, J.-R.

    2014-01-01

    Aim: To investigate the effects of age and gender on apparent diffusion coefficient (ADC) measurements of bilateral kidneys at 3 T MRI, and compare the ADC values of left and right kidneys. Materials and methods: In all, 137 healthy participants (mean age 42.8 ± 14.7 years; age range 16–75 years) comprising 68 male and 69 female participants were enrolled. Three Tesla echo-planar diffusion-weighted imaging (DWI) of bilateral kidneys was performed and ADC values were measured in the cortex, medulla, and whole parenchyma. Pearson correlation analysis and linear regression were performed to determine the associations between the ADC values in each region and age. Effects of age and gender on ADC values were analysed using two-factor analysis of variance (ANOVA). The paired-samples t-test was established to compare the ADC values between left and right kidneys. Results: ADC values were significantly higher in the young group (≤50 years) than in the old group (>50 years), and correlated inversely with the age in all regions. Male participants had higher ADC values than female participants in all regions except left medulla. Two-factor ANOVA of age × gender showed no significant interactions between the variables age and gender were found. No significant differences in ADC values between left and right kidneys were observed. Conclusion: Renal ADC values are age- and gender-dependent, and show no significant difference between left and right kidneys. Age- and gender-related effects should be taken into consideration in future renal DWI studies when using normal ADC values from health controls. - Highlights: • Renal apparent diffusion coefficient (ADC) values decrease with ageing. • Men tend to have higher renal ADC values than women. • Bilateral kidneys seem to have no significantly different ADC values

  14. Contemporary, age-based trends in the incidence and management of patients with early-stage kidney cancer.

    Science.gov (United States)

    Tan, Hung-Jui; Filson, Christopher P; Litwin, Mark S

    2015-01-01

    Although kidney cancer incidence and nephrectomy rates have risen in tandem, clinical advances have generated new uncertainty regarding the optimal management of patients with small renal tumors, especially the elderly. To clarify existing practice patterns, we assessed contemporary trends in the incidence and management of patients with early-stage kidney cancer. Using Surveillance, Epidemiology, and End Results data, we identified adult patients diagnosed with T1aN0M0 kidney cancer from 2000 to 2010. We determined age-adjusted and age-specific incidence and management rates (i.e., nonoperative, ablation, partial nephrectomy [PN], and radical nephrectomy) per 100,000 adults and determined the average annual percent change (AAPC). Finally, we compared management groups using multinomial logistic regression accounting for patient characteristics, cancer information, and county-level measures for health. From 2000 to 2010, we identified 41,645 adults diagnosed with T1aN0M0 kidney cancer. Overall incidence increased from 3.7 to 7.0 per 100,000 adults (AAPC = 7.0%, Pmanagement and ablation approached nephrectomy rates for those aged 75 to 84 years and became the predominant strategy for patients older than 84 years. Adjusting for clinical, oncological, and environmental factors, older patients less frequently underwent PN and more often received ablative or nonoperative management (P<0.001). As the incidence of early-stage kidney cancer rises, patients are increasingly treated with nonoperative and nephron-sparing strategies, especially among the most elderly. The broader array of treatment options suggests opportunities to better personalize kidney cancer care for seniors. Published by Elsevier Inc.

  15. Mouse models of ageing and their relevance to disease.

    Science.gov (United States)

    Kõks, Sulev; Dogan, Soner; Tuna, Bilge Guvenc; González-Navarro, Herminia; Potter, Paul; Vandenbroucke, Roosmarijn E

    2016-12-01

    Ageing is a process that gradually increases the organism's vulnerability to death. It affects different biological pathways, and the underlying cellular mechanisms are complex. In view of the growing disease burden of ageing populations, increasing efforts are being invested in understanding the pathways and mechanisms of ageing. We review some mouse models commonly used in studies on ageing, highlight the advantages and disadvantages of the different strategies, and discuss their relevance to disease susceptibility. In addition to addressing the genetics and phenotypic analysis of mice, we discuss examples of models of delayed or accelerated ageing and their modulation by caloric restriction. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  16. Oxidative Stress as a Mechanism Involved in Kidney Damage After Subchronic Exposure to Vanadium Inhalation and Oral Sweetened Beverages in a Mouse Model.

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    Espinosa-Zurutuza, Maribel; González-Villalva, Adriana; Albarrán-Alonso, Juan Carlos; Colín-Barenque, Laura; Bizarro-Nevares, Patricia; Rojas-Lemus, Marcela; López-Valdéz, Nelly; Fortoul, Teresa I

    Kidney diseases have notably increased in the last few years. This is partially explained by the increase in metabolic syndrome, diabetes, and systemic blood hypertension. However, there is a segment of the population that has neither of the previous risk factors, yet suffers kidney damage. Exposure to atmospheric pollutants has been suggested as a possible risk factor. Air-suspended particles carry on their surface a variety of fuel combustion-related residues such as metals, and vanadium is one of these. Vanadium might produce oxidative stress resulting in the damage of some organs such as the kidney. Additionally, in countries like Mexico, the ingestion of sweetened beverages is a major issue; whether these beverages alone are responsible for direct kidney damage or whether their ingestion promotes the progression of an existing renal damage generates controversy. In this study, we report the combined effect of vanadium inhalation and sweetened beverages ingestion in a mouse model. Forty CD-1 male mice were distributed in 4 groups: control, vanadium inhalation, 30% sucrose in drinking water, and vanadium inhalation plus sucrose 30% in drinking water. Our results support that vanadium inhalation and the ingestion of 30% sucrose induce functional and histological kidney damage and an increase in oxidative stress biomarkers, which were higher in the combined effect of vanadium plus 30% sucrose. The results also support that the ingestion of 30% sucrose alone without hyperglycemia also produces kidney damage.

  17. Inhibiting Effects of Achyranthes Bidentata Polysaccharide and Lycium Barbarum Polysaccharide on Nonenzyme Glycation in D-galactose Induced Mouse Aging Model

    Institute of Scientific and Technical Information of China (English)

    HONG-BIN DENG; DA-PENG CUI; JIAN-MING JIANG; YAN-CHUN FENG; NIAN-SHENG CAI; DIAN-DONG LI

    2003-01-01

    To investigate the inhibiting effects and mechanism of achyranthes bidentata polysaccharide (ABP) and lycium barbarum polysaccharide (LBP) on nonenzyme glycation in D-galactose induced mouse aging model. Methods Serum AGE levels were determined by AGE-ELISA, MTT method was used to determine lymphocyte proliferation, IL-2 activity was determined by a bioassay method. Spontaneous motor activity was used to detect mouse's neuromuscular movement, latency of step-through method was used to examine learning and memory abilities of mouse, colormetric assay was used to determine hydroxyproline concentration in mouse skin, pyrogallol autoxidation method was used to determine superoxide dismutase (SOD) activity of erythrocytes. Results Decreased levels of serum AGE, hydroxyproline concentration in mouse skin and spontaneous motor activity in D-galactose mouse aging model were detected after treated with ABP or LBP, while lymphocyte proliferation and IL-2 activity, learning and memory abilities,SOD activity of erythrocytes, were enhanced. Conclusions ABP and LBP could inhibit nonenzyme glycation in D-galactose induced mouse aging model in vivo and ABP has a better inhibiting effect than LBP.

  18. Antitumour and Antioxidant Activities of Activin in Kidney Tissue of Mouse Bearing Murine Mammary Adenocarcinoma and Exposed to Gamma Radiation

    International Nuclear Information System (INIS)

    EI-Tahawy, N.A.; Hanafi, N.; Said, U.Z.

    2009-01-01

    Activin (a grape seed-derived proanthocyanidins extract) possess a broad spectrum of biological, pharmacological and therapeutic activities. The present study performed to investigate the preventive and modulating effects of dietary activin in radiation or murine mammary adenocarcinoma (MMA) induced damage in kidneys of albino mice throughout in vitro and in vivo studies. Activin was orally administered to mice for 5 consecutive days (100 mg/ kg body wt) before and 10 days post tumour inoculation. In irradiated group, animals were exposed to 6 Gy whole body gamma-radiations on the fifth day of tumour inoculation. Biochemical and histopathological studies were investigated. In vitro studies using MMA cells revealed that activin increase non viable tumour cell counts. In vivo studies, either MMA or gamma-irradiation resulted in biochemical, and histopathological changes leading to kidney damage. Biochemical studies revealed that activin treatment significantly restored the elevated activity of lactate dehydrogenase (LDH), ameliorated kidney functions profile, and depressed the levels of tumour markers, also enhanced glutathione content (GSH) and activities of superoxide dismutase (SOD) and catalase (CAT). It also reduced kidney lipid peroxides and improves serum total protein level. Histopathological changes in the kidney tissues were attenuated by activin treatment either in MMA-bearing mice group or irradiation group. Exposure of MMA-bearing mouse to gamma- radiations slightly improves the above mentioned damage. While dual treatment of MMA-bearing mice with activin and subsequence with gamma-radiation exposure was more effective. It could be concluded that activin through its antioxidant properties might attenuate radiation or MMA induced renal damage suggesting that activin may have a potential benefit in enhancing radiotherapy

  19. Brain perfusion SPECT in the mouse: normal pattern according to gender and age.

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    Apostolova, Ivayla; Wunder, Andreas; Dirnagl, Ulrich; Michel, Roger; Stemmer, Nina; Lukas, Mathias; Derlin, Thorsten; Gregor-Mamoudou, Betina; Goldschmidt, Jürgen; Brenner, Winfried; Buchert, Ralph

    2012-12-01

    Regional cerebral blood flow (rCBF) is a useful surrogate marker of neuronal activity and a parameter of primary interest in the diagnosis of many diseases. The increasing use of mouse models spawns the demand for in vivo measurement of rCBF in the mouse. Small animal SPECT provides excellent spatial resolution at adequate sensitivity and is therefore a promising tool for imaging the mouse brain. This study evaluates the feasibility of mouse brain perfusion SPECT and assesses the regional pattern of normal Tc-99m-HMPAO uptake and the impact of age and gender. Whole-brain kinetics was compared between Tc-99m-HMPAO and Tc-99m-ECD using rapid dynamic planar scans in 10 mice. Assessment of the regional uptake pattern was restricted to the more suitable tracer, HMPAO. Two HMPAO SPECTs were performed in 18 juvenile mice aged 7.5 ± 1.5weeks, and in the same animals at young adulthood, 19.1 ± 4.0 weeks (nanoSPECT/CTplus, general purpose mouse apertures: 1.2kcps/MBq, 0.7mm FWHM). The 3-D MRI Digital Atlas Database of an adult C57BL/6J mouse brain was used for region-of-interest (ROI) analysis. SPECT images were stereotactically normalized using SPM8 and a custom made, left-right symmetric HMPAO template in atlas space. For testing lateral asymmetry, each SPECT was left-right flipped prior to stereotactical normalization. Flipped and unflipped SPECTs were compared by paired testing. Peak brain uptake was similar for ECD and HMPAO: 1.8 ± 0.2 and 2.1 ± 0.6 %ID (p=0.357). Washout after the peak was much faster for ECD than for HMPAO: 24 ± 7min vs. 4.6 ± 1.7h (p=0.001). The general linear model for repeated measures with gender as an intersubject factor revealed an increase in relative HMPAO uptake with age in the neocortex (p=0.018) and the hippocampus (p=0.012). A decrease was detected in the midbrain (p=0.025). Lateral asymmetry, with HMPAO uptake larger in the left hemisphere, was detected primarily in the neocortex, both at juvenile age (asymmetry index AI=2.7 ± 1

  20. Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

    Science.gov (United States)

    2013-01-01

    Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

  1. Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

    Science.gov (United States)

    Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

    2013-08-16

    Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

  2. CXC chemokine receptor 7 (CXCR7 regulates CXCR4 protein expression and capillary tuft development in mouse kidney.

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    Sammy Haege

    Full Text Available BACKGROUND: The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. METHODOLOGY/PRINCIPAL FINDINGS: We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. CONCLUSIONS/SIGNIFICANCE: We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries.

  3. CXC Chemokine Receptor 7 (CXCR7) Regulates CXCR4 Protein Expression and Capillary Tuft Development in Mouse Kidney

    Science.gov (United States)

    Haege, Sammy; Mueller, Wiebke; Nietzsche, Sandor; Lupp, Amelie; Mackay, Fabienne; Schulz, Stefan; Stumm, Ralf

    2012-01-01

    Background The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. Methodology/Principal Findings We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. Conclusions/Significance We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries. PMID:22880115

  4. Dopaminergic Immunofluorescence Studies in Kidney Tissue.

    Science.gov (United States)

    Gildea, J J; Van Sciver, R E; McGrath, H E; Kemp, B A; Jose, P A; Carey, R M; Felder, R A

    2017-01-01

    The kidney is a highly integrated system of specialized differentiated cells that are responsible for fluid and electrolyte balance in the body. While much of today's research focuses on isolated nephron segments or cells from nephron segments grown in tissue culture, an often overlooked technique that can provide a unique view of many cell types in the kidney is slice culture. Here, we describe techniques that use freshly excised kidney tissue from rats to perform a variety of experiments shortly after isolating the tissue. By slicing the rat kidney in a "bread loaf" format, multiple studies can be performed on slices from the same tissue in parallel. Cryosectioning and staining of the tissue allow for the evaluation of physiological or biochemical responses in a wide variety of specific nephron segments. The procedures described within this chapter can also be extended to human or mouse kidney tissue.

  5. The use of urinary proteomics in the assessment of suitability of mouse models for ageing.

    Science.gov (United States)

    Nkuipou-Kenfack, Esther; Schanstra, Joost P; Bajwa, Seerat; Pejchinovski, Martin; Vinel, Claire; Dray, Cédric; Valet, Philippe; Bascands, Jean-Loup; Vlahou, Antonia; Koeck, Thomas; Borries, Melanie; Busch, Hauke; Bechtel-Walz, Wibke; Huber, Tobias B; Rudolph, Karl L; Pich, Andreas; Mischak, Harald; Zürbig, Petra

    2017-01-01

    Ageing is a complex process characterised by a systemic and progressive deterioration of biological functions. As ageing is associated with an increased prevalence of age-related chronic disorders, understanding its underlying molecular mechanisms can pave the way for therapeutic interventions and managing complications. Animal models such as mice are commonly used in ageing research as they have a shorter lifespan in comparison to humans and are also genetically close to humans. To assess the translatability of mouse ageing to human ageing, the urinary proteome in 89 wild-type (C57BL/6) mice aged between 8-96 weeks was investigated using capillary electrophoresis coupled to mass spectrometry (CE-MS). Using age as a continuous variable, 295 peptides significantly correlated with age in mice were identified. To investigate the relevance of using mouse models in human ageing studies, a comparison was performed with a previous correlation analysis using 1227 healthy subjects. In mice and humans, a decrease in urinary excretion of fibrillar collagens and an increase of uromodulin fragments was observed with advanced age. Of the 295 peptides correlating with age, 49 had a strong homology to the respective human age-related peptides. These ortholog peptides including several collagen (N = 44) and uromodulin (N = 5) fragments were used to generate an ageing classifier that was able to discriminate the age among both wild-type mice and healthy subjects. Additionally, the ageing classifier depicted that telomerase knock-out mice were older than their chronological age. Hence, with a focus on ortholog urinary peptides mouse ageing can be translated to human ageing.

  6. Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change.

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    Mitchell S Turker

    Full Text Available Exposure to a small number of high-energy heavy charged particles (HZE ions, as found in the deep space environment, could significantly affect astronaut health following prolonged periods of space travel if these ions induce mutations and related cancers. In this study, we used an in vivo mutagenesis assay to define the mutagenic effects of accelerated 56Fe ions (1 GeV/amu, 151 keV/μm in the mouse kidney epithelium exposed to doses ranging from 0.25 to 2.0 Gy. These doses represent fluences ranging from 1 to 8 particle traversals per cell nucleus. The Aprt locus, located on chromosome 8, was used to select induced and spontaneous mutants. To fully define the mutagenic effects, we used multiple endpoints including mutant frequencies, mutation spectrum for chromosome 8, translocations involving chromosome 8, and mutations affecting non-selected chromosomes. The results demonstrate mutagenic effects that often affect multiple chromosomes for all Fe ion doses tested. For comparison with the most abundant sparsely ionizing particle found in space, we also examined the mutagenic effects of high-energy protons (1 GeV, 0.24 keV/μm at 0.5 and 1.0 Gy. Similar doses of protons were not as mutagenic as Fe ions for many assays, though genomic effects were detected in Aprt mutants at these doses. Considered as a whole, the data demonstrate that Fe ions are highly mutagenic at the low doses and fluences of relevance to human spaceflight, and that cells with considerable genomic mutations are readily induced by these exposures and persist in the kidney epithelium. The level of genomic change produced by low fluence exposure to heavy ions is reminiscent of the extensive rearrangements seen in tumor genomes suggesting a potential initiation step in radiation carcinogenesis.

  7. Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change.

    Science.gov (United States)

    Turker, Mitchell S; Grygoryev, Dmytro; Lasarev, Michael; Ohlrich, Anna; Rwatambuga, Furaha A; Johnson, Sorrel; Dan, Cristian; Eckelmann, Bradley; Hryciw, Gwen; Mao, Jian-Hua; Snijders, Antoine M; Gauny, Stacey; Kronenberg, Amy

    2017-01-01

    Exposure to a small number of high-energy heavy charged particles (HZE ions), as found in the deep space environment, could significantly affect astronaut health following prolonged periods of space travel if these ions induce mutations and related cancers. In this study, we used an in vivo mutagenesis assay to define the mutagenic effects of accelerated 56Fe ions (1 GeV/amu, 151 keV/μm) in the mouse kidney epithelium exposed to doses ranging from 0.25 to 2.0 Gy. These doses represent fluences ranging from 1 to 8 particle traversals per cell nucleus. The Aprt locus, located on chromosome 8, was used to select induced and spontaneous mutants. To fully define the mutagenic effects, we used multiple endpoints including mutant frequencies, mutation spectrum for chromosome 8, translocations involving chromosome 8, and mutations affecting non-selected chromosomes. The results demonstrate mutagenic effects that often affect multiple chromosomes for all Fe ion doses tested. For comparison with the most abundant sparsely ionizing particle found in space, we also examined the mutagenic effects of high-energy protons (1 GeV, 0.24 keV/μm) at 0.5 and 1.0 Gy. Similar doses of protons were not as mutagenic as Fe ions for many assays, though genomic effects were detected in Aprt mutants at these doses. Considered as a whole, the data demonstrate that Fe ions are highly mutagenic at the low doses and fluences of relevance to human spaceflight, and that cells with considerable genomic mutations are readily induced by these exposures and persist in the kidney epithelium. The level of genomic change produced by low fluence exposure to heavy ions is reminiscent of the extensive rearrangements seen in tumor genomes suggesting a potential initiation step in radiation carcinogenesis.

  8. Evaluation of the normal fetal kidney length and its correlation with gestational age.

    Science.gov (United States)

    Seilanian Toosi, Farrokh; Rezaie-Delui, Hossein

    2013-05-30

    A true estimation of gestational age (GA) plays an important role in quality maternity care and scheduling the labor date. This study aimed to evaluate the normal fetal kidney length (KL) and its correlation with GA. A cross-sectional study on 92 pregnant women between 8th and 10th week of gestation with normal singleton pregnancy underwent standard ultrasound fetal biometry and kidney length measurement. univariate and multivariate linear regression analysis was used to create a predictive equation to estimate GA on the KL and fetobiometry parameters. A significant correlation was found between GA and KL (r=0.83, P<0.002). The best GA predictor was obtained by combining head circumference, fetal biparietal diameter, femur length and KL with a standard error (SE) about 14.2 days. Our findings showed that KL measurements combination with other fetal biometric parameters could predict age of pregnancy with a better precision.

  9. Metabolism of choline in brain of the aged CBF-1 mouse

    International Nuclear Information System (INIS)

    Saito, M.; Kindel, G.; Karczmar, A.G.; Rosenberg, A.

    1986-01-01

    In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM [ 3 H] choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min. In contrast, distribution of label into intracellular free choline (Ch) and phosphorylcholine (Pch) changed continuously over this period suggesting that the Ch pool for Ach synthesis in brain cortex is different from that for Pch synthesis. Incorporation of radioactivity into Ach was not influenced by administration of 10 microM eserine, showing that the increment of radioactivity in Ach reflects rate of Ach formation, independently from degradation by acetylcholine esterases. Under our experimental conditions, slices from cortices of aged 24-month-old mouse brain showed a significantly greater (27%) incorporation of radioactivity into intracellular Ach than those from young, 2-4-month-old, brain cortices. Inhibitors of Ach release, 1 mM ATP or GABA, had no effect. Since concentration of radioactive precursor in the incubation medium was very low (31 nM), the Ch pool for Ach synthesis in slices was labelled without measurably changing the size of the endogenous pool. These data suggest a compensatory acceleration of Ach synthesis or else a smaller precursor pool specific for Ach synthesis into which labelled Ch migrated in aged brain

  10. Air-pulse OCE for assessment of age-related changes in mouse cornea in vivo

    International Nuclear Information System (INIS)

    Li, Jiasong; Wang, Shang; Singh, M; Larin, K V; Aglyamov, S; Emelianov, S; Twa, M D

    2014-01-01

    We demonstrate the use of phase-stabilized swept source optical coherence elastography (PhS-SSOCE) to assess the relaxation rate of deformation created by a focused air-pulse in tissue-mimicking gelatin phantoms of various concentrations and mouse corneas of different ages in vivo. The results show that the relaxation rate can be quantified and is different for gels with varying concentrations of gelatin and mouse corneas of different ages. The results indicate that gel phantoms with higher concentrations of gelatin as well as older mouse corneas have faster relaxation rates indicating stiffer material. This non-contact and non-invasive measurement technique utilizes low surface displacement amplitude (in µm scale) for tissue excitation and, therefore, can be potentially used to study the biomechanical properties of ocular and other sensitive tissues. (letter)

  11. Species diversity regarding the presence of proximal tubular progenitor cells of the kidney

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    J. Hansson

    2016-02-01

    Full Text Available The cellular source for tubular regeneration following kidney injury is a matter of dispute, with reports suggesting a stem or progenitor cells as the regeneration source while linage tracing studies in mice seemingly favor the classical theory, where regeneration is performed by randomly surviving cells. We, and others have previously described a scattered cell population localized to the tubules of human kidney, which increases in number following injury. Here we have characterized the species distribution of these proximal tubular progenitor cells (PTPCs in kidney tissue from chimpanzee, pig, rat and mouse using a set of human PTPC markers. We detected PTPCs in chimpanzee and pig kidneys, but not in mouse tissue. Also, subjecting mice to the unilateral urethral obstruction model, caused clear signs of tubular injury, but failed to induce the PTPC phenotype in renal tubules.

  12. Endogenous retinoic acid activity in principal cells and intercalated cells of mouse collecting duct system.

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    Yuen Fei Wong

    2011-02-01

    Full Text Available Retinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in post-natal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys.RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, β-galactosidase. Double immunostaining was performed for β-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules.Endogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the

  13. Short-term high dose of quercetin and resveratrol alters aging markers in human kidney cells

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    Fatemeh Abharzanjani

    2017-01-01

    Full Text Available Background: Hyperglycemia-mediated oxidative stress implicates in etiology of kidney cell aging and diabetic nephropathy. We evaluated the effects of different doses of resveratrol and quercetin and their combination therapy on aging marker in human kidney cell culture under hyperglycemia condition. Methods: Human embryonic kidney cell (HEK-293 was cultured in Dulbecco's Modified Eagle Medium (DMEM containing 100 mM (18 mg/L for 24 h. The cells were treated with resveratrol (2.5, 5, 10 μm, quercetin (3, 6, 12 μm, and combination of these (R 2.5 μm, Q 3 μm and (R 5 μm, Q 6 μm and (R 10 μm, Q 12 μm for 48 h, and then, cells were lysed to access RNA and lysate. Results: The analysis of data showed that beta-galactosidase enzyme gene expression as an aging marker in all treatment groups has reduced in a dose-dependent manner. Gene expression of Sirtuin1 and thioredoxin (Trx in all treated groups in comparison to control group increased in a dose-dependent fashion. Trx interacting protein (TXNIP gene expression decreased in a dose-dependent manner in all treated groups, especially in resveratrol and combination therapy. Conclusions: According to the results of this research, quercetin, resveratrol, and especially combination treatments with increased expression levels of antioxidants, can reduce aging markers in HEK cell line in hyperglycemia conditions. These results lead us to use flavonoids such as resveratrol for anti-aging potential.

  14. Time trend and age-period-cohort effect on kidney cancer mortality in Europe, 1981–2000

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    López-Abente Gonzalo

    2006-05-01

    Full Text Available Abstract Background The incorporation of diagnostic and therapeutic improvements, as well as the different smoking patterns, may have had an influence on the observed variability in renal cancer mortality across Europe. This study examined time trends in kidney cancer mortality in fourteen European countries during the last two decades of the 20th century. Methods Kidney cancer deaths and population estimates for each country during the period 1981–2000 were drawn from the World Health Organization Mortality Database. Age- and period-adjusted mortality rates, as well as annual percentage changes in age-adjusted mortality rates, were calculated for each country and geographical region. Log-linear Poisson models were also fitted to study the effect of age, death period, and birth cohort on kidney cancer mortality rates within each country. Results For men, the overall standardized kidney cancer mortality rates in the eastern, western, and northern European countries were 20, 25, and 53% higher than those for the southern European countries, respectively. However, age-adjusted mortality rates showed a significant annual decrease of -0.7% in the north of Europe, a moderate rise of 0.7% in the west, and substantial increases of 1.4% in the south and 2.0% in the east. This trend was similar among women, but with lower mortality rates. Age-period-cohort models showed three different birth-cohort patterns for both men and women: a decrease in mortality trend for those generations born after 1920 in the Nordic countries, a similar but lagged decline for cohorts born after 1930 in western and southern European countries, and a continuous increase throughout all birth cohorts in eastern Europe. Similar but more heterogeneous regional patterns were observed for period effects. Conclusion Kidney cancer mortality trends in Europe showed a clear north-south pattern, with high rates on a downward trend in the north, intermediate rates on a more marked rising

  15. Evaluation of the Normal Fetal Kidney Length and Its Correlation with Gestational Age

    Directory of Open Access Journals (Sweden)

    Farrokh Seilanian Toosi

    2013-05-01

    Full Text Available A true estimation of gestational age (GA plays an important role in quality maternity care and scheduling the labor date. This study aimed to evaluate the normal fetal kidney length (KL and its correlation with GA. A cross-sectional study on 92 pregnant women between 8th and 10th week of gestation with normal singleton pregnancy underwent standard ultrasound fetal biometry and kidney length measurement. univariate and multivariate linear regression analysis was used to create a predictive equation to estimate GA on the KL and fetobiometry parameters. A significant correlation was found between GA and KL (r=0.83, P<0.002. The best GA predictor was obtained by combining head circumference, fetal biparietal diameter, femur length and KL with a standard error (SE about 14.2 days. Our findings showed that KL measurements combination with other fetal biometric parameters could predict age of pregnancy with a better precision.

  16. Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Kaneko, Mika K; Nakamura, Takuro; Ichii, Osamu; Konnai, Satoru; Kato, Yukinari

    2017-04-01

    Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG 2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG 2a , which was derived from rat PMab-1 mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.

  17. The senile kidney

    Directory of Open Access Journals (Sweden)

    Denisova Т.Р.

    2015-03-01

    Full Text Available The given work summarizes external data and self-obtained results on development and diagnostic of kidney involution modifications. Article discusses definition of "senile kidney" as a clinical and pathomorphological term. Major statements on pathophysiological causes of age-associated renal disorders and their prognosis, specifics of chronic kidney disease in elderly and senile patients have been reviewed. Phenomenon of renal "multimorbidity" in eldely maximizes worsening risk of unmodifiable kidney function.

  18. Immunohistochemical examination of effects of kefir, koumiss and commercial probiotic capsules on platelet derived growth factor-c and platelet derived growth factor receptor-alpha expression in mouse liver and kidney.

    Science.gov (United States)

    Bakir, B; Sari, E K; Aydin, B D; Yildiz, S E

    2015-04-01

    We investigated using immunohistochemistry the effects of kefir, koumiss and commercial probiotic capsules on the expression of platelet derived growth factor-c (PDGF-C) and platelet derived growth factor receptor-alpha (PDGFR-α) in mouse liver and kidney. Mice were assigned to four groups: group 1 was given commercial probiotic capsules, group 2 was given kefir, group 3 was given koumiss and group 4 was untreated. After oral administration for 15 days, body weights were recorded and liver and kidney tissue samples were obtained. Hematoxylin and eosin staining was used to examine histology. PDGF-C and PDGFR-α in liver and kidney were localized using the streptavidin-biotin peroxidase complex method (ABC). We found that the weights of the mice in the kefir, koumiss and commercial probiotic capsules groups increased compared to the control group. No differences in liver and kidney histology were observed in any of the experimental groups. Kefir, koumiss and the commercial probiotic preparation increased PDGF-C and PDGFR-α expression.

  19. Kidney disease and aging: A reciprocal relation.

    Science.gov (United States)

    Kooman, Jeroen P; van der Sande, Frank M; Leunissen, Karel M L

    2017-01-01

    Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are overrepresented in elderly patients. This provides specific challenges for the treatment, as the start of dialysis in vulnerable elderly patients may be associated with a rapid decline in functional performance. However, prognosis in elderly patients with ESRD is quite variable and related to the presence of comorbidity and geriatric impairments. The decision to start dialysis in elderly patients should always be based on shared decision making, which may be aided by the use of prediction models which should however not be used to withhold dialysis treatment. The treatment of ESRD in elderly patients should be based on a multidimensional treatment plan with a role for active rehabilitation. Moreover, there also appears to be a reciprocal relationship between aging and CKD, as the presence of geriatric complications is also high in younger patients with ESRD. This has led to the hypothesis of a premature aging process associated with CKD, resulting in different phenotypes such as premature vascular aging, muscle wasting, bone disease, cognitive dysfunction and frailty. Prevention and treatment of this phenotype is based on optimal treatment of CKD, associated comorbidities, and lifestyle factors by established treatments. For the future, interventions, which are developed to combat the aging process in general, might also have relevance for the treatment of patients with CKD, but their role should always be investigated in adequately powered clinical trials, as results obtained in experimental trials may not be directly translatable to the clinical situation of elderly patients. In the meantime, physical exercise is a very important intervention, by improving both physical capacity and functional performance, as well as by a direct effect on the aging process. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Contribution of stone size to chronic kidney disease in kidney stone formers.

    Science.gov (United States)

    Ahmadi, Farrokhlagha; Etemadi, Samira Motedayen; Lessan-Pezeshki, Mahbob; Mahdavi-Mazdeh, Mitra; Ayati, Mohsen; Mir, Alireza; Yazdi, Hadi Rokni

    2015-01-01

    To determine whether stone burden correlates with the degree of chronic kidney disease in kidney stone formers. A total of 97 extracorporeal shockwave lithotripsy candidates aged 18 years and older were included. Size, number and location of the kidney stones, along with cumulative stone size, defined as the sum of diameters of all stones) were determined. Estimated glomerular filtration rate was determined using the Chronic Kidney Disease Epidemiology Collaboration cystatin C/creatinine equation, and chronic kidney disease was defined as estimated glomerular filtration rate chronic kidney disease. The relationship persisted even after adjustment for age, sex, body mass index, C-reactive protein, fasting plasma glucose, thyroid stimulating hormone, presence of microalbuminuria, history of renal calculi, history of extracorporeal shockwave lithotripsy, number and location of the stones (odds ratio 1.24, 95% confidence interval 1.02-1.52). The same was not observed for individuals with a cumulative stone size ≥ 20 mm. In kidney stone formers with a cumulative stone size up to 20 mm, estimated glomerular filtration rate linearly declines with increasing cumulative stone size. Additionally, cumulative stone size is an independent predictor of chronic kidney disease in this group of patients. © 2014 The Japanese Urological Association.

  1. [Study on prevention and treatment of middle and aged women diabetes with kidney deficiency and bone metabolic disturbance].

    Science.gov (United States)

    Zhu, L; Li, H; Liu, Y

    1999-04-01

    To Study the therapeutic effect of Chinese herbal medicine (CHM) for supplementing Qi, activating blood circulation and tonifying Kidney on prevention and treatment of middle and aged women diabetes with Kidney Deficiency and bone metabolic disturbance. Clinical observation was taken in 52 patients, who were divided into two groups, the control group (treated with hypoglycemic agent alone) and the treated group (treated with hypoglycemic agent and CHM). Before treatment, patients of both groups showed obvious higher blood alkaline phosphatase, beta 2-microglobulin (beta 2-MG) level, urinary beta 2-MG, calcium and phosphorus level, but lower serum estradiol level than those in normal subjects. After 3 months' treatment, no apparent change on serum estradiol level was observed, but other parameters were all lowered obviously in the two groups, the changes revealed more obvious in the treated group. The symptoms of Kidney Deficiency, such as lumbodorsal pain, general fatigue, palpitation and vertigo, were improved after treatment, and the improvement was also more obvious in the treated group. CHM for supplementing Qi, activating blood circulation and tonifying Kidney was effective in improving Kidney Deficiency and mineral substance loss of bone in middle and aged women diabetes patients. The CHM and western drugs may acted synergistically.

  2. Preliminary comparison of grating-based and in-line phase contrast X-ray imaging with synchrotron radiation for mouse kidney at TOMCAT

    International Nuclear Information System (INIS)

    Sun, J; Liu, P; Xu, L X; Irvine, S; Pinzer, B; Stampanoni, M

    2013-01-01

    Phase contrast imaging has been demonstrated to be advantageous in revealing detailed structures inside biological specimens without contrast agents. Grating-based differential phase contrast (DPC) and in-line phase contrast (ILPC) X-ray imaging are the two modalities frequently used at the beamline of TOmographic Microscopy and Coherent rAdiology experimenTs (TOMCAT) at the Swiss Light Source (SLS). In this paper, we preliminarily compared the abilities of two types of phase contrast imaging in distinguishing micro structures in mouse kidneys. The 3D reconstructions showed that the microstructures in kidney, such as micro vessels and renal tubules, were displayed clearly with both imaging modalities. The two techniques may be viewed as complementary. For larger features with very small density variations DPC is the desirable method. In cases where dose and time limits may prohibit the multiple steps required for DPC, and when the focus is on finer features, the ILPC method may be considered as a more viable alternative. Moreover, high resolution ILPC images are comparable with histological results.

  3. MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging.

    Science.gov (United States)

    Bates, David J; Li, Na; Liang, Ruqiang; Sarojini, Harshini; An, Jin; Masternak, Michal M; Bartke, Andrzej; Wang, Eugenia

    2010-02-01

    The Ames dwarf mouse is well known for its remarkable propensity to delay the onset of aging. Although significant advances have been made demonstrating that this aging phenotype results primarily from an endocrine imbalance, the post-transcriptional regulation of gene expression and its impact on longevity remains to be explored. Towards this end, we present the first comprehensive study by microRNA (miRNA) microarray screening to identify dwarf-specific lead miRNAs, and investigate their roles as pivotal molecular regulators directing the long-lived phenotype. Mapping the signature miRNAs to the inversely expressed putative target genes, followed by in situ immunohistochemical staining and in vitro correlation assays, reveals that dwarf mice post-transcriptionally regulate key proteins of intermediate metabolism, most importantly the biosynthetic pathway involving ornithine decarboxylase and spermidine synthase. Functional assays using 3'-untranslated region reporter constructs in co-transfection experiments confirm that miRNA-27a indeed suppresses the expression of both of these proteins, marking them as probable targets of this miRNA in vivo. Moreover, the putative repressed action of this miRNA on ornithine decarboxylase is identified in dwarf mouse liver as early as 2 months of age. Taken together, our results show that among the altered aspects of intermediate metabolism detected in the dwarf mouse liver--glutathione metabolism, the urea cycle and polyamine biosynthesis--miRNA-27a is a key post-transcriptional control. Furthermore, compared to its normal siblings, the dwarf mouse exhibits a head start in regulating these pathways to control their normality, which may ultimately contribute to its extended health-span and longevity.

  4. Voxel-based morphometry analyses of in-vivo MRI in the aging mouse lemur primate

    Directory of Open Access Journals (Sweden)

    Stephen John Sawiak

    2014-05-01

    Full Text Available Cerebral atrophy is one of the most widely brain alterations associated to aging. A clear relationship has been established between age-associated cognitive impairments and cerebral atrophy. The mouse lemur (Microcebus murinus is a small primate used as a model of age-related neurodegenerative processes. It is the first nonhuman primate in which cerebral atrophy has been correlated with cognitive deficits. Previous studies of cerebral atrophy in this model were based on time consuming manual delineation or measurement of selected brain regions from magnetic resonance images (MRI. These measures could not be used to analyse regions that cannot be easily outlined such as the nucleus basalis of Meynert or the subiculum. In humans, morphometric assessment of structural changes with age is generally performed with automated procedures such as voxel-based morphometry (VBM. The objective of our work was to perform user-independent assessment of age-related morphological changes in the whole brain of large mouse lemur populations thanks to VBM. The study was based on the SPMMouse toolbox of SPM 8 and involved thirty mouse lemurs aged from 1.9 to 11.3 years. The automatic method revealed for the first time atrophy in regions where manual delineation is prohibitive (nucleus basalis of Meynert, subiculum, prepiriform cortex, Brodmann areas 13-16, hypothalamus, putamen, thalamus, corpus callosum. Some of these regions are described as particularly sensitive to age-associated alterations in humans. The method revealed also age-associated atrophy in cortical regions (cingulate, occipital, parietal, nucleus septalis, and the caudate. Manual measures performed in some of these regions were in good agreement with results from automatic measures. The templates generated in this study as well as the toolbox for SPM8 can be downloaded. These tools will be valuable for future evaluation of various treatments that are tested to modulate cerebral aging in lemurs.

  5. Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice.

    Directory of Open Access Journals (Sweden)

    Line S Bisgaard

    Full Text Available Chronic kidney disease (CKD leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes. Animal studies suggest that GLP-1 also dampens inflammation and atherosclerosis. Our aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX. Uremic (n = 29 and sham-operated (n = 14 atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.c. once daily or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-, CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation. Furthermore, markers of fibrosis (i.e. Col1a1 and Col3a1 were upregulated, and histological examinations showed increased glomerular diameter in NX mice. Importantly, liraglutide treatment attenuated atherosclerosis (~40%, p < 0.05 and reduced kidney inflammation in NX mice. There was no effect of liraglutide on expression of fibrosis markers and/or kidney histology. This study suggests that liraglutide has beneficial effects in a mouse model of moderate uremia by reducing atherosclerosis and attenuating kidney inflammation.

  6. Disparate phospho-Smad2 levels in advanced type 2 diabetes patients with diabetic nephropathy and early experimental db/db mouse model

    DEFF Research Database (Denmark)

    Thomsen, Lise Høj; Fog-Tonnesen, Morten; Nielsen Fink, Lisbeth

    2017-01-01

    Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients...... to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys...... surprisingly showed a decrease in pSmad2 in the tubular compartment. Structurally, kidney tissue showed dilated tubules and expanded glomeruli, but no clear fibrotic pattern was found in the diabetic mice. Selective TGF-β family members were up-regulated at the mRNA level. Antagonists of bone morphogenetic...

  7. Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

    Science.gov (United States)

    Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

    2017-01-01

    Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

  8. SIRT1, 2, 3 protect mouse oocytes from postovulatory aging.

    Science.gov (United States)

    Zhang, Teng; Zhou, Yang; Li, Li; Wang, Hong-Hui; Ma, Xue-Shan; Qian, Wei-Ping; Shen, Wei; Schatten, Heide; Sun, Qing-Yuan

    2016-04-01

    The quality of metaphase II oocytes will undergo a time-dependent deterioration following ovulation as the result of the oocyte aging process. In this study, we determined that the expression of sirtuin family members (SIRT1, 2, 3) was dramatically reduced in mouse oocytes aged in vivo or in vitro. Increased intracellular ROS was observed when SIRT1, 2, 3 activity was inhibited. Increased frequency of spindle defects and disturbed distribution of mitochondria were also observed in MII oocytes aged in vitro after treatment with Nicotinamide (NAM), indicating that inhibition of SIRT1, 2, 3 may accelerate postovulatory oocyte aging. Interestingly, when MII oocytes were exposed to caffeine, the decline of SIRT1, 2, 3 mRNA levels was delayed and the aging-associated defective phenotypes could be improved. The results suggest that the SIRT1, 2, 3 pathway may play a potential protective role against postovulatory oocyte aging by controlling ROS generation.

  9. Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis.

    Directory of Open Access Journals (Sweden)

    Jingyue Xu

    Full Text Available Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality with kidney defects in homozygotes. How OSR1 regulates kidney development and nephron endowment is not well understood, however. In this study, by using the recently developed CRISPR genome editing technology, we genetically labeled the endogenous Osr1 protein and show that Osr1 interacts with Wt1 in the developing kidney. Whereas mice heterozygous for either an Osr1 or Wt1 null allele have normal kidneys at birth, most mice heterozygous for both Osr1 and Wt1 exhibit defects in metanephric kidney development, including unilateral or bilateral kidney agenesis or hypoplasia. The developmental defects in the Osr1+/-Wt1+/- mouse embryos were detected as early as E10.5, during specification of the metanephric mesenchyme, with the Osr1+/-Wt1+/- mouse embryos exhibiting significantly reduced Pax2-positive and Six2-positive nephron progenitor cells. Moreover, expression of Gdnf, the major nephrogenic signal for inducing ureteric bud outgrowth, was significantly reduced in the metanephric mesenchyme in Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- littermates. By E11.5, as the ureteric buds invade the metanephric mesenchyme and initiate branching morphogenesis, kidney morphogenesis was significantly impaired in the Osr1+/-Wt1+/- embryos in comparison with the Osr1+/- or Wt1+/- embryos. These results indicate that Osr1 and Wt1 act synergistically to regulate nephron endowment by controlling metanephric mesenchyme specification during early nephrogenesis.

  10. Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.

    Science.gov (United States)

    Tanaka, Mari; Asada, Misako; Higashi, Atsuko Y; Nakamura, Jin; Oguchi, Akiko; Tomita, Mayumi; Yamada, Sachiko; Asada, Nariaki; Takase, Masayuki; Okuda, Tomohiko; Kawachi, Hiroshi; Economides, Aris N; Robertson, Elizabeth; Takahashi, Satoru; Sakurai, Takeshi; Goldschmeding, Roel; Muso, Eri; Fukatsu, Atsushi; Kita, Toru; Yanagita, Motoko

    2010-03-01

    The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

  11. Concise Review: Kidney Generation with Human Pluripotent Stem Cells.

    Science.gov (United States)

    Morizane, Ryuji; Miyoshi, Tomoya; Bonventre, Joseph V

    2017-11-01

    Chronic kidney disease (CKD) is a worldwide health care problem, resulting in increased cardiovascular mortality and often leading to end-stage kidney disease, where patients require kidney replacement therapies such as hemodialysis or kidney transplantation. Loss of functional nephrons contributes to the progression of CKD, which can be attenuated but not reversed due to inability to generate new nephrons in human adult kidneys. Human pluripotent stem cells (hPSCs), by virtue of their unlimited self-renewal and ability to differentiate into cells of all three embryonic germ layers, are attractive sources for kidney regenerative therapies. Recent advances in stem cell biology have identified key signals necessary to maintain stemness of human nephron progenitor cells (NPCs) in vitro, and led to establishment of protocols to generate NPCs and nephron epithelial cells from human fetal kidneys and hPSCs. Effective production of large amounts of human NPCs and kidney organoids will facilitate elucidation of developmental and pathobiological pathways, kidney disease modeling and drug screening as well as kidney regenerative therapies. We summarize the recent studies to induce NPCs and kidney cells from hPSCs, studies of NPC expansion from mouse and human embryonic kidneys, and discuss possible approaches in vivo to regenerate kidneys with cell therapies and the development of bioengineered kidneys. Stem Cells 2017;35:2209-2217. © 2017 AlphaMed Press.

  12. Comparative Effects of Phosphoenolpyruvate, a Glycolytic Intermediate, as an Organ Preservation Agent with Glucose and N-Acetylcysteine against Organ Damage during Cold Storage of Mouse Liver and Kidney

    OpenAIRE

    Ishitsuka, Yoichi; Fukumoto, Yusuke; Kondo, Yuki; Irikura, Mitsuru; Kadowaki, Daisuke; Narita, Yuki; Hirata, Sumio; Moriuchi, Hiroshi; Maruyama, Toru; Hamasaki, Naotaka; Irie, Tetsumi

    2013-01-01

    We evaluated the usefulness of phosphoenolpyruvate (PEP), a glycolytic intermediate with antioxidative and energy supplementation potentials, as an organ preservation agent. Using ex vivo mouse liver and kidney of a static cold storage model, we compared the effects of PEP against organ damage and oxidative stress during cold preservation with those of glucose or N-acetylcysteine (NAC). Lactate dehydrogenase (LDH) leakage, histological changes, and oxidative stress parameters (measured as thi...

  13. Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Diaz, Ricardo Gredilla; Weissman, Lior; Yang, JL

    2012-01-01

    Brain aging is associated with synaptic decline and synaptic function is highly dependent on mitochondria. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging...... process and the pathogenesis of several neurodegenerative diseases. Here we have investigated the repair of oxidative base damage, in synaptosomes of mouse brain during normal aging and in an AD model. During normal aging, a reduction in the base excision repair (BER) capacity was observed...... suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms...

  14. Does the Age of Donor Kidneys Affect Nocturnal Polyuria in Patients With Successful Real Transplantation?

    Science.gov (United States)

    Mitsui, T; Morita, K; Iwami, D; Kitta, T; Kanno, Y; Moriya, K; Takeda, M; Shinohara, N

    We investigated whether the age of donor kidneys influences the incidence of nocturnal polyuria in patients with successful renal transplantation (RTX). Eighty-five patients (45 men and 40 women) undergoing RTX (median age, 47 years) were included in this study. Twenty-four-hour bladder diaries were kept for 3 days, and nocturnal polyuria was defined as a nocturnal polyuria index (nocturnal urine volume/24-hour urine volume) of >0.33. Risk factors for nocturnal polyuria were analyzed in patients with RTX by means of the Mann-Whitney U test, χ 2 test, and a logistic regression analysis. End-stage renal disease (ESRD) developed from diabetes mellitus in 16 patients (19%). Sixty-five patients (76%) received pre-transplant dialysis, with a median duration of 5 years. The median serum creatinine level and body mass index at the most recent visit were 1.2 mg/dL and 21.2 kg/m 2 , respectively. On the basis of the 24-hour bladder diaries, nocturnal polyuria was identified in 48 patients (56%). A logistic regression analysis revealed that diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria (odds ratio, 8.95; 95% confidence interval, 2.01-65.3; P = .0028). The age of donor kidneys at examination did not affect the incidence of nocturnal polyuria (P = .9402). Nocturnal polyuria was not uncommon in patients with successful RTX. Diabetes mellitus as the original disease for ESRD was the only risk factor for nocturnal polyuria, whereas the age of donor kidneys at examination did not affect the incidence of nocturnal polyuria. Thus, nocturnal polyuria is caused by recipient factors but not donor factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A dual agonist of farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, INT-767, reverses age-related kidney disease in mice.

    Science.gov (United States)

    Wang, Xiaoxin X; Luo, Yuhuan; Wang, Dong; Adorini, Luciano; Pruzanski, Mark; Dobrinskikh, Evgenia; Levi, Moshe

    2017-07-21

    Even in healthy individuals, renal function gradually declines during aging. However, an observed variation in the rate of this decline has raised the possibility of slowing or delaying age-related kidney disease. One of the most successful interventional measures that slows down and delays age-related kidney disease is caloric restriction. We undertook the present studies to search for potential factors that are regulated by caloric restriction and act as caloric restriction mimetics. Based on our prior studies with the bile acid-activated nuclear hormone receptor farnesoid X receptor (FXR) and G protein-coupled membrane receptor TGR5 that demonstrated beneficial effects of FXR and TGR5 activation in the kidney, we reasoned that FXR and TGR5 could be excellent candidates. We therefore determined the effects of aging and caloric restriction on the expression of FXR and TGR5 in the kidney. We found that FXR and TGR5 expression levels are decreased in the aging kidney and that caloric restriction prevents these age-related decreases. Interestingly, in long-lived Ames dwarf mice, renal FXR and TGR5 expression levels were also increased. A 2-month treatment of 22-month-old C57BL/6J mice with the FXR-TGR5 dual agonist INT-767 induced caloric restriction-like effects and reversed age-related increases in proteinuria, podocyte injury, fibronectin accumulation, TGF-β expression, and, most notably, age-related impairments in mitochondrial biogenesis and mitochondrial function. Furthermore, in podocytes cultured in serum obtained from old mice, INT-767 prevented the increases in the proinflammatory markers TNF-α, toll-like receptor 2 (TLR2), and TLR4. In summary, our results indicate that FXR and TGR5 may play an important role in modulation of age-related kidney disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

    Science.gov (United States)

    Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

    2016-01-12

    The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

  17. Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.

    Science.gov (United States)

    Vlassara, Helen; Torreggiani, Massimo; Post, James B; Zheng, Feng; Uribarri, Jaime; Striker, Gary E

    2009-12-01

    Oxidant stress (OS) and inflammation increase in normal aging and in chronic kidney disease (CKD), as observed in human and animal studies. In cross-sectional studies of the US population, these changes are associated with a decrease in renal function, which is exhibited by a significant proportion of the population. However, since many normal adults have intact renal function, and longitudinal studies show that some persons maintain normal renal function with age, the link between OS, inflammation, and renal decline is not clear. In aging mice, greater oxidant intake is associated with increased age-related CKD and mortality, which suggests that interventions that reduce OS and inflammation may be beneficial for older individuals. Both OS and inflammation can be readily lowered in normal subjects and patients with CKD stage 3-4 by a simple dietary modification that lowers intake and results in reduced serum and tissue levels of advanced glycation end products. Diabetic patients, including those with microalbuminuria, have a decreased ability to metabolize and excrete oxidants prior to observable changes in serum creatinine. Thus, OS and inflammation may occur in the diabetic kidney at an early time. We review the evidence that oxidants in the diet directly lead to increased serum levels of OS and inflammatory mediators in normal aging and in CKD. We also discuss a simple dietary intervention that helps reduce OS and inflammation, an important and achievable therapeutic goal for patients with CKD and aging individuals with reduced renal function.

  18. Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.

    Science.gov (United States)

    Yun, Kangsun; Perantoni, Alan O

    The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme. The conditional mutants fail to form a normal renal medulla but no longer exhibit duplex kidney formation. Approximately 1/3 of the mutants develop hydronephrosis in the kidneys either uni- or bilaterally when using Dll1Cre. The abnormal kidney phenotype becomes prominent at E16.5, which approximates the time when urine production begins in the mouse embryonic kidney, and is associated with a dramatic increase in apoptosis only in mutant kidneys with hydronephrosis. Methylene blue dye injection and histologic examination reveal that aberrant cell death likely results from urine toxicity due to an abnormal ureter-bladder connection. This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection. Published by Elsevier B.V.

  19. Structural organization of the human and mouse laminin beta2 chain genes, and alternative splicing at the 5' end of the human transcript

    DEFF Research Database (Denmark)

    Durkin, M E; Gautam, M; Loechel, F

    1996-01-01

    We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon-intron organ......We have determined the structural organization of the human and mouse genes that encode the laminin beta2 chain (s-laminin), an essential component of the basement membranes of the neuromuscular synapse and the kidney glomerulus. The human and mouse genes have a nearly identical exon...

  20. Urine cytokine and chemokine levels predict urinary tract infection severity independent of uropathogen, urine bacterial burden, host genetics, and host age.

    Science.gov (United States)

    Armbruster, Chelsie E; Smith, Sara N; Mody, Lona; Mobley, Harry L T

    2018-06-11

    Urinary tract infections (UTIs) are among the most common infections worldwide. Diagnosing UTIs in older adults poses a significant challenge as asymptomatic colonization is common. Identification of a non-invasive profile that predicts likelihood of progressing from urine colonization to severe disease would provide a significant advantage in clinical practice. We monitored colonization susceptibility, disease severity, and immune response to two uropathogens in two mouse strains across three age groups to identify predictors of infection outcome. Proteus mirabilis caused more severe disease than Escherichia coli, regardless of mouse strain or age, and was associated with differences in IL-1β, IFN-β, CXCL5 (LIX), CCL5 (RANTES), and CCL2 (MCP-1). In comparing the response to infection across age groups, mature adult mice were better able to control colonization and prevent progression to kidney colonization and bacteremia than young or aged mice, regardless of mouse strain or bacterial species, and this was associated with differences in IL-23, CXCL1, and CCL5. A bimodal distribution was noted for urine colonization, which was strongly associated with bladder CFUs and the magnitude of the immune response but independent of age or disease severity. To determine the value of urine cytokine and chemokine levels for predicting severe disease, all infection datasets were combined and subjected to a series of logistic regressions. A multivariate model incorporating IL-1β, CXCL1, and CCL2 had strong predictive value for identifying mice that did not develop kidney colonization or bacteremia, regardless of mouse genetic background, age, infecting bacterial species, or urine bacterial burden. In conclusion, urine cytokine profiles could potentially serve as a non-invasive decision-support tool in clinical practice and contribute to antimicrobial stewardship. Copyright © 2018 American Society for Microbiology.

  1. Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.

    Directory of Open Access Journals (Sweden)

    Gerda A Noordmans

    Full Text Available Renal aging is characterized by functional and structural changes like decreased glomerular filtration rate, and glomerular, tubular and interstitial damage. To gain insight in pathways involved in renal aging, we studied aged mouse strains and used genetic analysis to identify genes associated with aging phenotypes.Upon morphological screening in kidneys from 20-month-old mice from 26 inbred strains we noted intracapillary PAS-positive deposits. The severity of these deposits was quantified by scoring of a total of 50 glomeruli per section (grade 0-4. Electron microscopy and immunohistochemical staining for apoE, apoB, apoA-IV and perilipin-2 was performed to further characterize the lesions. To identify loci associated with these PAS-positive intracapillary glomerular deposits, we performed haplotype association mapping.Six out of 26 mouse strains showed glomerular PAS-positive deposits. The severity of these deposits varied: NOD(0.97, NZW(0.41, NON(0.30, B10(0.21, C3 H(0.9 and C57BR(0.7. The intracapillary deposits were strongly positive for apoE and weakly positive for apoB and apoA-IV. Haplotype association mapping showed a strong association with a 30-Kb haplotype block on Chr 1 within the Esrrg gene. We investigated 1 Mb on each site of this region, which includes the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3.By analyzing 26 aged mouse strains we found that some strains developed an intracapillary PAS and apoE-positive lesion and identified a small haplotype block on Chr 1 within the Esrrg gene to be associated with these lipoprotein deposits. The region spanning this haplotype block contains the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3, which are all highly expressed in the kidney. Esrrg might be involved in the evolvement of these glomerular deposits by influencing lipid metabolism and possibly immune reponses.

  2. Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index.

    Science.gov (United States)

    Hoy, W E; Hughson, M D; Zimanyi, M; Samuel, T; Douglas-Denton, R; Holden, L; Mott, S; Bertram, J F

    2010-11-01

    Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.

  3. Dual Kidney Transplantation Offers a Valuable Source for Kidneys With Good Functional Outcome.

    Science.gov (United States)

    Khalid, U; Asderakis, A; Rana, T; Szabo, L; Chavez, R; Ilham, M A; Ablorsu, E

    2016-01-01

    Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5-79) and 42 (range, 15-85) mL/min compared with SKT of 35 (range, 10-65) and 32 (range, 6-65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% (P = .52), and patient survival was 94% and 98%, respectively (P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. A mouse model for Costello syndrome reveals an Ang II–mediated hypertensive condition

    Science.gov (United States)

    Schuhmacher, Alberto J.; Guerra, Carmen; Sauzeau, Vincent; Cañamero, Marta; Bustelo, Xosé R.; Barbacid, Mariano

    2008-01-01

    Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin–Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies. PMID:18483625

  5. The ageing kidney: biochemical and morphological study after irradiation

    International Nuclear Information System (INIS)

    Franciolini, F.; Becciolini, A.; Torcini, G.; Lanini, A.

    1982-01-01

    The behaviour of some activities of the kidney was studied both in young-adult and in adult rats exposed to an 8-Gy dose of γ-rays and killed at various intervals after irradiation (both in the morning and in the evening). Brush border and lysosomal enzymes did not show marked differences among control rats of the same age even if adult animals showed levels of maltase, alkaline phosphatase and LAP activities higher than the young-adult group. Moreover, irradiation did not induce typical modifications of the same enzyme activities in young-adult and adult rats. Adult animals showed a reduction in the brush border enzyme activities at 120 hours after irradiation while, at the same interval, lysosomal activities underwent an increase both in young and in adult animals. (orig.) [de

  6. Prolonged CT urography in duplex kidney.

    Science.gov (United States)

    Gong, Honghan; Gao, Lei; Dai, Xi-Jian; Zhou, Fuqing; Zhang, Ning; Zeng, Xianjun; Jiang, Jian; He, Laichang

    2016-05-13

    Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

  7. Immunohistochemical Examination of Novel Rat Monoclonal Antibodies against Mouse and Human Podoplanin

    International Nuclear Information System (INIS)

    Kaji, Chiaki; Tsujimoto, Yuta; Kato Kaneko, Mika; Kato, Yukinari; Sawa, Yoshihiko

    2012-01-01

    This study aims to develop new monoclonal antibodies (mAbs) against mouse and human podoplanin. Rats were immunized with synthetic peptides, corresponding to amino acids 38–51 of mouse podoplanin or human podoplanin which is 100% homologous to the same site of monkey podoplanin; anti-mouse podoplanin mAb PMab-1 (IgG 2a ) and anti-human mAb NZ-1.2 (IgG 2a ) were established. In immunocytochemistry, the mouse melanoma B16-F10 and mouse podoplanin (mPDPN)-expressed CHO transfectant were stained by PMab-1; human lymphatic endothelial cells (LEC) and human podoplanin (hPDPN)-expressed squamous cell carcinoma HSC3 transfectant, were stained by NZ-1.2. Western-blot analysis detected an about 40-kDa protein in CHO-mPDPN and B16-F10 by PMab-1, and in HSC3-hPDPN and LEC by NZ-1.2. In frozen sections, PMab-1 reacted with mouse kidney, pulmonary alveoli, pulmonary pleura, and salivary gland myoepithelial cells while NZ-1.2 reacted to the human salivary gland myoepithelial cells. The immunostaining of paraffin-embedded sections also showed the reaction of PMab-1 or NZ-1.2 to the mouse or monkey kidney glomerulus, pulmonary alveoli, and lung lymphatic vessels. These results indicate that the two novel rat mAbs to the mouse and human/monkey podoplanin are useful for Western-blot and immunostaining of somatic tissues on paraffin-embedded sections as well as frozen sections

  8. MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction

    Science.gov (United States)

    Kim, Kyung Mok; Chung, Ki Wung; Jeong, Hyeong Oh; Lee, Bonggi; Kim, Dae Hyun; Park, June Whoun; Kim, Seong Min; Yu, Byung Pal; Chung, Hae Young

    2018-01-01

    Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein–protein interaction (PPI). Both mRNA and protein levels of MMP2 and A2M were increased during aging. Furthermore, the interaction between MMP2 and A2M was verified by immunoprecipitation and immunohistochemistry. MMP2 activity was further measured under the presence or absence of A2M-MMP2 interaction. MMP2 activity, which was increased under the absence of A2M-MMP2 interaction, was significantly decreased under the presence of interactions in aged kidney. We further hypothesized that the interaction between A2M-MMP2 played a role in the inactivation of MMP2 leading to accumulation of ECM including collagen type I and IV. Aged kidney showed highly accumulated MMP2 substrate proteins despite of increased MMP2 protein expression and CR blunted these accumulation. Additional in vivo analysis revealed that the signal transducer and activator of transcription (STAT) 3 transcriptional factor was significantly increased thus increasing A2M expression during aging. STAT3 activating cytokines were also highly increased in aged kidney. In conclusion, the results of the present study indicate that A2M-MMP2 interaction has a role in age-associated renal ECM accumulation and in the suppression such fibrosis by CR. PMID:29464020

  9. Inflammation and premature aging in advanced chronic kidney disease.

    Science.gov (United States)

    Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

    2017-10-01

    Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

  10. Suramin protects from cisplatin-induced acute kidney injury

    Science.gov (United States)

    Dupre, Tess V.; Doll, Mark A.; Shah, Parag P.; Sharp, Cierra N.; Kiefer, Alex; Scherzer, Michael T.; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E.; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G.; Beverly, Levi J.

    2015-01-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer. PMID:26661653

  11. Bcl-2 over-expression fails to prevent age-related loss of calretinin positive neurons in the mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Han Mingbo

    2006-08-01

    Full Text Available Abstract Background Cognitive performance declines with increasing age. Possible cellular mechanisms underlying this age-related functional decline remain incompletely understood. Early studies attributed this functional decline to age-related neuronal loss. Subsequent studies using unbiased stereological techniques found little or no neuronal loss during aging. However, studies using specific cellular markers found age-related loss of specific neuronal types. To test whether there is age-related loss of specific neuronal populations in the hippocampus, and subsequently, whether over-expression of the B-cell lymphoma protein-2 (Bcl-2 in these neurons could delay possible age-related neuronal loss, we examined calretinin (CR positive neurons in the mouse dentate gyrus during aging. Result In normal mice, there was an age-related loss of CR positive cells in the dentate gyrus. At the same region, there was no significant decrease of total numbers of neurons, which suggested that age-related loss of CR positive cells was due to the decrease of CR expression in these cells instead of cell death. In the transgenic mouse line over-expressing Bcl-2 in neurons, there was an age-related loss of CR positive cells. Interestingly, there was also an age-related neuronal loss in this transgenic mouse line. Conclusion These data suggest an age-related loss of CR positive neurons but not total neuronal loss in normal mice and this age-related neuronal change is not prevented by Bcl-2 over-expression.

  12. Making new kidneys: On the road from science fiction to science fact.

    Science.gov (United States)

    Volovelsky, Oded; Kopan, Raphael

    2016-12-01

    Allogenic kidney transplantation use is limited because of a shortage of kidney organ donors and the risks associated with a long-term immunosuppression. An emerging treatment prospect is autologous transplants of ex vivo produced human kidneys. Here we will review the research advances in this area. The creation of human induced pluripotent cells (iPSCs) from somatic cells and the emergence of several differentiation protocols that are able to convert iPSCs cells into self-organizing kidney organoids are two large steps toward assembling a human kidney in vitro. Several groups have successfully generated urine-producing kidney organoids upon transplantation in a mouse host. Additional advances in culturing nephron progenitors in vitro may provide another source for kidney engineering, and the emergence of genome editing technology will facilitate correction of congenital mutations. Basic research into the development of metanephric kidneys and iPSC differentiation protocols, the therapeutic use of iPSCs, along with emergence of new technologies such as CRISPR/Cas9 genome editing have accelerated a trend that may prove transformative in the treatment of ESRD and congenital kidney disorders.

  13. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity.

    Science.gov (United States)

    Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

    2016-01-01

    Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II -/- ) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II -/- mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II -/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II -/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

  14. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

    Directory of Open Access Journals (Sweden)

    Ji Huang

    2016-11-01

    Full Text Available Obesity is associated with development and progression of chronic kidney disease (CKD. Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I and arginase-II (Arg-II in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS, leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT C57BL/6 mice and mice deficient in Arg-II gene (Arg-II-/- were fed with either a normal chow (NC or a high-fat-diet (HFD for 14 weeks (starting at the age of 7 weeks to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal ROS levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II-/- mice. Moreover, mesangial expansion as analysed by Periodic Acid Schiff (PAS staining and renal expression of vascular adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II-/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II-/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

  15. Three-Dimensional Reconstruction of the Mouse Nephron

    DEFF Research Database (Denmark)

    Zhai, Xiao-Yue; Thomsen, Jesper Skovhus; Birn, Henrik

    2006-01-01

    Renal function is crucially dependent on renal microstructure which provides the basis for the regulatory mechanisms that control the transport of water and solutes between filtrate and plasma and the urinary concentration. This study provides new, detailed information on mouse renal architecture...... and collecting ducts was performed on aligned digital images, obtained from 2.5-µm-thick serial sections of mouse kidneys. Important new findings were highlighted: (1) A tortuous course of the descending thin limbs of long-looped nephrons and a winding course of the thick ascending limbs of short-looped nephrons...

  16. 77 FR 38075 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-06-26

    ... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel; Type 1 Diabetes Mouse Resource. Date: July 23, 2012. Time: 1 p.m. to 3 p.m. Agenda: To review and evaluate grant applications. Place... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the...

  17. Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice

    DEFF Research Database (Denmark)

    Bisgaard, Line S; Bosteen, Markus H; Fink, Lisbeth N

    2016-01-01

    Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosc......Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis...... aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX)). Uremic (n = 29) and sham-operated (n = 14) atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s.......c. once daily) or vehicle for 13 weeks. As expected, uremia increased aortic atherosclerosis. In the remnant kidneys from NX mice, flow cytometry revealed an increase in the number of monocyte-like cells (CD68+F4/80-), CD4+, and CD8+ T-cells, suggesting that moderate uremia induced kidney inflammation...

  18. Measurement of kidney by computed tomography

    International Nuclear Information System (INIS)

    Hamada, Tatsumi; Nakagawa, Kenichi; Tamura, Kenji; Yoshida, Akio; Fujii, Koichi

    1983-01-01

    Several measurements of normal kidney in vivo were obtained from computed tomography and were correlated with age, sex and body dimensions. Forty four males and 21 females without a history of renal disease were studied. 1. Angle between renal coronal section and body frontal (degree): The mean value (+- SD) of the angle was 44.0 +- 11.1 for right kidney and 42.3 +- 11.2 for left, with a low correlation coefficient. The angle had no significant correlation with age nor sex. 2. The largest width of kidney (cm): The mean value of the width was 4.6 +- 0.6 for male right kidney, 5.1 +- 0.6 for male left, 4.6 +- 0.7 for female right and 4.7 +- 1.0 for female left. The values correlated with age under 40 positively and over 40 negatively. 3. Renal volume (cm 3 ): Renal volume was calculated by adding together the area measurements obtained from successive 1 cm thick scans, excluding renal sinus. The mean volume was 107 +- 27 for male right kidney, 114 +- 24 for male left, 101 +- 33 for female right and 111 +- 41 for female left. The correlation coefficient of right versus left renal volume was significantly high. Total renal volume, i. e. left + right renal volume, had significant negative correlation with age over 40. 4. CT numbers of kidney: Average value of right kidney was 31.4 +- 6.0 and that of left was 30.7 +- 5.9. Though the correlation coefficient between right and left was nearly 1, no significant correlation was found with other values. (author)

  19. Cognitive and kidney function: results from a British birth cohort reaching retirement age.

    Directory of Open Access Journals (Sweden)

    Richard J Silverwood

    Full Text Available Previous studies have found associations between cognitive function and chronic kidney disease. We aimed to explore possible explanations for this association in the Medical Research Council National Survey of Health and Development, a prospective birth cohort representative of the general British population.Cognitive function at age 60-64 years was quantified using five measures (verbal memory, letter search speed and accuracy, simple and choice reaction times and glomerular filtration rate (eGFR at the same age was estimated using cystatin C. The cross-sectional association between cognitive function and eGFR was adjusted for background confounding factors (socioeconomic position, educational attainment, prior cognition, and potential explanations for any remaining association (smoking, diabetes, hypertension, inflammation, obesity.Data on all the analysis variables were available for 1306-1320 study members (depending on cognitive measure. Verbal memory and simple and choice reaction times were strongly associated with eGFR. For example, the lowest quartile of verbal memory corresponded to a 4.1 (95% confidence interval 2.0, 6.2 ml/min/1.73 m(2 lower eGFR relative to the highest quartile. Some of this association was explained by confounding due to socioeconomic factors, but very little of it by prior cognition. Smoking, diabetes, hypertension, inflammation and obesity explained some but not all of the remaining association.These analyses support the notion of a shared pathophysiology of impaired cognitive and kidney function at older age, which precedes clinical disease. The implications of these findings for clinical care and research are important and under-recognised, though further confirmatory studies are required.

  20. Characterization of blood biochemical markers during aging in the Grey Mouse Lemur (Microcebus murinus: impact of gender and season

    Directory of Open Access Journals (Sweden)

    Marchal Julia

    2012-11-01

    Full Text Available Abstract Background Hematologic and biochemical data are needed to characterize the health status of animal populations over time to determine the habitat quality and captivity conditions. Blood components and the chemical entities that they transport change predominantly with sex and age. The aim of this study was to utilize blood chemistry monitoring to establish the reference levels in a small prosimian primate, the Grey Mouse Lemur (Microcebus murinus. Method In the captive colony, mouse lemurs may live 10–12 years, and three age groups for both males and females were studied: young (1–3 years, middle-aged (4–5 years and old (6–10 years. Blood biochemical markers were measured using the VetScan Comprehensive Diagnostic Profile. Because many life history traits of this primate are highly dependent on the photoperiod (body mass and reproduction, the effect of season was also assessed. Results The main effect of age was observed in blood markers of renal functions such as creatinine, which was higher among females. Additionally, blood urea nitrogen significantly increased with age and is potentially linked to chronic renal insufficiency, which has been described in captive mouse lemurs. The results demonstrated significant effects related to season, especially in blood protein levels and glucose rates; these effects were observed regardless of gender or age and were likely due to seasonal variations in food intake, which is very marked in this species. Conclusion These results were highly similar with those obtained in other primate species and can serve as references for future research of the Grey Mouse Lemur.

  1. Perspectives of Older Kidney Transplant Recipients on Kidney Transplantation.

    Science.gov (United States)

    Pinter, Jule; Hanson, Camilla S; Chapman, Jeremy R; Wong, Germaine; Craig, Jonathan C; Schell, Jane O; Tong, Allison

    2017-03-07

    Older kidney transplant recipients are susceptible to cognitive impairment, frailty, comorbidities, immunosuppression-related complications, and chronic graft failure, however, there has been limited focus on their concerns and expectations related to transplantation. This study aims to describe the perspectives of older kidney transplant recipients about their experience of kidney transplantation, self-management, and treatment goals to inform strategies and interventions that address their specific needs. Face-to-face semistructured interviews were conducted with 30 kidney transplant recipients aged 65-80 years from five renal units in Australia. Transcripts were analyzed thematically. Six themes were identified: restoring vitality of youth (with subthemes of revived mindset for resilience, embracing enjoyment in life, drive for self-actualization); persisting through prolonged recovery (yielding to aging, accepting functional limitations, pushing the limit, enduring treatment responsibilities); imposing sicknesses (combatting devastating comorbidities, painful restrictions, emerging disillusionment, anxieties about accumulating side effects, consuming treatment burden); prioritizing graft survival (privileged with a miracle, negotiating risks for longevity, enacting a moral duty, preserving the last opportunity); confronting health deterioration (vulnerability and helplessness, narrowing focus to immediate concerns, uncertainty of survival); and value of existence (purpose through autonomy, refusing the burden of futile treatment, staying alive by all means). Older kidney transplant recipients felt able to enjoy life and strived to live at their newly re-established potential and capability, which motivated them to protect their graft. However, some felt constrained by slow recuperation and overwhelmed by unexpected comorbidities, medication-related side effects, and health decline. Our findings suggest the need to prepare and support older recipients for self

  2. Effect of age on the expression of Pex (Phex) in the mouse.

    Science.gov (United States)

    Meyer, R A; Young, C G; Meyer, M H; Garges, P L; Price, D K

    2000-04-01

    Pex is a newly discovered gene (also called Phex) whose mutation is the cause of X-linked hypophosphatemia. Other members of this gene family encode endopeptidases that activate or inactivate endocrine and paracrine factors. Though embryonic bone expresses mRNA for the Pex gene at relatively high levels, we have found Pex expression to be widespread in adult organs and to be poorly expressed in adult bone. This led to the hypothesis that Pex mRNA expression changes with age. To test this, genetically normal mice of the B6C3H hybrid strain were studied at 0 (newborn), 2, 3, 10, and 72 weeks of age. Organs known to express Pex were collected, and RNA was extracted from them. Following reverse transcription, cDNA was amplified by the polymerase chain reaction with primers for Pex and G3PDH, a housekeeping gene. The amplimers were separated by electrophoresis, blotted onto nylon membranes, and hybridized with radioactively labeled internal oligonucleotide probes. The radioactivity was quantified, and the data were analyzed as the Pex/G3PDH ratio. The brain samples had high levels of Pex mRNA expression that rose slightly with age. Calvaria, kidney, and lung samples had the highest Pex mRNA expression at birth. In these organs Pex mRNA expression fell with age to undetectable or barely detectable levels. Thymus, heart, and skeletal muscle samples had low Pex mRNA expression at birth that did not change with age. Some organs showed a decline in G3PDH levels with age, but Pex expression decreased more, leading to a reduced Pex/G3PDH ratio. The widespread expression of mRNA for Pex suggests a role beyond that of phosphate homeostasis. The high level of expression in newborn animals suggests a role in growth and development. This seems to occur in addition to its role for the endocrine regulation of phosphate homeostasis by as yet unknown humoral agents that must occur throughout life. In summary, Pex mRNA expression is high in brain and bone at birth. Expression remains

  3. Mequindox-Induced Kidney Toxicity Is Associated With Oxidative Stress and Apoptosis in the Mouse

    Directory of Open Access Journals (Sweden)

    Qianying Liu

    2018-05-01

    Full Text Available Mequindox (MEQ, belonging to quinoxaline-di-N-oxides (QdNOs, is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo.

  4. Expression of apolipoprotein B in the kidney attenuates renal lipid accumulation

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Pedersen, Tanja Xenia; Bartels, Emil Daniel

    2010-01-01

    The ability to produce apolipoprotein (apo) B-containing lipoproteins enables hepatocytes, enterocytes, and cardiomyocytes to export triglycerides. In this study, we examined secretion of apoB-containing lipoproteins from mouse kidney and its putative impact on triglyceride accumulation in the tu...

  5. Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

    Science.gov (United States)

    Mazidi, Moshen; Rezaie, Peyman; Covic, Adriac; Malyszko, Jolanta; Rysz, Jacek; Kengne, Andre Pascal; Banach, Maciej

    2017-10-06

    Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

  6. Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney

    Directory of Open Access Journals (Sweden)

    Tom L. Broderick

    2017-06-01

    Full Text Available Background/Aims: Carnitine is essential for the transport of long-chain FAs (FA into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. Methods: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [14C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH, organic cation transporter (OCTN2, and peroxisome proliferator-activated receptor (PPARα, a regulator of fatty acid oxidation activated by FAs. Results: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. Conclusions: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

  7. The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.

    NARCIS (Netherlands)

    Huls, M.; Brown, C.D.; Windass, A.S.; Sayer, R.; Heuvel, J.J.M.W. van den; Heemskerk, S.; Russel, F.G.M.; Masereeuw, R.

    2008-01-01

    The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney,

  8. Acute Kidney Injury in the Elderly

    Science.gov (United States)

    Abdel-Kader, Khaled; Palevsky, Paul

    2009-01-01

    Synopsis The aging kidney undergoes a number of important anatomic and physiologic changes that increase the risk of acute kidney injury (formerly acute renal failure) in the elderly. This article reviews these changes and discusses the diagnoses frequently encountered in the elderly patient with acute kidney injury. The incidence, staging, evaluation, management, and prognosis of acute kidney injury are also examined with special focus given to older adults. PMID:19765485

  9. Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources,

    Energy Technology Data Exchange (ETDEWEB)

    Barregard, Lars, E-mail: lars.barregard@amm.gu.se [Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, P.O. Box 414, SE 405 30 Gothenburg (Sweden); Fabricius-Lagging, Elisabeth [Department of Nephrology, Sahlgrenska University Hospital and Boras Hospital (Sweden); Lundh, Thomas [Department of Occupational and Environmental Medicine, Lund University Hospital and Lund University (Sweden); Moelne, Johan [Department of Clinical Pathology, Sahlgrenska University Hospital and University of Gothenburg (Sweden); Wallin, Maria [Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, P.O. Box 414, SE 405 30 Gothenburg (Sweden); Olausson, Michael [Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital and University of Gothenburg (Sweden); Modigh, Cecilia; Sallsten, Gerd [Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, P.O. Box 414, SE 405 30 Gothenburg (Sweden)

    2010-01-15

    Background: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. Objectives: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. Methods: Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated. Results: The median kidney concentrations were 12.9 {mu}g/g (wet weight) for cadmium, 0.21 {mu}g/g for mercury, and 0.08 {mu}g/g for lead. Kidney Cd increased by 3.9 {mu}g/g for a 10 year increase in age, and by 3.7 {mu}g/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5 {mu}g/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. Conclusions: In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.

  10. Cadmium, mercury, and lead in kidney cortex of living kidney donors: Impact of different exposure sources,

    International Nuclear Information System (INIS)

    Barregard, Lars; Fabricius-Lagging, Elisabeth; Lundh, Thomas; Moelne, Johan; Wallin, Maria; Olausson, Michael; Modigh, Cecilia; Sallsten, Gerd

    2010-01-01

    Background: Most current knowledge on kidney concentrations of nephrotoxic metals like cadmium (Cd), mercury (Hg), or lead (Pb) comes from autopsy studies. Assessment of metal concentrations in kidney biopsies from living subjects can be combined with information about exposure sources like smoking, diet, and occupation supplied by the biopsied subjects themselves. Objectives: To determine kidney concentrations of Cd, Hg, and Pb in living kidney donors, and assess associations with common exposure sources and background factors. Methods: Metal concentrations were determined in 109 living kidney donors aged 24-70 years (median 51), using inductively coupled plasma-mass spectrometry (Cd and Pb) and cold vapor atomic fluorescence spectrometry (Hg). Smoking habits, occupation, dental amalgam, fish consumption, and iron stores were evaluated. Results: The median kidney concentrations were 12.9 μg/g (wet weight) for cadmium, 0.21 μg/g for mercury, and 0.08 μg/g for lead. Kidney Cd increased by 3.9 μg/g for a 10 year increase in age, and by 3.7 μg/g for an extra 10 pack-years of smoking. Levels in non-smokers were similar to those found in the 1970s. Low iron stores (low serum ferritin) in women increased kidney Cd by 4.5 μg/g. Kidney Hg increased by 6% for every additional amalgam surface, but was not associated with fish consumption. Lead was unaffected by the background factors surveyed. Conclusions: In Sweden, kidney Cd levels have decreased due to less smoking, while the impact of diet seems unchanged. Dental amalgam is the main determinant of kidney Hg. Kidney Pb levels are very low due to decreased exposure.

  11. Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea.

    Science.gov (United States)

    Abuyassin, Bisher; Badran, Mohammad; Ayas, Najib T; Laher, Ismail

    2018-01-01

    Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA) and accelerated loss of kidney function. It is unclear whether the decline in function is due to OSA per se or to other confounding factors such as obesity. In addition, the structural kidney abnormalities associated with OSA are unclear. The objective of this study was to determine whether intermittent hypoxia (IH), a key pathological feature of OSA, induces renal histopathological damage using a mouse model. Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA) for 60 days. After euthanasia, one kidney per animal was paraformaldehyde-fixed and then sectioned for histopathological and immunohistochemical analysis. Measurements of glomerular hypertrophy and mesangial matrix expansion were made in periodic acid-Schiff stained kidney sections, while glomerular transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and vascular endothelial growth factor-A (VEGF-A) proteins were semi-quantified by immunohistochemistry. The antigen-antibody reaction was detected by 3,3'-diaminobenzidine chromogen where the color intensity semi-quantified glomerular protein expression. To enhance the accuracy of protein semi-quantification, the percentage of only highly-positive staining was used for analysis. Levels of TGF-β, CTGF and VEGF-A proteins in the kidney cortex were further quantified by western blotting. Cellular apoptosis was also investigated by measuring cortical antiapoptotic B-cell lymphoma 2 (Bcl-2) and apoptotic Bcl-2-associated X (Bax) proteins by western blotting. Further investigation of cellular apoptosis was carried out by fluorometric terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining. Finally, the levels of serum creatinine and 24-hour urinary albumin were measured as a general index of renal function. Our results indicate that mice exposed to IH have an

  12. Intermittent hypoxia causes histological kidney damage and increases growth factor expression in a mouse model of obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Bisher Abuyassin

    Full Text Available Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA and accelerated loss of kidney function. It is unclear whether the decline in function is due to OSA per se or to other confounding factors such as obesity. In addition, the structural kidney abnormalities associated with OSA are unclear. The objective of this study was to determine whether intermittent hypoxia (IH, a key pathological feature of OSA, induces renal histopathological damage using a mouse model. Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA for 60 days. After euthanasia, one kidney per animal was paraformaldehyde-fixed and then sectioned for histopathological and immunohistochemical analysis. Measurements of glomerular hypertrophy and mesangial matrix expansion were made in periodic acid-Schiff stained kidney sections, while glomerular transforming growth factor-β1 (TGF-β1, connective tissue growth factor (CTGF and vascular endothelial growth factor-A (VEGF-A proteins were semi-quantified by immunohistochemistry. The antigen-antibody reaction was detected by 3,3'-diaminobenzidine chromogen where the color intensity semi-quantified glomerular protein expression. To enhance the accuracy of protein semi-quantification, the percentage of only highly-positive staining was used for analysis. Levels of TGF-β, CTGF and VEGF-A proteins in the kidney cortex were further quantified by western blotting. Cellular apoptosis was also investigated by measuring cortical antiapoptotic B-cell lymphoma 2 (Bcl-2 and apoptotic Bcl-2-associated X (Bax proteins by western blotting. Further investigation of cellular apoptosis was carried out by fluorometric terminal deoxynucleotidyl transferase (TdT dUTP Nick-End Labeling (TUNEL staining. Finally, the levels of serum creatinine and 24-hour urinary albumin were measured as a general index of renal function. Our results indicate that mice exposed to IH

  13. Kidney transplant outcomes from older deceased donors

    DEFF Research Database (Denmark)

    Pippias, Maria; Jager, Kitty J; Caskey, Fergus

    2018-01-01

    As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor...

  14. Lysyl oxidase‑like 2 is expressed in kidney tissue and is associated with the progression of tubulointerstitial fibrosis.

    Science.gov (United States)

    Choi, Sung-Eun; Jeon, Nara; Choi, Hoon Young; Shin, Jae Il; Jeong, Hyeon Joo; Lim, Beom Jin

    2017-09-01

    Tubulointerstitial fibrosis is a common end point of chronic kidney diseases, and preventing its progression is key to avoiding renal failure. Transforming growth factor‑β (TGF‑β) and associated molecules promote tubulointerstitial fibrosis; however, effective therapies targeting these molecules have yet to be developed. Lysyl oxidase‑like 2 (LOXL2), which is involved in invasive growth and metastasis of malignant neoplasms, has recently been reported to serve a key role in hepatic and pulmonary fibrosis. However, little is currently known regarding LOXL2 expression in the kidney and its involvement in tubulointerstitial fibrosis. The present study evaluated LOXL2 expression in human and mouse kidney tissues, as well as in cultured renal cells. LOXL2 protein expression was detected in glomerular capillary loops and tubular epithelial cells in human and mouse kidneys. Glomerular LOXL2 was localized to the cytoplasm of podocytes, as determined by double immunofluorescence microscopy using a podocyte marker (synaptopodin). This result was supported by western blot analysis, which demonstrated that LOXL2 protein expression is present in cultured human podocytes and HK‑2 human proximal tubular cells. In addition, the mRNA and protein expression levels of LOXL2 were higher in a mouse model of tubulointerstitial fibrosis compared with in control mice. In addition, immunohistochemistry results demonstrated that LOXL2 is present in the fibrous interstitium and infiltrating mononuclear cells in a mouse model of tubulointerstitial fibrosis. The present study demonstrated that LOXL2 is expressed in compartments of renal tissue, where it appears to contribute to the progression of tubulointerstitial fibrosis.

  15. Less overdiagnosis of kidney cancer? an age-period-cohort analysis of incidence trends in 16 populations worldwide.

    Science.gov (United States)

    Znaor, Ariana; Laversanne, Mathieu; Bray, Freddie

    2017-09-01

    The increasing rates of kidney cancer incidence, reported in many populations globally, have been attributed both to increasing exposures to environmental risk factors, as well as increasing levels of incidental diagnosis due to widespread use of imaging. To better understand these trends, we examine long-term cancer registry data worldwide, focusing on the roles of birth cohort and calendar period, proxies for changes in risk factor prevalence and detection practice respectively. We used an augmented version of the Cancer Incidence in Five Continents series to analyze kidney cancer incidence rates 1978-2007 in 16 geographically representative populations worldwide by sex for ages 30-74, using age-period-cohort (APC) analysis. The full APC model provided the best fit to the data in most studied populations. While kidney cancer incidence rates have been increasing in successive generations born from the early twentieth century in most countries, equivalent period-specific rises were observed from the late-1970s, although these have subsequently stabilized in certain European countries (the Czech Republic, Lithuania, Finland, Spain) as well as Japan from the mid-1990s, and from the mid-2000s, in Colombia, Costa Rica and Australia. Our results indicate that the effects of both birth cohort and calendar period contribute to the international kidney cancer incidence trends. While cohort-specific increases may partly reflect the rising trends in obesity prevalence and the need for more effective primary prevention policies, the attenuations in period-specific increases (observed in 8 of the 16 populations) highlight a possible change in imaging practices that could lead to mitigation of overdiagnosis and overtreatment. © 2017 UICC.

  16. Age-associated metabolic and morphologic changes in mitochondria of individual mouse and hamster oocytes.

    Directory of Open Access Journals (Sweden)

    Fatma Simsek-Duran

    Full Text Available BACKGROUND: In human oocytes, as in other mammalian ova, there is a significant variation in the pregnancy potential, with approximately 20% of oocyte-sperm meetings resulting in pregnancies. This frequency of successful fertilization decreases as the oocytes age. This low proportion of fruitful couplings appears to be influenced by changes in mitochondrial structure and function. In this study, we have examined mitochondrial biogenesis in both hamster (Mesocricetus auratus and mouse (Mus musculus ova as models for understanding the effects of aging on mitochondrial structure and energy production within the mammalian oocyte. METHODOLOGY/PRINCIPAL FINDINGS: Individual metaphase II oocytes from a total of 25 young and old mice and hamsters were collected from ovarian follicles after hormone stimulation and prepared for biochemical or structural analysis. Adenosine triphosphate levels and mitochondrial DNA number were determined within individual oocytes from young and old animals. In aged hamsters, oocyte adenosine triphosphate levels and mitochondrial DNA molecules were reduced 35.4% and 51.8%, respectively. Reductions of 38.4% and 44% in adenosine triphosphate and mitochondrial genomes, respectively, were also seen in aged mouse oocytes. Transmission electron microscopic (TEM analysis showed that aged rodent oocytes had significant alterations in mitochondrial and cytoplasmic lamellae structure. CONCLUSIONS/SIGNIFICANCE: In both mice and hamsters, decreased adenosine triphosphate in aged oocytes is correlated with a similar decrease in mtDNA molecules and number of mitochondria. Mitochondria in mice and hamsters undergo significant morphological change with aging including mitochondrial vacuolization, cristae alterations, and changes in cytoplasmic lamellae.

  17. Micro-MRI study of cerebral aging: ex vivo detection of hippocampal sub-field reorganization, micro-hemorrhages and amyloid plaques in mouse lemur primates

    International Nuclear Information System (INIS)

    Bertrand, Anne; Petiet, Alexandra; Dhenain, Marc; Pasquier, Adrien; Kraska, Audrey; Joseph-Mathurin, Nelly; Wiggins, Christopher; Aujard, Fabienne; Mestre-Frances, Nadine

    2013-01-01

    Mouse lemurs are non-human primate models of cerebral aging and neuro-degeneration. Much smaller than other primates, they recapitulate numerous features of human brain aging, including progressive cerebral atrophy and correlation between regional atrophy and cognitive impairments. Characterization of brain atrophy in mouse lemurs has been done by MRI measures of regional CSF volume and by MRI measures of regional atrophy. Here, we further characterize mouse lemur brain aging using ex vivo MR microscopy (31 μm in-plane resolution). First, we performed a non-biased, direct volumetric quantification of dentate gyrus and extended Ammon's horn. We show that both dentate gyrus and Ammon's horn undergo an age-related reorganization leading to a growth of the dentate gyrus and an atrophy of the Ammon's horn, even in the absence of global hippocampal atrophy. Second, on these first MR microscopic images of the mouse lemur brain, we depicted cortical and hippocampal hypointense spots. We demonstrated that their incidence increases with aging and that they correspond either to amyloid deposits or to cerebral micro-hemorrhages. (authors)

  18. Age-Associated Lipidome Changes in Metaphase II Mouse Oocytes.

    Directory of Open Access Journals (Sweden)

    Hyuck Jun Mok

    Full Text Available The quality of mammalian oocytes declines with age, which negatively affects fertilization and developmental potential. The aging process often accompanies damages to macromolecules such as proteins, DNA, and lipids. To investigate if aged oocytes display an altered lipidome compared to young oocytes, we performed a global lipidomic analysis between oocytes from 4-week-old and 42 to 50-week-old mice. Increased oxidative stress is often considered as one of the main causes of cellular aging. Thus, we set up a group of 4-week-old oocytes treated with hydrogen peroxide (H2O2, a commonly used oxidative stressor, to compare if similar lipid species are altered between aged and oxidative-stressed oocytes. Between young and aged oocytes, we identified 26 decreased and 6 increased lipids in aged oocytes; and between young and H2O2-treated oocytes, we identified 35 decreased and 26 increased lipids in H2O2-treated oocytes. The decreased lipid species in these two comparisons were overlapped, whereas the increased lipid species were distinct. Multiple phospholipid classes, phosphatidic acid (PA, phosphatidylinositol (PI, phosphatidylserine (PS, and lysophosphatidylserine (LPS significantly decreased both in H2O2-treated and aged oocytes, suggesting that the integrity of plasma membrane is similarly affected under these conditions. In contrast, a dramatic increase in diacylglycerol (DG was only noted in H2O2-treated oocytes, indicating that the acute effect of H2O2-caused oxidative stress is distinct from aging-associated lipidome alteration. In H2O2-treated oocytes, the expression of lysophosphatidylcholine acyltransferase 1 increased along with increases in phosphatidylcholine. Overall, our data reveal that several classes of phospholipids are affected in aged oocytes, suggesting that the integrity of plasma membrane is associated with maintaining fertilization and developmental potential of mouse oocytes.

  19. Growth and morphogenesis of embryonic mouse organs on non-coated and extracellular matrix-coated Biopore membrane

    Science.gov (United States)

    Hardman, P.; Klement, B. J.; Spooner, B. S.

    1993-01-01

    Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.

  20. In vitro regeneration of kidney from pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Osafune, Kenji, E-mail: osafu@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); JST Yamanaka iPS Cell Special Project, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan)

    2010-10-01

    Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

  1. In vitro regeneration of kidney from pluripotent stem cells

    International Nuclear Information System (INIS)

    Osafune, Kenji

    2010-01-01

    Although renal transplantation has proved a successful treatment for the patients with end-stage renal failure, the therapy is hampered by the problem of serious shortage of donor organs. Regenerative medicine using stem cells, including cell transplantation therapy, needs to be developed to solve the problem. We previously identified the multipotent progenitor cells in the embryonic mouse kidney that can give rise to several kinds of epithelial cells found in adult kidney, such as glomerular podocytes and renal tubular epithelia. Establishing the method to generate the progenitors from human pluripotent stem cells that have the capacity to indefinitely proliferate in vitro is required for the development of kidney regeneration strategy. We review the current status of the research on the differentiation of pluripotent stem cells into renal lineages and describe cues to promote this research field.

  2. Viewing ageing eyes: diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages.

    Directory of Open Access Journals (Sweden)

    Jaimie Hoh Kam

    Full Text Available BACKGROUND: Amyloid beta (Aβ accumulates in the ageing central nervous system and is associated with a number of age-related diseases, including age-related macular degeneration (AMD in the eye. AMD is characterised by accumulation of extracellular deposits called drusen in which Aβ is a key constituent. Aβ activates the complement cascade and its deposition is associated with activated macrophages. So far, little is known about the quantitative measurements of Aβ accumulation and definitions of its relative sites of ocular deposition in the normal ageing mouse. METHODOLOGY/PRINCIPAL FINDINGS: We have traced Aβ accumulation quantitatively in the ageing mouse retina using immunohistochemistry and Western blot analysis. We reveal that it is not only deposited at Bruch's membrane and along blood vessels, but unexpectedly, it also coats photoreceptor outer segments. While Aβ is present at all sites of deposition from 3 months of age, it increases markedly from 6 months onward. Progressive accumulation of deposits on outer segments was confirmed with scanning electron microscopy, revealing age-related changes in their morphology. Such progress of accumulation of Aβ on photoreceptor outer segments with age was also confirmed in human retinae using immunohistochemistry. We also chart the macrophage response to increases in Aβ showing up-regulation in their numbers using both confocal laser imaging of the eye in vivo followed by in vitro immunostaining. With age macrophages become bloated with cellular debris including Aβ, however, their increasing numbers fail to stop Aβ accumulation. CONCLUSIONS: Increasing Aβ deposition in blood vessels and Bruch's membrane will impact upon retinal perfusion and clearance of cellular waste products from the outer retina, a region of very high metabolic activity. This accumulation of Aβ may contribute to the 30% reduction of photoreceptors found throughout life and the shortening of those that remain. The

  3. Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury.

    Science.gov (United States)

    James, Matthew T; Pannu, Neesh; Hemmelgarn, Brenda R; Austin, Peter C; Tan, Zhi; McArthur, Eric; Manns, Braden J; Tonelli, Marcello; Wald, Ron; Quinn, Robert R; Ravani, Pietro; Garg, Amit X

    2017-11-14

    Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Demographic, laboratory, and comorbidity variables measured prior to discharge. Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher

  4. Making new kidneys – On the road from science fiction to science fact

    Science.gov (United States)

    Volovelsky, Oded; Kopan, Raphael

    2017-01-01

    Purpose of Review Allogenic kidney transplantation use is limited due to a shortage of kidney organ donors and the risks associated with a long-term immunosuppression. An emerging treatment prospect is autologous transplants of ex-vivo produced human kidneys. Here we will review the research advances in this area. Recent findings The creation of human induced pluripotent cells (iPSCs) from somatic cells and the emergence of several differentiation protocols that are able to convert iPSCs cells into self-organizing kidney organoids are two large steps towards assembling a human kidney in vitro. Several groups have successfully generated urine-producing kidney organoids upon transplantation in a mouse host. Additional advances in culturing nephron progenitors in vitro may provide another source for kidney engineering, and the emergence of genome editing technology will facilitate correction of congenital mutations. Summary Basic research into the development of metanephric kidneys and iPSC differentiation protocols, the therapeutic use of iPSCs, along with emergence of new technologies such as CRISPR/Cas9 genome editing have accelerated a trend that may prove transformative in the treatment of ESRD as well as congenital kidney disorders. PMID:27805946

  5. Altered myogenic vasoconstriction and regulation of whole kidney blood flow in the ASIC2 knockout mouse.

    Science.gov (United States)

    Gannon, Kimberly P; McKey, Susan E; Stec, David E; Drummond, Heather A

    2015-02-15

    Previous studies from our laboratory have suggested that degenerin proteins contribute to myogenic constriction, a mechanism of blood flow regulation and protection against pressure-dependent organ injury, in renal vessels. The goal of the present study was to determine the importance of one family member, acid-sensing ion channel 2 (ASIC2), in myogenic constriction of renal interlobar arteries, myogenic regulation of whole kidney blood flow, renal injury, and blood pressure using ASIC2(+/+), ASIC2(+/-), and ASIC2(-/-) mice. Myogenic constriction in renal interlobar arteries was impaired in ASIC2(+/-) and ASIC2(-/-) mice, whereas constriction to KCl/phenylephrine was unchanged. Correction of whole kidney renal vascular resistance (RVR) during the first 5 s after a 10- to 20-mmHg step increase in perfusion pressure, a timeframe associated with myogenic-mediated correction of RVR, was slowed (4.2 ± 0.9, 0.3 ± 0.7, and 2.4 ± 0.3 resistance units/s in ASIC2(+/+), ASIC2(+/-), and ASIC2(-/-) mice). Although modest reductions in function were observed in ASIC2(-/-) mice, greater reductions were observed in ASIC2(+/-) mice, which may be explained by protein-protein interactions of ASIC2 with other degenerins. Isolated glomeruli from ASIC2(+/-) and ASIC2(-/-) mice had modest alterations in the expression of inflammation and injury markers (transforming growth factor-β, mouse anti-target of antiproliferative antibody-1, and nephrin), whereas ASIC2(+/-) mice had an increase in the remodeling marker collagen type III. Consistent with a more severe loss of function, mean arterial pressure was increased in ASIC2(+/-) mice (131 ± 3 mmHg) but not in ASIC2(-/-) mice (122 ± 3 vs. 117 ± 2 mmHg in ASIC2(+/+) mice). These results suggest that ASIC2 contributes to transduction of the renal myogenic response and are consistent with the protective role of myogenic constriction against renal injury and hypertension. Copyright © 2015 the American Physiological Society.

  6. A Kidney Graft Survival Calculator that Accounts for Mismatches in Age, Sex, HLA, and Body Size.

    Science.gov (United States)

    Ashby, Valarie B; Leichtman, Alan B; Rees, Michael A; Song, Peter X-K; Bray, Mathieu; Wang, Wen; Kalbfleisch, John D

    2017-07-07

    Outcomes for transplants from living unrelated donors are of particular interest in kidney paired donation (KPD) programs where exchanges can be arranged between incompatible donor-recipient pairs or chains created from nondirected/altruistic donors. Using Scientific Registry of Transplant Recipients data, we analyzed 232,705 recipients of kidney-alone transplants from 1998 to 2012. Graft failure rates were estimated using Cox models for recipients of kidney transplants from living unrelated, living related, and deceased donors. Models were adjusted for year of transplant and donor and recipient characteristics, with particular attention to mismatches in age, sex, human leukocyte antigens (HLA), body size, and weight. The dependence of graft failure on increasing donor age was less pronounced for living-donor than for deceased-donor transplants. Male donor-to-male recipient transplants had lower graft failure, particularly better than female to male (5%-13% lower risk). HLA mismatch was important in all donor types. Obesity of both the recipient (8%-18% higher risk) and donor (5%-11% higher risk) was associated with higher graft loss, as were donor-recipient weight ratios of transplants where both parties were of similar weight (9%-12% higher risk). These models are used to create a calculator of estimated graft survival for living donors. This calculator provides useful information to donors, candidates, and physicians of estimated outcomes and potentially in allowing candidates to choose among several living donors. It may also help inform candidates with compatible donors on the advisability of joining a KPD program. Copyright © 2017 by the American Society of Nephrology.

  7. Apoptotic Effects of Reduced Brain Derived Neurotrophic Factor (BDNF on Mouse Liver and Kidney

    Directory of Open Access Journals (Sweden)

    Berna Tezcan

    2017-12-01

    Full Text Available Objective: Brainderived neurotrophic factor (BDNF promotes the development and differentiation of neurons and synapses, as well as neuronal survival, by acting on specific neuronal groups in the central and peripheral nervous systems. However, the direct effect of BDNF on apoptosis in peripheral tissues is not known. The aim of this study was to investigate the relationship between BDNF and apoptosis, and the density and distribution of BDNF receptors in liver and kidney tissues by histological and immunehistochemical methods. Methods: Seven wild-type and 7 BDNF heterozygous (reduced BDNF levels male mice were used in the study. Caspase-3 and TUNEL immunehistochemical stainings were performed in order to investigate the presence of apoptosis in the liver and kidney tissues of the studied groups. Apoptosis-entering cells were counted and the groups were compared. Concentration and distribution of BDNF receptors, tropomyosin-related kinase B (TrkB and nerve growth factor receptor p75 (NGFR p75, in liver and kidney tissues were also examined by immunehistochemical analyzes. Results: As a result of Caspase-3 and TUNEL immune histochemical staining, more cells were counted to enter the apoptotic process in sections of BDNF heterozygous group compared to control group (p<0.0001. In both groups TrkB and NGFR p75 receptors in liver and kidney tissues were determined in trace amounts, but there was no difference in intensity and distribution between the studied groups. Conclusion: According to our histological and immune histochemical stainings and statistical analysis of cell count between groups, it was found that BDNF is protect ive against apoptosis in liver and kidney. The lack of difference between the studied groups in terms of intensity and distribution of BDNF receptors, suggests that BDNF receptor distribution in the liver and kidney tissues may be different from the nervous system or that BDNF may differ in affinity for these receptors.

  8. Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

    Science.gov (United States)

    Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

    2011-01-01

    Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

  9. Impaired kidney growth in low-birth-weight children

    DEFF Research Database (Denmark)

    Schmidt, Ida M; Chellakooty, Marla; Boisen, Kirsten A

    2005-01-01

    BACKGROUND: Low birth weight is an important risk factor for hypertension and unfavorable prognoses of a number of renal diseases. It is also associated with reduced kidney size and nephron number. A differentiation between the effects of low birth weight versus being born premature or small...... for gestational age has, however, not been addressed. METHODS: The influence of weight for gestational age (percentage deviation from expected mean), gestational age, birth weight, and early diet on kidney growth was studied in 178 children born pre- or postmature and/or small or large for gestational age......, comparing them to 717 mature children, birth weight appropriate for gestational age. Kidney size was determined by bilateral ultrasonography measuring length, width and depth, using the equation of an ellipsoid for volume calculation. The examinations were performed at 0, 3, and 18 months of age together...

  10. Correlates of kidney stone disease differ by race in a multi-ethnic middle-aged population: The ARIC study

    NARCIS (Netherlands)

    S. Akoudad (Saloua); M. Szklo (Moyses); M.A. McAdams (Mara); T. Fulop (Tibor); C.A.M. Anderson (Cheryl); J. Coresh (Josef); A. Köttgen (Anna)

    2010-01-01

    textabstractObjective: To identify correlates of kidney stone disease in white and African American men and women in a population-based longitudinal study starting in four US communities, and to assess differences in correlates across racial groups. Methods: Between 1993 and 1995, 12,161 middle-aged

  11. Urinary acylcarnitines are altered in human kidney cancer.

    Science.gov (United States)

    Ganti, Sheila; Taylor, Sandra L; Kim, Kyoungmi; Hoppel, Charles L; Guo, Lining; Yang, Joy; Evans, Christopher; Weiss, Robert H

    2012-06-15

    Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length-dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF-κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer. Copyright © 2011 UICC.

  12. Identification of novel genes associated with renal tertiary lymphoid organ formation in aging mice.

    Science.gov (United States)

    Huang, Yuan; Caputo, Christina R; Noordmans, Gerda A; Yazdani, Saleh; Monteiro, Luiz Henrique; van den Born, Jaap; van Goor, Harry; Heeringa, Peter; Korstanje, Ron; Hillebrands, Jan-Luuk

    2014-01-01

    A hallmark of aging-related organ deterioration is a dysregulated immune response characterized by pathologic leukocyte infiltration of affected tissues. Mechanisms and genes involved are as yet unknown. To identify genes associated with aging-related renal infiltration, we analyzed kidneys from aged mice (≥20 strains) for infiltrating leukocytes followed by Haplotype Association Mapping (HAM) analysis. Immunohistochemistry revealed CD45+ cell clusters (predominantly T and B cells) in perivascular areas coinciding with PNAd+ high endothelial venules and podoplanin+ lymph vessels indicative of tertiary lymphoid organs. Cumulative cluster size increased with age (analyzed at 6, 12 and 20 months). Based on the presence or absence of clusters in male and female mice at 20 months, HAM analysis revealed significant associations with loci on Chr1, Chr2, Chr8 and Chr14 in male mice, and with loci on Chr4, Chr7, Chr13 and Chr14 in female mice. Wisp2 (Chr2) showed the strongest association (P = 5.00×10(-137)) in male mice; Ctnnbip1 (P = 6.42×10(-267)) and Tnfrsf8 (P = 5.42×10(-245)) (both on Chr4) showed the strongest association in female mice. Both Wisp2 and Ctnnbip1 are part of the Wnt-signaling pathway and the encoded proteins were expressed within the tertiary lymphoid organs. In conclusion, this study revealed differential lymphocytic infiltration and tertiary lymphoid organ formation in aged mouse kidneys across different inbred mouse strains. HAM analysis identified candidate genes involved in the Wnt-signaling pathway that may be causally linked to tertiary lymphoid organ formation.

  13. Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

    Energy Technology Data Exchange (ETDEWEB)

    Skröder, Helena [Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Hawkesworth, Sophie [Medical Research Council (MRC), International Nutrition Group, London School of Hygiene and Tropical Medicine, London, UK. (United Kingdom); Kippler, Maria [Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); El Arifeen, Shams [International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka (Bangladesh); Wagatsuma, Yukiko [Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. (Japan); Moore, Sophie E. [MRC Human Nutrition Research, Cambridge (United Kingdom); Vahter, Marie, E-mail: marie.vahter@ki.se [Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden)

    2015-07-15

    Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4–5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water was assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m{sup 2}, corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=−2.8; 95% CI: −5.5, −0.20; p=0.035), compared to those with higher selenium (B=−0.79; 95% CI: −3.0, 1.4; p=0.49). Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young

  14. Kidney function and blood pressure in preschool-aged children exposed to cadmium and arsenic - potential alleviation by selenium

    International Nuclear Information System (INIS)

    Skröder, Helena; Hawkesworth, Sophie; Kippler, Maria; El Arifeen, Shams; Wagatsuma, Yukiko; Moore, Sophie E.; Vahter, Marie

    2015-01-01

    Background: Early-life exposure to toxic compounds may cause long-lasting health effects, but few studies have investigated effects of childhood exposure to nephrotoxic metals on kidney and cardiovascular function. Objectives: To assess effects of exposure to arsenic and cadmium on kidney function and blood pressure in pre-school-aged children, and potential protection by selenium. Methods: This cross-sectional study was part of the 4.5 years of age (range: 4.4–5.4 years) follow-up of the children from a supplementation trial in pregnancy (MINIMat) in rural Bangladesh, and nested studies on early-life metal exposures. Exposure to arsenic, cadmium and selenium from food and drinking water was assessed by concentrations in children's urine, measured by ICP-MS. Kidney function was assessed by the estimated glomerular filtration rate (eGFR, n=1106), calculated from serum cystatin C, and by kidney volume, measured by ultrasound (n=375). Systolic and diastolic blood pressure was measured (n=1356) after five minutes rest. Results: Multivariable-adjusted regression analyzes showed that exposure to cadmium, but not arsenic, was inversely associated with eGFR, particularly in girls. A 0.5 µg/L increase in urinary cadmium among the girls (above spline knot at 0.12) was associated with a decrease in eGFR of 2.6 ml/min/1.73 m 2 , corresponding to 0.2SD (p=0.022). A slightly weaker inverse association with cadmium was also indicated for kidney volume, but no significant associations were found with blood pressure. Stratifying on children's urinary selenium (below or above median of 12.6 µg/L) showed a three times stronger inverse association of U-Cd with eGFR (all children) in the lower selenium stratum (B=−2.8; 95% CI: −5.5, −0.20; p=0.035), compared to those with higher selenium (B=−0.79; 95% CI: −3.0, 1.4; p=0.49). Conclusions: Childhood cadmium exposure seems to adversely affect kidney function, but not blood pressure, in this population of young

  15. Taurine deficiency, synthesis and transport in the mdx mouse model for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Terrill, Jessica R; Grounds, Miranda D; Arthur, Peter G

    2015-09-01

    The amino acid taurine is essential for the function of skeletal muscle and administration is proposed as a treatment for Duchenne Muscular Dystrophy (DMD). Taurine homeostasis is dependent on multiple processes including absorption of taurine from food, endogenous synthesis from cysteine and reabsorption in the kidney. This study investigates the cause of reported taurine deficiency in the dystrophic mdx mouse model of DMD. Levels of metabolites (taurine, cysteine, cysteine sulfinate and hypotaurine) and proteins (taurine transporter [TauT], cysteine deoxygenase and cysteine sulfinate dehydrogenase) were quantified in juvenile control C57 and dystrophic mdx mice aged 18 days, 4 and 6 weeks. In C57 mice, taurine content was much higher in both liver and plasma at 18 days, and both cysteine and cysteine deoxygenase were increased. As taurine levels decreased in maturing C57 mice, there was increased transport (reabsorption) of taurine in the kidney and muscle. In mdx mice, taurine and cysteine levels were much lower in liver and plasma at 18 days, and in muscle cysteine was low at 18 days, whereas taurine was lower at 4: these changes were associated with perturbations in taurine transport in liver, kidney and muscle and altered metabolism in liver and kidney. These data suggest that the maintenance of adequate body taurine relies on sufficient dietary intake of taurine and cysteine availability and metabolism, as well as retention of taurine by the kidney. This research indicates dystrophin deficiency not only perturbs taurine metabolism in the muscle but also affects taurine metabolism in the liver and kidney, and supports targeting cysteine and taurine deficiency as a potential therapy for DMD. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  16. Kidney transplantation fails to provide adequate growth in children with chronic kidney disease born small for gestational age.

    Science.gov (United States)

    Franke, Doris; Steffens, Rena; Thomas, Lena; Pavičić, Leo; Ahlenstiel, Thurid; Pape, Lars; Gellermann, Jutta; Müller, Dominik; Querfeld, Uwe; Haffner, Dieter; Živičnjak, Miroslav

    2017-03-01

    Children with chronic kidney disease are frequently born small for gestational age (SGA) and prone to disproportionately short stature. It is unclear how SGA affects growth after kidney transplantation (KTx). Linear growth (height, sitting height, and leg length) was prospectively investigated in a cohort of 322 pediatric KTx recipients, with a mean follow-up of 4.9 years. Sitting height index (ratio of sitting height to total body height) was used to assess body proportions. Predictors of growth outcome in KTx patients with (n = 94) and without (n = 228) an SGA history were evaluated by the use of linear mixed-effects models. Mean z-scores for all linear body dimensions were lower in SGA compared with non-SGA patients (p deficit and degree of body disproportion (p growth during childhood. Pubertal trunk growth was diminished in SGA patients, and the pubertal growth spurt of legs was delayed in both groups, resulting in further impairment of adult height, which was more frequently reduced in SGA than in non-SGA patients (50 % vs 18 %, p growth hormone treatment in the pre-transplant period, preemptive KTx, transplant function, and control of metabolic acidosis were the only potentially modifiable correlates of post-transplant growth in SGA groups. By contrast, living related KTx, steroid exposure, and degree of anemia proved to be correlates in non-SGA only. In children born SGA, growth outcome after KTx is significantly more impaired and affected by different clinical parameters compared with non-SGA patients.

  17. The role of mitochondrial superoxide anion (O2-) on physiological aging in C57BL/6J mice

    International Nuclear Information System (INIS)

    Miyazawa, Masaki; Ishii, Takamasa; Yasuda, Kayo; Onouchi, Hiromi; Ishii, Naoaki; Noda, Setsuko; Hartman, Philip S.

    2009-01-01

    Much attention has been focused on the mitochondrial superoxide anion (O 2 - ), which is also a critical free radical produced by ionizing radiation. The specific role of the mitochondrial O 2 - on physiological aging in mammals is still nuclear despite wide-spread evidence that oxidative stress is involved in aging and age-related diseases. The major endogenous source of O 2 - is generated as a byproduct of energy metabolism from mitochondria. In order to better understand how O 2 - relates to metazoan aging, we have comprehensively examined age-related changes in the levels of oxidative damage, mitochondrial O 2 - production, mitochondrial antioxidant enzyme activity and apoptosis induction in key organs of an inbred mouse strain (C57BL/6J). Oxidative damage accumulated and excess apoptosis occurred in the brain, oculus and kidney with aging, but comparatively little occurred in the heart and muscle. These rates are correlated with O 2 - levels. Mitochondrial O 2 - production levels increased with aging in the brain, oculus and kidney, and did not significantly increased in the heart and muscle. In contrast to O 2 - production, mitochondrial SOD activities increased in heart and muscle, and remained unchanged in the brain, oculus and kidney with aging. These results suggest that O 2 - production has high organ specificity, and oxidative damage by O 2 - from mitochondria mediated apoptosis can lead to organ atrophy and physiological dysfunction. In addition, O 2 - from mitochondria plays a core role in physiological aging. (author)

  18. The role of mitochondrial superoxide anion (O2(-)) on physiological aging in C57BL/6J mice.

    Science.gov (United States)

    Miyazawa, Masaki; Ishii, Takamasa; Yasuda, Kayo; Noda, Setsuko; Onouchi, Hiromi; Hartman, Philip S; Ishii, Naoaki

    2009-01-01

    Much attention has been focused on the mitochondrial superoxide anion (O2(-)), which is also a critical free radial produced by ionizing radiation. The specific role of the mitochondrial O2(-) on physiological aging in mammals is still unclear despite wide-spread evidence that oxidative stress is involved in aging and age-related diseases. The major endogenous source of O2(-) is generated as a byproduct of energy metabolism from mitochondria. In order to better understand how O2(-)relates to metazoan aging, we have comprehensively examined age-related changes in the levels of oxidative damage, mitochondrial O2(-) production, mitochondrial antioxidant enzyme activity and apoptosis induction in key organs of an inbred mouse strain (C57BL/6J). Oxidative damage accumulated and excess apoptosis occurred in the brain, oculus and kidney with aging, but comparatively little occurred in the heart and muscle. These rates are correlated with O2(-) levels. Mitochondrial O2(-) production levels increased with aging in the brain, oculus and kidney, and did not significantly increased in the heart and muscle. In contrast to O2(-) production, mitochondrial SOD activities increased in heart and muscle, and remained unchanged in the brain, oculus and kidney with aging. These results suggest that O2(-) production has high organ specificity, and oxidative damage by O2(-) from mitochondria mediated apoptosis can lead to organ atrophy and physiological dysfunction. In addition, O2(-) from mitochondria plays a core role in physiological aging.

  19. Mouse cell culture - Methods and protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-12-01

    Full Text Available The mouse is, out of any doubt, the experimental animal par excellence for many many colleagues within the scientific community, notably for those working in mammalian biology (in a broad sense, from basic genetic to modeling human diseases, starting at least from 1664 Robert Hooke experiments on air’s propertyn. Not surprising then that mouse cell cultures is a well established field of research itself and that there are several handbooks devoted to this discipline. Here, Andrew Ward and David Tosh provide a necessary update of the protocols currently needed. In fact, nearly half of the book is devoted to stem cells culture protocols, mainly embryonic, from a list of several organs (kidney, lung, oesophagus and intestine, pancreas and liver to mention some........

  20. pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent

    Science.gov (United States)

    Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C.; Yu, Jing; Vinogradov, Elena; Lenkinski, Robert E.; Sherry, A. Dean

    2015-01-01

    Purpose This study explored the feasibility of using a pH responsive paraCEST agent to image the pH gradient in kidneys of healthy mice. Methods CEST signals were acquired on an Agilent 9.4 T small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. Results Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min post-injection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. Conclusion This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. PMID:26173637

  1. When kidneys get old: an essay on nephro-geriatrics

    Directory of Open Access Journals (Sweden)

    Richard Glassock

    Full Text Available Abstract Aging is a nearly universal phenomenon in biology only partially controlled by genetic endowment. Individuals and their organs age at varying rates. The kidneys manifest the aging process by steady loss of nephrons and a corresponding decrease in glomerular filtration rate (GFR beginning about age 30 years. The mechanisms responsible for this observation is are elusive. However, defining chronic kidney disease based on arbitrary, fixed thresholds of GFR in the later phases of life can be problematical as it may over-diagnosis CKD in the elderly. A modest, persisting reduction of GFR (around 45-59 ml/min/1.73m2 without abnormal proteinuria does not seem to confer much of an adverse effect on mortality and remaining life expectancy in older adults and the development of end-stage renal disease in such subjects is very uncommon. Old kidneys should not be equated with "diseased" kidneys.

  2. Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model

    NARCIS (Netherlands)

    Hassane, S.; Claij, N.; Lantinga-van Leeuwen, I.S.; Munsteren, J.C. van; Lent, N. van; Hanemaaijer, R.; Breuning, M.H.; Peters, D.J.M.; Ruiter, M.C. de

    2007-01-01

    OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have

  3. Deficits of psychomotor and mnesic functions across aging in mouse lemur primates

    Directory of Open Access Journals (Sweden)

    Solène eLanguille

    2015-01-01

    Full Text Available Owing to a similar cerebral neuro-anatomy, non-human primates are viewed as the most valid models for understanding cognitive deficits. This study evaluated psychomotor and mnesic functions of 41 young to old mouse lemurs (Microcebus murinus. Psychomotor capacities and anxiety-related behaviors decreased abruptly from middle to late adulthood. However, Mnesic functions were not affected in the same way with increasing age. While results of the spontaneous alternation task point to a progressive and widespread age-related decline of spatial working memory, both spatial reference and novel object recognition memory tasks did not reveal any tendency due to large inter-individual variability in the middle-aged and old animals. Indeed, some of the aged animals performed as well as younger ones, whereas some others had bad performances in the Barnes maze and in the object recognition test. Hierarchical cluster analysis revealed that declarative-like memory was strongly impaired only in 7 out of 25 middle-aged/old animals. These results suggest that this analysis allows to distinguish elder populations of good and bad performers in this non-human primate model and to closely compare this to human aging.

  4. No amelioration of uromodulin maturation and trafficking defect by sodium 4-phenylbutyrate in vivo: studies in mouse models of uromodulin-associated kidney disease.

    Science.gov (United States)

    Kemter, Elisabeth; Sklenak, Stefanie; Rathkolb, Birgit; Hrabě de Angelis, Martin; Wolf, Eckhard; Aigner, Bernhard; Wanke, Ruediger

    2014-04-11

    Uromodulin (UMOD)-associated kidney disease (UAKD) belongs to the hereditary progressive ER storage diseases caused by maturation defects of mutant UMOD protein. Current treatments of UAKD patients are symptomatic and cannot prevent disease progression. Two in vitro studies reported a positive effect of the chemical chaperone sodium 4-phenylbutyrate (4-PBA) on mutant UMOD maturation. Thus, 4-PBA was suggested as a potential treatment for UAKD. This study evaluated the effects of 4-PBA in two mouse models of UAKD. In contrast to previous in vitro studies, treatment with 4-PBA did not increase HSP70 expression or improve maturation and trafficking of mutant UMOD in vivo. Kidney function of UAKD mice was actually deteriorated by 4-PBA treatment. In transfected tubular epithelial cells, 4-PBA did not improve maturation but increased the expression level of both mutant and wild-type UMOD protein. Activation of NF-κB pathway in thick ascending limb of Henle's loop cells of UAKD mice was detected by increased abundance of RelB and phospho-IκB kinase α/β, an indirect activator of NF-κB. Furthermore, the abundance of NF-κB1 p105/p50, NF-κB2 p100/p52, and TRAF2 was increased in UAKD. NF-κB activation was identified as a novel disease mechanism of UAKD and might be a target for therapeutic intervention.

  5. Asymmetric BMP4 signalling improves the realism of kidney organoids.

    Science.gov (United States)

    Mills, Christopher G; Lawrence, Melanie L; Munro, David A D; Elhendawi, Mona; Mullins, John J; Davies, Jamie A

    2017-11-01

    We present a strategy for increasing the anatomical realism of organoids by applying asymmetric cues to mimic spatial information that is present in natural embryonic development, and demonstrate it using mouse kidney organoids. Existing methods for making kidney organoids in mice yield developing nephrons arranged around a symmetrical collecting duct tree that has no ureter. We use transplant experiments to demonstrate plasticity in the fate choice between collecting duct and ureter, and show that an environment rich in BMP4 promotes differentiation of early collecting ducts into uroplakin-positive, unbranched, ureter-like epithelial tubules. Further, we show that application of BMP4-releasing beads in one place in an organoid can break the symmetry of the system, causing a nearby collecting duct to develop into a uroplakin-positive, broad, unbranched, ureter-like 'trunk' from one end of which true collecting duct branches radiate and induce nephron development in an arrangement similar to natural kidneys. The idea of using local symmetry-breaking cues to improve the realism of organoids may have applications to organoid systems other than the kidney.

  6. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney.

    Science.gov (United States)

    Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V; Park, Kwon Moo

    2009-03-01

    Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was higher than in the S3 segment, which is much more susceptible to I/R. IDPc protein was also highly expressed in the mitochondrion-rich intercalated cells of the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in various kidney regions. This study identifies that IDPc may be the primary source of NADPH in the kidney. I/R significantly reduced IDPc expression and activity and NADPH production and increased the ratio of oxidized glutathione to total glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell damage, and lipid peroxidation. In LLC-PK(1) cells, upregulation of IDPc by IDPc gene transfer protected the cells against hydrogen peroxide, enhancing NADPH production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid peroxidation. IDPc downregulation by small interference RNA treatment presented results contrasting with the upregulation. In conclusion, these results demonstrate that IDPc is expressed differentially along tubules in patterns that may contribute to differences in susceptibility to injury, is a major enzyme in cytosolic NADPH generation in kidney, and is downregulated with I/R.

  7. Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.

    Science.gov (United States)

    Herbach, Nadja; Schairer, Irene; Blutke, Andreas; Kautz, Sabine; Siebert, Angela; Göke, Burkhard; Wolf, Eckhard; Wanke, Ruediger

    2009-04-01

    Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.

  8. Unique sex- and age-dependent effects in protective pathways in acute kidney injury.

    Science.gov (United States)

    Boddu, Ravindra; Fan, Chunlan; Rangarajan, Sunil; Sunil, Bhuvana; Bolisetty, Subhashini; Curtis, Lisa M

    2017-09-01

    Sex and age influence susceptibility to acute kidney injury (AKI), with young females exhibiting lowest incidence. In these studies, we investigated mechanisms which may underlie the sex/age-based dissimilarities. Cisplatin (Cp)-induced AKI resulted in morphological evidence of injury in all groups. A minimal rise in plasma creatinine (PCr) was seen in Young Females, whereas in Aged Females, PCr rose precipitously. Relative to Young Males, Aged Males showed significantly, but temporally, comparably elevated PCr. Notably, Aged Females showed significantly greater mortality, whereas Young Females exhibited none. Tissue KIM-1 and plasma NGAL were significantly lower in Young Females than all others. IGFBP7 levels were modestly increased in both Young groups. IGFBP7 levels in Aged Females were significantly elevated at baseline relative to Aged Males, and increased linearly through day 3 , when these levels were comparable in both Aged groups. Plasma cytokine levels similarly showed a pattern of protective effects preferentially in Young Females. Expression of the drug transporter MATE2 did not explain the sex/age distinctions. Heme oxygenase-1 (HO-1) levels (~28-kDa species) showed elevation at day 1 in all groups with highest levels seen in Young Males. Exclusively in Young Females, these levels returned to baseline on day 3 , suggestive of a more efficient recovery. In aggregate, we demonstrate, for the first time, a distinctive pattern of response to AKI in Young Females relative to males which appears to be significantly altered in aging. These distinctions may offer novel targets to exploit therapeutically in both females and males in the treatment of AKI.

  9. Influence of ageing on quantitative contrast-enhanced ultrasound of the kidneys in healthy cats.

    Science.gov (United States)

    Stock, Emmelie; Paepe, Dominique; Daminet, Sylvie; Duchateau, Luc; Saunders, Jimmy H; Vanderperren, Katrien

    2018-05-05

    The degenerative effects of ageing on the kidneys have been extensively studied in humans. However, only recently interest has been focused on renal ageing in veterinary medicine. Contrast-enhanced ultrasound allows non-invasive evaluation of renal perfusion in conscious cats. Renal perfusion parameters were obtained in 43 healthy cats aged 1-16 years old, and the cats were divided in four age categories: 1-3 years, 3-6 years, 6-10 years and over 10 years. Routine renal parameters as serum creatinine, serum urea, urine-specific gravity, urinary protein:creatinine ratio and systolic blood pressure were also measured. No significant differences in any of the perfusion parameters were observed among the different age categories. A trend towards a lower peak enhancement and wash-in area under the curve with increasing age, suggestive for a lower blood volume, was detected when comparing the cats over 10 years old with the cats of 1-3 years old. Additionally, no significant age-effect was observed for the serum and urine parameters, whereas a higher blood pressure was observed in healthy cats over 10 years old. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Sonographic Dimensions of Normal Kidney in Korean Male

    International Nuclear Information System (INIS)

    Lee, Hyeon Kyeong

    1996-01-01

    This study was performed to determine the sonographic dimensions of normal kidney in Korean male and to investigate their correlation with age, height, and weight. The ultrasound examinations were performed in 532healthy Korean male from July 1993 to December 1993. We measured the length, the width, and the thickness of both kidneys and those of both central echogenic area. Then renal shape index (RSI), renal volume (RV), volume of central (CEV) echogenic area, and renal parenchymal volume (RPV) were calculated from these measurements. The mean RV of the right kidney was 129.30 ± 30.20 cm 3 (Mean ± Standard Deviation) and that of the left kidney was 137.06± 29.73 cm 3 . Meanwhile the mean renal length of right kidney was 10.42 ± 0.61 cm and that of the left kidney was 10.63 ± 0.62 cm being distributed more compactly near mean value than the RV. Therefore the renal length could be more useful than RV in discrimination of abnormally increased or decreased kidney. While renal width, thickness and RV were increased with age, CEV showed no corresponding change. Therefore, the increase in RV could be attributed to the increase in RPV. Meanwhile the RSI was decreased with age. The renal length, renal thickness,thickness of central echogenic area, RV, CEV, and RPV showed strong correlation with weight. The renal length and the length of central echogenic area showed good correlation with height

  11. Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom

    Directory of Open Access Journals (Sweden)

    Cinthya Kimori Okamoto

    2017-03-01

    Full Text Available Envenomation by Loxosceles spider can result in two clinical manifestations: cutaneous and systemic loxoscelism, the latter of which includes renal failure. Although incidence of renal failure is low, it is the main cause of death, occurring mainly in children. The sphingomyelinase D (SMase D is the main component in Loxosceles spider venom responsible for local and systemic manifestations. This study aimed to investigate the toxicity of L. intermedia venom and SMase D on kidney cells, using both In vitro and in vivo models, and the possible involvement of endogenous metalloproteinases (MMP. Results demonstrated that venom and SMase D are able to cause death of human kidney cells by apoptosis, concomitant with activation and secretion of extracellular matrix metalloproteases, MMP-2 and MMP-9. Furthermore, cell death and MMP synthesis and secretion can be prevented by tetracycline. In a mouse model of systemic loxoscelism, Loxosceles venom-induced kidney failure was observed, which was abrogated by administration of tetracycline. These results indicate that MMPs may play an important role in Loxosceles venom-induced kidney injury and that tetracycline administration may be useful in the treatment of human systemic loxoscelism.

  12. Kidney transplantation in the elderly.

    Science.gov (United States)

    Singh, Neeraj; Nori, Uday; Pesavento, Todd

    2009-08-01

    Recent outcome data, ongoing organ shortage and proposed changes in allocation policies are driving the need to review current practices and possible future course of kidney transplantation in the elderly patients. A proposed new kidney allocation system based on matching donor and recipient characteristics to enable 'age-matched' kidney allocation is currently being discussed in the USA. While this system benefits younger recipients, implications for elderly recipients receiving older grafts remain a matter of debate. Despite improved outcomes, there remain significant challenges to kidney transplantation in the elderly, including organ shortage, poor transplant rate, evolving allocation policies, high wait-list mortality and nonstandardized immunosuppression. Prospective studies are needed to evaluate the strategies to meet these challenges and to study the impact of proposed new allocation system.

  13. Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses

    OpenAIRE

    Jenna M. Bartley; Jenna M. Bartley; Xin Zhou; Xin Zhou; George A. Kuchel; George A. Kuchel; George M. Weinstock; George M. Weinstock; Laura Haynes; Laura Haynes

    2017-01-01

    Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu). Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection t...

  14. A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

    Directory of Open Access Journals (Sweden)

    Faikah Gueler

    Full Text Available Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx. In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV, might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days was initiated 24 hours after IRI when acute kidney injury (AKI was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF and glomerular filtration rate (GFR at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

  15. Social participation after successful kidney transplantation.

    Science.gov (United States)

    van der Mei, Sijrike F; van Sonderen, Eric L P; van Son, Willem J; de Jong, Paul E; Groothoff, Johan W; van den Heuvel, Wim J A

    2007-03-30

    To explore and describe the degree of social participation after kidney transplantation and to examine associated factors. A cross-sectional study on 239 adult patients 1-7.3 years after kidney transplantation was performed via in-home interviews on participation in obligatory activities (i.e., employment, education, household tasks) and leisure activities (volunteer work, assisting others, recreation, sports, clubs/associations, socializing, going out). Kidney transplantation patients had a lower educational level, spent less time on obligatory activities, had part-time jobs more often, and participated less in sports compared to a control group from the general population. No difference was found in socializing, church attendance, volunteer work and going out. Multivariate regression analysis showed a negative association of age and a positive association of educational status and time since transplantation with obligatory participation. Multivariate logistic regression showed positive associations of education and time since transplantation with volunteer work; age was negatively and education positively associated with sports and going out, whereas living arrangement was also associated with going out. Although kidney transplantation patients participate less in employment and sports, they do participate in household tasks, volunteer work, going out, socializing and other leisure activities. Participation is associated with factors as age, educational status and time since transplantation.

  16. Interkinetic nuclear migration in the mouse embryonic ureteric epithelium: Possible implication for congenital anomalies of the kidney and urinary tract.

    Science.gov (United States)

    Motoya, Tomoyuki; Ogawa, Noriko; Nitta, Tetsuya; Rafiq, Ashiq Mahmood; Jahan, Esrat; Furuya, Motohide; Matsumoto, Akihiro; Udagawa, Jun; Otani, Hiroki

    2016-05-01

    Interkinetic nuclear migration (INM) is a phenomenon in which progenitor cell nuclei migrate along the apico-basal axis of the pseudostratified epithelium, which is characterized by the presence of apical primary cilia, in synchrony with the cell cycle in a manner of apical mitosis. INM is suggested to regulate not only stem/progenitor cell proliferation/differentiation but also organ size and shape. INM has been reported in epithelia of both ectoderm and endoderm origin. We examined whether INM exists in the mesoderm-derived ureteric epithelium. At embryonic day (E) 11.5, E12.5 and E13.5, C57BL/6J mouse dams were injected with 5-bromo-2'-deoxyuridine (BrdU) and embryos were killed 1, 2, 4, 6, 8, 10 and 12 h later. We immunostained transverse sections of the ureter for BrdU, and measured the position of BrdU (+) nuclei in the ureteric epithelia along the apico-basal axis at each time point. We analyzed the distribution patterns of BrdU (+) nuclei in histograms using the multidimensional scaling. Changes in the nucleus distribution patterns suggested nucleus movement characteristic of INM in the ureteric epithelia, and the mode of INM varied throughout the ureter development. While apical primary cilia are related with INM by providing a centrosome for the apical mitosis, congenital anomalies of the kidney and urinary tract (CAKUT) include syndromes linked to primary ciliary dysfunction affecting epithelial tubular organs such as kidney, ureter, and brain. The present study showed that INM exists in the ureteric epithelium and suggests that INM may be related with the CAKUT etiology via primary ciliary protein function. © 2015 Japanese Teratology Society.

  17. Renal Aging: Causes and Consequences.

    Science.gov (United States)

    O'Sullivan, Eoin D; Hughes, Jeremy; Ferenbach, David A

    2017-02-01

    Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis-age-associated histologic changes in the kidneys. Recent studies have shown that the aged kidney undergoes a range of structural changes and has altered transcriptomic, hemodynamic, and physiologic behavior at rest and in response to renal insults. These changes impair the ability of the kidney to withstand and recover from injury, contributing to the high susceptibility of the aged population to AKI and their increased propensity to develop subsequent progressive CKD. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging in both experimental animal models and humans. We also discuss the potential for additional study to increase understanding of the aged kidney and lead to novel therapeutic strategies. Copyright © 2017 by the American Society of Nephrology.

  18. Protective role of ginseng against gentamicin induced changes in kidney of albino mice

    International Nuclear Information System (INIS)

    Hafeez, M.; Saeed, F.

    2011-01-01

    Background: Use of gentamicin is now limited due to its toxic effects, mainly on kidney and vestibular system. Herbal products including ginseng has been reported to possess protective effects against drugs induced nephrotoxicity in experimental animals. The current investigation was designed to evaluate the effects of ginseng on gentamicin induced nephrotoxicity. Methods: Eighteen male albino mice of 6-8 weeks age, were divided into 3 groups. Group-A served as control and was given normal mouse diet; Group-B was given 80 mg/Kg/day of gentamicin intraperitoneally dissolved in 1 ml of distilled water for fifteen days. Group-C was given 80 mg/Kg/day of gentamicin intraperitoneally dissolved in 1 ml of distilled water along with 100 mg/Kg/day of ginseng orally dissolved in 1 ml of distilled water, also for fifteen days. At the end of the experiment, blood was drawn from each animal by cardiac puncture for renal function tests. Each animal was then sacrificed and kidneys removed for routine histological studies. Results: In group B, weight of the animals and kidneys decreased and there was significant increase in mean serum urea, creatinine and intraluminal diameter (p<0.001) of proximal convoluted tubules as compared to the controls (group-A). Moderate to severe necrotic and degenerative changes in proximal convoluted tubules were seen in this group. When the Ginseng and gentamicin were given together (group-C), a statistically significant improvement in the mean body and kidney weight along with improvement in renal function tests and tubular diameter were seen (p<0.001). Conclusion: It appears that Ginseng has some protective role against gentamicin induced nephrotoxicity. (author)

  19. PATHOMORPHOLOGY OF ZERO BIOPSIES OF DONOR KIDNEYS

    Directory of Open Access Journals (Sweden)

    M. L. Arefjev

    2011-01-01

    Full Text Available There is well known fact that kidney transplants from Extended Criteria Donors may increase risk of De- layed Graft Function and Primary Non-Function of transplants. We have collected and tested 65 «zero» kidney biopsies from cadaver donors aged from 19 to 71 years old. In the pool of elderly donors who died from cerebrovascular accident the frequency of nephrosclerosis presentation was higher than in donors of yonger age who died from craniocephalic trauma. Nevertheless in the general donor pool the number of sclerosed glomeruli was no more than 12%. We did not meet at all in the whole volume of material any bi- opsy with the severe degree of arteriosclerosis. The «zero» biopsies of cadaver kidneys is quite usable and unexpensive tool to measure the degree of nephrosclerosis in order to exclude kidneys which are not fitable for transplantation. 

  20. A voxel-based mouse for internal dose calculations using Monte Carlo simulations (MCNP).

    Science.gov (United States)

    Bitar, A; Lisbona, A; Thedrez, P; Sai Maurel, C; Le Forestier, D; Barbet, J; Bardies, M

    2007-02-21

    Murine models are useful for targeted radiotherapy pre-clinical experiments. These models can help to assess the potential interest of new radiopharmaceuticals. In this study, we developed a voxel-based mouse for dosimetric estimates. A female nude mouse (30 g) was frozen and cut into slices. High-resolution digital photographs were taken directly on the frozen block after each section. Images were segmented manually. Monoenergetic photon or electron sources were simulated using the MCNP4c2 Monte Carlo code for each source organ, in order to give tables of S-factors (in Gy Bq-1 s-1) for all target organs. Results obtained from monoenergetic particles were then used to generate S-factors for several radionuclides of potential interest in targeted radiotherapy. Thirteen source and 25 target regions were considered in this study. For each source region, 16 photon and 16 electron energies were simulated. Absorbed fractions, specific absorbed fractions and S-factors were calculated for 16 radionuclides of interest for targeted radiotherapy. The results obtained generally agree well with data published previously. For electron energies ranging from 0.1 to 2.5 MeV, the self-absorbed fraction varies from 0.98 to 0.376 for the liver, and from 0.89 to 0.04 for the thyroid. Electrons cannot be considered as 'non-penetrating' radiation for energies above 0.5 MeV for mouse organs. This observation can be generalized to radionuclides: for example, the beta self-absorbed fraction for the thyroid was 0.616 for I-131; absorbed fractions for Y-90 for left kidney-to-left kidney and for left kidney-to-spleen were 0.486 and 0.058, respectively. Our voxel-based mouse allowed us to generate a dosimetric database for use in preclinical targeted radiotherapy experiments.

  1. Resistive index for kidney evaluation in normal and diseased cats.

    Science.gov (United States)

    Tipisca, Vlad; Murino, Carla; Cortese, Laura; Mennonna, Giuseppina; Auletta, Luigi; Vulpe, Vasile; Meomartino, Leonardo

    2016-06-01

    The objectives were to determine the resistive index (RI) in normal cats and in cats with various renal diseases, and to evaluate the effect of age on RI. The subjects were cats that had ultrasonography (US) of the urinary tract and RI measurement at our centre between January 2003 and April 2014. Based on clinical evaluation, biochemical and haematological tests, urinalysis and US, the cats were classified as healthy or diseased. RI measurements were made from the interlobar or arcuate arteries. Data were analysed for differences between the right and the left kidney, the two sexes, different age groups in healthy cats, and between healthy and diseased cats. A total of 116 cats (68 males, 48 females) were included: 24 healthy and 92 diseased. In the healthy cats, RI (mean ± SD) differed significantly (P = 0.02) between the right kidney (0.54 ± 0.07) and the left kidney (0.59 ± 0.08). For the left kidney, RI was significantly higher in cats with chronic kidney disease (0.73 ± 0.12) and acute kidney injury (0.72 ± 0.08) (P = 0.0008). For the right kidney, RI was significantly higher in cats with chronic kidney disease (0.72 ± 0.11), acute kidney injury (0.74 ± 0.08), polycystic kidney disease (0.77 ± 0.11) and renal tumour (0.74 ± 0.001) (P cats, useful in the differential diagnosis of diffuse renal diseases. While it does not change with the age of the cat, ultrasonographers should be aware that RI may differ between the two kidneys. © ISFM and AAFP 2015.

  2. Chronic kidney disease: an inherent risk factor for acute kidney injury?

    Science.gov (United States)

    Singh, Prabhleen; Rifkin, Dena E; Blantz, Roland C

    2010-09-01

    Epidemiologic evidence suggests that chronic kidney disease (CKD) is a risk factor for acute kidney injury (AKI) due to the prevalence of CKD in patients who have episodes of AKI. However, the high burden of comorbidities such as age, diabetes, peripheral vascular, cardiovascular, and liver disease accompanying CKD, and the difficulties of defining AKI in the setting of CKD make these observations difficult to interpret. These comorbidities not only could alter the course of AKI but also may be the driving force behind the epidemiologic association between CKD and AKI because of systemic changes and/or increased exposure to potential nephrotoxic risks. Here, we contend that studies suggesting that CKD is a risk factor for AKI may suffer from residual confounding and reflect an overall susceptibility to illness rather than biologic susceptibility of the kidney parenchyma to injury. In support of our argument, we discuss the clinical evidence from epidemiologic studies, and the knowledge obtained from animal models on the pathophysiology of AKI and CKD, demonstrating a preconditioning influence of the previously impaired kidneys against subsequent injury. We conclude that, under careful analysis, factors apart from the inherent pathophysiology of the diseased kidney may be responsible for the increased frequency of AKI in CKD patients, and the impact of CKD on the risk and severity of AKI needs further investigation. Moreover, certain elements in the pathophysiology of a previously injured kidney may, surprisingly, bear out to be protective against AKI.

  3. Dual kidney transplantation with organs from extended criteria cadaveric donors.

    LENUS (Irish Health Repository)

    D'Arcy, Frank T

    2009-10-01

    The critical shortage of kidneys available for transplantation has led to alternate strategies to expand the pool. Transplantation of the 2 kidneys into a single recipient using organs suboptimal for single kidney transplantation was suggested. We assessed results in 24 grafts allocated for dual kidney transplantation vs those in a control group of 44 designated for single kidney transplantation. Each group underwent pretransplant biopsy and recipients were age matched.

  4. Sox10 expressing cells in the lateral wall of the aged mouse and human cochlea.

    Directory of Open Access Journals (Sweden)

    Xinping Hao

    Full Text Available Age-related hearing loss (presbycusis is a common human disorder, affecting one in three Americans aged 60 and over. Previous studies have shown that presbyacusis is associated with a loss of non-sensory cells in the cochlear lateral wall. Sox10 is a transcription factor crucial to the development and maintenance of neural crest-derived cells including some non-sensory cell types in the cochlea. Mutations of the Sox10 gene are known to cause various combinations of hearing loss and pigmentation defects in humans. This study investigated the potential relationship between Sox10 gene expression and pathological changes in the cochlear lateral wall of aged CBA/CaJ mice and human temporal bones from older donors. Cochlear tissues prepared from young adult (1-3 month-old and aged (2-2.5 year-old mice, and human temporal bone donors were examined using quantitative immunohistochemical analysis and transmission electron microscopy. Cells expressing Sox10 were present in the stria vascularis, outer sulcus and spiral prominence in mouse and human cochleas. The Sox10(+ cell types included marginal and intermediate cells and outer sulcus cells, including those that border the scala media and those extending into root processes (root cells in the spiral ligament. Quantitative analysis of immunostaining revealed a significant decrease in the number of Sox10(+ marginal cells and outer sulcus cells in aged mice. Electron microscopic evaluation revealed degenerative alterations in the surviving Sox10(+ cells in aged mice. Strial marginal cells in human cochleas from donors aged 87 and older showed only weak immunostaining for Sox10. Decreases in Sox10 expression levels and a loss of Sox10(+ cells in both mouse and human aged ears suggests an important role of Sox10 in the maintenance of structural and functional integrity of the lateral wall. A loss of Sox10(+ cells may also be associated with a decline in the repair capabilities of non-sensory cells in the

  5. Twist2 Is Upregulated in Early Stages of Repair Following Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Grunz-Borgmann

    2017-02-01

    Full Text Available The aging kidney is a marked by a number of structural and functional changes, including an increased susceptibility to acute kidney injury (AKI. Previous studies from our laboratory have shown that aging male Fischer 344 rats (24 month are more susceptible to apoptosis-mediated injury than young counterparts. In the current studies, we examined the initial injury and early recovery phases of mercuric chloride-induced AKI. Interestingly, the aging kidney had decreased serum creatinine compared to young controls 1 day following mercuric chloride injury, but by day 4, serum creatinine was significantly elevated, suggesting that the aging kidney did not recover from injury. This conclusion is supported by the findings that serum creatinine and kidney injury molecule-1 (Kim-1 gene expression remain elevated compared to young controls at 10 days post-injury. To begin to elucidate mechanism(s underlying dysrepair in the aging kidney, we examined the expression of Twist2, a helix-loop-helix transcription factor that may mediate renal fibrosis. Interestingly, Twist2 gene expression was elevated following injury in both young and aged rats, and Twist2 protein expression is elevated by mercuric chloride in vitro.

  6. Renal cancer in recipients of kidney transplant

    Directory of Open Access Journals (Sweden)

    Prajwal Dhakal

    2017-03-01

    Full Text Available The aim of our study is to determine characteristics and outcomes of kidney cancer in renal transplant recipients. MEDLINE ® database was searched in June 2015 to identify cases of kidney cancer in renal transplant recipients. We include also a new case. Descriptive statistics were used for analysis. Forty-eight (48 recipients reported in 25 papers met the eligibility criteria. The median age was 47 years (range 9-66; 27% were females. Chronic glomerulonephritis, cystic kidney disease and hypertension were common indications for renal transplant. Among donors 24% were females and the median age was 52.5 years (17- 73; 62% of kidney cancers were donor-derived. The median interval between transplant and cancer diagnosis was shorter for cancer of recipient versus donor origin (150 vs. 210 days. Clear cell carcinoma was diagnosed in 17%. 25% had metastasis at diagnosis. Kidney explantation or excision was done in 90% and 84% of cases with and without metastasis respectively. The median survival was 72 months. Actuarial 1-year and 5-year survival rates were 73.4% and 55.1% respectively. Among the recipients from 7 donors who subsequently developed malignancy, 57% were dead within a year. Kidney transplant recipients have a small risk of kidney cancer, which affects younger patients and occurs within a year of transplant, likely due to immunosuppression. Whether the use of older donors may increase the likelihood needs further investigation. The presence of metastasis, explantation or excision of affected kidney and development of cancer in donors predict outcomes. The results may guide patient education and informed decision-making.

  7. New biomarkers of acute kidney injury

    Directory of Open Access Journals (Sweden)

    Ruya Ozelsancak

    2013-04-01

    Full Text Available Acute kidney injury is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid-base disorders. It is an important clinical problem increasing mortality in patient with several co-morbid conditions. The frequency of acute kidney injury occurrence varies from 5% on the inpatients wards to 30-50% in patients from intensive care units. Serial measurement of creatinine and urine volume do not make it possible to diagnose acute kidney injury at early stages. Serum creatinine may be influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reasons we need new markers. Here, we are reviewing the most promising new acute kidney injury markers, neutrophil gelatinase associated lipocalin, cystatin-C, kidney injury molecule-1, liver fatty acid binding proteins and IL-18. [Archives Medical Review Journal 2013; 22(2.000: 221-229

  8. Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys

    International Nuclear Information System (INIS)

    Jaggi, Jaspreet Singh; Seshan, Surya V.; McDevitt, Michael R.; Sgouros, George; Hyjek, Elizabeth; Scheinberg, David A.

    2006-01-01

    Purpose: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium ( 225 Ac) nanogenerator, an in vivo generator of α- and β-particle emitting elements. Methods and Materials: The animals were injected with 0.35 μCi of the 225 Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-1 blocker), spironolactone (aldosterone receptor antagonist), or a placebo. Results: Forty weeks after the 225 Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 ± 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 ± 4.0 mg/dL; p <0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 ± 3.9 mg/dL; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 ± 2.5 mg/dL; p <0.001 vs. placebo controls). Conclusions: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-1 blockade can offer renal protection in a mouse model of internal α-particle irradiation

  9. Vitamin D status in kidney transplant patients

    DEFF Research Database (Denmark)

    Ewers, Bettina; Gasbjerg, Ane; Mølgaard, Christian

    2008-01-01

    BACKGROUND: A high prevalence of vitamin D insufficiency has been found in the general population and in patients with chronic kidney disease. OBJECTIVE: The aim was to examine vitamin D status and determinants and metabolic correlates of serum 25-hydroxyvitamin D in a population of adult Danish...... kidney transplant patients. DESIGN: This was a cross-sectional study of 173 adult kidney transplant patients with a mean (+/-SD) age of 53.4 +/- 11.7 y and a median graft age of 7.4 y (interquartile range: 3.3-12.7 y). Serum concentrations of intact parathyroid hormone (S-PTH), 25-hydroxyvitamin D [S-25....... Low S-25(OH)D concentrations were associated with 1) increased S-PTH concentrations (P = 0.0002), independently of S-1,25(OH)(2)D concentrations, and 2) decreased S-1,25(OH)(2)D concentrations (P = 0.002), independently of graft function. CONCLUSIONS: Hypovitaminosis D is common among Danish kidney...

  10. Testosterone increases renal anti-aging klotho gene expression via the androgen receptor-mediated pathway.

    Science.gov (United States)

    Hsu, Shih-Che; Huang, Shih-Ming; Lin, Shih-Hua; Ka, Shuk-Man; Chen, Ann; Shih, Meng-Fu; Hsu, Yu-Juei

    2014-12-01

    Gender is known to be associated with longevity and oestrogen administration induced longevity-associated gene expression is one of the potential mechanisms underlying the benefits of oestrogen on lifespan, whereas the role of testosterone in the regulation of longevity-associated gene expressions remains largely unclear. The klotho gene, predominantly expressed in the kidney, has recently been discovered to be an aging suppressor gene. In the present study, we investigated the regulatory effects of testosterone on renal klotho gene expression in vivo and in vitro. In testosterone-administered mouse kidney and NRK-52E cells, increased klotho expression was accompanied by the up-regulation of the nuclear androgen receptor (AR). Overexpression of AR enhanced the expression of klotho mRNA and protein. Conversely, testosterone-induced klotho expression was attenuated in the presence of flutamide, an AR antagonist. A reporter assay and a chromatin immunoprecipitation (ChIP) assay demonstrated that AR directly binds to the klotho promoter via androgen response elements (AREs) which reconfirmed its importance for AR binding via the element mutation. In summary, our study demonstrates that testosterone up-regulates anti-aging klotho together with AR expression in the kidney in vivo and in vitro by recruiting AR on to the AREs of the klotho promoter.

  11. Gender- and age-dependent gamma-secretase activity in mouse brain and its implication in sporadic Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    Lisa Placanica

    Full Text Available Alzheimer disease (AD is an age-related disorder. Aging and female gender are two important risk factors associated with sporadic AD. However, the mechanism by which aging and gender contribute to the pathogenesis of sporadic AD is unclear. It is well known that genetic mutations in gamma-secretase result in rare forms of early onset AD due to the aberrant production of Abeta42 peptides, which are the major constituents of senile plaques. However, the effect of age and gender on gamma-secretase has not been fully investigated. Here, using normal wild-type mice, we show mouse brain gamma-secretase exhibits gender- and age-dependent activity. Both male and female mice exhibit increased Abeta42ratioAbeta40 ratios in aged brain, which mimics the effect of familial mutations of Presenilin-1, Presenlin-2, and the amyloid precursor protein on Abeta production. Additionally, female mice exhibit much higher gamma-secretase activity in aged brain compared to male mice. Furthermore, both male and female mice exhibit a steady decline in Notch1 gamma-secretase activity with aging. Using a small molecule affinity probe we demonstrate that male mice have less active gamma-secretase complexes than female mice, which may account for the gender-associated differences in activity in aged brain. These findings demonstrate that aging can affect gamma-secretase activity and specificity, suggesting a role for gamma-secretase in sporadic AD. Furthermore, the increased APP gamma-secretase activity seen in aged females may contribute to the increased incidence of sporadic AD in women and the aggressive Abeta plaque pathology seen in female mouse models of AD. In addition, deceased Notch gamma-secretase activity may also contribute to neurodegeneration. Therefore, this study implicates altered gamma-secretase activity and specificity as a possible mechanism of sporadic AD during aging.

  12. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    Science.gov (United States)

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  13. Peroxisome proliferator activated receptor alpha regulates a male-specific cytochrome P450 in mouse liver.

    Science.gov (United States)

    Jeffery, Brett; Choudhury, Agharul I; Horley, Neill; Bruce, Mary; Tomlinson, Simon R; Roberts, Ruth A; Gray, Tim J B; Barrett, David A; Shaw, P Nicholas; Kendall, David; Bell, David R

    2004-09-15

    We set out to find if the strain-specific, male-specific hepatic expression of Cyp4a protein in mouse was due to expression of Cyp4a12 and to understand the genetic basis for reported differences in expression. 12-Lauric acid hydroxylase (LAH) activity was found to show higher levels in male ddY, but not C57Bl/6, mouse liver microsomes. The expression of Cyp4a12 mRNA was studied using RNAase protection assays in male and female liver and kidney of nine mouse strains. Cyp4a12 was found to be highly expressed in male liver and kidney, but at much lower levels in female liver and kidney, in all strains studied. Western blotting with an antibody specific for Cyp4a12 confirmed that Cyp4a12 was expressed in a male specific fashion in C57Bl/6 mouse liver. RNAase protection analysis for Cyp4a10 and 14 in ddY mice revealed that neither of these genes showed male-specific expression. To further investigate genetic factors that control male-specific Cyp4a12 expression, PPARalpha+/+ and -/- mice were studied, showing that total P450 and 12-LAH activity was male-specific in +/+, but not -/- mice. RNAase protection assays were used to confirm that Cyp4a12 was lower in -/- mice. However, the male-specific Slp and MUP-1 genes retained hepatic male-specific levels of expression in +/+ and -/- mice, showing that the decrease in Cyp4a12 was not a general effect on male-specific expression. Thus, PPARalpha has a specific effect on constitutive expression of Cyp4a12.

  14. Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis.

    Science.gov (United States)

    Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D; Davies, John E; Stanford, William L

    2016-05-01

    Age-related osteoporosis is driven by defects in the tissue-resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low-turnover state precipitated by MSC loss leads to low-quality bone that is unable to perform remodeling-mediated maintenance--replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age-related osteoporosis, we show long-term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age-related osteoporosis. This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteoporosis. ©AlphaMed Press.

  15. Efficiency and fidelity of cell-free protein synthesis by transfer RNA from aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Foote, R.S.; Stulberg, M.P.

    1980-01-01

    Transfer RNAs (tRNAs) from heart, kidney, liver, and spleen of mature (10 to 12 months old) and aged (29 months old) C57BL/6 mice were tested for their ability to translate encephalomyocarditis viral RNA in a tRNA-dependent cell-free system derived from mouse ascites tumor cells. The rates of in vitro protein synthesis were compared as a function of tRNA concentration, and the fidelity of translation was examined by sodium dodecyl sulfate gel electrophoresis and isoelectric focusing of the viral polypeptides synthesized in vitro. No significant age-related differences in either the efficiency or fidelity of synthesis were discovered, indicating that alternations in tRNAs are probably not involved in the cellular aging of these tissues.

  16. Role of Integrin-Beta1 in Polycystic Kidney Disease

    Science.gov (United States)

    2012-04-01

    interactions affect proliferation and cell differentiation2. We previously showed an increase of integrin-!2ŕ expression in polycystin-1 (PC1) deficient...that since the Cre activity in TgAqp2-Cre transgenic mouse was observed also in testes, our breeding scheme was devised to ensure maternal ...inheritance of the transgene, as paternal transmission would lead to gene recombination not only in the kidneys, but also in sperm and the resulting

  17. Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis.

    Science.gov (United States)

    Lindström, Nils O; De Sena Brandine, Guilherme; Tran, Tracy; Ransick, Andrew; Suh, Gio; Guo, Jinjin; Kim, Albert D; Parvez, Riana K; Ruffins, Seth W; Rutledge, Elisabeth A; Thornton, Matthew E; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

    2018-06-04

    Mammalian nephrons arise from a limited nephron progenitor pool through a reiterative inductive process extending over days (mouse) or weeks (human) of kidney development. Here, we present evidence that human nephron patterning reflects a time-dependent process of recruitment of mesenchymal progenitors into an epithelial nephron precursor. Progressive recruitment predicted from high-resolution image analysis and three-dimensional reconstruction of human nephrogenesis was confirmed through direct visualization and cell fate analysis of mouse kidney organ cultures. Single-cell RNA sequencing of the human nephrogenic niche provided molecular insights into these early patterning processes and predicted developmental trajectories adopted by nephron progenitor cells in forming segment-specific domains of the human nephron. The temporal-recruitment model for nephron polarity and patterning suggested by direct analysis of human kidney development provides a framework for integrating signaling pathways driving mammalian nephrogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Trends in kidney cancer among the elderly in Denmark, 1980-2012

    DEFF Research Database (Denmark)

    Azawi, Nessn H; Joergensen, Simon Moeller; Jensen, Niels Viggo

    2016-01-01

    Background The purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark. Material and methods Cancer of the kidney was defined as ICD-10 code DC 64. Data derived from the NORDCAN database...... of patients diagnosed with kidney cancer over the age of 70 years has decreased from 43% in 1980 to 32% in 2012 in men and remained almost constant in women, around 50%. Incidence rates were at least five times higher in men aged 70 years more but there was no particular trend with time. In men aged less than......-year relative survival increased steadily over time for all age groups but the survival was lower for patients aged 70 years or more than for younger patients. The prevalence increased three times from 1559 patients being alive after kidney cancer in1980 to 4713 in 2012. Conclusion A challenge in managing...

  19. The mouse as a model for understanding chronic diseases of aging: the histopathologic basis of aging in inbred mice

    Directory of Open Access Journals (Sweden)

    David Harrison

    2011-06-01

    Full Text Available Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.

  20. (Pro)renin Receptor Is an Amplifier of Wnt/β-Catenin Signaling in Kidney Injury and Fibrosis.

    Science.gov (United States)

    Li, Zhen; Zhou, Lili; Wang, Yongping; Miao, Jinhua; Hong, Xue; Hou, Fan Fan; Liu, Youhua

    2017-08-01

    The (pro)renin receptor (PRR) is a transmembrane protein with multiple functions. However, its regulation and role in the pathogenesis of CKD remain poorly defined. Here, we report that PRR is a downstream target and an essential component of Wnt/ β -catenin signaling. In mouse models, induction of CKD by ischemia-reperfusion injury (IRI), adriamycin, or angiotensin II infusion upregulated PRR expression in kidney tubular epithelium. Immunohistochemical staining of kidney biopsy specimens also revealed induction of renal PRR in human CKD. Overexpression of either Wnt1 or β -catenin induced PRR mRNA and protein expression in vitro Notably, forced expression of PRR potentiated Wnt1-mediated β -catenin activation and augmented the expression of downstream targets such as fibronectin, plasminogen activator inhibitor 1, and α -smooth muscle actin ( α -SMA). Conversely, knockdown of PRR by siRNA abolished β -catenin activation. PRR potentiation of Wnt/ β -catenin signaling did not require renin, but required vacuolar H + ATPase activity. In the mouse model of IRI, transfection with PRR or Wnt1 expression vectors promoted β -catenin activation, aggravated kidney dysfunction, and worsened renal inflammation and fibrotic lesions. Coexpression of PRR and Wnt1 had a synergistic effect. In contrast, knockdown of PRR expression ameliorated kidney injury and fibrosis after IRI. These results indicate that PRR is both a downstream target and a crucial element in Wnt signal transmission. We conclude that PRR can promote kidney injury and fibrosis by amplifying Wnt/ β -catenin signaling. Copyright © 2017 by the American Society of Nephrology.

  1. Renal scar formation and kidney function following antibiotic-treated murine pyelonephritis

    Directory of Open Access Journals (Sweden)

    Patrick D. Olson

    2017-11-01

    Full Text Available We present a new preclinical model to study treatment, resolution and sequelae of severe ascending pyelonephritis. Urinary tract infection (UTI, primarily caused by uropathogenic Escherichia coli (UPEC, is a common disease in children. Severe pyelonephritis is the primary cause of acquired renal scarring in childhood, which may eventually lead to hypertension and chronic kidney disease in a small but important fraction of patients. Preclinical modeling of UTI utilizes almost exclusively females, which (in most mouse strains exhibit inherent resistance to severe ascending kidney infection; consequently, no existing preclinical model has assessed the consequences of recovery from pyelonephritis following antibiotic treatment. We recently published a novel mini-surgical bladder inoculation technique, with which male C3H/HeN mice develop robust ascending pyelonephritis, highly prevalent renal abscesses and evidence of fibrosis. Here, we devised and optimized an antibiotic treatment strategy within this male model to more closely reflect the clinical course of pyelonephritis. A 5-day ceftriaxone regimen initiated at the onset of abscess development achieved resolution of bladder and kidney infection. A minority of treated mice displayed persistent histological abscess at the end of treatment, despite microbiological cure of pyelonephritis; a matching fraction of mice 1 month later exhibited renal scars featuring fibrosis and ongoing inflammatory infiltrates. Successful antibiotic treatment preserved renal function in almost all infected mice, as assessed by biochemical markers 1 and 5 months post-treatment; hydronephrosis was observed as a late effect of treated pyelonephritis. An occasional mouse developed chronic kidney disease, generally reflecting the incidence of this late sequela in humans. In total, this model offers a platform to study the molecular pathogenesis of pyelonephritis, response to antibiotic therapy and emergence of sequelae

  2. Specific macrophage subtypes influence the progression of rhabdomyolysis-induced kidney injury.

    Science.gov (United States)

    Belliere, Julie; Casemayou, Audrey; Ducasse, Laure; Zakaroff-Girard, Alexia; Martins, Frédéric; Iacovoni, Jason S; Guilbeau-Frugier, Céline; Buffin-Meyer, Bénédicte; Pipy, Bernard; Chauveau, Dominique; Schanstra, Joost P; Bascands, Jean-Loup

    2015-06-01

    Rhabdomyolysis can be life threatening if complicated by AKI. Macrophage infiltration has been observed in rat kidneys after glycerol-induced rhabdomyolysis, but the role of macrophages in rhabdomyolysis-induced AKI remains unknown. Here, in a patient diagnosed with rhabdomyolysis, we detected substantial macrophage infiltration in the kidney. In a mouse model of rhabdomyolysis-induced AKI, diverse renal macrophage phenotypes were observed depending on the stage of the disease. Two days after rhabdomyolysis, F4/80(low)CD11b(high)Ly6b(high)CD206(low) kidney macrophages were dominant, whereas by day 8, F4/80(high)CD11b(+)Ly6b(low)CD206(high) cells became the most abundant. Single-cell gene expression analyses of FACS-sorted macrophages revealed that these subpopulations were heterogeneous and that individual cells simultaneously expressed both M1 and M2 markers. Liposomal clodronate-mediated macrophage depletion significantly reduced the early infiltration of F4/80(low)CD11b(high)Ly6b(high)CD206(low) macrophages. Furthermore, transcriptionally regulated targets potentially involved in disease progression, including fibronectin, collagen III, and chemoattractants that were identified via single-cell analysis, were verified as macrophage-dependent in situ. In vitro, myoglobin treatment induced proximal tubular cells to secrete chemoattractants and macrophages to express proinflammatory markers. At day 30, liposomal clodronate-mediated macrophage depletion reduced fibrosis and improved both kidney repair and mouse survival. Seven months after rhabdomyolysis, histologic lesions were still present but were substantially reduced with prior depletion of macrophages. These results suggest an important role for macrophages in rhabdomyolysis-induced AKI progression and advocate the utility of long-term follow-up for patients with this disease. Copyright © 2015 by the American Society of Nephrology.

  3. Angelica Sinensis Polysaccharide Prevents Hematopoietic Stem Cells Senescence in D-Galactose-Induced Aging Mouse Model

    Directory of Open Access Journals (Sweden)

    Xinyi Mu

    2017-01-01

    Full Text Available Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP, a major active ingredient in dong quai (Chinese Angelica Sinensis, on the Sca-1+ HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse. We further found that multiple mechanisms were involved: (1 ASP treatment prevented oxidative damage as total antioxidant capacity was increased and levels of reactive oxygen species (ROS, 8-OHdG, and 4-HNE were declined, (2 ASP reduced the expression of γ-H2A.X which is a DNA double strand breaks (DSBs marker and decreased the subsequent ectopic expressions of effectors in p16Ink4a-RB and p19Arf-p21Cip1/Waf senescent pathways, and (3 ASP inhibited the excessive activation of Wnt/β-catenin signaling in aged HSC/HPCs, as the expressions of β-catenin, phospho-GSK-3β, and TCF-4 were decreased, and the cyto-nuclear translocation of β-catenin was inhibited. Moreover, compared with the positive control of Vitamin E, ASP exhibited a better antiaging effect and a weaker antioxidation ability, suggesting a novel protective role of ASP in the hematopoietic system.

  4. Age-related variability of some characters of karyotype instability in the mouse line CC57W/Mv

    International Nuclear Information System (INIS)

    Glazko, T.T.; Safonova, N.A.; Kovaleva, O.A.; Stolina, M.P.; Solomko, A.P.; Malyuta, S.S.; Glazko, V.I.; AN Ukrainskoj SSR, Kiev

    1995-01-01

    The investigations of relations between cytogenetical variability in cells of bone marrow of the mouse line CC57W/Mv and factors of age and radioactivity pollution (the specific vivarium in the 30-km Chernobyl zone) were carried out. The karyotype instability on some characters were similarly between young mice in the Chernobyl zone and old mice under control conditions. The old Chernobyl mice differentiated from old control ones by a low frequency of some cytogenetic anomalies and higher values of the mitotic index. The contribution of the intensity of cell division into observed variabilities of cytogenetic character between different mouse groups was discussed

  5. Prognosis of Dialysed Patients after Kidney Transplant Failure

    Directory of Open Access Journals (Sweden)

    Réka P. Szabó

    2013-05-01

    Full Text Available Background/Aims: Patients with a failed kidney transplant represent a unique, high-risk chronic kidney disease population that is increasing in number, and may be sub-optimally managed. Our aim was to compare the survival of patients with failed allografts to patients with native kidney failure and to assess whether their survival is affected by the graft resection. Methods: Kaplan-Meier and Cox-regression survival analyses were performed on the data of 57 patients with graft failure and of 123 transplant-naive haemodialysed patients. Results: After adjustment for age and gender, there was no statistically significant difference in the mortality of patients in the two groups. The 43 patients, who had a transplanted kidney nephrectomy had a statistically not significant survival benefit over non-nephrectomised patients (age and gender adjusted hazard ratio: 0.56 95 % confidence interval: 0.24-1.58, p-value: 0.18. Conclusion: Elective graft resection is a safe, effective alternative for both the treatment and the prevention of the chronic inflammatory state associated with a failed kidney transplant.

  6. Age- and Hypertension-Associated Protein Aggregates in Mouse Heart Have Similar Proteomic Profiles.

    Science.gov (United States)

    Ayyadevara, Srinivas; Mercanti, Federico; Wang, Xianwei; Mackintosh, Samuel G; Tackett, Alan J; Prayaga, Sastry V S; Romeo, Francesco; Shmookler Reis, Robert J; Mehta, Jawahar L

    2016-05-01

    Neurodegenerative diseases are largely defined by protein aggregates in affected tissues. Aggregates contain some shared components as well as proteins thought to be specific for each disease. Aggregation has not previously been reported in the normal, aging heart or the hypertensive heart. Detergent-insoluble protein aggregates were isolated from mouse heart and characterized on 2-dimensional gels. Their levels increased markedly and significantly with aging and after sustained angiotensin II-induced hypertension. Of the aggregate components identified by high-resolution proteomics, half changed in abundance with age (392/787) or with sustained hypertension (459/824), whereas 30% (273/901) changed concordantly in both, each Phypertensive hearts, we posited that aging of fibroblasts may contribute to the aggregates observed in cardiac tissue. Indeed, as cardiac myofibroblasts "senesced" (approached their replicative limit) in vitro, they accrued aggregates with many of the same constituent proteins observed in vivo during natural aging or sustained hypertension. In summary, we have shown for the first time that compact (detergent-insoluble) protein aggregates accumulate during natural aging, chronic hypertension, and in vitro myofibroblast senescence, sharing many common proteins. Thus, aggregates that arise from disparate causes (aging, hypertension, and replicative senescence) may have common underlying mechanisms of accrual. © 2016 American Heart Association, Inc.

  7. Investigation and identification of etiologies involved in the development of acquired hydronephrosis in aged laboratory mice with the use of high-frequency ultrasound imaging

    Science.gov (United States)

    Springer, Danielle A.; Allen, Michele; Hoffman, Victoria; Brinster, Lauren; Starost, Matthew F.; Bryant, Mark; Eckhaus, Michael

    2014-01-01

    Laboratory mice develop naturally occurring lesions that affect biomedical research. Hydronephrosis is a recognized pathologic abnormality of the mouse kidney. Acquired hydronephrosis can affect any mouse, as it is caused by any naturally occurring disease that impairs free urine flow. Many etiologies leading to this condition are of particular significance to aging mice. Non-invasive ultrasound imaging detects renal pelvic dilation, renal enlargement, and parenchymal loss for pre-mortem identification of this condition. High-frequency ultrasound transducers produce high-resolution images of small structures, ideal for detecting organ pathology in mice. Using a 40 MHz linear array transducer, we obtained high-resolution images of a diversity of pathologic lesions occurring within the abdomen of seven geriatric mice with acquired hydronephrosis that enabled a determination of the underlying etiology. Etiologies diagnosed from the imaging results include pyelonephritis, neoplasia, urolithiasis, mouse urologic syndrome, and spontaneous hydronephrosis, and were confirmed at necropsy. A retrospective review of abdominal scans from an additional 149 aging mice shows that the most common etiologies associated with acquired hydronephrosis are mouse urologic syndrome and abdominal neoplasia. This report highlights the utility of high-frequency ultrasound for surveying research mice for age-related pathology, and is the first comprehensive report of multiple cases of acquired hydronephrosis in mice. PMID:25143818

  8. Aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes as revealed by microscopic radioautography

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Tetsuji [Shinshu University, Matsumoto (Japan). Dept. of Anatomy and Cell Biology

    2007-07-01

    This mini-review reports aging changes of macromolecular synthesis in the mitochondria of mouse hepatocytes. We have observed the macromolecular synthesis, such as DNA, RNA and proteins, in the mitochondria of various mammalian cells by means of electron microscopic radioautography technique developed in our laboratory. The number of mitochondria per cell, number of labeled mitochondria per cell with 3H-thymidine, 3H-uridine and 3H-leucine, precursors for DNA, RNA and proteins, respectively, were counted and the labeling indices at various ages, from fetal to postnatal early days and several months to 1 and 2 years in senescence, were calculated, which showed variations due to aging. (author)

  9. Expression of Ambra1 in mouse brain during physiological and Alzheimer type aging.

    Science.gov (United States)

    Sepe, Sara; Nardacci, Roberta; Fanelli, Francesca; Rosso, Pamela; Bernardi, Cinzia; Cecconi, Francesco; Mastroberardino, Pier G; Piacentini, Mauro; Moreno, Sandra

    2014-01-01

    Autophagy is a major protein degradation pathway, essential for stress-induced and constitutive protein turnover. In nervous tissue, autophagy is constitutively active and crucial to neuronal survival. The efficiency of the autophagic pathway reportedly undergoes age-related decline, and autophagy defects are observed in neurodegenerative diseases. Since Ambra1 plays a fundamental role in regulating the autophagic process in developing nervous tissue, we investigated the expression of this protein in mature mouse brain and during physiological and Alzheimer type aging. The present study accomplished the first complete map of Ambra1 protein distribution in the various brain areas, and highlights differential expression in neuronal/glial cell populations. Differences in Ambra1 content are possibly related to specific neuronal features and properties, particularly concerning susceptibility to neurodegeneration. Furthermore, the analysis of Ambra1 expression in physiological and pathological brain aging supports important, though conflicting, functions of autophagy in neurodegenerative processes. Thus, novel therapeutic approaches, based on autophagy modulation, should also take into account the age-dependent roles of this mechanism in establishing, promoting, or counteracting neurodegeneration. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. SECRETED KLOTHO AND CHRONIC KIDNEY DISEASE

    Science.gov (United States)

    Hu, Ming Chang; Kuro-o, Makoto; Moe, Orson W.

    2013-01-01

    Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane-anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging, anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence reveals that Klotho deficiency is an early biomarker for chronic kidney diseases as well as a pathogenic factor. Klotho deficiency is associated with progression and chronic complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In multiple experimental models, replacement of sKl, or manipulated up-regulation of endogenous Klotho protect the kidney from renal insults, preserve kidney function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease. PMID:22396167

  11. Omega-3 PUFA supplementation differentially affects behavior and cognition in the young and aged non-human primate Grey mouse lemur (Microcebus murinus

    Directory of Open Access Journals (Sweden)

    Pifferi Fabien

    2014-01-01

    Full Text Available Data are divergent about the ability of dietary ω3 fatty acids to prevent age-associated cognitive decline. Most of the clinical trials failed to demonstrate a protective effect of ω3 fatty acids against cognitive decline and methodological issues are still under debate. Conversely to human studies, experiments performed in adult rodents clearly indicate that long chain ω3 fatty acids play a beneficial role in behavioral and cognitive functions. Inconsistent observations between human and rodent studies highlight the importance of the use of non-human primate models. We recently started a series of experiments on Grey mouse lemurs, an emerging non-human primate model of aging in order to assess the impact of ω3 fatty acids dietary supplementation on several brain functions. These experiments started with the determination of the fatty acids composition of target organs (brain, adipose tissue, liver, plasma of animals fed under control diet. We then explored the impact of ω3 polyunsaturated fatty acids (PUFA supplementation on cognition and behavior in young and aged grey mouse lemurs. The aim of the present review is to compare the observations made in young and aged grey mouse lemurs and to explore the possibilities of new experiments in order to bridge the gap between rodents and Humans.

  12. Frailty in elderly people with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Maria Eugenia Portilla Franco

    2016-11-01

    Frailty can be reversed, which is why a study of frailty in patients with chronic kidney disease is of particular interest. This article aims to describe the association between ageing, frailty and chronic kidney disease in light of the most recent and relevant scientific publications.

  13. Application of small RNA sequencing to identify microRNAs in acute kidney injury and fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrini, Kathryn L. [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Gerlach, Cory V. [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA (United States); Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States); Craciun, Florin L.; Ramachandran, Krithika [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Bijol, Vanesa [Department of Pathology, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Kissick, Haydn T. [Department of Surgery, Urology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States); Vaidya, Vishal S., E-mail: vvaidya@bwh.harvard.edu [Department of Medicine, Renal Division, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA (United States); Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Sciences, Harvard Medical School, Boston, MA (United States)

    2016-12-01

    Establishing a microRNA (miRNA) expression profile in affected tissues provides an important foundation for the discovery of miRNAs involved in the development or progression of pathologic conditions. We conducted small RNA sequencing to generate a temporal profile of miRNA expression in the kidneys using a mouse model of folic acid-induced (250 mg/kg i.p.) kidney injury and fibrosis. From the 103 miRNAs that were differentially expressed over the time course (> 2-fold, p < 0.05), we chose to further investigate miR-18a-5p, which is expressed during the acute stage of the injury; miR-132-3p, which is upregulated during transition between acute and fibrotic injury; and miR-146b-5p, which is highly expressed at the peak of fibrosis. Using qRT-PCR, we confirmed the increased expression of these candidate miRNAs in the folic acid model as well as in other established mouse models of acute injury (ischemia/reperfusion injury) and fibrosis (unilateral ureteral obstruction). In situ hybridization confirmed high expression of miR-18a-5p, miR-132-3p and miR-146b-5p throughout the kidney cortex in mice and humans with severe kidney injury or fibrosis. When primary human proximal tubular epithelial cells were treated with model nephrotoxicants such as cadmium chloride (CdCl{sub 2}), arsenic trioxide, aristolochic acid (AA), potassium dichromate (K{sub 2}Cr{sub 2}O{sub 7}) and cisplatin, miRNA-132-3p was upregulated 4.3-fold after AA treatment and 1.5-fold after K{sub 2}Cr{sub 2}O{sub 7} and CdCl{sub 2} treatment. These results demonstrate the application of temporal small RNA sequencing to identify miR-18a, miR-132 and miR-146b as differentially expressed miRNAs during distinct phases of kidney injury and fibrosis progression. - Highlights: • We used small RNA sequencing to identify differentially expressed miRNAs in kidney. • Distinct patterns were found for acute injury and fibrotic stages in the kidney. • Upregulation of miR-18a, -132 and -146b was confirmed in mice

  14. Combination of ACE inhibitor with nicorandil provides further protection in chronic kidney disease.

    Science.gov (United States)

    Shiraishi, Takeshi; Tamura, Yoshifuru; Taniguchi, Kei; Higaki, Masato; Ueda, Shuko; Shima, Tomoko; Nagura, Michito; Nakagawa, Takahiko; Johnson, Richard J; Uchida, Shunya

    2014-12-15

    An inhibition in the renin-angiotensin system (RAS) is one of the most widely used therapies to treat chronic kidney disease. However, its effect is occasionally not sufficient and additional treatments may be required. Recently, we reported that nicorandil exhibited renoprotective effects in a mouse model of diabetic nephropathy. Here we examined if nicorandil can provide an additive protection on enalapril in chronic kidney disease. Single treatment with either enalapril or nicorandil significantly ameliorated glomerular and tubulointerstitial injury in the rat remnant kidney while the combination of these two compounds provided additive effects. In addition, an increase in oxidative stress in remnant kidney was also blocked by either enalapril or nicorandil while the combination of the drugs was more potent. A mechanism was likely due for nicorandil to preventing manganase superoxide dismutase (MnSOD) and sirtuin (Sirt)3 from being reduced in injured kidneys. A study with cultured podocytes indicated that the antioxidative effect could be mediated through sulfonylurea receptor (SUR) in the mitochondrial KATP channel since blocking SUR with glibenclamide reduced MnSOD and Sirt3 expression in podocytes. In conclusion, nicorandil may synergize with enalapril to provide superior protection in chronic kidney disease. Copyright © 2014 the American Physiological Society.

  15. Diabetic kidney disease.

    Science.gov (United States)

    Thomas, Merlin C; Brownlee, Michael; Susztak, Katalin; Sharma, Kumar; Jandeleit-Dahm, Karin A M; Zoungas, Sophia; Rossing, Peter; Groop, Per-Henrik; Cooper, Mark E

    2015-07-30

    The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.

  16. Quantified kidney echogenicity in mice with renal ischemia reperfusion injury: evaluation as a noninvasive biomarker of acute kidney injury.

    Science.gov (United States)

    Murata, Shinya; Sugiyama, Noriyuki; Maemura, Kentaro; Otsuki, Yoshinori

    2017-09-01

    The purpose is to evaluate quantified kidney echogenicity as a biomarker for the early diagnosis of acute kidney injury (AKI) and predicting progression to chronic kidney disease (CKD) in a mouse model of ischemia-reperfusion injury (IRI). Two separate protocols of murine models of IRI were used: (1) 10, 30, and 40 min of bilateral ischemia duration and (2) 45 and 60 min of unilateral ischemia duration. Renal echogenicity was measured with ultrasound and compared with serum creatinine or urine neutrophil gelatinase-associated lipocalin (NGAL) at various timepoints after IRI. In mice subjected to 10, 30, and 40 min of bilateral ischemia, renal echogenicity increased about 2 h after IRI for all ischemia times, earlier than serum creatinine or urine NGAL. In those subjected to 45 and 60 min of unilateral ischemia, 60 min of unilateral ischemia, which represents atrophic changes 28 days after IRI, resulted in a sustained high level of echogenicity and was significantly different 24 h after IRI, while 45 min of unilateral ischemia resulted in trivial levels of histological damage 28 days after IRI. Renal echogenicity might have the potential to be a biomarker for the early diagnosis of AKI and the prognosis of CKD.

  17. Accuracy of repeated kidney size estimation by ultrasonography and urography in children

    International Nuclear Information System (INIS)

    Hederstroem, E.; Forsberg, L.

    1985-01-01

    The accuracy of repeated sonographic and urographic kidney length measurements in kidney size evaluation was investigated in 80 children 0 to 14 years of age, mean age 4.5 years. At sonography 250 kidney lengths were compared. A difference of 0 to 1.0 cm in repeated length measurement was considered to be good accuracy and 94 per cent of right and 96 per cent of left kidney length were found within this interval-a better result than for urography with 76 per cent of repeated right kidney and 79 per cent of kidney lengths within the same interval (94 lengths). Both methods display a variation of kidney lengths which may lead to under- and overestimation of kidney size and growth. The investigation thus indicates good accuracy for repeated sonographic kidney size assessment which should be repeated often enough to estabilish a growth chart displaying the trend rather than rely too much on single measurements. Sonography can be highly recommended as a convenient and harmless alternative to urography. (orig.)

  18. Extracellular microRNA signature in chronic kidney disease.

    Science.gov (United States)

    Muralidharan, Jagdeesan; Ramezani, Ali; Hubal, Monica; Knoblach, Susan; Shrivastav, Shashi; Karandish, Sara; Scott, Richard; Maxwell, Nirmal; Ozturk, Savas; Beddhu, Srinivasan; Kopp, Jeffrey B; Raj, Dominic S

    2017-06-01

    MicroRNAs (miRNAs) are noncoding RNAs that regulate posttranscriptional gene expression. In this study we characterized the circulating and urinary miRNA pattern associated with reduced glomerular filtration rate, using Affymetrix GeneChip miR 4.0 in 28 patients with chronic kidney disease (CKD). Top miRNA discoveries from the human studies were validated in an Alb/TGFβ mouse model of CKD, and in rat renal proximal tubular cells (NRK52E) exposed to TGFβ1. Plasma and urinary levels of procollagen III N-terminal propeptide and collagen IV were elevated in patients with decreased estimated glomerular filtration rate (eGFR). Expression of 384 urinary and 266 circulatory miRNAs were significantly different between CKD patients with eGFR ≥30 vs. kidney fibrosis, and specific urinary and plasma miRNA profile may have diagnostic and prognostic utility in CKD. Copyright © 2017 the American Physiological Society.

  19. In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei, E-mail: weiwang2@illinois.edu; Hafner, Katlyn S., E-mail: katlynhafner@gmail.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2014-04-15

    Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in

  20. In utero bisphenol A exposure disrupts germ cell nest breakdown and reduces fertility with age in the mouse

    International Nuclear Information System (INIS)

    Wang, Wei; Hafner, Katlyn S.; Flaws, Jodi A.

    2014-01-01

    Bisphenol A (BPA) is a known reproductive toxicant in rodents. However, the effects of in utero BPA exposure on early ovarian development and the consequences of such exposure on female reproduction in later reproductive life are unclear. Thus, we determined the effects of in utero BPA exposure during a critical developmental window on germ cell nest breakdown, a process required for establishment of the finite primordial follicle pool, and on female reproduction. Pregnant FVB mice (F0) were orally dosed daily with tocopherol-striped corn oil (vehicle), diethylstilbestrol (DES; 0.05 μg/kg, positive control), or BPA (0.5, 20, and 50 μg/kg) from gestational day 11 until birth. Ovarian morphology and gene expression profiles then were examined in F1 female offspring on postnatal day (PND) 4 and estrous cyclicity was examined daily after weaning for 30 days. F1 females were also subjected to breeding studies with untreated males at three to nine months. The results indicate that BPA inhibits germ cell nest breakdown via altering expression of selected apoptotic factors. BPA also significantly advances the age of first estrus, shortens the time that the females remain in estrus, and increases the time that the females remain in metestrus and diestrus compared to controls. Further, F1 females exposed to low doses of BPA exhibit various fertility problems and have a significantly higher percentage of dead pups compared to controls. These results indicate that in utero exposure to low doses of BPA during a critical ovarian developmental window interferes with early ovarian development and reduces fertility with age. - Highlights: • In utero BPA exposure inhibits germ cell nest breakdown in female mouse offspring. • In utero BPA exposure alters expression of apoptosis regulators in the ovaries of mouse offspring. • In utero BPA exposure advances first estrus age and alters cyclicity in mouse offspring. • In utero BPA exposure causes various fertility problems in

  1. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  2. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

    2015-01-01

    BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  3. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

  4. Shear wave velocity measurements using acoustic radiation force impulse in young children with normal kidneys versus hydronephrotic kidneys

    International Nuclear Information System (INIS)

    Shon, Beom Seok; Kim, Myung Joon; Han, Sang Won; Im, Young Jae; Lee, Mi Jung

    2014-01-01

    To measure shear wave velocities (SWVs) by acoustic radiation force impulse (ARFI) ultrasound elastography in normal kidneys and in hydronephrotic kidneys in young children and to compare SWVs between the hydronephrosis grades. This study was approved by an institutional review board, and informed consent was obtained from the parents of all the children included. Children under the age of 24 months were prospectively enrolled. Hydronephrosis grade was evaluated on ultrasonography, and three valid ARFI measurements were attempted using a high-frequency transducer for both kidneys. Hydronephrosis was graded from 0 to 4, and high-grade hydronephrosis was defined as grades 3 and 4. Fifty-one children underwent ARFI measurements, and three valid measurements for both kidneys were obtained in 96% (49/51) of the patients. Nineteen children (38.8%) had no hydronephrosis. Twenty-three children (46.9%) had unilateral hydronephrosis, and seven children (14.3%) had bilateral hydronephrosis. Seven children had ureteropelvic junction obstruction (UPJO). Median SWVs in kidneys with high-grade hydronephrosis (2.02 m/sec) were higher than those in normal kidneys (1.75 m/sec; P=0.027). However, the presence of UPJO did not influence the median SWVs in hydronephrotic kidneys (P=0.362). Obtaining ARFI measurements of the kidney is feasible in young children with median SWVs of 1.75 m/sec in normal kidneys. Median SWVs increased in high-grade hydronephrotic kidneys but were not different between hydronephrotic kidneys with and without UPJO.

  5. Shear wave velocity measurements using acoustic radiation force impulse in young children with normal kidneys versus hydronephrotic kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Shon, Beom Seok; Kim, Myung Joon; Han, Sang Won; Im, Young Jae; Lee, Mi Jung [Severance Children' s Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2014-04-15

    To measure shear wave velocities (SWVs) by acoustic radiation force impulse (ARFI) ultrasound elastography in normal kidneys and in hydronephrotic kidneys in young children and to compare SWVs between the hydronephrosis grades. This study was approved by an institutional review board, and informed consent was obtained from the parents of all the children included. Children under the age of 24 months were prospectively enrolled. Hydronephrosis grade was evaluated on ultrasonography, and three valid ARFI measurements were attempted using a high-frequency transducer for both kidneys. Hydronephrosis was graded from 0 to 4, and high-grade hydronephrosis was defined as grades 3 and 4. Fifty-one children underwent ARFI measurements, and three valid measurements for both kidneys were obtained in 96% (49/51) of the patients. Nineteen children (38.8%) had no hydronephrosis. Twenty-three children (46.9%) had unilateral hydronephrosis, and seven children (14.3%) had bilateral hydronephrosis. Seven children had ureteropelvic junction obstruction (UPJO). Median SWVs in kidneys with high-grade hydronephrosis (2.02 m/sec) were higher than those in normal kidneys (1.75 m/sec; P=0.027). However, the presence of UPJO did not influence the median SWVs in hydronephrotic kidneys (P=0.362). Obtaining ARFI measurements of the kidney is feasible in young children with median SWVs of 1.75 m/sec in normal kidneys. Median SWVs increased in high-grade hydronephrotic kidneys but were not different between hydronephrotic kidneys with and without UPJO.

  6. Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

    Science.gov (United States)

    Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

    2018-05-02

    DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

  7. Duplex kidney: not just a drooping lily.

    Science.gov (United States)

    Doery, Ashlea J; Ang, Eileen; Ditchfield, Michael R

    2015-04-01

    Duplex kidneys are common, mostly asymptomatic and of no clinical significance. However, they can be associated with significant pathology, often with long-term morbidity. There is minimal literature on the review of the duplex kidney, its associated anomalies and complications. The purpose of this paper is to review our experience of imaging the spectrum of abnormalities associated with duplex kidneys in the paediatric population and correlate this with contemporary literature. A retrospective review of the radiology database in a tertiary paediatric centre was performed. A word search of the Radiology Information System for 'duplex' of patients under the age of 16 was undertaken and limited to studies performed between 2006 and 2013. Two hundred seventy-four patients were identified (age range 0-16, median 3 years, gender 59.9% female) who had 836 studies: ultrasound 598/836 (71.6%), nuclear medicine 180/836 (21.5%), micturating cystourethrogram 52/836 (6.2%), MRI 5/836 (duplex and no complication (151/274 = 55.1%), upper moiety obstruction, lower moiety reflux/scarring, multicystic dysplastic kidney, abnormal ureteric insertion and other pathology. Duplex kidneys are common and often not clinically significant. However, this study demonstrates almost 50% of paediatric patients investigated for duplex kidneys had complications requiring treatment. The most common complications were upper moiety obstruction associated with a ureterocele and lower moiety vesicoureteric reflux. Ultrasound was the most common modality for early detection of these complications. © 2015 The Royal Australian and New Zealand College of Radiologists.

  8. Accumulation of cadmium in livers and kidneys in Greenlanders

    International Nuclear Information System (INIS)

    Johansen, Poul; Mulvad, Gert; Pedersen, Henning Sloth; Hansen, Jens C.; Riget, Frank

    2006-01-01

    In the Arctic, the traditional diet exposes its people to a very high intake of cadmium because it is highly concentrated in the liver and kidneys of commonly eaten marine mammals. In one study in Greenland, the cadmium intake was estimated to 182 μg/day/person in the fall and 346 in the spring. To determine whether the cadmium is accumulated in humans, we analyzed autopsy samples of liver and kidneys from 95 ethnic Greenlanders (aged 19-89) who died from a wide range of causes. The cadmium concentration in liver (overall mean 1.97 μg/g wet wt) appeared to be unrelated to any particular age group, whereas the concentrations in the kidneys peaked in Greenlanders between 40 and 50 years of age (peak concentration 22.3 μg/g wet wt). Despite the high cadmium levels in the typical Greenlander diet, we found that the cadmium concentrations in livers and kidneys were comparable to those reported from Denmark, Sweden, Australia and Great Britain. Furthermore, even though the mean cadmium intake from the diet was estimated to be 13-25 times higher in Greenlanders than in Danes, we found similar cadmium levels in the kidneys of both. Seal livers and kidneys are the main source of cadmium in the diet of Greenlanders, but these tissues are not eaten in Denmark. Thus, our results suggest that the accumulation of cadmium from Greenlander's marine diet is very low

  9. Accumulation of cadmium in livers and kidneys in Greenlanders

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, Poul [National Environmental Research Institute, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)]. E-mail: poj@dmu.dk; Mulvad, Gert [Primary Health Care Center, DK-3900 Nuuk, Greenland (Denmark); Centre for Arctic Environmental Medicine, University of Aarhus, Universitetsparken, DK-8000 Aarhus C (Denmark); Pedersen, Henning Sloth [Primary Health Care Center, DK-3900 Nuuk, Greenland (Denmark); Centre for Arctic Environmental Medicine, University of Aarhus, Universitetsparken, DK-8000 Aarhus C (Denmark); Hansen, Jens C. [Centre for Arctic Environmental Medicine, University of Aarhus, Universitetsparken, DK-8000 Aarhus C (Denmark); Riget, Frank [National Environmental Research Institute, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)

    2006-12-15

    In the Arctic, the traditional diet exposes its people to a very high intake of cadmium because it is highly concentrated in the liver and kidneys of commonly eaten marine mammals. In one study in Greenland, the cadmium intake was estimated to 182 {mu}g/day/person in the fall and 346 in the spring. To determine whether the cadmium is accumulated in humans, we analyzed autopsy samples of liver and kidneys from 95 ethnic Greenlanders (aged 19-89) who died from a wide range of causes. The cadmium concentration in liver (overall mean 1.97 {mu}g/g wet wt) appeared to be unrelated to any particular age group, whereas the concentrations in the kidneys peaked in Greenlanders between 40 and 50 years of age (peak concentration 22.3 {mu}g/g wet wt). Despite the high cadmium levels in the typical Greenlander diet, we found that the cadmium concentrations in livers and kidneys were comparable to those reported from Denmark, Sweden, Australia and Great Britain. Furthermore, even though the mean cadmium intake from the diet was estimated to be 13-25 times higher in Greenlanders than in Danes, we found similar cadmium levels in the kidneys of both. Seal livers and kidneys are the main source of cadmium in the diet of Greenlanders, but these tissues are not eaten in Denmark. Thus, our results suggest that the accumulation of cadmium from Greenlander's marine diet is very low.

  10. THE CAUSES AND THE COURSE OF CHRONIC KIDNEY DISEASE IN CHILDREN OF PRESCHOOL AGE

    Directory of Open Access Journals (Sweden)

    T. Yu. Abaseeva

    2015-01-01

    Full Text Available Background: Data on etiology and clinical course of CKD stage  3 to 5 in children of preschool  age could help obstetricians, pediatricians, and nephrologists with proper diagnostics and management of this condition and prediction of outcomes. Aim: To study causes and clinical features of CKD stage 3 to 5 in preschool  children. Materials and methods: The causes and clinical features of CKD stage 3 to 5 were investigated in 55 preschool children aged from 7 months  to 8 years. Twenty four had  CKD stage  3 to 4 and  31 children with endstage  CKD  were  on  peritoneal  dialysis. Results:96% of CKD stage 3 to 5 in preschool children were due  to  congenital/genetic kidney abnormalities. Predictors  of renal  replacement therapy  beginning in the first 5 years of life were as follows: antenatal detection of congenital  abnormalities  of the kidney and urinary tract, oligohydroamnion, high neonatal  BUN levels.  Anemia, hyperparathyroidism, arterial hypertension were more prevalent  in children on the dialysis stage of CKD, and myocardial hypertrophy and/or of the left ventricle dilatation were found in 26% of them. Forty two percent of children had growth retardation, and 40% had delayed  speech  development. Conclusion: The course CKD in preschool  children is characterized by a combination of typical metabolic  disorders with the growth  retardation (often dramatic and delayed mental development that significantly limits the possibilities of the social adaptation of these children and social activities of their parents. Participation  of  neuropsychiatrists,  clinical psychologists, and teachers, rather than pediatricians and  nephrologists only, is desirable  in management of preschool children with CKD stage 3 to 5.

  11. Cadmium and other heavy metal concentrations in bovine kidneys in the Republic of Ireland

    Energy Technology Data Exchange (ETDEWEB)

    Canty, Mary J., E-mail: mary.canty@agriculture.gov.ie [Centre for Veterinary Epidemiology and Risk Analysis (CVERA), UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4 (Ireland); Department of Agriculture, Food and the Marine, Backweston Campus, Celbridge, Co. Kildare (Ireland); Scanlon, Aiden, E-mail: aiden.scanlon@agriculture.gov.ie [Department of Agriculture, Food and the Marine, Agriculture House, Kildare St, Dublin 2 (Ireland); Collins, Daniel M., E-mail: daniel.collins@ucd.ie [Centre for Veterinary Epidemiology and Risk Analysis (CVERA), UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4 (Ireland); McGrath, Guy, E-mail: guy.mcgrath@ucd.ie [Centre for Veterinary Epidemiology and Risk Analysis (CVERA), UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4 (Ireland); Clegg, Tracy A., E-mail: tracy.clegg@ucd.ie [Centre for Veterinary Epidemiology and Risk Analysis (CVERA), UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4 (Ireland); Lane, Elizabeth, E-mail: elizabeth.lane@agriculture.gov.ie [Centre for Veterinary Epidemiology and Risk Analysis (CVERA), UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4 (Ireland); Department of Agriculture, Food and the Marine, Backweston Campus, Celbridge, Co. Kildare (Ireland); Sheridan, Michael K., E-mail: michael.sheridan@agriculture.gov.ie [Department of Agriculture, Food and the Marine, Agriculture House, Kildare St, Dublin 2 (Ireland); More, Simon J., E-mail: simon.more@ucd.ie [Centre for Veterinary Epidemiology and Risk Analysis (CVERA), UCD School of Veterinary Medicine, University College Dublin, Belfield, Dublin 4 (Ireland)

    2014-07-01

    In Ireland, an estimated 15% of Irish soils exceed the EU threshold limit for soil Cd of 1 mg/kg. The aim was to determine the concentrations of Cd and other heavy metals (As, Hg and Pb) in kidneys collected from cattle at slaughter. Systematic sampling of eligible animals (animals that were born and reared until slaughter in the same Irish county) at the time of slaughter was conducted, until a threshold number of animals from all 26 counties and 6 age categories was reached. A predictive surface of soil Cd was generated, by kriging the Cd values of 1310 previously reported soil samples. A linear regression weighted model was developed to model kidney Cd concentration, using the risk factors of age, sex, breed, province and estimated soil Cd concentration. Kidney Cd (n = 393) concentrations varied between 0.040 and 8.630 mg/kg wet weight; while concentrations of As, Hg and Pb were low. The estimated weighted proportion of animals with a high (≥ 1 mg/kg) kidney Cd concentration was 11.25% (95% CI: 8.63–14.53%). Key predictors for high kidney Cd concentration were soil Cd, animal age and province. At a soil Cd concentration of 1.5 mg/kg, it was predicted that an age threshold to avoid exceeding a kidney Cd concentration of 1 mg/kg in most animals would be ∼ 3 y in Connacht, > 4 y in Ulster, and > 5 y in Leinster and Munster. In naturally occurring areas of high Cd levels in soils in Ireland, the Cd level in bovine kidneys can exceed the current EU ML of 1 mg/kg in older animals. Kidneys of most cattle under three years of age will conform with EU requirements. - Highlights: • An estimated 15% of Irish soils exceed the EU Cd threshold limit of 1 mg/kg. • 11.3% of cattle had kidney Cd concentrations in excess of the EU ML of 1 mg/kg. • Age, soil Cd concentrations and region were key predictors of elevated kidney Cd. • Kidneys of most Irish cattle under three years of age will conform with EU requirements.

  12. Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model.

    Science.gov (United States)

    Omachi, Kohei; Miyakita, Rui; Fukuda, Ryosuke; Kai, Yukari; Suico, Mary Ann; Yokota, Tsubasa; Kamura, Misato; Shuto, Tsuyoshi; Kai, Hirofumi

    2017-12-01

    Alport syndrome (AS) is a hereditary kidney disease caused by mutation of type IV collagen. Loss of collagen network induces collapse of glomerular basement membrane (GBM) structure. The previous studies showed that upregulation of some tyrosine kinase receptors signaling accompanied GBM disorder in AS mouse model. EGFR signaling is one of the well-known receptor kinase signaling that is involved in glomerular diseases. However, whether EGFR signaling is relevant to AS progression is still uninvestigated. Here, we determined the involvement of EGFR in AS and the effect of suppressing EGFR signaling by erlotinib treatment on AS progression. Phosphorylated EGFR expression was investigated by Western blotting analysis and immunostaining of kidney tissues of Col4a5 mutant mice (a mouse model of X-linked AS). To check the effect of blocking EGFR signaling in AS, we administered erlotinib to AS mice once a day (10 mg/kg/day) orally for 18 weeks. Renal function parameters (proteinuria, serum creatinine, and BUN) and renal histology were assessed, and the gene expressions of inflammatory cytokines were analyzed in renal tissues. Phosphorylated EGFR expression was upregulated in AS mice kidney tissues. Erlotinib slightly reduced the urinary protein and suppressed the expression of renal injury markers (Lcn2, Lysozyme) and inflammatory cytokines (Il-6, Il-1β and KC). Erlotinib did not improve renal pathology, such as glomerular sclerosis and fibrosis. These findings suggest that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model.

  13. Kidney transplant

    Science.gov (United States)

    ... always take your medicine as directed. Alternative Names Renal transplant; Transplant - kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney - blood and urine flow Kidneys Kidney transplant - ...

  14. Radioprotection of normal tissues of the mouse by hypoxic breathing

    International Nuclear Information System (INIS)

    Stevens, G.N.; Joiner, B.; Denekamp, J.

    1989-01-01

    Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

  15. Reduced developmental competence of immature, in-vitro matured and postovulatory aged mouse oocytes following IVF and ICSI

    Directory of Open Access Journals (Sweden)

    Trounson Alan

    2008-12-01

    Full Text Available Abstract Background The present study highlights basic physiological differences associated with oocyte maturation and ageing. The study explores the fertilizing capacity and resistance to injury of mouse oocytes at different stages of maturation and ageing following IVF and ICSI. Also, the study examines the developmental competence of embryos obtained from these oocytes. The outcome of the study supports views that the mouse can be a model for human IVF suggesting that utilizing in-vitro matured and failed fertilized oocytes to produce embryos mainly when limited number of oocytes is retrieved in a specific cycle, should be carefully considered. Methods Hybrid strain mouse oocytes were inseminated by in-vitro fertilization (IVF or intracytoplasmic sperm injection (ICSI. Oocytes groups that were used were germinal vesicle (GV in-vitro matured metaphase II (IVM-MII, freshly ovulated MII (OV-MII, 13 hrs in-vitro aged MII (13 hrs-MII and 24 hrs in-vitro aged MII (24 hrs-MII. Fertilization and embryo development to the blastocyst stage were monitored up to 5 days in culture for IVF and ICSI zygotes. Sperm head decondensation and pronuclear formation were examined up to 9 hrs in oocytes following ICSI. Apoptotic events in blocked embryos were examined using the TUNNEL assay. Differences between females for the number and quality of GV and OV-MII oocytes were examined by ANOVA analyses. Differences in survival after ICSI, fertilization by IVF and ICSI and embryo development were analysed by Chi-square test with Yates correction. Results No differences in number and quality of oocytes were identified between females. The findings suggest that inability of GV oocytes to participate in fertilization and embryo development initiates primarily from their inability to support initial post fertilization events such as sperm decondensation and pronuclei formation. These events occur in all MII oocytes in similar rates (87–98% for IVF and ICSI. Following

  16. [Study on the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse].

    Science.gov (United States)

    Wang, Hui; Zhang, Jiaxiang; Li, Shulong; Zha, Wansheng; Wang, Feng; Zhu, Qixing

    2015-07-01

    To study the expression of bradykinin and its receptors B1R and B2R in the kidney immune injury in trichloroethylene-sensitized mouse and discuss the pathogenesis of Dermatitis Medicamentosa-like of TCE (ODMLT). On the first days, intradermal injection by 50% TCE and the amount of FCA mixture 100 µl for initial sensitization; on 4, 7, 10 days, painted abdominal skin by 100 µl 50% TCE for three sensitization, on 17, 19 days, painted on the back skin by 100 µl 30% TCE for initial excitation and the last challenge; 24 h before each challenge, PKSI-527+TCE group received intraperitoneal injection by inhibitor PKSI-527 (50 mg/kg); solvent control group treat without TCE and sensitization and excitation reagent the same proportion of olive oil and acetone mixture, blank control group without any treatment. Before killing the mouse, renal weight and body weight were recorded. The renals and plasma were separated at 24 h, 48 h, 72 h and 7 d after the last challenge and observed pathological of the renals. Expression of B1R and B2R in renal were examined by immunofluorescence technique. Plasma were examined by ELISA for BK. The renal pathological examination revealed the apparent damage of TCE sensitized mice which compared to solvent control group showed obvious cellular infiltration, vacuolar degeneration of renal tubular epithelial cells. The renal damage of PKSI-527+TCE-sensitized groups which compared to the corresponding point of TCE-sensitized groups showed significantly reduced. The expression of BK in 24 h, 48 h and 72 h TCE-sensitized groups were significant higher than solvent control group and related TCE non-sensitized groups (P trichloroethylene-sensitized mouse and the expression change of bradykinin and its receptors B1R and B2R which may play an important role in the process.

  17. Megalin is a receptor for apolipoprotein M, and kidney-specific megalin-deficiency confers urinary excretion of apolipoprotein M

    DEFF Research Database (Denmark)

    Faber, Kirsten; Hvidberg, Vibeke; Moestrup, Søren K

    2006-01-01

    . In addition, apoM is expressed at high levels in the kidney tubule cells. In this study, we show that the multiligand receptor megalin, which is expressed in kidney proximal tubule cells, is a receptor for apoM and mediates its uptake in the kidney. To examine apoM binding to megalin, a recombinant apo....... To examine the importance of apoM binding by megalin in vivo, we analyzed mice with a tissue-specific deficiency of megalin in the kidney. Megalin deficiency was associated with pronounced urinary excretion of apoM, whereas apoM was not detected in normal mouse, human, or rat urine. Gel filtration analysis...... showed that the urinary apoM-containing particles were small and devoid of apoA-I. The results suggest that apoM binds to megalin and that megalin-mediated endocytosis in kidney proximal tubules prevents apoM excretion in the urine....

  18. Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation

    DEFF Research Database (Denmark)

    Magnusson, Nils Erik; Hornum, Mads; Jørgensen, Kaj Anker

    2012-01-01

    Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14...... healthy subjects matched for age, sex and body mass index (BMI). The kidney graft recipients were studied at baseline before transplantation and 3 and 12 months after transplantation and the uraemic group at baseline and after 12 months....

  19. Cystogenesis in ARPKD results from increased apoptosis in collecting duct epithelial cells of Pkhd1 mutant kidneys

    International Nuclear Information System (INIS)

    Hu, Bo; He, Xiusheng; Li, Ao; Qiu, Qingchao; Li, Cunxi; Liang, Dan; Zhao, Ping; Ma, Jie; Coffey, Robert J.; Zhan, Qimin; Wu, Guanqing

    2011-01-01

    Mutations in the PKHD1 gene result in autosomal recessive polycystic kidney disease (ARPKD) in humans. To determine the molecular mechanism of the cystogenesis in ARPKD, we recently generated a mouse model for ARPKD that carries a targeted mutation in the mouse orthologue of human PKHD1. The homozygous mutant mice display hepatorenal cysts whose phenotypes are similar to those of human ARPKD patients. By littermates of this mouse, we developed two immortalized renal collecting duct cell lines with Pkhd1 and two without. Under nonpermissive culture conditions, the Pkhd1 -/- renal cells displayed aberrant cell-cell contacts and tubulomorphogenesis. The Pkhd1 -/- cells also showed significantly reduced cell proliferation and elevated apoptosis. To validate this finding in vivo, we examined proliferation and apoptosis in the kidneys of Pkhd1 -/- mice and their wildtype littermates. Using proliferation (PCNA and Histone-3) and apoptosis (TUNEL and caspase-3) markers, similar results were obtained in the Pkhd1 -/- kidney tissues as in the cells. To identify the molecular basis of these findings, we analyzed the effect of Pkhd1 loss on multiple putative signaling regulators. We demonstrated that the loss of Pkhd1 disrupts multiple major phosphorylations of focal adhesion kinase (FAK), and these disruptions either inhibit the Ras/C-Raf pathways to suppress MEK/ERK activity and ultimately reduce cell proliferation, or suppress PDK1/AKT to upregulate Bax/caspase-9/caspase-3 and promote apoptosis. Our findings indicate that apoptosis may be a major player in the cyst formation in ARPKD, which may lead to new therapeutic strategies for human ARPKD.

  20. Epidemiology of chronic kidney disease, with special emphasis on chronic kidney disease of uncertain etiology, in the north central region of Sri Lanka.

    Science.gov (United States)

    Jayasekara, Kithsiri Bandara; Dissanayake, Dhammika Menike; Sivakanesan, Ramiah; Ranasinghe, Asanga; Karunarathna, Ranawaka Hewage; Priyantha Kumara, Gardiye Waligamage Gamini

    2015-01-01

    The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka. A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology. The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30-40 years; 7% in those aged 41-50 years, 20% in those aged 51-60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%. Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages.

  1. Urology and nephrology update: bladder and kidney cancer.

    Science.gov (United States)

    Fiore, David C; Fox, Cara-Louise

    2014-01-01

    It has been estimated that bladder and kidney cancers would be diagnosed in approximately 140,000 Americans in 2013, with approximately 30,000 dying from these cancers. Urinary tract cancers affect men more commonly than they do women, and the median age at diagnosis is 65 years. Major risk factors for these cancers include tobacco smoking, certain chemical exposures, family history, age, and obesity. Unexplained hematuria in adults should be evaluated to exclude bladder and kidney cancer. Staging of bladder and kidney cancer should be based on the TNM staging system, which, along with tumor grade, provides important treatment and prognostic information. Urothelial cell carcinoma is the most common type of bladder cancer; it also can occur in the kidneys or ureters. Renal cell carcinoma is the most common type of kidney cancer. Treatment options for bladder cancer vary widely, depending on the grade of the cancer. Early non-muscle-invasive bladder cancer may be removed cystoscopically and/or treated with intravesical immunotherapy or chemotherapy, whereas patients with muscle-invasive bladder tumors typically require surgery. Management of kidney cancer is almost always surgical, unless the patient is too ill to undergo surgery or chooses palliative care. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  2. Increased kidney growth in formula-fed versus breast-fed healthy infants

    DEFF Research Database (Denmark)

    Schmidt, Ida M; Damgaard, Ida N; Boisen, Kirsten A

    2004-01-01

    versus breast feeding on kidney growth in a cohort of 631 healthy children examined at birth, and at 3 and 18 months of age. Kidney size was determined by ultrasonography and related to gender, age, body size, and feeding category (fully breast fed, partially breast fed, or fully formula fed at 3 months...

  3. Life cycle analysis of kidney gene expression in male F344 rats.

    Directory of Open Access Journals (Sweden)

    Joshua C Kwekel

    Full Text Available Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age. Kidneys were collected for histology and gene expression analysis. Agilent whole-genome rat microarrays were used to query global expression profiles. An ANOVA (p1.5 in relative mRNA expression, was used to identify 3,724 unique differentially expressed genes (DEGs. Principal component analyses of these DEGs revealed three major divisions in life-cycle renal gene expression. K-means cluster analysis identified several groups of genes that shared age-specific patterns of expression. Pathway analysis of these gene groups revealed age-specific gene networks and functions related to renal function and aging, including extracellular matrix turnover, immune cell response, and renal tubular injury. Large age-related changes in expression were also demonstrated for the genes that code for qualified renal injury biomarkers KIM-1, Clu, and Tff3. These results suggest specific groups of genes that may underlie age-specific susceptibilities to adverse drug reactions and disease. This analysis of the basal gene expression patterns of renal genes throughout the life cycle of the rat will improve the use of current and future renal biomarkers and inform our assessments of kidney injury and disease.

  4. Healthy Kidneys (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    Kidney disease is among the leading causes of death in the U.S. More than one in 10 people over the age of 20 are impacted by this condition, and most don’t know it. In this podcast, Nilka Rios Burrows discusses the risks for kidney disease.

  5. Risk of a Second Kidney Carcinoma Following Childhood Cancer: Role of Chemotherapy and Radiation Dose to Kidneys.

    Science.gov (United States)

    de Vathaire, Florent; Scwhartz, Boris; El-Fayech, Chiraz; Allodji, Rodrigue Sètchéou; Escudier, Bernard; Hawkins, Mike; Diallo, Ibrahima; Haddy, Nadia

    2015-11-01

    Kidney carcinoma is a rare second malignancy following childhood cancer. We sought to quantify risk and assess risk factors for kidney carcinoma following treatment for childhood cancer. We evaluated a cohort of 4,350 patients who were 5-year cancer survivors and had been treated for cancer as children in France and the United Kingdom. Patients were treated between 1943 and 1985, and were followed for an average of 27 years. Radiation dose to the kidneys during treatment was estimated with dedicated software, regardless of the site of childhood cancer. Kidney carcinoma developed in 13 patients. The cumulative incidence of kidney carcinoma was 0.62% (95% CI 0.27%-1.45%) at 40 years after diagnosis, which was 13.3-fold higher (95% CI 7.1-22.3) than in the general population. The absolute excess risk strongly increased with longer duration of followup (p kidney carcinoma was 5.7-fold higher (95% CI 1.4-14.7) if radiotherapy was not performed or less than 1 Gy had been absorbed by the kidney but 66.3-fold higher (95% CI 23.8-142.5) if the radiation dose to the kidneys was 10 to 19 Gy and 14.5-fold higher (95% CI 0.8-63.9) for larger radiation doses to the kidney. Treatment with chemotherapy increased the risk of kidney carcinoma (RR 5.1, 95% CI 1.1-22.7) but we were unable to identify a specific drug or drug category responsible for this effect. Moderate radiation dose to the kidneys during childhood cancer treatment increases the risk of a second kidney carcinoma. This incidence will be further increased when childhood cancer survivors reach old age. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Hoxd11 specifies a program of metanephric kidney development within the intermediate mesoderm of the mouse embryo.

    Science.gov (United States)

    Mugford, Joshua W; Sipilä, Petra; Kobayashi, Akio; Behringer, Richard R; McMahon, Andrew P

    2008-07-15

    The mammalian kidney consists of an array of tubules connected to a ductal system that collectively function to control water/salt balance and to remove waste from the organisms' circulatory system. During mammalian embryogenesis, three kidney structures form within the intermediate mesoderm. The two most anterior structures, the pronephros and the mesonephros, are transitory and largely non-functional, while the most posterior, the metanephros, persists as the adult kidney. We have explored the mechanisms underlying regional specific differentiation of the kidney forming mesoderm. Previous studies have shown a requirement for Hox11 paralogs (Hoxa11, Hoxc11 and Hoxd11) in metanephric development. Mice lacking all Hox11 activity fail to form metanephric kidney structures. We demonstrate that the Hox11 paralog expression is restricted in the intermediate mesoderm to the posterior, metanephric level. When Hoxd11 is ectopically activated in the anterior mesonephros, we observe a partial transformation to a metanephric program of development. Anterior Hoxd11(+) cells activate Six2, a transcription factor required for the maintenance of metanephric tubule progenitors. Additionally, Hoxd11(+) mesonephric tubules exhibit an altered morphology and activate several metanephric specific markers normally confined to distal portions of the functional nephron. Collectively, our data support a model where Hox11 paralogs specify a metanephric developmental program in responsive intermediate mesoderm. This program maintains tubule forming progenitors and instructs a metanephric specific pattern of nephron differentiation.

  7. Better recovery of kidney function in patients with de novo chronic kidney disease after partial nephrectomy compared with those with pre-existing chronic kidney disease.

    Science.gov (United States)

    Takagi, Toshio; Kondo, Tsunenori; Iizuka, Junpei; Omae, Kenji; Kobayashi, Hirohito; Hashimoto, Yasunobu; Yoshida, Kazuhiko; Tanabe, Kazunari

    2014-06-01

    We compared kidney functional recovery between patients with pre-existing chronic kidney disease, those with de novo chronic kidney disease and those with normal kidney function, after partial nephrectomy. A total of 311 patients who underwent partial nephrectomy at Tokyo Women's Medical University Hospital, Tokyo, Japan, between January 2004 and July 2011 with sufficient kidney functional data participated in the study. Patients with pre-existing chronic kidney disease (group1: 78 patients) were defined as those with estimated glomerular filtration rate under 60 mL/min/m(2) before partial nephrectomy. Patients with de novo chronic kidney disease (group 2: 49) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) before surgery and who developed estimated glomerular filtration rate under 60 mL/min/m(2) 3 months after partial nephrectomy. Normal patients (group 3: 184) were defined as those with estimated glomerular filtration rate over 60 mL/min/m(2) both before and after partial nephrectomy. Group 1 was associated with older age and higher comorbidity, including hypertension and diabetes mellitus, compared with other groups. R.E.N.A.L. score was not significantly different between the groups. Although the percent change of estimated glomerular filtration rate between the preoperative period and 3 months after partial nephrectomy in group 2 was significantly decreased compared with that in other groups (group 1: -6.8%, group 2: -18%, group 3: -7.3%), the renal functional recovery between 3 and 12 months after partial nephrectomy in group 2 was better than that in other groups (group 1: -0.5%, group 2: 5.6%, group 3: -0.4%). Patients with de novo chronic kidney disease had better kidney functional recovery than the other two groups, which might suggest that they were surgically assaulted and developed chronic kidney disease in the early postoperative period, and were essentially different from those with pre-existing chronic kidney

  8. Health Literacy of Living Kidney Donors and Kidney Transplant Recipients

    Science.gov (United States)

    Dageforde, Leigh Anne; Petersen, Alec W.; Feurer, Irene D.; Cavanaugh, Kerri L.; Harms, Kelly A.; Ehrenfeld, Jesse M.; Moore, Derek E.

    2015-01-01

    Background Health literacy (HL) may be a mediator for known socioeconomic and racial disparities in living kidney donation. Methods We evaluated the associations of patient and demographic characteristics with HL in living kidney donors (LD), living donor kidney transplant recipients (LDR), and deceased donor recipients (DDR) in a single center retrospective review of patients undergoing kidney donation or transplantation from September 2010 to July 2012. HL and demographic data were collected. HL was assessed via the Short Literacy Survey (SLS) comprising three self-reported screening questions scored using the 5-point Likert scale [low (3-8), moderate (9-14), high (15)]. Chi-square and logistic regression were used to test factors associated with lower HL. Results The sample included 360 adults (105 LD, 103 LDR, 152 DDR; 46±14 years; 70% white; 56% male; 14±3 years of education). HL scores were skewed (49% high, 41% moderate, 10% low). The distribution of HL categories differed significantly among groups (p=0.019). After controlling for age, race, gender, education and a race-education interaction term, DDR were more likely to have moderate or low HL than LDR (OR 1.911; 95%CI 1.096, 3.332; p=0.022) Conclusions Overall, living donors had high HL. The distribution of low, moderate and high HL differed significantly between LD, DDR and LDR. DDR had a higher likelihood of having low HL than LDR. Screening kidney transplant candidates and donors for lower HL may identify barriers to living donation. Future interventions addressing HL may be important to increase living donation and reduce disparities. PMID:24573114

  9. Origin and function of myofibroblasts in kidney fibrosis.

    Science.gov (United States)

    LeBleu, Valerie S; Taduri, Gangadhar; O'Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

    2013-08-01

    Myofibroblasts are associated with organ fibrosis, but their precise origin and functional role remain unknown. We used multiple genetically engineered mice to track, fate map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Through this comprehensive analysis, we identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts through proliferation. The nonproliferating myofibroblasts derive through differentiation from bone marrow (35%), the endothelial-to-mesenchymal transition program (10%) and the epithelial-to-mesenchymal transition program (5%). Specific deletion of Tgfbr2 in α-smooth muscle actin (αSMA)(+) cells revealed the importance of this pathway in the recruitment of myofibroblasts through differentiation. Using genetic mouse models and a fate-mapping strategy, we determined that vascular pericytes probably do not contribute to the emergence of myofibroblasts or fibrosis. Our data suggest that targeting diverse pathways is required to substantially inhibit the composite accumulation of myofibroblasts in kidney fibrosis.

  10. Study on radiation sickness and aging using the senescense accelerated mouse

    International Nuclear Information System (INIS)

    Kondo, Hisayoshi; Kishikawa, Masao; Iseki, Masachika

    1989-01-01

    We compared several statistical methods for dealing with the results from the step-down passive avoidance test using the senescense accelerated mouse, which is recently used to investigate aging. Testing the difference of step-down latency between the irradiated group and control group, we often obtained conflicting results from different statistical methods. Step-down latency does not obey a normal distribution, and includes censoring observations. Therefore, the log rank test, which is usually regarded as one of the statistical methods for life time analysis, seems more suitable than t-test or Wilcoxon's rank-sum test for comparing step-down latency. Namely, the log rank test treats cases which step down within 180 seconds as failures and cases which do not step down within 180 seconds as censored cases. (author)

  11. Cake kidney: a rare anomaly of renal fusion

    Directory of Open Access Journals (Sweden)

    Guilherme Lippi Ciantelli

    2012-06-01

    Full Text Available ABSTRACT The cake kidney is a rare congenital anomaly of the urinogenital tract that can be diagnosed at any age. Few more than 20 cases have been described in the literature. The authors describe in this article another case of this rare malformation. Key-words: kidney, congenital abnormalities, rare diseases.

  12. Diagnostic imaging of lymphoma of the kidney

    International Nuclear Information System (INIS)

    Grzesiakowska, U.; Smorczewska, M.; Huczynska-Szubert, E.

    2010-01-01

    Purpose. The aim of this paper is to discuss both the clinical and radiological signs and the diagnostic principles of lymphomatous infiltrations of the kidney. Materials and methods. The studied group consisted of 20 patients (9 women, 11 men) aged 18-79 years. The follows-up varied from 2 to 156 months. All patients underwent CT and ultrasound investigations, while only 1 patient had an MRI examination. In 7 cases surgical treatment was performed, while the remaining 13 patients received chemotherapy. One patient died, 12 are in remission and seven are under observation and considered cured. Results. The radiological signs of kidney lymphoma may be divided into groups: a) kidney enlargement, obliteration of the cortex-core differentiation and obliteration of the outline; b) heterogenous kidney structure with undefined hypodense fociand lack of enhancement after the administration of contrasting material; c) presence of a well-defined tumor within the renal pelvis and external infiltration of the kidney, d) infiltration of the kidney originating from the retroperitoneal space encompassing the organ from the outside. Conclusions. The radiological signs of lymphoma differ in the kidney and exhibit a characteristic set of features. Radiology results combined with clinical symptoms may suggest lymphoma in the kidney and thus advocate the necessity of pathological evaluation prior to surgical treatment. (authors)

  13. Tear drops of kidney: a historical overview of Polycystic Kidney Disease.

    Science.gov (United States)

    Balat, Ayse

    2016-02-01

    Polycystic kidneydisease (PKD) is one of the most common inheritedkidneydiseases causing end stage renal disease. Although it has been in existence with humanity, it was defined in 18th century. The most detailed observations on PKD have been written after the disease of Stephen Bathory, the King of Poland. He had fatigue and chest pain accompanied by unconsciousness within a few days after a hunting trip, and died within 9 days, at the age of 53 years in 1586. Surgeon Jan Zigulitz described the cysts in his kidneys as large like those of a bull, with an uneven and bumpy surface during the mummification. Based on available information, 347 years later, a group of physicians and historians in Krakow concluded that the probable cause of Kings death was PKD and uremia. Unfortunately, PKD did not attracted the interest of physicians until the 18th century. In late 18th century, Matthew Baillie noted that these vesicular cysts in kidney were different from hydatid cysts, and described them as "false hydatids of kidney". In 1888, Flix Lejars used the term of "polycystic kidney" for the first time, and stressed that these cysts were bilateral, and causing clinically identifiable symptoms. At the end of 19th century, the basic clinical signs, and genetic basis of the disease have been better defined. However, the inheritance pattern could only be understood long years later. In this study, the history of PKD, i.e., the tear drops (cysts) of kidney will try to be explained by the light of old and current knowledge.

  14. Increased circulating miR-21 levels are associated with kidney fibrosis.

    Directory of Open Access Journals (Sweden)

    François Glowacki

    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

  15. Reconstructive surgery in eight children with solitary kidneys

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens

    1989-01-01

    Within a 10-year period reconstructive urinary tract surgery has been carried out in eight children with solitary kidneys. The children were 0-5 years old. Six had unilateral renal agenesis and two had unilateral multicystic kidney. In five children ureteroneocystostomy was performed, in two of t...... months of age. Postoperatively, the renal function was subnormal (although improved) in two children; in six it was normal. The most important prognostic factors in solitary kidneys with urinary tract obstruction are infection and developmental injury.......Within a 10-year period reconstructive urinary tract surgery has been carried out in eight children with solitary kidneys. The children were 0-5 years old. Six had unilateral renal agenesis and two had unilateral multicystic kidney. In five children ureteroneocystostomy was performed, in two...

  16. Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses

    Directory of Open Access Journals (Sweden)

    Jenna M. Bartley

    2017-09-01

    Full Text Available Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu. Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection to explore the impact of flu infection, aging, and caloric restriction on the gut microbiome. Young, middle-aged, and aged caloric restricted (CR and ad lib fed (AL mice were examined after a sublethal flu infection. All mice lost 10–20% body weight and, as expected for these early time points, losses were similar at different ages and between diet groups. Cytokine and chemokine levels were also similar with the notable exception of IL-1α, which rose more than fivefold in aged AL mouse serum, while it remained unchanged in aged CR serum. Fecal microbiome phyla abundance profiles were similar in young, middle-aged, and aged AL mice at baseline and at 4 days post flu infection, while increases in Proteobacteria were evident at 7 days post flu infection in all three age groups. CR mice, compared to AL mice in each age group, had increased abundance of Proteobacteria and Verrucomicrobia at all time points. Interestingly, principal coordinate analysis determined that diet exerts a greater effect on the microbiome than age or flu infection. Percentage body weight loss correlated with the relative abundance of Proteobacteria regardless of age, suggesting flu pathogenicity is related to Proteobacteria abundance. Further, several microbial Operational Taxonomic Units from the Bacteroidetes phyla correlated with serum chemokine/cytokines regardless of both diet and age suggesting an interplay between flu-induced systemic inflammation and gut microbiota. These

  17. A spatially-averaged mathematical model of kidney branching morphogenesis

    KAUST Repository

    Zubkov, V.S.

    2015-08-01

    © 2015 Published by Elsevier Ltd. Kidney development is initiated by the outgrowth of an epithelial ureteric bud into a population of mesenchymal cells. Reciprocal morphogenetic responses between these two populations generate a highly branched epithelial ureteric tree with the mesenchyme differentiating into nephrons, the functional units of the kidney. While we understand some of the mechanisms involved, current knowledge fails to explain the variability of organ sizes and nephron endowment in mice and humans. Here we present a spatially-averaged mathematical model of kidney morphogenesis in which the growth of the two key populations is described by a system of time-dependant ordinary differential equations. We assume that branching is symmetric and is invoked when the number of epithelial cells per tip reaches a threshold value. This process continues until the number of mesenchymal cells falls below a critical value that triggers cessation of branching. The mathematical model and its predictions are validated against experimentally quantified C57Bl6 mouse embryonic kidneys. Numerical simulations are performed to determine how the final number of branches changes as key system parameters are varied (such as the growth rate of tip cells, mesenchyme cells, or component cell population exit rate). Our results predict that the developing kidney responds differently to loss of cap and tip cells. They also indicate that the final number of kidney branches is less sensitive to changes in the growth rate of the ureteric tip cells than to changes in the growth rate of the mesenchymal cells. By inference, increasing the growth rate of mesenchymal cells should maximise branch number. Our model also provides a framework for predicting the branching outcome when ureteric tip or mesenchyme cells change behaviour in response to different genetic or environmental developmental stresses.

  18. A spatially-averaged mathematical model of kidney branching morphogenesis

    KAUST Repository

    Zubkov, V.S.; Combes, A.N.; Short, K.M.; Lefevre, J.; Hamilton, N.A.; Smyth, I.M.; Little, M.H.; Byrne, H.M.

    2015-01-01

    © 2015 Published by Elsevier Ltd. Kidney development is initiated by the outgrowth of an epithelial ureteric bud into a population of mesenchymal cells. Reciprocal morphogenetic responses between these two populations generate a highly branched epithelial ureteric tree with the mesenchyme differentiating into nephrons, the functional units of the kidney. While we understand some of the mechanisms involved, current knowledge fails to explain the variability of organ sizes and nephron endowment in mice and humans. Here we present a spatially-averaged mathematical model of kidney morphogenesis in which the growth of the two key populations is described by a system of time-dependant ordinary differential equations. We assume that branching is symmetric and is invoked when the number of epithelial cells per tip reaches a threshold value. This process continues until the number of mesenchymal cells falls below a critical value that triggers cessation of branching. The mathematical model and its predictions are validated against experimentally quantified C57Bl6 mouse embryonic kidneys. Numerical simulations are performed to determine how the final number of branches changes as key system parameters are varied (such as the growth rate of tip cells, mesenchyme cells, or component cell population exit rate). Our results predict that the developing kidney responds differently to loss of cap and tip cells. They also indicate that the final number of kidney branches is less sensitive to changes in the growth rate of the ureteric tip cells than to changes in the growth rate of the mesenchymal cells. By inference, increasing the growth rate of mesenchymal cells should maximise branch number. Our model also provides a framework for predicting the branching outcome when ureteric tip or mesenchyme cells change behaviour in response to different genetic or environmental developmental stresses.

  19. The role of renal proximal tubule P450 enzymes in chloroform-induced nephrotoxicity: Utility of renal specific P450 reductase knockout mouse models

    International Nuclear Information System (INIS)

    Liu, Senyan; Yao, Yunyi; Lu, Shijun; Aldous, Kenneth; Ding, Xinxin; Mei, Changlin; Gu, Jun

    2013-01-01

    The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity with the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200 mg/kg. Blood, liver and kidney samples were obtained at 24 h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity. - Highlights: • New mouse models were developed with varying P450 activities in the proximal tubule. • These mouse models were treated with chloroform, a nephrotoxicant. • Studies showed the importance of local P450s in chloroform-induced nephrotoxicity

  20. Urinary metabonomics elucidate the therapeutic mechanism of Orthosiphon stamineus in mouse crystal-induced kidney injury.

    Science.gov (United States)

    Gao, Songyan; Chen, Wei; Peng, Zhongjiang; Li, Na; Su, Li; Lv, Diya; Li, Ling; Lin, Qishan; Dong, Xin; Guo, Zhiyong; Lou, Ziyang

    2015-05-26

    Orthosiphon stamineus (OS), a traditional Chinese herb, is often used for promoting urination and treating nephrolithiasis. Urolithiasis is a major worldwide public health burden due to its high incidence of recurrence and damage to renal function. However, the etiology for urolithiasis is not well understood. Metabonomics, the systematic study of small molecule metabolites present in biological samples, has become a valid and powerful tool for understanding disease phenotypes. In this study, a urinary metabolic profiling analysis was performed in a mouse model of renal calcium oxalate crystal deposition to identify potential biomarkers for crystal-induced renal damage and the anti-crystal mechanism of OS. Thirty six mice were randomly divided into six groups including Saline, Crystal, Cystone and OS at dosages of 0.5g/kg, 1g/kg, and 2g/kg. A metabonomics approach using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was developed to perform the urinary metabolic profiling analysis. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were utilized to identify differences between the metabolic profiles of mice in the saline control group and crystal group. Using partial least squares-discriminant analysis, 30 metabolites were identified as potential biomarkers of crystal-induced renal damage. Most of them were primarily involved in amino acid metabolism, taurine and hypotaurine metabolism, purine metabolism, and the citrate cycle (TCA). After the treatment with OS, the levels of 20 biomarkers had returned to the levels of the control samples. Our results suggest that OS has a protective effect for mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways primarily involving amino acid, energy and choline metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Kidney cancer in Lebanon: a specific histological distribution?

    Science.gov (United States)

    Khafaja, Sarah; Kourie, Hampig Raphael; Matar, Dany; Sader-Ghorra, Claude; Kattan, Joseph

    2015-01-01

    Kidney cancer is the third most frequent urologic cancer in Lebanon after prostate and bladder cancer, accounting for 1.5% of all diagnosed cancers. In this paper, we report the histologic characteristics and distribution of kidney cancer, never described in Lebanon or the Middle East. Pathology results of operated kidney cancer were collected during a two year period (2010-2011) from two different Lebanese hospitals (Hotel-Dieu de France University Hospital and Saint Joseph Hospital). A total of 124 reports were reviewed and analyzed according to WHO classification of 2009. The 124 patients diagnosed with kidney cancer had a median age of 62.4 [18-86], 75% being men and 25% women. Some 71 % of the lesions were renal cell carcinoma (RCC), 25.8% had a urothelial histology, 1.6% were lymphomas and 1.6% were metastases to the kidney. Patients having RCC had a median age of 60.3 [18-85], 77.3% were men and 22.7% women. Of the RCCs, 59.1% were clear cell carcinoma, 22.7% papillary, 11.4% chromophobic, 3.4% rom the collecting ducts of Bellini and 3.4% were not otherwise classified. Histological distribution of Lebanese kidney cancer seems unusual when compared to the literature. The percentage of urothelial renal pelvis tumors is strikingly high. Moreover, clear cell carcinoma accounts for only 59.1% of RCCS in contrast to the 75% described elsewhere, while papillary carcinoma represents more than 22.7% compared to 10%.

  2. Rhythmic expression of Nocturnin mRNA in multiple tissues of the mouse

    Directory of Open Access Journals (Sweden)

    Green Carla B

    2001-05-01

    Full Text Available Abstract Background Nocturnin was originally identified by differential display as a circadian clock regulated gene with high expression at night in photoreceptors of the African clawed frog, Xenopus laevis. Although encoding a novel protein, the nocturnin cDNA had strong sequence similarity with a C-terminal domain of the yeast transcription factor CCR4, and with mouse and human ESTs. Since its original identification others have cloned mouse and human homologues of nocturnin/CCR4, and we have cloned a full-length cDNA from mouse retina, along with partial cDNAs from human, cow and chicken. The goal of this study was to determine the temporal pattern of nocturnin mRNA expression in multiple tissues of the mouse. Results cDNA sequence analysis revealed a high degree of conservation among vertebrate nocturnin/CCR4 homologues along with a possible homologue in Drosophila. Northern analysis of mRNA in C3H/He and C57/Bl6 mice revealed that the mNoc gene is expressed in a broad range of tissues, with greatest abundance in liver, kidney and testis. mNoc is also expressed in multiple brain regions including suprachiasmatic nucleus and pineal gland. Furthermore, mNoc exhibits circadian rhythmicity of mRNA abundance with peak levels at the time of light offset in the retina, spleen, heart, kidney and liver. Conclusion The widespread expression and rhythmicity of mNoc mRNA parallels the widespread expression of other circadian clock genes in mammalian tissues, and suggests that nocturnin plays an important role in clock function or as a circadian clock effector.

  3. Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging.

    Science.gov (United States)

    Wang, Feng; Jiang, Rosie; Takahashi, Keiko; Gore, John; Harris, Raymond C; Takahashi, Takamune; Quarles, C Chad

    2014-11-01

    The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T1-weighted, T2-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T1 and T2 weighted images were collected in UUO mice on day 0 (~3h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (prenal cortical and medullary atrophy, cortical-medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Distinct distribution of specific members of protein 4.1 genefamily in the mouse nephron

    Energy Technology Data Exchange (ETDEWEB)

    Ramez, Mohamed; Blot-Chabaud, Marcel; Cluzeaud, Francoise; Chanan, Sumita; Patterson, Michael; Walensky, Loren D.; Marfatia, Shirin; Baines, Anthony J.; Chasis, Joel A.; Conboy, John G.; Mohandas, Narla; Gascard, Philippe

    2002-12-11

    Background: Protein 4.1 is an adapter protein which linksthe actin cytoskeleton to various transmembrane proteins. 4.1 proteinsare encoded by four homologous genes, 4.1R, 4.1G, 4.1N, and 4.1B, whichundergo complex alternative splicing. Here we performed a detailedcharacterization of the expression of specific 4.1 proteins in the mousenephron. Methods: Distribution of renal 4.1 proteins was investigated bystaining of paraformaldehyde fixed mouse kidney sections with antibodieshighly specific for each 4.1 protein. Major 4.1 splice forms, amplifiedfrom mouse kidney marathon cDNA, were expressed in transfected COS-7cells in order to assign species of known exon composition to proteinsdetected in kidney. Results: A 105kDa4.1R splice form, initiating atATG-2 translation initiation site and lacking exon 16, but including exon17B, was restricted to thick ascending limb of Henle's loop. A 95kDa 4.1Nspliceform,lacking exons 15 and 17D, was expressed in either descendingor ascending thin limb of Henle'sloop, distal convoluted tubule and allregions of the collecting duct system. A major 108kDa 4.1B spliceform,initiating at a newly characterized ATG translation initiation site, andlacking exons 15, 17B, and 21, was present only in Bowman's capsule andproximal convoluted tubule (PCT). There was no expression of 4.1G inkidney. Conclusion: Distinct distribution of 4.1 proteins along thenephron suggests their involvement in targeting of selected transmembraneproteins in kidney epithelium andtherefore in regulation of specifickidney functions.

  5. Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors

    Directory of Open Access Journals (Sweden)

    Dabora Sandra L

    2010-02-01

    Full Text Available Abstract Background Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor disorder characterized by the growth of hamartomas in various organs including the kidney, brain, skin, lungs, and heart. Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC; however, tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment. Mouse models of TSC2 related tumors are useful for evaluating new approaches to drug therapy for TSC. Methods In cohorts of Tsc2+/- mice, we compared kidney cystadenoma severity in A/J and C57BL/6 mouse strains at both 9 and 12 months of age. We also investigated age related kidney tumor progression and compared three different rapamycin treatment schedules in cohorts of A/J Tsc2+/- mice. In addition, we used nude mice bearing Tsc2-/- subcutaneous tumors to evaluate the therapeutic utility of sunitinib, bevacizumab, vincristine, and asparaginase. Results TSC related kidney disease severity is 5-10 fold higher in A/J Tsc2+/- mice compared with C57BL/6 Tsc2+/- mice. Similar to kidney angiomyolipomas associated with TSC, the severity of kidney cystadenomas increases with age in A/J Tsc2+/- mice. When rapamycin dosing schedules were compared in A/J Tsc2+/- cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks. In the Tsc2-/- subcutaneous tumor mouse model, vincristine is not effective, but angiogenesis inhibitors (sunitinib and bevacizumab and asparaginase are effective as single agents. However, these drugs are not as effective as rapamycin in that they increased median survival only by 24-27%, while rapamycin increased median survival by 173%. Conclusions Our results indicate that the A/J Tsc2+/- mouse model is an improved, higher through-put mouse model for future TSC

  6. Donor-estimated GFR as an appropriate criterion for allocation of ECD kidneys into single or dual kidney transplantation.

    Science.gov (United States)

    Snanoudj, R; Rabant, M; Timsit, M O; Karras, A; Savoye, E; Tricot, L; Loupy, A; Hiesse, C; Zuber, J; Kreis, H; Martinez, F; Thervet, E; Méjean, A; Lebret, T; Legendre, C; Delahousse, M

    2009-11-01

    It has been suggested that dual kidney transplantation (DKT) improves outcomes for expanded criteria donor (ECD) kidneys. However, no criteria for allocation to single or dual transplantation have been assessed prospectively. The strategy of DKT remains underused and potentially eligible kidneys are frequently discarded. We prospectively compared 81 DKT and 70 single kidney transplant (SKT) receiving grafts from ECD donors aged >65 years, allocated according to donor estimated glomerular filtration rate (eGFR): DKT if eGFR between 30 and 60 mL/min, SKT if eGFR greater than 60 mL/min. Patient and graft survival were similar in the two groups. In the DKT group, 13/81 patients lost one of their two kidneys due to hemorrhage, arterial or venous thrombosis. Mean eGFR at month 12 was similar in the DKT and SKT groups (47.8 mL/min and 46.4 mL/min, respectively). Simulated allocation of kidneys according to criteria based on day 0 donor parameters such as those described by Remuzzi et al., Andres et al. and UNOS, did not indicate an improvement in 12-month eGFR compared to our allocation based on donor eGFR.

  7. Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of homing pigeons in Beijing, China.

    Science.gov (United States)

    Cui, Jia; Wu, Bin; Halbrook, Richard S; Zang, Shuying

    2013-12-01

    Biomonitoring provides direct evidence of the bioavailability and accumulation of toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year old homing pigeons collected from the Haidian District of Beijing during 2011 were necropsied and concentrations of cadmium, lead, and mercury were measured in liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the margins of the lungs was observed in 98 % of the pigeons. There were no significant differences in metal concentrations as a function of gender. Cadmium concentrations in all tissues and Pb concentrations in the lung tissues were significantly greater in 9-10+ year old pigeons compared to other age groups indicating that Cd and Pb were bioavailable. Mercury concentrations were not significantly different among age groups. Cadmium concentrations in kidney and lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations of Cd reported in pigeons from another high traffic urban area and most wild avian species from Korea suggesting that Cd in this region of Beijing may be of concern. Homing pigeons provide valuable exposure and bioaccumulation data not readily available from air monitoring alone, thus providing information regarding potential health effects in wildlife and humans in urban areas. As environmental quality standards are implemented in China, homing pigeons will serve as a valuable bio-monitor of the efficacy of these actions.

  8. Temperature effects on hospital admissions for kidney morbidity in Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yu-Kai [Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115 (United States); Wang, Yu-Chun [Department of Bioenvironmental Engineering, College of Engineering, Chung Yuan Christian University, 200 Chung-Pei Road, Chung Li 320, Taiwan (China); Research Center for Environmental Risk Management, Chung Yuan Christian University, 200 Chung-Pei Road, Chung Li 320, Taiwan (China); Ho, Tsung-Jung [The Division of Chinese Medicine, China Medical University Beigang Hospital, Taiwan (China); School Of Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Xueshi Road, Taichung City 404, Taiwan (China); Lu, Chensheng, E-mail: cslu@hsph.harvard.edu [Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115 (United States)

    2013-01-15

    Objective: This study aimed to associate hospital admissions of kidney diseases with extreme temperature and prolonged heat/cold events in 7 regions of Taiwan. Methods: Age-specific (< 65 years, 65 + years and all ages) hospital admission records of nephritis, nephrotic syndrome, or nephrosis, in the form of electronic insurance reimbursement claims, were retrieved from Taiwan's National Health Insurance Research Database during the period of 2000–2008. The area–age-specific relative risk (RR) accounting for 8 days of lag for temperature on hospital admissions of kidney diseases were estimated using distributed lag non-linear models with the Poisson distribution controlling for extreme temperature events, levels of air pollutants (PM{sub 10}, O{sub 3}, and NO{sub 2}) and potential confounders. Results: We observed a V or J-shape association between daily average temperatures and the RR estimates for hospital admissions of kidney diseases in Taiwan. The lowest risk for hospital admissions of kidney diseases was found at around 25 °C, and risk increased as temperatures deviated from 25 °C. The pooled cumulative 8-day RR for all ages of population of the 7 study areas were 1.10 (95% confidence interval (CI): 1.01, 1.19) at 18 °C and 1.45 (95% CI: 1.27, 1.64) at 30 °C. High temperature has more profound influence on hospital admission of kidney diseases than low temperature. Temperature risks for hospital admissions were similar between younger (< 65 years) and elderly (65 + years) population. This study observed no significant effects of prolonged heat extremes on hospital admissions of kidney diseases. Conclusions: The heat effect for kidney morbidities leading to hospital admission was more significant than that of the cold temperature. This study did not find the age-dependent relative risks for temperature associating with hospital admissions of kidney diseases. - Highlights: ► V or J-shaped association was observed between daily temperatures and

  9. Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

    Science.gov (United States)

    Imai, Rika; Asai, Kanae; Hanai, Jun-ichi; Takenaka, Masaru

    2015-07-01

    Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

  10. Impact of vitamin D status and obesity on C-reactive protein in kidney-transplant patients

    DEFF Research Database (Denmark)

    Ewers, B.; Gasbjerg, A.; Zerahn, B.

    2008-01-01

    and Patients: Data were collected between December 2005 and April 2006 from 161 adult (aged >18 years) kidney-transplant patients (mean age, 53.1 years; SD, 11.5 years; females/males, 78/83), with a median kidney-graft age of 7.0 years and serum CRP levels :... was found. Fat mass correlated positively with CRP, suggesting that obesity may increase the risk of cardiovascular disease and chronic allograft rejection in kidney-transplant patients. (C) 2008 by the National Kidney Foundation, Inc Udgivelsesdato: 2008/5......Objective: We examined whether vitamin D status and obesity are associated with low-grade systemic inflammation, as assessed by serum concentrations of C-reactive protein (CRP) in an adult population of kidney-transplant patients. Design: This was a single-center, cross-sectional study. Setting...

  11. Dose-dependent effects of (anti)folate preinjection on 99mTc-radiofolate uptake in tumors and kidneys

    International Nuclear Information System (INIS)

    Mueller, Cristina; Schibli, Roger; Forrer, Flavio; Krenning, Eric P.; Jong, Marion de

    2007-01-01

    Introduction: The folate receptor (FR) is frequently overexpressed in tumors and can be targeted with folate-based (radio)pharmaceuticals. However, significant accumulation of radiofolates in FR-positive kidneys represents a drawback. We have shown that preadministration of the antifolate pemetrexed (PMX) significantly improved the tumor-to-kidney ratio of radiofolates in mice. The aim of this study was to investigate the dose dependence of these effects and whether the same results could be achieved with folic acid (FA) or 5-methyl-tetrahydrofolate (5-Me-THF). Methods: Biodistribution was assessed 4 h postinjection of the organometallic 99m Tc-picolylamine monoacetic acid folate in nude mice bearing FR-positive KB tumor xenografts. PMX (50-400 μg/mouse) was injected 1 h previous to radioactivity. The effects of FA and 5-Me-THF (0.5-50 μg/mouse) were investigated likewise. Tissues and organs were collected and counted for radioactivity and the values tabulated as percentage of injected dose per gram tissue (% ID/g). Results: PMX administration reduced renal retention ( 10% ID/g), while the tumor uptake (average 1.35%±0.40% ID/g vs. control: 1.79%±0.49% ID/g) was only slightly affected independent of the PMX dose. Replacement of PMX by FA or 5-Me-THF (50 μg/mouse) resulted in a significant renal blockade (<0.1% ID/g) but at the same time in an undesired reduction of tumor uptake (<0.2% ID/g). Conclusions: Selective reduction of radiofolate uptake in kidneys under retention of high tumor accumulation could be achieved in combination with PMX over a broad dose range but not with FA or 5-Me-THF

  12. Novel Omega-3 Fatty Acid Epoxygenase Metabolite Reduces Kidney Fibrosis

    Science.gov (United States)

    Sharma, Amit; Khan, Md. Abdul Hye; Levick, Scott P.; Lee, Kin Sing Stephen; Hammock, Bruce D.; Imig, John D.

    2016-01-01

    Cytochrome P450 (CYP) monooxygenases epoxidize the omega-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid into novel epoxydocosapentaenoic acids (EDPs) that have multiple biological actions. The present study determined the ability of the most abundant EDP regioisomer, 19,20-EDP to reduce kidney injury in an experimental unilateral ureteral obstruction (UUO) renal fibrosis mouse model. Mice with UUO developed kidney tubular injury and interstitial fibrosis. UUO mice had elevated kidney hydroxyproline content and five-times greater collagen positive fibrotic area than sham control mice. 19,20-EDP treatment to UUO mice for 10 days reduced renal fibrosis with a 40%–50% reduction in collagen positive area and hydroxyproline content. There was a six-fold increase in kidney α-smooth muscle actin (α-SMA) positive area in UUO mice compared to sham control mice, and 19,20-EDP treatment to UUO mice decreased α-SMA immunopositive area by 60%. UUO mice demonstrated renal epithelial-to-mesenchymal transition (EMT) with reduced expression of the epithelial marker E-cadherin and elevated expression of multiple mesenchymal markers (FSP-1, α-SMA, and desmin). Interestingly, 19,20-EDP treatment reduced renal EMT in UUO by decreasing mesenchymal and increasing epithelial marker expression. Overall, we demonstrate that a novel omega-3 fatty acid metabolite 19,20-EDP, prevents UUO-induced renal fibrosis in mice by reducing renal EMT. PMID:27213332

  13. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.

    Directory of Open Access Journals (Sweden)

    Shengchang Zhang

    Full Text Available INTRODUCTION: Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. MATERIALS AND METHODS: Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP-expressing ASCs, aminoguanidine (AG or phosphate-buffered saline (PBS. Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD and malondialdehyde (MDA. RESULTS: Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. CONCLUSIONS: These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

  14. Simple Kidney Cysts

    Science.gov (United States)

    ... Solitary Kidney Your Kidneys & How They Work Simple Kidney Cysts What are simple kidney cysts? Simple kidney cysts are abnormal, fluid-filled ... that form in the kidneys. What are the kidneys and what do they do? The kidneys are ...

  15. Pain Medicines and Kidney Damage

    Science.gov (United States)

    ... acute illnesses involving fluid loss or decreased fluid intake. Other patients in these reports had risk factors such as systemic lupus erythematosus, advanced age, chronic kidney disease, or recent heavy alcohol consumption. These cases involved a single dose in ...

  16. In Vivo Clonal Analysis Reveals Lineage-Restricted Progenitor Characteristics in Mammalian Kidney Development, Maintenance, and Regeneration

    Directory of Open Access Journals (Sweden)

    Yuval Rinkevich

    2014-05-01

    Full Text Available The mechanism and magnitude by which the mammalian kidney generates and maintains its proximal tubules, distal tubules, and collecting ducts remain controversial. Here, we use long-term in vivo genetic lineage tracing and clonal analysis of individual cells from kidneys undergoing development, maintenance, and regeneration. We show that the adult mammalian kidney undergoes continuous tubulogenesis via expansions of fate-restricted clones. Kidneys recovering from damage undergo tubulogenesis through expansions of clones with segment-specific borders, and renal spheres developing in vitro from individual cells maintain distinct, segment-specific fates. Analysis of mice derived by transfer of color-marked embryonic stem cells (ESCs into uncolored blastocysts demonstrates that nephrons are polyclonal, developing from expansions of singly fated clones. Finally, we show that adult renal clones are derived from Wnt-responsive precursors, and their tracing in vivo generates tubules that are segment specific. Collectively, these analyses demonstrate that fate-restricted precursors functioning as unipotent progenitors continuously maintain and self-preserve the mouse kidney throughout life.

  17. STIM1fl/fl Ksp-Cre Mouse has Impaired Renal Water Balance

    Directory of Open Access Journals (Sweden)

    Liudmila Cebotaru

    2016-06-01

    Full Text Available Background/AIM: STIM1 is as an essential component in store operated Ca2+ entry. However give the paucity of information on the role of STIM1 in kidney, the aim was to study the function of STIM1 in the medulla of the kidney. Methods: we crossed a Ksp-cre mouse with another mouse containing two loxP sites flanking Exon 6 of STIM1. The Ksp-cre mouse is based upon the Ksp-cadherin gene promoter which expresses cre recombinase in developing nephrons, collecting ducts (SD and thick ascending limbs (TAL of the loop of Henle. Results: The offspring of these mice are viable without gross morphological changes, however, we noticed that the STIM1 Ksp-cre knockout mice produced more urine compared to control. To examine this more carefully, we fed mice low (LP and high protein (HP diets respectively. When mice were fed HP diet STIM1 ko mice had significantly increased urinary volume and lower specific gravity compared to wt mice. In STIM1 ko mice fed HP diet urine creatinine and urea were significantly lower compared to wt mice fed HP diet, however the fractional excretion was the same. Conclusion: These data support the idea that STIM1 ko mice have impaired urinary concentrating ability when challenged with HP diet is most likely caused by impaired Ca2+-dependent signal transduction through the vasopressin receptor cascade.

  18. Evaluation of regenerative capacity after kidney ischemic/reperfustion injury using 99mTc-DMSA

    International Nuclear Information System (INIS)

    Kwak, W. J.; Kim, J. W.; Park, K. M.; Lee, S. W.; Ahn, B. C.; Lee, J. T.; Yoo, J. S.

    2007-01-01

    Acute renal failure can be caused by a reduced renal blood flow induced because of ischemic injury. The damaged kidney can be completely restored in structure and function. 99m Tc-DMSA binds to cortical tubules in kidney and its uptake has been suggested to indicate function of cortical mass. Herein, the generative capacity of kidney after bilateral or unilateral ischemia/reperfusion (I/R) injury was evaluated non-invasively by scintigraphic imaging. Three different animal models were used. One or both kidneys of mice were subjected ischemic for 30 min for unilateral or bilateral I/R model, respectively. In third model, one kidney was excised and the other kidney was subjected ischemic for 30 min to give nephrectomy model. At 1 hr, 1 d, 3 d, 1 w, 2 w, 3 w after reperfusion, 99m Tc-DMSA (27.7 MBq) was injected via tail vein. After 3 hr, the mice were scanned for 30 min with pinhole equipped gamma camera. The ratio of ROI counts of kidney to total counts was calculated. In unilateral I/R mouse, the 99m Tc-DMSA uptake of injured kidney was decreased continuously up to 3 w (13.9 to 7.7%), while uptake in normal kidney is slowly increased. In case of nephrectomy model, 99m Tc-DMSA uptake of injured kidney was rapidly restored within 1 w after I/R operation (8.5 to 30%). Bilateral model showed reduced 99m Tc-DMSA uptake at 1 d, but total uptake in both I/R kidney was also increase up to 30% after 1 w and the uptake was maintained up to 3 w. In unilateral model, the 99m Tc-DMSA uptake of injured kidney kept decreasing up to 3 w while normal kidney showed increased 99m Tc-DMSA uptake. The restoration of I/R kidney was not observed within 3 w. However, in case of animal models which have only I/R kidneys such as bilateral and nephrectomy models, the 99m Tc-DMSA uptake was restored within 1 w and the excised kidney size was also normal in contrast to much smaller I/R kidney of unilateral model

  19. Temperature effects on hospital admissions for kidney morbidity in Taiwan

    International Nuclear Information System (INIS)

    Lin, Yu-Kai; Wang, Yu-Chun; Ho, Tsung-Jung; Lu, Chensheng

    2013-01-01

    Objective: This study aimed to associate hospital admissions of kidney diseases with extreme temperature and prolonged heat/cold events in 7 regions of Taiwan. Methods: Age-specific ( 10 , O 3 , and NO 2 ) and potential confounders. Results: We observed a V or J-shape association between daily average temperatures and the RR estimates for hospital admissions of kidney diseases in Taiwan. The lowest risk for hospital admissions of kidney diseases was found at around 25 °C, and risk increased as temperatures deviated from 25 °C. The pooled cumulative 8-day RR for all ages of population of the 7 study areas were 1.10 (95% confidence interval (CI): 1.01, 1.19) at 18 °C and 1.45 (95% CI: 1.27, 1.64) at 30 °C. High temperature has more profound influence on hospital admission of kidney diseases than low temperature. Temperature risks for hospital admissions were similar between younger (< 65 years) and elderly (65 + years) population. This study observed no significant effects of prolonged heat extremes on hospital admissions of kidney diseases. Conclusions: The heat effect for kidney morbidities leading to hospital admission was more significant than that of the cold temperature. This study did not find the age-dependent relative risks for temperature associating with hospital admissions of kidney diseases. - Highlights: ► V or J-shaped association was observed between daily temperatures and hospital admissions for renal diseases in Taiwan. ► The pooled relative risks accounting for 8 days of lag for the 7 study areas were 1.1 at 18 °C and 1.46 at 30 °C. ► There is no difference of the relative risk estimates for hospital admissions between younger and elderly population. ► We found significant protective effects of hospital admissions for prolonged cold extremes, but not for heat extremes

  20. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiao [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Shetty, Sreerama [Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, TX 75708 (United States); Zhang, Ping [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Gao, Rong; Hu, Yuxin [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Wang, Shuxia [Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Li, Zhenyu [Division of Cardiovascular Medicine, University of Kentucky, Lexington, KY 40536 (United States); Fu, Jian, E-mail: jian.fu@uky.edu [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States)

    2014-06-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia.

  1. Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury

    International Nuclear Information System (INIS)

    Chen, Jiao; Shetty, Sreerama; Zhang, Ping; Gao, Rong; Hu, Yuxin; Wang, Shuxia; Li, Zhenyu; Fu, Jian

    2014-01-01

    The presence of endotoxin in blood can lead to acute kidney injury (AKI) and septic shock. Resolvins, the endogenous lipid mediators derived from docosahexaenoic acid, have been reported to exhibit potent anti-inflammatory action. Using a mouse model of lipopolysaccharide (LPS)-induced AKI, we investigated the effects of aspirin-triggered resolvin D1 (AT-RvD1) on inflammatory kidney injury. Administration of AT-RvD1 1 h after LPS challenge protected the mice from kidney injury as indicated by the measurements of blood urea nitrogen, serum creatinine, and morphological alterations associated with tubular damage. The protective effects were evidenced by decreased neutrophil infiltration in the kidney indicating reduction in inflammation. AT-RvD1 treatment restored kidney cell junction protein claudin-4 expression, which was otherwise reduced after LPS challenge. AT-RvD1 treatment inhibited endotoxin-induced NF-κB activation and suppressed LPS-induced ICAM-1 and VCAM-1 expression in the kidney. Moreover, AT-RvD1 treatment markedly decreased LPS-induced IL-6 level in the kidney and blocked IL-6-mediated signaling including STAT3 and ERK phosphorylation. Our findings demonstrate that AT-RvD1 is a potent anti-inflammatory mediator in LPS-induced kidney injury, and AT-RvD1 has therapeutic potential against AKI during endotoxemia

  2. Prion Protein Promotes Kidney Iron Uptake via Its Ferrireductase Activity*

    Science.gov (United States)

    Haldar, Swati; Tripathi, Ajai; Qian, Juan; Beserra, Amber; Suda, Srinivas; McElwee, Matthew; Turner, Jerrold; Hopfer, Ulrich; Singh, Neena

    2015-01-01

    Brain iron-dyshomeostasis is an important cause of neurotoxicity in prion disorders, a group of neurodegenerative conditions associated with the conversion of prion protein (PrPC) from its normal conformation to an aggregated, PrP-scrapie (PrPSc) isoform. Alteration of iron homeostasis is believed to result from impaired function of PrPC in neuronal iron uptake via its ferrireductase activity. However, unequivocal evidence supporting the ferrireductase activity of PrPC is lacking. Kidney provides a relevant model for this evaluation because PrPC is expressed in the kidney, and ∼370 μg of iron are reabsorbed daily from the glomerular filtrate by kidney proximal tubule cells (PT), requiring ferrireductase activity. Here, we report that PrPC promotes the uptake of transferrin (Tf) and non-Tf-bound iron (NTBI) by the kidney in vivo and mainly NTBI by PT cells in vitro. Thus, uptake of 59Fe administered by gastric gavage, intravenously, or intraperitoneally was significantly lower in PrP-knock-out (PrP−/−) mouse kidney relative to PrP+/+ controls. Selective in vivo radiolabeling of plasma NTBI with 59Fe revealed similar results. Expression of exogenous PrPC in immortalized PT cells showed localization on the plasma membrane and intracellular vesicles and increased transepithelial transport of 59Fe-NTBI and to a smaller extent 59Fe-Tf from the apical to the basolateral domain. Notably, the ferrireductase-deficient mutant of PrP (PrPΔ51–89) lacked this activity. Furthermore, excess NTBI and hemin caused aggregation of PrPC to a detergent-insoluble form, limiting iron uptake. Together, these observations suggest that PrPC promotes retrieval of iron from the glomerular filtrate via its ferrireductase activity and modulates kidney iron metabolism. PMID:25572394

  3. Kidney recipients experiences before during and after kidney transplantation

    DEFF Research Database (Denmark)

    Nielsen, Charlotte

    Background Kidney transplantation is considered to be the best treatment for terminal renal insufficiency. Kidney transplant patients report higher quality of life because they avoid regular dialysis treatment that causes side effects, complications, restrictions and limitations in their daily...... and after the kidney transplant, through outpatient visits and during possible hospitalization, which can occur due to complications or disease progression. Objective To explore the coherence of the kidney transplant process in order to explain the lived experiences of kidney recipients before, during...... and after kidney transplantation. Method Participant observation and semi-structured individual interviews was conducted with kidney recipients before, during and after kidney transplantation. Data analysis is inspired by Ricoeur's interpretation theory on three levels: Naive reading; structural analysis...

  4. Double versus single renal allografts from aged donors.

    Science.gov (United States)

    Andrés, A; Morales, J M; Herrero, J C; Praga, M; Morales, E; Hernández, E; Ortuño, T; Rodício, J L; Martínez, M A; Usera, G; Díaz, R; Polo, G; Aguirre, F; Leiva, O

    2000-05-27

    The age limit of the cadaver kidney donors is increasing in response to the growing demand for renal transplantation. Simultaneous double kidney transplantation (SDKT) with kidneys obtained from elderly adults has been proposed to increase the transplantation number and improve its results. However, if SDKT is performed when there are no clear indications, a negative effect could be produced on the total number of transplanted patients as both kidneys would be used for only one recipient. In December 1996 we designed a transplantation protocol to be able to extend the selection of cadaver kidney donors with normal serum creatinine levels without establishing any age limit. A pregraft renal biopsy was always performed to analyze the glomerulosclerosis (GE) percentage whenever the donors were 60 years of age or older. A SDKT was performed in a single recipient when the donor age was 75 years or older or when the donors between 60 and 74 years old had a GE rate of more than 15%. On the contrary, a single kidney transplantation was performed in two different recipients for kidneys from donors between 60 and 74 years of age with a GE rate of less than 15%. Kidneys having GE rates of more than 50% were discarded for transplantation. Donor kidneys from subjects younger than 60 years of age were always used for a single kidney transplantation. Based on the above mentioned protocol, from December 1996 to May 1998, 181 patients received a kidney transplantation in our hospital. These patients were divided into three groups: group I which included the SDKT recipients (n=21), group II or single kidney recipients from 60- to 74-year-old donors (n=40), and group III or recipients from actuarial patient survival (100, 95, and 98%, respectively) or graft survival rates (95, 90, and 93%, respectively). The 6-month serum creatinine levels were excellent in the three groups, although there were significant differences between groups I and II (1.6+/-0.3 vs. 1.9+/-0.6 mg/dl, P75 years

  5. Kidney Disease

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Kidney Disease KidsHealth / For Teens / Kidney Disease What's in ... Coping With Kidney Conditions Print What Do the Kidneys Do? You might never think much about some ...

  6. Healthy Kidneys (A Cup of Health with CDC)

    Centers for Disease Control (CDC) Podcasts

    2015-03-12

    Kidney disease is among the leading causes of death in the U.S. More than one in 10 people over the age of 20 are impacted by this condition, and most don’t know it. In this podcast, Nilka Rios Burrows discusses the risks for kidney disease.  Created: 3/12/2015 by MMWR.   Date Released: 3/12/2015.

  7. Pancreatic protective and hypoglycemic effects of Vitex agnus-castus L. fruit hydroalcoholic extract in D-galactose-induced aging mouse model

    OpenAIRE

    Ahangarpour, Akram; Oroojan, Ali Akbar; Khorsandi, Layasadat; Najimi, Seyedeh Asma

    2017-01-01

    D-galactose induces pancreatic disorder along with aging mouse model. Vitex agnus-castus (VAC) has potential pancreatic protective effect. Hence, this study was designed to evaluate the hypoglycemic and pancreas protective effects of VAC hydroalcoholic extract in D-galactose-induced aging female mice. In the present experimental study, 72 adult female Naval Medical Research Institute (NMRI) mice (weighing 30–35 g) were divided into 6 groups of control, VAC hydroalcoholic extract, D-galactose,...

  8. Progression of autosomal dominant kidney disease: measurement of the stage transitions of chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Christopher M Blanchette

    2015-04-01

    Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. Methods: This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000–2/28/2013 and ≥6 months of previous continuous enrollment (baseline within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. Results: ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. Conclusions: These results suggest that distribution of patients by age at transition

  9. Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK cells

    Directory of Open Access Journals (Sweden)

    Akira Marine

    2014-01-01

    Full Text Available Superoxide is widely regarded as the primary reactive oxygen species (ROS which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1α expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ, a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS inhibitor demonstrated that peroxynitrite (at low micromolar levels induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation.

  10. Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3beta?

    LENUS (Irish Health Repository)

    Carew, Rosemarie M.

    2010-07-06

    Abstract Background Male Irs2-\\/- mice develop fatal type 2 diabetes at 13-14 weeks. Defects in neuronal proliferation, pituitary development and photoreceptor cell survival manifest in Irs2-\\/- mice. We identify retarded renal growth in male and female Irs2-\\/- mice, independent of diabetes. Results Kidney size and kidney:body weight ratio were reduced by approximately 20% in Irs2-\\/- mice at postnatal day 5 and was maintained in maturity. Reduced glomerular number but similar glomerular density was detected in Irs2-\\/- kidney compared to wild-type, suggesting intact global kidney structure. Analysis of insulin signalling revealed renal-specific upregulation of PKBβ\\/Akt2, hyperphosphorylation of GSK3β and concomitant accumulation of β-catenin in Irs2-\\/- kidney. Despite this, no significant upregulation of β-catenin targets was detected. Kidney-specific increases in Yes-associated protein (YAP), a key driver of organ size were also detected in the absence of Irs2. YAP phosphorylation on its inhibitory site Ser127 was also increased, with no change in the levels of YAP-regulated genes, suggesting that overall YAP activity was not increased in Irs2-\\/- kidney. Conclusions In summary, deletion of Irs2 causes reduced kidney size early in mouse development. Compensatory mechanisms such as increased β-catenin and YAP levels failed to overcome this developmental defect. These data point to Irs2 as an important novel mediator of kidney size.

  11. Trends in kidney cancer among the elderly in Denmark, 1980-2012.

    Science.gov (United States)

    Azawi, Nessn H; Joergensen, Simon Moeller; Jensen, Niels Viggo; Clark, Peter E; Lund, Lars

    2016-01-01

    The purpose of this study is to elucidate incidence, mortality, survival, and prevalence of kidney cancer in elderly persons compared with younger persons in Denmark. Cancer of the kidney was defined as ICD-10 code DC 64. Data derived from the NORDCAN database with comparable data on cancer incidence, mortality, prevalence and relative survival in the Nordic countries, where the Danish data were delivered from the Danish Cancer Registry and the Danish Cause of Death Registry with follow-up for death or emigration until the end of 2013. The proportion of patients diagnosed with kidney cancer over the age of 70 years has decreased from 43% in 1980 to 32% in 2012 in men and remained almost constant in women, around 50%. Incidence rates were at least five times higher in men aged 70 years more but there was no particular trend with time. In men aged less than 70 years, the incidence rates started increasing around 2000. The incidence rates were lower in women but with a similar pattern as in men. Mortality rates remained stable over time in persons aged 70 years or more while they decreased with time in younger women. Both the one- and the five-year relative survival increased steadily over time for all age groups but the survival was lower for patients aged 70 years or more than for younger patients. The prevalence increased three times from 1559 patients being alive after kidney cancer in 1980 to 4713 in 2012. A challenge in managing kidney cancer in the elderly is to establish interdisciplinary collaborations between different specialties, such as surgeons, clinical oncologists, and geriatricians to be able to deliver the best possible care in the future.

  12. Nanoscale protein architecture of the kidney glomerular basement membrane

    Science.gov (United States)

    Suleiman, Hani; Zhang, Lei; Roth, Robyn; Heuser, John E; Miner, Jeffrey H; Shaw, Andrey S; Dani, Adish

    2013-01-01

    In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly oriented macromolecular organization. Our analysis also revealed disruptions in this GBM architecture in a mouse model of Alport syndrome. These results provide the first nanoscopic glimpse into the organization of a complex ECM. DOI: http://dx.doi.org/10.7554/eLife.01149.001 PMID:24137544

  13. Senescence-accelerated mouse prone 8 (SAMP8) as a model of age-related hearing loss.

    Science.gov (United States)

    Marie, Aurore; Larroze-Chicot, Philippe; Cosnier-Pucheu, Sylvie; Gonzalez-Gonzalez, Sergio

    2017-08-24

    Hearing loss is the most common form of sensory impairment in humans, affecting 5.3% worldwide population. In industrial countries, age-related hearing loss is a major health problem affecting one-third of individuals over 65years old. However, the physiological and molecular changes involved in this senescence process remain unclear. In this study, we determined the influence of age on auditory brainstem response (ABR) and the distortion product otoacoustic emissions (DPOAE) in the premature senescence mouse model SAMP8 for five months. We showed a progressive increase of ABR thresholds and a decrease of distortion product amplitude from 37days old in SAMP8 compared to CBA mice. The data we show here provide new knowledge in functional auditory changes during the senescence process and open up new opportunities for the development of new drugs involved in age-related hearing loss treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Percutaneous nephrolithotomy in patients with a solitary kidney

    Directory of Open Access Journals (Sweden)

    Tufan Süelözgen

    2014-12-01

    Full Text Available Material and method: The results of percutaneous nephrolithotomy applied to 716 patients in our clinic between January 2008 and January 2014 were retrospectively evaluated. Age, gender, urinary calculi size (mm2, urinary calculi localization, ESWL history, operation duration (min, fluoroscopy duration (sec, access type, reason of solitary kidney, hemoglobin drawdown (g/dl and operation success of the patients with a solitary kidney were recorded. The patients having no preoperative and postoperative non contrast abdominal tomography were excluded from the study. Results: Fifteen of nineteen patients (79% were men and 4 of them (21% were women. The average age of the patients was 42.52 ± 16.72 (14-72. Ten patients had anatomical solitary kidney and nine patients had physiological solitary kidney. In fact counter kidney was non functional in 9 patients (47% whereas there was agenesis in 2 (11% and outcome of nephrectomy in 8 (42% patients. In our study, presence of residual stone less than 4 mm at 1st month postoperative non contrast abdominal tomography was accepted as a successful result and accordingly our success rate was detected as 84%. Mean urinary calculi size was 405 ± 252.9 mm2; urinary calculi localization was pelvic, lower pole, upper-middle pole, middle-lower pole and staghorn in 11 (58%, 4 (21%, 1 (5%, 1 (5% and 1 (5% patients, respectively; previous ESWL history was 16%; operation duration was 55.47-± 28.1 min and fluoroscopy duration 131.10 ± 87.6 sec; access type was subcostal in 79%, supracostal in 10.5% and multiple in 10.5%; hemoglobin drawdown was 1.75 ± 0.97 mg/dl. Conclusions: PNL can be effectively and safely administered for the treatment of solitary kidney. In the treatment of large urinary calculi in patients with a solitary kidney, PNL has some advantages such as short surgery duration, less complication, acceptable hemoglobin drawdown and high success rates. According to our study, PNL operation in patients with a

  15. A new Cre driver mouse line, Tcf21/Pod1-Cre, targets metanephric mesenchyme.

    Directory of Open Access Journals (Sweden)

    Yoshiro Maezawa

    Full Text Available Conditional gene targeting in mice has provided great insight into the role of gene function in kidney development and disease. Although a number of Cre-driver mouse strains already exist for the kidney, development of additional strains with unique expression patterns is needed. Here we report the generation and validation of a Tcf21/Pod1-Cre driver strain that expresses Cre recombinase throughout the condensing and stromal mesenchyme of developing kidneys and in their derivatives including epithelial components of the nephron and interstitial cells. To test the efficiency of this line, we crossed it to mice transgenic for either loss or gain of function β-catenin conditional alleles. Mice with deletion of β-catenin from Tcf21-expressing cells are born with hypoplastic kidneys, hydroureters and hydronephrosis. By contrast, Tcf21-Cre driven gain of function for β-catenin in mice results in fused midline kidneys and hypoplastic kidneys. Finally, we report the first renal mesenchymal deletion of Patched1 (Ptch1, the receptor for sonic hedgehog (Shh, which results in renal cysts demonstrating a functional role of Shh signaling pathway in renal cystogensis. In summary, we report the generation and validation of a new Cre driver strain that provides robust excision in metanephric mesenchyme.

  16. Aberrant Smad3 phosphoisoforms in cyst-lining epithelial cells in the cpk mouse, a model of autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Hama, Taketsugu; Nakanishi, Koichi; Sato, Masashi; Mukaiyama, Hironobu; Togawa, Hiroko; Shima, Yuko; Miyajima, Masayasu; Nozu, Kandai; Nagao, Shizuko; Takahashi, Hisahide; Sako, Mayumi; Iijima, Kazumoto; Yoshikawa, Norishige; Suzuki, Hiroyuki

    2017-12-01

    Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-β/Smad3 signaling is involved; however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L), COOH-terminal regions (pSmad3C), and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in the TGF-β/Smad3 pathway are implicated in carcinomas. In this study, we confirmed mesenchymal features and examined Smad3 phosphoisoforms in the cpk mouse, a model of autosomal recessive PKD. Kidney sections were stained with antibodies against mesenchymal markers and domain-specific phospho-Smad3. TGF-β, pSmad3L, pSmad3C, JNK, cyclin-dependent kinase (CDK) 4, and c-Myc were evaluated by Western blotting. Cophosphorylation of pSmad3L/C was assessed by immunoprecipitation. α-Smooth muscle actin, which indicates mesenchymal features, was expressed higher in cpk mice. pSmad3L expression was increased in cpk mice and was predominantly localized in the nuclei of tubular epithelial cells in cysts; however, pSmad3C was equally expressed in both cpk and control mice. Levels of pSmad3L, JNK, CDK4, and c-Myc protein in nuclei were significantly higher in cpk mice than in controls. Immunoprecipitation showed that Smad3 was cophosphorylated (pSmad3L/C) in cpk mice. Smad3 knockout/ cpk double-mutant mice revealed amelioration of cpk abnormalities. These findings suggest that upregulating c-Myc through the JNK/CDK4-dependent pSmad3L pathway may be key to the pathophysiology in cpk mice. In conclusion, a qualitative rather than a quantitative abnormality of the TGF-β/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention. Copyright © 2017 the American Physiological Society.

  17. PGE2 receptor EP3 inhibits water reabsorption and contributes to polyuria and kidney injury in a streptozotocin-induced mouse model of diabetes.

    Science.gov (United States)

    Hassouneh, Ramzi; Nasrallah, Rania; Zimpelmann, Joe; Gutsol, Alex; Eckert, David; Ghossein, Jamie; Burns, Kevin D; Hébert, Richard L

    2016-06-01

    The first clinical manifestation of diabetes is polyuria. The prostaglandin E2 (PGE2) receptor EP3 antagonises arginine vasopressin (AVP)-mediated water reabsorption and its expression is increased in the diabetic kidney. The purpose of this work was to study the contribution of EP3 to diabetic polyuria and renal injury. Male Ep 3 (-/-) (also known as Ptger3 (-/-)) mice were treated with streptozotocin (STZ) to generate a mouse model of diabetes and renal function was evaluated after 12 weeks. Isolated collecting ducts (CDs) were microperfused to study the contribution of EP3 to AVP-mediated fluid reabsorption. Ep 3 (-/-)-STZ mice exhibited attenuated polyuria and increased urine osmolality compared with wild-type STZ (WT-STZ) mice, suggesting enhanced water reabsorption. Compared with WT-STZ mice, Ep 3 (-/-)-STZ mice also had increased protein expression of aquaporin-1, aquaporin-2, and urea transporter A1, and reduced urinary AVP excretion, but increased medullary V2 receptors. In vitro microperfusion studies indicated that Ep 3 (-/-) and WT-STZ CDs responded to AVP stimulation similarly to those of wild-type mice, with a 60% increase in fluid reabsorption. In WT non-injected and WT-STZ mice, EP3 activation with sulprostone (PGE2 analogue) abrogated AVP-mediated water reabsorption; this effect was absent in mice lacking EP3. A major finding of this work is that Ep 3 (-/-)-STZ mice showed blunted renal cyclooxygenase-2 protein expression, reduced renal hypertrophy, reduced hyperfiltration and reduced albuminuria, as well as diminished tubular dilation and nuclear cysts. Taken together, the data suggest that EP3 contributes to diabetic polyuria by inhibiting expression of aquaporins and that it promotes renal injury during diabetes. EP3 may prove to be a promising target for more selective management of diabetic kidney disease.

  18. Alleviation of senescence and epithelial-mesenchymal transition in aging kidney by short-term caloric restriction and caloric restriction mimetics via modulation of AMPK/mTOR signaling.

    Science.gov (United States)

    Dong, Dan; Cai, Guang-Yan; Ning, Yi-Chun; Wang, Jing-Chao; Lv, Yang; Hong, Quan; Cui, Shao-Yuan; Fu, Bo; Guo, Ya-Nan; Chen, Xiang-Mei

    2017-03-07

    Renal fibrosis contributes to declining renal function in the elderly. What is unclear however, is whether epithelial-mesenchymal transition (EMT) contributes to this age-related renal fibrosis. Here, we analyzed indicators of EMT during kidney aging and investigated the protective effects and mechanisms of short-term regimens of caloric restriction (CR) or caloric restriction mimetics (CRMs), including resveratrol and metformin. High glucose was used to induce premature senescence and EMT in human primary proximal tubular cells (PTCs) in vitro. To test the role of AMPK-mTOR signaling, siRNA was used to deplete AMPK. Cellular senescence and AMPK-mTOR signaling markers associated with EMT were detected. CR or CRMs treatment alleviated age-related EMT in aging kidneys, which was accompanied by activation of AMPK-mTOR signaling. High glucose induced premature senescence and EMT in PTCs in vitro, which was accompanied by down-regulation of AMPK/mTOR signaling. CRMs alleviated high glucose-induced senescence and EMT via stimulation of AMPK/mTOR signaling. Activation of AMPK/mTOR signaling protected PTCs from high glucose-induced EMT and cellular senescence. Short-term regimens of CR and CRMs alleviated age-related EMT via AMPK-mTOR signaling, suggesting a potential approach to reducing renal fibrosis during aging.

  19. Phosphorus Regulation in Chronic Kidney Disease.

    Science.gov (United States)

    Suki, Wadi N; Moore, Linda W

    2016-01-01

    Serum phosphorus levels stay relatively constant through the influence of multiple factors-such as parathyroid hormone, fibroblast growth factor 23, and vitamin D-on the kidney, bone, and digestive system. Whereas normal serum phosphorus ranges between 3 mg/dL to 4.5 mg/dL, large cross-sectional studies have shown that even people with normal kidney function are sometimes found to have levels ranging between 1.6 mg/dL and 6.2 mg/dL. While this may partially be due to diet and the factors mentioned above, total understanding of these atypical ranges of serum phosphorus remains uncertain. Risks for bone disease are high in people aged 50 and older, and this group comprises a large proportion of people who also have chronic kidney disease. Consuming diets low in calcium and high in phosphorus, especially foods with phosphate additives, further exacerbates bone turnover. Existing bone disease increases the risk for high serum phosphorus, and higher serum phosphorus has been associated with increased adverse events and cardiovascular-related mortality both in people with chronic kidney disease and in those with no evidence of disease. Once kidney function has deteriorated to end-stage disease (Stage 5), maintaining normal serum phosphorus requires dietary restrictions, phosphate-binding medications, and dialysis. Even so, normal serum phosphorus remains elusive in many patients with Stage 5 kidney disease, and researchers are testing novel targets that may inhibit intestinal transport of phosphorus to achieve better phosphate control. Protecting and monitoring bone health should also aid in controlling serum phosphorus as kidney disease advances.

  20. Kidney pain (image)

    Science.gov (United States)

    A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the size of sand or ... A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the ...

  1. High mortality in diabetic recipients of high KDPI deceased donor kidneys.

    Science.gov (United States)

    Pelletier, Ronald P; Pesavento, Todd E; Rajab, Amer; Henry, Mitchell L

    2016-08-01

    Deceased donor (DD) kidney quality is determined by calculating the Kidney Donor Profile Index (KDPI). Optimizing high KDPI (≥85%) DD transplant outcome is challenging. This retrospective study was performed to review our high KDPI DD transplant results to identify clinical practices that can improve future outcomes. We retrospectively calculated the KDPI for 895 DD kidney recipients transplanted between 1/2002 and 11/2013. Age, race, body mass index (BMI), retransplantation, gender, diabetes (DM), dialysis time, and preexisting coronary artery disease (CAD) (previous myocardial infarction (MI), coronary artery bypass (CABG), or stenting) were determined for all recipients. About 29.7% (266/895) of transplants were from donors with a KDPI ≥85%. By Cox regression older age, diabetes, female gender, and dialysis time >4 years correlated with shorter patient survival time. Diabetics with CAD who received a high KDPI donor kidney had a significantly increased risk of death (HR 4.33 (CI 1.82-10.30), P=.001) compared to low KDPI kidney recipients. The Kaplan-Meier survival curve for diabetic recipients of high KDPI kidneys was significantly worse if they had preexisting CAD (P<.001 by log-rank test). Patient survival using high KDPI donor kidneys may be improved by avoiding diabetic candidates with preexisting CAD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. [Kidney transplantation epidemiology in France].

    Science.gov (United States)

    Hiesse, Christian

    2013-11-01

    Kidney transplantation activity in France is among the most important worldwide: in 2011, 2976 transplants have been performed (47.5 per million population), and the number of patients living with a functional graft is estimated around 30,000, representing 44.7% of all patients (n = 67,270) treated for end-stage renal failure. However, the rate of preemptive kidney transplants remains very low, only 3.3% of incident patients starting renal replacement therapy. The analysis of demand showed a progressive increase in recent years, as demonstrated by the registration rate on the kidney transplantation waiting list, increasing by 5% yearly between 2006 and 2010, but with huge differences according to age categories and regional registration areas, reflecting discrepant appreciations in indications for kidney transplantation. The median waiting time between registration and transplantation increased progressively in recent years, reaching 22.3 months with considerable variations according to regional areas and transplantation teams. Kidney transplantation activity, while increasing continuously, is far to cover the rising demand, and inexorably patients accumulate on the waiting list (around 9000 patients were registered by January 2012). This situation is the consequence of insufficient organ procurement activity. The deceased organ procurement rate remained high: 1572 harvested donors in 2011 (24.1 per million population), but the proportion of older donors rose in recent years, to reach the rate of 26% of donors older than 65 years in 2011. The procurement activity of donors after cardiac arrest was reintroduced in 2006, but increased slowly: 65 transplants were performed in 2011 using kidney procured in non heart-beating donors. The living donor kidney transplantation activity has markedly increased recently: 302 living donor transplantations were performed in 2011, representing 10.1% of the kidney transplantations. Facing the predictable increase in the number of

  3. Residual kidney function after donor nephrectomy. Assessment by 99mTc-MAG3-Clearance

    International Nuclear Information System (INIS)

    Hamscho, N.; Doebert, N.; Menzel, C.; Berner, U.; Zaplatnikov, K.; Gruenwald, F.; Wilhelm, A.; Gossmann, J.; Scheuermann, E.H.

    2005-01-01

    Aim: We evaluated the long-term residual renal function after donor nephrectomy using 99m Tc-mercaptoacetyltriglycin (MAG3)-clearance. Donors, methods: Altogether 49 kidney donors were examined using 99m Tc-MAG3-clearance after nephrectomy for donation to a relative (m:f=11.38; age 55±27 years). The donors were examined 16±8 years postoperatively (1.5-26 years). 42 donors (86%) showed normal creatinine values, whereas the other seven (14%) exhibited slightly elevated levels. 20 donors were examined pre- and postoperatively and compared intraindividually. The kidney function was compared to the age adapted normal values of healthy persons with two kidneys (67-133% of age related mean). Results: After nephrectomy all donors showed a normal perfusion, good secretion, merely physiological intrarenal transit and a normal elimination from the kidneys. The 99m Tc-MAG3-clearance was 69±15% of the normal mean value of healthy carriers of two kidneys regardless of the gender. 20 donors with a preoperative examination showed a significantly reduced total renal function from 84±15% of the mean normal value preoperatively to 60±15% postoperatively (p 99m Tc-MAG3-clearance measured prior to nephrectomy and the clearance levels after nephrectomy. Also, no correlation between the preoperative 99m Tc-MAG3-clearance and the postoperative serum creatinine values could be observed. Althogether, 22% of the donors (11/49) developed arterial hypertension 10±8 years after donation (1-23 years). This corresponds to the normal age prevalence of hypertension in the carriers of two kidneys. Three donors suffered from arterial hypertension prior to the operation. Conclusion: Kidney donors with normal or slightly elevated creatinine values postoperatively show a 99m Tc-MAG3 clearance value of 69% of the mean value of healthy carriers of two kidneys. This may serve as a reference value for healthy carriers of one kidney. In our study we demonstrated a good compensation of the contralateral

  4. Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.

    Science.gov (United States)

    Huang, Yihung; Tilea, Anca; Gillespie, Brenda; Shahinian, Vahakn; Banerjee, Tanushree; Grubbs, Vanessa; Powe, Neil; Rios-Burrows, Nilka; Pavkov, Meda; Saran, Rajiv

    2017-08-01

    Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m 2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m 2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care. Copyright © 2017 by the American Society of Nephrology.

  5. Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.

    Science.gov (United States)

    Idowu, Jessica; Home, Trisha; Patel, Nisha; Magenheimer, Brenda; Tran, Pamela V; Maser, Robin L; Ward, Christopher J; Calvet, James P; Wallace, Darren P; Sharma, Madhulika

    2018-02-20

    Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the kidney and liver that ultimately leads to end-stage renal disease. Currently there is no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation and de-differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that the Notch pathway plays a critical role in PKD. Evaluation of protein expression of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that Notch pathway members, particularly Notch3, were consistently upregulated or activated in cyst-lining epithelial cells. Notch3 expression correlated with rapidly growing cysts and co-localized with the proliferation marker, PCNA. Importantly, Notch inhibition significantly decreased forskolin-induced Notch3 activation and proliferation of primary human ADPKD cells, and significantly reduced cyst formation and growth of human ADPKD cells cultured in collagen gels. Thus our data indicate that Notch3 is aberrantly activated and facilitates epithelial cell proliferation in PKD, and that inhibition of Notch signaling may prevent cyst formation and growth.

  6. Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance.

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2015-01-01

    To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus. A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3-2.1, Pkidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization. Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.

  7. Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice

    International Nuclear Information System (INIS)

    Schüler, Emil; Rudqvist, Nils; Parris, Toshima Z.; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

    2014-01-01

    Introduction: The kidneys are one of the main dose limiting organs in 177 Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from 177 Lu-octreotate exposure. Methods: Female Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq 177 Lu-octreotate. The animals were killed 24 h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes. Results: Distinct transcriptional responses were observed following 177 Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex. Conclusion: Specific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues

  8. Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

    Directory of Open Access Journals (Sweden)

    Michail S Lionakis

    Full Text Available Invasive candidiasis is the 4(th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo to Ccr1(high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+ and Ccr1(-/- donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

  9. Effects of Resveratrol on Daily Rhythms of Locomotor Activity and Body Temperature in Young and Aged Grey Mouse Lemurs

    Directory of Open Access Journals (Sweden)

    Fabien Pifferi

    2013-01-01

    Full Text Available In several species, resveratrol, a polyphenolic compound, activates sirtuin proteins implicated in the regulation of energy balance and biological clock processes. To demonstrate the effect of resveratrol on clock function in an aged primate, young and aged mouse lemurs (Microcebus murinus were studied over a 4-week dietary supplementation with resveratrol. Spontaneous locomotor activity and daily variations in body temperature were continuously recorded. Reduction in locomotor activity onset and changes in body temperature rhythm in resveratrol-supplemented aged animals suggest an improved synchronisation on the light-dark cycle. Resveratrol could be a good candidate to restore the circadian rhythms in the elderly.

  10. Molecular mechanisms of renal aging.

    Science.gov (United States)

    Schmitt, Roland; Melk, Anette

    2017-09-01

    Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons. Mechanistically, this has been linked to different processes, such as podocyte hypertrophy, glomerulosclerosis, tubular atrophy, and gradual microvascular rarefaction. Renal functional recovery after an episode of acute kidney injury is significantly worse in elderly patients. This decreased regenerative potential, which is a hallmark of the aging process, may be caused by cellular senescence. Accumulation of senescent cells could explain insufficient repair and functional loss, a view that has been strengthened by recent studies showing that removal of senescent cells results in attenuation of renal aging. Other potential mechanisms are alterations in autophagy as an important component of a disturbed renal stress response and functional differences in the inflammatory system. Promising therapeutic measures to counteract these age-related problems include mimetics of caloric restriction, pharmacologic renin-angiotensin-aldosterone system inhibition, and novel strategies of senotherapy with the goal of reducing the number of senescent cells to decrease aging-related disease in the kidney. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  11. Mercury localization in mouse kidney over time: autoradiography versus silver staining

    International Nuclear Information System (INIS)

    Rodier, P.M.; Kates, B.; Simons, R.

    1988-01-01

    Several methods of silver staining have been employed to localize mercury in tissue, under the assumption that the techniques represent total Hg, but recent reports have suggested that these stains are specific for a limited fraction of the Hg present in some samples. Magos et al. hypothesized that the stains actually vary with inorganic mercury content. The purpose of the present study was to compare localization by radiolabeling to localization by one silver stain, the photoemulsion histochemical technique, in tissues prepared to contain a range of levels of total Hg and a range of levels of inorganic Hg. Mice dosed with 8 mg Hg/kg as MeHg were killed 24 hr, 1 week, or 2 weeks after exposure, to allow a decrease in total Hg and an increase in the proportion of demethylated Hg over time. Mice dosed with 4 mg Hg/kg as HgCl 2 provided samples in which all the Hg present was in the inorganic form. Atomic absorption of kidneys of mice dosed with MeHg showed that total Hg fell from 55 micrograms/g to 39 to 25 over 2 weeks, while the inorganic fraction climbed from about 2 to 27 to 35%. Grain counts from autoradiographs of 203 Hg-labeled sections correlated with total Hg content at +0.88, but silver staining was correlated with inorganic Hg content, appearing only at late termination times in MeHg-exposed animals, but soon after dosing in mice exposed to inorganic Hg. The photoemulsion histochemical technique revealed a substance strictly localized in the proximal tubules, while autoradiographs and grain counts showed total Hg to be present throughout the kidney tissue. These results support the contention that silver stains are selective for inorganic Hg

  12. Chronic Kidney Diseases

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Chronic Kidney Diseases KidsHealth / For Kids / Chronic Kidney Diseases What's ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  13. Novel systems biology insights using antifibrotic approaches for diabetic kidney disease

    KAUST Repository

    RamachandraRao, Satish Posettihalli; Talwar, Priti; Ravasi, Timothy; Sharma, Kumar

    2010-01-01

    Although several interventions slow the progression of diabetic nephropathy, current therapies do not halt progression completely. Recent preclinical studies suggested that pirfenidone (PFD) prevents fibrosis in various diseases, but the mechanisms underlying its antifibrotic action are incompletely understood. To explore the therapeutic potential of PFD, we studied the PFD-treated db/db diabetic mouse kidney by liquid chromatography-tandem mass spectrometry proteomics. A total of 21 proteins unique to PFD-treated diabetic kidneys were identified. Analysis of gene ontology and protein-protein interactions of these proteins suggested that PFD may regulate RNA translation. Two key proteins involved in mRNA translation initiation and elongation were further evaluated and found to be regulated by PFD at the level of phosphorylation. In conclusion, insights from combining proteomics and bioinformatics improve the likelihood of rapid advancement of novel clinical therapies focused on reducing inflammation and fibrosis for diabetic complications. © 2010 Expert Reviews Ltd.

  14. Advanced glycation end-products (AGEs accumulation in skin: relations with chronic kidney disease-mineral and bone disorder

    Directory of Open Access Journals (Sweden)

    Renata de Almeida França

    2017-08-01

    Full Text Available Abstract Introduction: Chronic kidney disease (CKD is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD and bone mineral disorder (CKD-BMD. Uremic toxins, as advanced glycation end products (AGEs, are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. Objective: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF and its relations with CVD and BMD parameters in HD patients. Methods: Twenty prevalent HD patients (HD group and healthy subjects (Control group, n = 24, performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH, transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. Results: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Conclusion: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

  15. Environmental cadmium and zinc concentrations in liver and kidney of European hare from different Serbian regions

    Directory of Open Access Journals (Sweden)

    Petrović Zoran I.

    2013-01-01

    Full Text Available The hares assayed (n=84 were divided into five age groups: 3-6; 12; 12-24; 24-36 and 36 + months. Between all sampling regions (11 significant differences of Cd levels were found in kidney and liver (p value, p=0.001 and 0.007, respectively . Significant statistical differences (p=0.001 are registered between Cd content in kidney and liver of hares among all represented age groups. Looking at all investigated hare samples, moderately higher concentrations of Zn were found in liver (median value: 25.4 mg/kg w.w compared to those in kidney (21.4 mg/kg. These differences were statistically significant (p=0.001. Zinc concentrations in liver, between all age groups, did not differ significantly (p=0.512 but in kidney these differences were statistically significant (p=0,001. Significant differences between Zn concentrations in liver in comparison to kidney (pairwise differences were found within every single age group with exception of the oldest (36+ . Strong statistically significant correlations (Ps- Pearson's correlation between Cd concentrations in kidney and liver were registered in three groups older than 12 months (Ps=0.81, p=0.001; 0.78, p=0.001; and 0.79, p=0.001, respectively. Negative correlation between Zn and Cd concentrations were found in liver samples within the age group of 12 months (Ps= -0,67, p=0.004.

  16. Filtration Markers, Cardiovascular Disease, Mortality, and Kidney Outcomes in Stable Kidney Transplant Recipients: The FAVORIT Trial.

    Science.gov (United States)

    Foster, M C; Weiner, D E; Bostom, A G; Carpenter, M A; Inker, L A; Jarolim, P; Joseph, A A; Kusek, J W; Pesavento, T; Pfeffer, M A; Rao, M; Solomon, S D; Levey, A S

    2017-09-01

    Cystatin C and beta-2-microglobulin (B2M) are filtration markers associated with adverse outcomes in nontransplant populations, sometimes with stronger associations than for creatinine. We evaluated associations of estimated glomerular filtration rate from cystatin C (eGFR cys ), B2M (eGFR B 2M ), and creatinine (eGFR cr ) with cardiovascular outcomes, mortality, and kidney failure in stable kidney transplant recipients using a case-cohort study nested within the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial. A random subcohort was selected (N = 508; mean age 51.6 years, median transplant vintage 4 years, 38% women, 23.6% nonwhite race) with enrichment for cardiovascular events (N = 306; 54 within the subcohort), mortality (N = 208; 68 within the subcohort), and kidney failure (N = 208; 52 within the subcohort). Mean eGFR cr , eGFR cys , and eGFR B 2M were 46.0, 43.8, and 48.8 mL/min/1.73m 2 , respectively. After multivariable adjustment, hazard ratios for eGFR cys and eGFR B 2M mortality; and 9.49 (4.28-21.00) and 15.53 (6.99-34.51; both p mortality, and kidney failure in stable kidney transplant recipients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Clinical use of estimated glomerular filtration rate for evaluation of kidney function

    DEFF Research Database (Denmark)

    Broberg, Bo; Lindhardt, Morten; Rossing, Peter

    2013-01-01

    is a significant predictor for cardiovascular disease and may along with classical cardiovascular risk factors add useful information to risk estimation. Several cautions need to be taken into account, e.g. rapid changes in kidney function, dialysis, high age, obesity, underweight and diverging and unanticipated......Estimating glomerular filtration rate by the Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration formulas gives a reasonable estimate of kidney function for e.g. classification of chronic kidney disease. Additionally the estimated glomerular filtration rate...

  18. The Impact of Chronic Obstructive Pulmonary Disease and Smoking on Mortality and Kidney Transplantation in End-Stage Kidney Disease.

    LENUS (Irish Health Repository)

    Kent, Brian D

    2012-09-07

    Background: Chronic obstructive pulmonary disease (COPD) and tobacco use are leading causes of morbidity and mortality. The prevalence and clinical impact of COPD on mortality and kidney transplantation among patients who begin dialysis therapy is unclear. Methods: We explored the clinical impact of COPD and continued tobacco use on overall mortality and kidney transplantation in a national cohort study of US dialysis patients. National data on all dialysis patients (n = 769,984), incident between May 1995 and December 2004 and followed until October 31, 2006, were analyzed from the United States Renal Data System. Prevalence and period trends were determined while multivariable Cox regression evaluated relative hazard ratios (RR) for death and kidney transplantation. Results: The prevalence of COPD was 7.5% overall and increased from 6.7 to 8.1% from 1995-2004. COPD correlated significantly with older age, cardiovascular conditions, cancer, malnutrition, poor functional status, and tobacco use. Adjusted mortality risks were significantly higher for patients with COPD (RR = 1.20, 95% CI 1.18-1.21), especially among current smokers (RR = 1.28, 95% CI 1.25-1.32), and varied inversely with advancing age. In contrast, the adjusted risks of kidney transplantation were significantly lower for patients with COPD (RR = 0.47, 95% CI 0.41-0.54, for smokers and RR = 0.54, 95% CI 0.50-0.58, for non-smokers) than without COPD [RR = 0.72, 95% CI 0.70-0.75, for smokers and RR = 1.00 for non-smokers (referent category)]. Conclusions: Patients with COPD who begin dialysis therapy in the US experience higher mortality and lower rates of kidney transplantation, outcomes that are far worse among current smokers.

  19. Kidney biopsy

    Science.gov (United States)

    ... the kidney (in rare cases, may require a blood transfusion) Bleeding into the muscle, which might cause soreness Infection (small risk) Alternative Names Renal biopsy; Biopsy - kidney Images Kidney anatomy ...

  20. Application of Hanging Drop Technique for Kidney Tissue Culture.

    Science.gov (United States)

    Wang, Shaohui; Wang, Ximing; Boone, Jasmine; Wie, Jin; Yip, Kay-Pong; Zhang, Jie; Wang, Lei; Liu, Ruisheng

    2017-01-01

    The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli. © 2017 The Author(s). Published by S. Karger AG, Basel.

  1. Application of Hanging Drop Technique for Kidney Tissue Culture

    Directory of Open Access Journals (Sweden)

    Shaohui Wang

    2017-05-01

    Full Text Available Background/Aims: The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. Methods: In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. Results: The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. Conclusions: We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli.

  2. An analysis of respiratory induced kidney motion on four-dimensional computed tomography and its implications for stereotactic kidney radiotherapy

    International Nuclear Information System (INIS)

    Siva, Shankar; Pham, Daniel; Gill, Suki; Bressel, Mathias; Dang, Kim; Devereux, Thomas; Kron, Tomas; Foroudi, Farshad

    2013-01-01

    Stereotactic ablative body radiotherapy (SABR) is an emerging treatment modality for primary renal cell carcinoma. To account for respiratory-induced target motion, an internal target volume (ITV) concept is often used in treatment planning of SABR. The purpose of this study is to assess patterns of kidney motion and investigate potential surrogates of kidney displacement with the view of ITV verification during treatment. Datasets from 71 consecutive patients with free breathing four-dimensional computed tomography (4DCT) planning scans were included in this study. The displacement of the left and right hemi-diaphragm, liver dome and abdominal wall were measured and tested for correlation with the displacement of the both kidneys and patient breathing frequency. Nine patients were excluded due to severe banding artifact. Of 62 evaluable patients, the median age was 68 years, with 41 male patients and 21 female patients. The mean (range) of the maximum, minimum and average breathing frequency throughout the 4DCTs were 20.1 (11–38), 15.1 (9–24) and 17.3 (9–27.5) breaths per minute, respectively. The mean (interquartile range) displacement of the left and right kidneys was 0.74 cm (0.45-0.98 cm) and 0.75 cm (0.49-0.97) respectively. The amplitude of liver-dome motion was correlated with right kidney displacement (r=0.52, p<0.001), but not with left kidney displacement (p=0.796). There was a statistically significant correlation between the magnitude of right kidney displacement and that of abdominal displacement (r=0.36, p=0.004), but not the left kidney (r=0.24, p=0.056). Hemi-diaphragm displacements were correlated with kidney displacements respectively, with a weaker correlation for the left kidney/left diaphragm (r=0.45, [95% CI 0.22 to 0.63], p=<0.001) than for the right kidney/right diaphragm (r=0.57, [95% CI 0.37 to 0.72], p=<0.001). For the majority of patients, maximal left and right kidney displacement is subcentimeter in magnitude. The magnitude of

  3. Estimation of Total Glomerular Number Using an Integrated Disector Method in Embryonic and Postnatal Kidneys

    Directory of Open Access Journals (Sweden)

    Michel G Arsenault

    2014-06-01

    Full Text Available Congenital Anomalies of the Kidney and Urinary Tract (CAKUT are a polymorphic group of clinical disorders comprising the major cause of renal failure in children. Included within CAKUT is a wide spectrum of developmental malformations ranging from renal agenesis, renal hypoplasia and renal dysplasia (maldifferentiation of renal tissue, each characterized by varying deficits in nephron number. First presented in the Brenner Hypothesis, low congenital nephron endowment is becoming recognized as an antecedent cause of adult-onset hypertension, a leading cause of coronary heart disease, stroke, and renal failure in North America. Genetic mouse models of impaired nephrogenesis and nephron endowment provide a critical framework for understanding the origins of human kidney disease. Current methods to quantitate nephron number include (i acid maceration (ii estimation of nephron number from a small number of tissue sections (iii imaging modalities such as MRI and (iv the gold standard physical disector/fractionator method. Despite its accuracy, the physical disector/fractionator method is rarely employed because it is labour-intensive, time-consuming and costly to perform. Consequently, less rigourous methods of nephron estimation are routinely employed by many laboratories. Here we present an updated, digitized version of the physical disector/fractionator method using free open source Fiji software, which we have termed the integrated disector method. This updated version of the gold standard modality accurately, rapidly and cost-effectively quantitates nephron number in embryonic and post-natal mouse kidneys, and can be easily adapted for stereological measurements in other organ systems.

  4. Radiological evaluation of nonvisualizing kidney on IVP

    International Nuclear Information System (INIS)

    Moon, J. H.; Sung, K. B.; Cho, O. K.; Hahm, C. K.

    1983-01-01

    IVP is simple, noninvasive screening examination of the kidneys and is helpful for evaluation of the functional and structural changes if the pyelogram was obtained. Unilateral nonvisualizing kidney may be resulted from various diseases that can produce vascular obstruction, functional determination of the glomerular filtration and obstruction of the lower urinary tract. In cases of nonvisualizing kidney further study including RGP, renal angiography, CT, ultrasonography and RI imaging is needed. During the perfect of 10 years from 1972 to 1981, 100 cases of nonvisualizing kidney which could be diagnosed by other imaging studies. The authors reviews medical records and finding of RGP, renal angiography, CT and ultrasonography of the nonvisualizing kidneys. The results were as follows: 1. The material included 53 male and 47 female patterns. The age distribution was broad, but mostly in the twenties and forties of ages. 2. There was no remarkable differentiation between sides of involvement in both sexes. 3. The underlying diseases of nonvisualizng kidney on IVP were renal tuberculosis (33 patients), ureteral stricture (16 patients), ureteral stone (12 patients), real tumor (10 patients), pelvic mass (10 patients), chronic pyelonephritis (8 patients), renal agenesis (5 patients), renal trauma (4 patients), and renal disease of vascular origin (2 patients) respectively. 4. RGP was performed in 79 out of 100 cases. RGP was the most confirmative diagnostic procedure in cases of inflammatory diseases of the kidney and renal pelvic tumors. 5. Renal angiography was performed in 19 cases. Renal angiography was very helpful in the diagnosis and evaluation of the extent of the diseases in 6 cases of renal tumors, 3 cases renal trauma, 2 cases of renal vascular diseases and 3 cases of renal agenesis. 6. Body CT was performed in one case of renal cell carcinoma and other 6 cases of hydronephrosis mainly from tumors of the pelvic cavity including 4 cervical carcinomas and a

  5. CADMIUM ACCUMULATION IN HORSE MUSCLE, LIVER AND KIDNEY SLAUGHTERED IN BARI

    Directory of Open Access Journals (Sweden)

    P. Pinto

    2013-02-01

    Full Text Available The occurrence of Cadmium was measured in the muscle, liver and kidneys of 220 horses, 120 Polish, 55 Spanish and 45 Italian, subdivided into age-group. The kidneys were found to be the most contaminated and the concentration reveals a situation which should be under investigation.

  6. Histopathological changes in kidneys of free ranging animals in relation to lead and cadmium residues

    International Nuclear Information System (INIS)

    Beiglboeck, C.

    2000-05-01

    Kidney samples of 234 roe deer and 45 wild boars were collected in Lower Austria and Vienna, and were analyzed for lead and cadmium contents. Samples of the organs were examined histologically, considering 12 different morphological parameters. Influences of age, sex and origin of the animals on heavy metal burdens were assessed, and the possible correlation between histopathological changes and age, sex, origin and heavy metal concentrations in the kidneys was tested. Lead concentrations were low with medians (mg/kg wet tissue) being 0,062 in roe deer and 0,044 in wild boars. Neither age nor sex nor origin influenced the lead contents of the kidneys. Cadmium burden was fairly high, both in roe deer (median: 0,954) and wild boars (median: 3,009). It increased with age in both species, while female roe deer showed higher contents as well. No influence of the animals' origin was found. The correlation between histopathological changes and age, sex, origin and heavy metal concentrations in the kidneys was tested in 208 roe deer and 44 wild boars which showed no signs of kidney related diseases. In roe deer, the frequency of vacuolic degeneration, pycnotic nuclei, caryolysis and necrosis was related with increased cadmium concentrations. Increasing age correlated with lymphohistiocytic infiltration, interstitial fibrosis and swelling of glomeruli. Pigment deposits and thickening of the Bowman's capsule could be related to both cadmium and age. Furthermore, roe deer from Vienna more frequently showed alterations as observed in animals from Lower Austria. No correlation existed between morphological changes and lead concentrations or sex. In wild boars, there was no obvious relationship between all parameters tested and the frequency of histopathologic changes, except changes in pigmentation. Possible nephrotoxic agents in free ranging animals and the demonstrated influence of cadmium on severe kidney damage are discussed. (author)

  7. Novel genes in renal aging

    OpenAIRE

    Noordmans, Gerda Anke

    2015-01-01

    Renal aging is characterized by structural changes and functional decline. These changes make the elderly more vulnerable to chronic kidney disease, hypertension, and cardiovascular disease. Furthermore, they also make it more difficult to cope with stress factors, such as dehydration, toxicity, and obstruction. These stress factors can lead to acute kidney injury and reduced recovery from acute kidney injury and may result in chronic kidney disease or even end-stage renal disease. The rate o...

  8. Age-dependent change of HMGB1 and DNA double-strand break accumulation in mouse brain

    International Nuclear Information System (INIS)

    Enokido, Yasushi; Yoshitake, Ayaka; Ito, Hikaru; Okazawa, Hitoshi

    2008-01-01

    HMGB1 is an evolutionarily conserved non-histone chromatin-associated protein with key roles in maintenance of nuclear homeostasis; however, the function of HMGB1 in the brain remains largely unknown. Recently, we found that the reduction of nuclear HMGB1 protein level in the nucleus associates with DNA double-strand break (DDSB)-mediated neuronal damage in Huntington's disease [M.L. Qi, K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J. Botas, M. Saitoe, E.E. Wanker, H. Okazawa, Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases, Nat. Cell Biol. 9 (2007) 402-414]. In this study, we analyze the region- and cell type-specific changes of HMGB1 and DDSB accumulation during the aging of mouse brain. HMGB1 is localized in the nuclei of neurons and astrocytes, and the protein level changes in various brain regions age-dependently. HMGB1 reduces in neurons, whereas it increases in astrocytes during aging. In contrast, DDSB remarkably accumulates in neurons, but it does not change significantly in astrocytes during aging. These results indicate that HMGB1 expression during aging is differentially regulated between neurons and astrocytes, and suggest that the reduction of nuclear HMGB1 might be causative for DDSB in neurons of the aged brain

  9. New insights into potential functions for the protein 4.1superfamily of proteins in kidney epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Calinisan, Venice; Gravem, Dana; Chen, Ray Ping-Hsu; Brittin,Sachi; Mohandas, Narla; Lecomte, Marie-Christine; Gascard, Philippe

    2005-06-17

    Members of the protein 4.1 family of adapter proteins are expressed in a broad panel of tissues including various epithelia where they likely play an important role in maintenance of cell architecture and polarity and in control of cell proliferation. We have recently characterized the structure and distribution of three members of the protein 4.1 family, 4.1B, 4.1R and 4.1N, in mouse kidney. We describe here binding partners for renal 4.1 proteins, identified through the screening of a rat kidney yeast two-hybrid system cDNA library. The identification of putative protein 4.1-based complexes enables us to envision potential functions for 4.1 proteins in kidney: organization of signaling complexes, response to osmotic stress, protein trafficking, and control of cell proliferation. We discuss the relevance of these protein 4.1-based interactions in kidney physio-pathology in the context of their previously identified functions in other cells and tissues. Specifically, we will focus on renal 4.1 protein interactions with beta amyloid precursor protein (beta-APP), 14-3-3 proteins, and the cell swelling-activated chloride channel pICln. We also discuss the functional relevance of another member of the protein 4.1 superfamily, ezrin, in kidney physiopathology.

  10. Risk factors for renal injury in children with a solitary functioning kidney.

    NARCIS (Netherlands)

    Westland, R.; Kurvers, R.A.; Wijk, J.A. van; Schreuder, M.F.

    2013-01-01

    OBJECTIVE: The hyperfiltration hypothesis implies that children with a solitary functioning kidney are at risk to develop hypertension, proteinuria, and chronic kidney disease. We sought to determine the presenting age of renal injury and identify risk factors for children with a solitary

  11. Chronic Kidney Disease and Kidney Failure

    Science.gov (United States)

    ... death rates limited life expectancy. Some patients were lucky enough to get a kidney transplant, which greatly ... epidemic rates. Through the 1980s and 1990s, the number of patients developing end-stage kidney failure nearly ...

  12. Aspirin resistance as cardiovascular risk after kidney transplantation

    Science.gov (United States)

    Sandor, Barbara; Varga, Adam; Rabai, Miklos; Toth, Andras; Papp, Judit; Toth, Kalman; Szakaly, Peter

    2014-05-01

    International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

  13. [The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study: To better understand chronic kidney disease].

    Science.gov (United States)

    Stengel, Bénédicte; Combe, Christian; Jacquelinet, Christian; Briançon, Serge; Fouque, Denis; Laville, Maurice; Frimat, Luc; Pascal, Christophe; Herpe, Yves-Édouard; Morel, Pascal; Deleuze, Jean-François; Schanstra, Joost P; Pisoni, Ron L; Robinson, Bruce M; Massy, Ziad A

    2016-04-01

    Preserving kidney function and improving the transition from chronic kidney disease to end stage is a research and healthcare challenge. The national Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort was established to identify the determinants, biomarkers and practice patterns associated with chronic kidney disease outcomes. The study will include more than 3000 adult patients with moderate to advanced chronic kidney disease from a representative sample of 40 nephrology clinics with respect to regions and legal status, public or private. Patients are recruited during a routine visit and followed for 5 years, before and after starting renal replacement therapy. Patient-level clinical, biological, and lifestyle data are collected annually, as well as provider-level data on clinical practices, coordinated with the International Chronic Kidney Disease Outcomes and Practice Pattern Study. Blood and urine samples are stored in a biobank. Major studied outcomes include survival, patient-reported outcomes, disease progression and hospitalizations. More than 13,000 eligible patients with chronic kidney disease were identified, 60% with stage 3 and 40% with stage 4. Their median age is 72 years [interquartile range, 62-80 years], 60% are men and 38% have diabetes. By the end of December 2015, 2885 patients were included. The CKD-REIN cohort will serve to improve our understanding of chronic kidney disease and provide evidence to improve patient survival and quality of life as well as health care system performances. Copyright © 2016 Association Société de néphrologie. All rights reserved.

  14. Derivation of a Predictive Model for Graft Loss Following Acute Kidney Injury in Kidney Transplant Recipients.

    Science.gov (United States)

    Molnar, Amber O; van Walraven, Carl; Fergusson, Dean; Garg, Amit X; Knoll, Greg

    2017-01-01

    Acute kidney injury (AKI) is common in the kidney transplant population. To derive a multivariable survival model that predicts time to graft loss following AKI. Retrospective cohort study using health care administrative and laboratory databases. Southwestern Ontario (1999-2013) and Ottawa, Ontario, Canada (1996-2013). We included first-time kidney only transplant recipients who had a hospitalization with AKI 6 months or greater following transplant. AKI was defined using the Acute Kidney Injury Network criteria (stage 1 or greater). The first episode of AKI was included in the analysis. Graft loss was defined by return to dialysis or repeat kidney transplant. We performed a competing risk survival regression analysis using the Fine and Gray method and modified the model into a simple point system. Graft loss with death as a competing event was the primary outcome of interest. A total of 315 kidney transplant recipients who had a hospitalization with AKI 6 months or greater following transplant were included. The median (interquartile range) follow-up time was 6.7 (3.3-10.3) years. Graft loss occurred in 27.6% of the cohort. The final model included 6 variables associated with an increased risk of graft loss: younger age, increased severity of AKI, failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and receipt of a kidney from a deceased donor. The risk score had a concordance probability of 0.75 (95% confidence interval [CI], 0.69-0.82). The predicted 5-year risk of graft loss fell within the 95% CI of the observed risk more than 95% of the time. The CIs of the estimates were wide, and model overfitting is possible due to the limited sample size; the risk score requires validation to determine its clinical utility. Our prognostic risk score uses commonly available information to predict the risk of graft loss in kidney transplant patients hospitalized with AKI. If validated

  15. Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients.

    Science.gov (United States)

    Wolf, Mattie F; George, Roshan P; Warshaw, Barry; Wang, Elizabeth; Greenbaum, Larry A

    2016-12-01

    To quantify physical activity and grip strength in pediatric kidney transplant recipients and describe attitudes about exercise and exercise counseling given concerns about allograft injury. This was a cross-sectional analysis of 101 kidney transplant recipients (7-21 years old) >6 months post-transplant. Patients completed the Physical Activity Questionnaire (PAQ). Grip strength was measured with a dynamometer. We asked about activity limitations and provider counseling. Univariate analysis and multiple linear regression were used to determine independent predictors of PAQ score and grip strength z score. We enrolled 101 of 122 eligible patients. Median PAQ score was 2.2 (range 0-5) and was lower compared with controls (P < .001). The average grip strength z score was -1.1 and -0.7 in the right and left hand, respectively. Predictors of lower grip strength were younger age (P = .036), non-African American race (P = .029), lower height z score (P = .010), and longer percentage of lifetime with kidney disease (P = .029). Although 49% and 67% limited exercise before and after transplant, respectively, 67% reported increased activity after transplant. By parent report, provider counseling included limiting certain activities (71%) and encouraging regular exercise (45%). Physical activity and grip strength are low after kidney transplant. Patients perceive an emphasis on exercise limitations rather than the benefits of regular exercise. Interventions that encourage physical activity may be beneficial. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease

    Science.gov (United States)

    2016-09-01

    pathways that are involved in cyst development and expansion. These experiments will make use of cultured ADPKD cells and a mouse model of ADPKD to...AWARD NUMBER: W81XWH-15-1-0420 TITLE: Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease...PRINCIPAL INVESTIGATOR: Kenneth R. Hallows, MD, PhD, FASN CONTRACTING ORGANIZATION: University of Southern California Los Angeles, CA 90089-0701

  17. Transplantation of Kidneys From Donors With Acute Kidney Injury: Friend or Foe?

    NARCIS (Netherlands)

    Boffa, C.; van de Leemkolk, F.; Curnow, E.; Homan van der Heide, J.; Gilbert, J.; Sharples, E.; Ploeg, R. J.

    2017-01-01

    The gap between supply and demand in kidney transplantation has led to increased use of marginal kidneys; however, kidneys with acute kidney injury are often declined/discarded. To determine whether this policy is justified, we analyzed outcomes of donor kidneys with acute kidney injury (AKI) in a

  18. Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes.

    Science.gov (United States)

    Stratton, Kelly L; Alanee, Shaheen; Glogowski, Emily A; Schrader, Kasmintan A; Rau-Murthy, Rohini; Klein, Robert; Russo, Paul; Coleman, Jonathan; Offit, Kenneth

    2016-05-01

    To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was 5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data

  19. Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney Immunopathology and Mortality in Invasive Candidiasis

    Science.gov (United States)

    Lionakis, Michail S.; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I.; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M.

    2012-01-01

    Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1lo to Ccr1high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1+/+ and Ccr1−/− donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ. PMID:22916017

  20. Sonographic Determination of Spleen to Left Kidney Ratio among ...

    African Journals Online (AJOL)

    Background: Clinical determination of mild splenomegaly is notoriously inaccurate. Objectives: To determine sonographically the spleen to left kidney ratio according to age and somatometric parameters among school age children in a tropical environment. Methods: A cross sectional study and convenience sampling were ...

  1. Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis.

    Directory of Open Access Journals (Sweden)

    Eric Lefebvre

    Full Text Available Interactions between C-C chemokine receptor types 2 (CCR2 and 5 (CCR5 and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVC's anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVC's antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.CVC significantly reduced monocyte/macrophage recruitment in vivo at doses ≥20 mg/kg/day (p < 0.05. At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05, and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls. CVC treatment had no notable effect on body or liver/kidney weight.CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVC's antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475.

  2. Outcomes of high-dose unilateral kidney irradiation in patients with gastric lymphoma

    International Nuclear Information System (INIS)

    Maor, Moshe H.; North, Luceil B.; Cabanillas, Fernando F.; Ames, Angie L.; Hess, Mark A.; Cox, James D.

    1998-01-01

    Purpose: To review the long-term clinical effects of unilateral kidney irradiation on overall renal function and blood pressure in patients with gastric lymphoma. Methods and Materials: In the study were 27 patients with Stage I or II gastric lymphoma who had undergone irradiation of at least 24 Gy to ≥1/3 of the left kidney. They include 16 women and 11 men, aged 31 to 77, with a mean age of 57.6 years (median 56). Fifteen patients had Stage I and 12 had Stage II disease. In 13 patients the whole kidney had been irradiated, and 14 had had partial kidney irradiation, at doses ranging between 24 and 40.5 Gy. All patients received combined chemotherapy with various drugs: all patients received corticosteroids, and five received cis-platinum. Their follow-up ranged between 0.7 and 7.8 years (mean 3.4 years). Data on possible effects of the treatment on blood pressure, renal function as assessed by blood urea and creatinine, and kidney shrinkage as seen by serial computed tomography scanning were collected on all patients. Results: Three patients had persistent, mild elevations of urea and creatinine levels, which did not require special treatment. All three also received cis-platinum. Ipsilateral kidney shrinkage was evident in most patients. In 19 patients the craniocaudal measurement of the kidney shrank by ≥1.6 cm. Shrinkage in other dimensions was also evident. The degree of atrophy was related to the volume of kidney irradiated. Only two patients developed hypertension, both at a low level of 150/90; one patient had had 40 Gy to the whole kidney, the other 40 Gy to half the kidney. Neither patient had elevated urea or creatinine. Conclusions: Notwithstanding the shrinkage to the irradiated part of the kidney, the treatment did not lead to clinically significant hypertension or renal dysfunction. The administration of cis-platinum to patients with gastric lymphoma that requires kidney irradiation should be further evaluated

  3. Nephrectomy (Kidney Removal)

    Science.gov (United States)

    ... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

  4. Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury.

    Science.gov (United States)

    MacManes, Matthew David

    2017-08-01

    Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse. Copyright © 2017 the American Physiological Society.

  5. Analysis of spatiotemporal metabolomic dynamics for sensitively monitoring biological alterations in cisplatin-induced acute kidney injury.

    Science.gov (United States)

    Irie, Miho; Hayakawa, Eisuke; Fujimura, Yoshinori; Honda, Youhei; Setoyama, Daiki; Wariishi, Hiroyuki; Hyodo, Fuminori; Miura, Daisuke

    2018-01-29

    Clinical application of the major anticancer drug, cisplatin, is limited by severe side effects, especially acute kidney injury (AKI) caused by nephrotoxicity. The detailed metabolic mechanism is still largely unknown. Here, we used an integrated technique combining mass spectrometry imaging (MSI) and liquid chromatography-mass spectrometry (LC-MS) to visualize the diverse spatiotemporal metabolic dynamics in the mouse kidney after cisplatin dosing. Biological responses to cisplatin was more sensitively detected within 24 h as a metabolic alteration, which is much earlier than possible with the conventional clinical chemistry method of blood urea nitrogen (BUN) measurement. Region-specific changes (e.g., medulla and cortex) in metabolites related to DNA damage and energy generation were observed over the 72-h exposure period. Therefore, this metabolomics approach may become a novel strategy for elucidating early renal responses to cisplatin, prior to the detection of kidney damage evaluated by conventional method. Copyright © 2018. Published by Elsevier Inc.

  6. Treatment of D-galactose induced mouse aging with Lycium ...

    African Journals Online (AJOL)

    Kunming mice were randomly divided into the control group, the model group, the high-dose LBP group, and the low-dose LBP group. Except the control group, D-galactose was used for modelling. The drug was administrated when modelling. Mouse behavioural, learning and memory changes were observed, and the ...

  7. Interactive local super-resolution reconstruction of whole-body MRI mouse data: a pilot study with applications to bone and kidney metastases.

    Directory of Open Access Journals (Sweden)

    Oleh Dzyubachyk

    Full Text Available In small animal imaging studies, when the locations of the micro-structures of interest are unknown a priori, there is a simultaneous need for full-body coverage and high resolution. In MRI, additional requirements to image contrast and acquisition time will often make it impossible to acquire such images directly. Recently, a resolution enhancing post-processing technique called super-resolution reconstruction (SRR has been demonstrated to improve visualization and localization of micro-structures in small animal MRI by combining multiple low-resolution acquisitions. However, when the field-of-view is large relative to the desired voxel size, solving the SRR problem becomes very expensive, in terms of both memory requirements and computation time. In this paper we introduce a novel local approach to SRR that aims to overcome the computational problems and allow researchers to efficiently explore both global and local characteristics in whole-body small animal MRI. The method integrates state-of-the-art image processing techniques from the areas of articulated atlas-based segmentation, planar reformation, and SRR. A proof-of-concept is provided with two case studies involving CT, BLI, and MRI data of bone and kidney tumors in a mouse model. We show that local SRR-MRI is a computationally efficient complementary imaging modality for the precise characterization of tumor metastases, and that the method provides a feasible high-resolution alternative to conventional MRI.

  8. Interactive local super-resolution reconstruction of whole-body MRI mouse data: a pilot study with applications to bone and kidney metastases.

    Science.gov (United States)

    Dzyubachyk, Oleh; Khmelinskii, Artem; Plenge, Esben; Kok, Peter; Snoeks, Thomas J A; Poot, Dirk H J; Löwik, Clemens W G M; Botha, Charl P; Niessen, Wiro J; van der Weerd, Louise; Meijering, Erik; Lelieveldt, Boudewijn P F

    2014-01-01

    In small animal imaging studies, when the locations of the micro-structures of interest are unknown a priori, there is a simultaneous need for full-body coverage and high resolution. In MRI, additional requirements to image contrast and acquisition time will often make it impossible to acquire such images directly. Recently, a resolution enhancing post-processing technique called super-resolution reconstruction (SRR) has been demonstrated to improve visualization and localization of micro-structures in small animal MRI by combining multiple low-resolution acquisitions. However, when the field-of-view is large relative to the desired voxel size, solving the SRR problem becomes very expensive, in terms of both memory requirements and computation time. In this paper we introduce a novel local approach to SRR that aims to overcome the computational problems and allow researchers to efficiently explore both global and local characteristics in whole-body small animal MRI. The method integrates state-of-the-art image processing techniques from the areas of articulated atlas-based segmentation, planar reformation, and SRR. A proof-of-concept is provided with two case studies involving CT, BLI, and MRI data of bone and kidney tumors in a mouse model. We show that local SRR-MRI is a computationally efficient complementary imaging modality for the precise characterization of tumor metastases, and that the method provides a feasible high-resolution alternative to conventional MRI.

  9. Effects of IMOD and Angipars on Mouse D-Galactose-Induced Model of Aging

    Directory of Open Access Journals (Sweden)

    Samane Ghanbari

    2012-10-01

    Full Text Available The aim of this study was to evaluate the effects of two registered herbal drugs called IMOD and Angipars on mouse model of. Aging was induced by D-galactose (500 mg/kgadministered to animals for 6 weeks through drinking water. Male BALB/c mice were randomly divided into 5 groups receiving D-galactose (D-galactose, 500 mg/kg for 6 weeks; positive control (D-galactose [500 mg/kg] for 6 weeks + Vitamin E [200 mg/kg/day]intraperitoneally for 4 weeks; IMOD (D-galactose [500 mg/kg] for 6 weeks + IMOD [20 mg/kg/day] intraperitoneally for 4 weeks, Angipars (D-galactose [500 mg/kg] for 6 weeks + Angipars [2.1 mg/kg/day] by gavage for 4 weeks; and the fifth group that was sham and not given D-galactose. At the end of treatment, pro-inflammatory markers including tumor necrosis factor-α (TNF-α, interlukine-1β (IL-β, interlukine-6 (IL-6, NF-kappaB (NF-κb, total antioxidant power (TAP, lipid peroxides (LPO and male sex hormones i.e.testosterone and dehydroepiandrosterone-sulfate (DHEA-S were measured in the blood.Results showed that D-Galactose induces a significant oxidative stress and proinflammatory cascade of aging while both IMOD and Angipars recovered all of them. Interestingly, IMOD and Angipars were better than Vitamin E in improving male sex hormones that were declined in aged mice. This effect is so important and should be considered as an advantage although it cannot be explained with current knowledge. The conclusion is that IMOD and Angipars have marked anti-aging effect on D-galactose-induced model of aging.

  10. Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model

    Directory of Open Access Journals (Sweden)

    Park Seung S

    2012-12-01

    Full Text Available Abstract Background Advancing female age remains a difficult problem in infertility treatment. Ovarian angiogenesis plays an important role in follicular development and the activation of ovarian angiogenesis has been emerged as a new strategy for the improvement of age-related decline of oocyte quality. BMP-6 affect gonadotropin signals in granulosa cells and it promotes normal fertility by enabling appropriate response to LH and normal oocyte quality. BMP-6 has a potential role in regulation of angiogenesis and regulates the expression of inhibitor of DNA-binding proteins (Ids. Ids involved in the control and timing of follicle selection and granulosa cells differentiation. Especially, Id-1 is well-characterized target of BMP-6 signaling. Therefore, this study investigated whether co-administration of BMP-6 during superovulation process improves ovarian response, oocyte quality and expression of Id-1 and vascular endothelial growth factor (VEGF in the ovary of aged female using a mouse model. Methods Aged C57BL/6 female mice (26–31 weeks old were superovulated by injection with 0.1 mL of 5 IU equine chorionic gonadotropin (eCG containing recombinant mouse BMP-6 at various doses (0, 0.01, 0.1, 1, and 10 ng, followed by injection with 5 IU human chorionic gonadotropin (hCG 48 h later. Then, the mice were immediately paired with an individual male. The aged control group was superovulated without BMP-6. Young mice of 6–9 weeks old were superovulated without BMP-6 as a positive control for superovulation and in vitro culture of embryos. Eighteen hours after hCG injection, zygotes were retrieved and cultured for 4 days. Both ovaries of each mouse were provided in the examination of ovarian expression of Id-1 and VEGF by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry. Results Administration of 0.1 ng BMP-6 significantly increased the number and blastocyst formation rate of oocytes ovulated and ovarian

  11. Effects of aging and sensory loss on glial cells in mouse visual and auditory cortices

    Science.gov (United States)

    Tremblay, Marie-Ève; Zettel, Martha L.; Ison, James R.; Allen, Paul D.; Majewska, Ania K.

    2011-01-01

    Normal aging is often accompanied by a progressive loss of receptor sensitivity in hearing and vision, whose consequences on cellular function in cortical sensory areas have remained largely unknown. By examining the primary auditory (A1) and visual (V1) cortices in two inbred strains of mice undergoing either age-related loss of audition (C57BL/6J) or vision (CBA/CaJ), we were able to describe cellular and subcellular changes that were associated with normal aging (occurring in A1 and V1 of both strains) or specifically with age-related sensory loss (only in A1 of C57BL/6J or V1 of CBA/CaJ), using immunocytochemical electron microscopy and light microscopy. While the changes were subtle in neurons, glial cells and especially microglia were transformed in aged animals. Microglia became more numerous and irregularly distributed, displayed more variable cell body and process morphologies, occupied smaller territories, and accumulated phagocytic inclusions that often displayed ultrastructural features of synaptic elements. Additionally, evidence of myelination defects were observed, and aged oligodendrocytes became more numerous and were more often encountered in contiguous pairs. Most of these effects were profoundly exacerbated by age-related sensory loss. Together, our results suggest that the age-related alteration of glial cells in sensory cortical areas can be accelerated by activity-driven central mechanisms that result from an age-related loss of peripheral sensitivity. In light of our observations, these age-related changes in sensory function should be considered when investigating cellular, cortical and behavioral functions throughout the lifespan in these commonly used C57BL/6J and CBA/CaJ mouse models. PMID:22223464

  12. Impact of Acute Kidney Injury in Patients Hospitalized With Pneumonia.

    Science.gov (United States)

    Chawla, Lakhmir S; Amdur, Richard L; Faselis, Charles; Li, Ping; Kimmel, Paul L; Palant, Carlos E

    2017-04-01

    Pneumonia is a common cause of hospitalization and can be complicated by the development of acute kidney injury. Acute kidney injury is associated with major adverse kidney events (death, dialysis, and durable loss of renal function [chronic kidney disease]). Because pneumonia and acute kidney injury are in part mediated by inflammation, we hypothesized that when acute kidney injury complicates pneumonia, major adverse kidney events outcomes would be exacerbated. We sought to assess the frequency of major adverse kidney events after a hospitalization for either pneumonia, acute kidney injury, or the combination of both. We conducted a retrospective database analysis of the national Veterans Affairs database for patients with a admission diagnosis of International Classification of Diseases-9 code 584.xx (acute kidney injury) or 486.xx (pneumonia) between October 1, 1999, and December 31, 2005. Three groups of patients were created, based on the diagnosis of the index admission and serum creatinine values: 1) acute kidney injury, 2) pneumonia, and 3) pneumonia with acute kidney injury. Patients with mean baseline estimated glomerular filtration rate less than 45 mL/min/1.73 m were excluded. The primary endpoint was major adverse kidney events defined as the composite of death, chronic dialysis, or a permanent loss of renal function after the primary discharge. The observations of 54,894 subjects were analyzed. Mean age was 68.7 ± 12.3 years. The percentage of female was 2.4, 73.3% were Caucasian, and 19.7% were African-American. Differences across the three diagnostic groups were significant for death, 25% decrease in estimated glomerular filtration rate from baseline, major adverse kidney events following admission, and major adverse kidney events during admission (all p pneumonia + acute kidney injury group (51% died and 62% reached major adverse kidney events). In both unadjusted and adjusted time to event analyses, patients with pneumonia + acute kidney injury

  13. Gene expression of drug metabolizing enzymes in adult and aged mouse liver: A modulation by immobilization stress

    International Nuclear Information System (INIS)

    Mikhailova, O.N.; Gulyaeva, L.F.; Filipenko, M.L.

    2005-01-01

    The role of stress in the regulation of enzymatic systems involved in the biotransformation of xenobiotics, as well as endogenous substrates in the liver was investigated using single immobilization stress as a model. Adult (3 months of age) and aged (26 months) C3H/a male mice were used. Cytochrome P450 1A1 and 1A2 (CYP1A1 and CYP1A2), glutathione S-transferase M1 (GSTM1), aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT) and catechol-O-methyltransferase (COMT) mRNA levels in the mouse liver were measured by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Excluding CYP1A1, experiments revealed significant differences in the expression of these genes between adult- and aged-control animals. The influence of stress on the expression of genes studied was shown to be higher in adult mice than in aged ones. Our results clearly demonstrate the lack of response or even the attenuation of gene expression in aged animals that may play an important role in age-related pathologies and diseases

  14. CDKD: a clinical database of kidney diseases

    Directory of Open Access Journals (Sweden)

    Singh Sanjay

    2012-04-01

    Full Text Available Abstract Background The main function of the kidneys is to remove waste products and excess water from the blood. Loss of kidney function leads to various health issues, such as anemia, high blood pressure, bone disease, disorders of cholesterol. The main objective of this database system is to store the personal and laboratory investigatory details of patients with kidney disease. The emphasis is on experimental results relevant to quantitative renal physiology, with a particular focus on data relevant for evaluation of parameters in statistical models of renal function. Description Clinical database of kidney diseases (CDKD has been developed with patient confidentiality and data security as a top priority. It can make comparative analysis of one or more parameters of patient’s record and includes the information of about whole range of data including demographics, medical history, laboratory test results, vital signs, personal statistics like age and weight. Conclusions The goal of this database is to make kidney-related physiological data easily available to the scientific community and to maintain & retain patient’s record. As a Web based application it permits physician to see, edit and annotate a patient record from anywhere and anytime while maintaining the confidentiality of the personal record. It also allows statistical analysis of all data.

  15. Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

    Science.gov (United States)

    Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

    2017-08-01

    Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

  16. Multi-Scale Characterization of the PEPCK-Cmus Mouse through 3D Cryo-Imaging

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    Debashish Roy

    2010-01-01

    Full Text Available We have developed, for the Case 3D Cryo-imaging system, a specialized, multiscale visualization scheme which provides color-rich volume rendering and multiplanar reformatting enabling one to visualize an entire mouse and zoom in to organ, tissue, and microscopic scales. With this system, we have anatomically characterized, in 3D, from whole animal to tissue level, a transgenic mouse and compared it with its control. The transgenic mouse overexpresses the cytosolic form of phosphoenolpyruvate carboxykinase (PEPCK-C in its skeletal muscle and is capable of greatly enhanced physical endurance and has a longer life-span and reproductive life as compared to control animals. We semiautomatically analyzed selected organs such as kidney, heart, adrenal gland, spleen, and ovaries and found comparatively enlarged heart, much less visceral, subcutaneous, and pericardial adipose tissue, and higher tibia-to-femur ratio in the transgenic animal. Microscopically, individual skeletal muscle fibers, fine mesenteric blood vessels, and intestinal villi, among others, were clearly seen.

  17. Mitochondrial energy metabolism changes during aging-mouse cranial nerve cells treated with various doses and forms of Fructus schizandrae

    Institute of Scientific and Technical Information of China (English)

    Hongyan Guo; Jinhe Li

    2008-01-01

    BACKGROUND: During the cellular aging process, the number of mitochondria, generation of adenosine triphosphate (ATP), activity of respiratory chain enzyme complex 1 and 4, and oxidation decrease. OBJECTIVE: To observe the effects of aqueous and spirituous extract, as well as polysaccharides from Fructus schizandrae (Magnolia Vine) on energy metabolism and mitochondrial anti-oxidation in cranial nerve cells of a D-gal-induccd aging mouse model.DESIGN, TIME AND SETTING: A randomized, controlled, animal study. The experiment was conducted at the Department of Biochemistry, Qiqihar Medical College between March and July 2006.MATERIALS: Fifty healthy, Kunming mice of both sexes, aged 2 3 months old and weighing 18-22 g, were used for the present study. Fructus schizandrae was purchased from the Medical College of Jiamusi University. Aqueous extracts, spirituous extracts, and polysaccharides from Fructus schizandrae were prepared. D-galactose (D-gal) is a product of the Second Reagent Factory, Shanghai City, China. Mn-superoxide dismutase (Mn-SOD) kit, malonaldehyde (MDA) kit, protein quantification kit, and inorganic phosphorus testing kit were purchased from Jian Cheng Bioeng. Co., China.METHODS: Fifty mice were randomly divided into five groups, with 10 mice in each group: young control, aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides. Over a course of 30 days, mice in aging model, aqueous Fructus schizandrae extract, spirituous Fructus schizandrae extract, and Fructus schizandrae polysaccharides groups were injected subcutaneously with D-gal (100 mg/kg) into the nape of the neck daily, and administered intragastrically with an equal volume of sterile, warm water (aging model), aqueous Fructus schizandrae extract (2 g/kg), spirituous Fructus schizandrae extract (2 g/kg), or Fructus schizandrae polysaccharides (0.2 g/kg), respectively. Mice in the young control group were injected into

  18. Medication use and kidney cancer risk: A population-based study.

    Science.gov (United States)

    Nayan, Madhur; Juurlink, David N; Austin, Peter C; Macdonald, Erin M; Finelli, Antonio; Kulkarni, Girish S; Hamilton, Robert J

    2017-09-01

    Exposure to commonly prescribed medications may be associated with cancer risk. However, there is limited data in kidney cancer. Furthermore, methods of classifying cumulative medication exposure in previous studies may be prone to bias. We conducted a population-based case-control study of 10,377 incident kidney cancer cases aged ≥66 years matched with 35,939 controls on age, sex, history of hypertension, comorbidity score, and geographic location. Cumulative exposure to commonly prescribed medications hypothesised to modulate cancer risk was obtained using prescription claims data. We modelled exposure in four different fashions: (1) as continuous exposures using (a) fractional polynomials (which allow for a non-linear relationship between an exposure and outcome) or (b) assuming linear relationships; and 2) as dichotomous exposures denoting (a) ≥3 years versus kidney cancer. The directions of association were relatively consistent across analyses; however, the magnitudes were sensitive to the method of analysis. When utilising fractional polynomials, increasing cumulative exposure to acetylsalicylic acid, selective serotonin reuptake inhibitors, and proton-pump inhibitors was associated with significantly reduced risk of kidney cancer, while increasing exposure to antihypertensive drugs was associated with significantly increased risk. Our study provides impetus to further explore the effect of commonly prescribed medications on carcinogenesis to identify modifiable pharmacological interventions to reduce the risk of kidney cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Frailty, Disability and Physical Exercise in the Aging Process and in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Antonio Greco

    2014-07-01

    Full Text Available Frailty in the elderly is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. It is usually associated to adverse health outcomes and to one-year mortality risk. Physical exercise has found to be effective in preventing frailty and disability in this population. Chronic kidney disease (CKD is also a clinical condition where protein energy-wasting, sarcopenia and dynapenia ,very common symptoms in the frail elderly, may occur. Moreover elderly and CKD patients are both affected by an impaired physical performance that may be reversed by physical exercise with an improvement of the survival rate. These similarities suggest that frailty may be a common pathway of aging and CKD that may induce disability and that can be prevented by a multidimensional approach in which physical exercise plays an important role.

  20. Cloning, characterization and targeting of the mouse HEXA gene

    Energy Technology Data Exchange (ETDEWEB)

    Wakamatsu, N.; Trasler, J.M.; Gravel, R.A. [McGill Univ., Quebec (Canada)] [and others

    1994-09-01

    The HEXA gene, encoding the {alpha} subunit of {beta}-hexosaminidase A, is essential for the metabolism of ganglioside G{sub M2}, and defects in this gene cause Tay-Sachs disease in humans. To elucidate the role of the gene in the nervous system of the mouse and to establish a mouse model of Tay-Sachs disease, we have cloned and characterized the HEXA gene and targeted a disruption of the gene in mouse ES cells. The mouse HEXA gene spans {approximately}26 kb and consists of 14 exons, similar to the human gene. A heterogeneous transcription initiation site was identified 21-42 bp 5{prime} of the initiator ATG, with two of the sites fitting the consensus CTCA (A = start) as seen for some weak initiator systems. Promoter analysis showed that the first 150 bp 5{prime} of the ATG contained 85% of promoter activity observed in constructs containing up to 1050 bp of 5{prime} sequence. The active region contained a sequence matching that of the adenovirus major late promoter upstream element factor. A survey of mouse tissues showed that the highest mRNA levels were in (max to min): testis (5.5 x brain cortex), adrenal, epididymis, heart, brain, lung, kidney, and liver (0.3 x brain cortex). A 12 kb BstI/SalI fragment containing nine exons was disrupted with the insertion of the bacterial neo{sup r} gene in exon 11 and was targeted into 129/Sv ES cells by homologous recombination. Nine of 153 G418 resistant clones were correctly targeted as confirmed by Southern blotting. The heterozygous ES cells were microinjected into mouse blastocysts and implanted into pseudo-pregnant mice. Nine male chimeric mice, showing that 40-95% chimerism for the 129/Sv agouti coat color marker, are being bred in an effort to generate germline transmission of the disrupted HEXA gene.

  1. Effect of Immigration Status on Outcomes in Pediatric Kidney Transplant Recipients.

    Science.gov (United States)

    McEnhill, M E; Brennan, J L; Winnicki, E; Lee, M M; Tavakol, M; Posselt, A M; Stock, P G; Portale, A A

    2016-06-01

    Kidney transplantation is the optimal treatment for children with end-stage renal disease. For children with undocumented immigration status, access to kidney transplantation is limited, and data on transplant outcomes in this population are scarce. The goal of the present retrospective single-center study was to compare outcomes after kidney transplantation in undocumented children with those of US citizen children. Undocumented residency status was identified in 48 (17%) of 289 children who received a kidney transplant between 1998 and 2010. In undocumented recipients, graft survival at 1 and 5 years posttransplantation was similar, and mean estimated glomerular filtration rate at 1 year was higher than that in recipients who were citizens. The risk of allograft failure was lower in undocumented recipients relative to that in citizens at 5 years posttransplantation, after adjustment for patient age, donor age, donor type, and HLA mismatch (p immigration policies for the undocumented that facilitate access to work-permits and employment-related insurance for this disadvantaged group. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Relationship between intracranial aneurysms and the severity of autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Yoshida, Hiroki; Higashihara, Eiji; Maruyama, Keisuke; Nutahara, Kikuo; Nitatori, Toshiaki; Miyazaki, Isao; Shiokawa, Yoshiaki

    2017-12-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disease characterized by the progressive enlargement of innumerable renal cysts. Although the association of intracranial aneurysms (ICANs) with ADPKD is well known, the relationship between the ICAN and the disease severity including total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) is poorly understood. We screened 265 patients with ADPKD (mean age, 48.8 years; range, 14.9-88.3 years) with MR angiography. The patients with a past history related to ICANs were excluded from the study. The incidence and characteristics of ICAN in patients with ADPKD were evaluated. TKV was measured by volumetric analyses of MR imaging. We detected 65 ICANs in 49 patients (37 women and 12 men, mean age, 52.7 years; range, 20.4-86 years). The incidence of ICANs was 18.5% and female patients had was higher incidence (23.1%) than male patients (11.4%) (p = 0.02). An age of those with ICANs was significantly higher than those without (p = 0.006), and the cumulative risk of diagnosis of ICANs increased with age. TKV was significantly larger in those with ICANs than those without (p = 0.001), but eGFR was not different between two groups (p = 0.07). By multivariate analyses, only TKV was significantly related to the development of ICANs (p = 0.02). The incidence of ICANs increased with age, was higher in females, and correlated with kidney enlargement in patients with ADPKD. Necessity of screening ICANs would be particularly high in elderly women with large kidneys.

  3. High-resolution imaging of selenium in kidneys: a localized selenium pool associated with glutathione peroxidase 3

    Energy Technology Data Exchange (ETDEWEB)

    Malinouski, M.; Kehr, S.; Finney, L.; Vogt, S.; Carlson, B.A.; Seravalli, J.; Jin, R.; Handy, D.E.; Park, T.J.; Loscalzo, J.; Hatfield, D.L.; Gladyshev, V.N. (Harvard-Med)

    2012-04-17

    Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA{sup [Ser]Sec} and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution.

  4. Peripheral administration of antisense oligonucleotides targeting the amyloid-β protein precursor reverses AβPP and LRP-1 overexpression in the aged SAMP8 mouse brain.

    Science.gov (United States)

    Erickson, Michelle A; Niehoff, Michael L; Farr, Susan A; Morley, John E; Dillman, Lucy A; Lynch, Kristin M; Banks, William A

    2012-01-01

    The senescence accelerated mouse-prone 8 (SAMP8) mouse model of Alzheimer's disease has a natural mutation leading to age-related increases in the amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) in the brain, memory impairment, and deficits in Aβ removal from the brain. Previous studies show that centrally administered antisense oligonucleotide directed against AβPP can decrease AβPP expression and Aβ production in the brains of aged SAMP8 mice, and improve memory. The same antisense crosses the blood-brain barrier and reverses memory deficits when injected intravenously. Here, we give 6 μg of AβPP or control antisense 3 times over 2 week intervals to 12 month old SAMP8 mice. Object recognition test was done 48 hours later, followed by removal of whole brains for immunoblot analysis of AβPP, low-density lipoprotein-related protein-1 (LRP-1), p-glycoprotein (Pgp), receptor for advanced glycation endproducts (RAGE), or ELISA of soluble Aβ(40). Our results show that AβPP antisense completely reverses a 30% age-associated increase in AβPP signal (p < 0.05 versus untreated 4 month old SAMP8). Soluble Aβ(40) increased with age, but was not reversed by antisense. LRP-1 large and small subunits increased significantly with age (147.7%, p < 0.01 and 123.7%, p < 0.05 respectively), and AβPP antisense completely reversed these increases (p < 0.05). Pgp and RAGE were not significantly altered with age or antisense. Antisense also caused improvements in memory (p < 0.001). Together, these data support the therapeutic potential of AβPP antisense and show a unique association between AβPP and LRP-1 expression in the SAMP8 mouse.

  5. Knowledge and Attitude of Healthcare Workers towards Kidney ...

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-09-13

    Sep 13, 2013 ... care workers towards kidney transplantation are fundamental in ... that culture, socio-demographic characteristics such as age, gender, education ... were excluded from the logistic regression analysis. Results. Response rate ...

  6. Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

    Science.gov (United States)

    Rees, M A; Dunn, T B; Kuhr, C S; Marsh, C L; Rogers, J; Rees, S E; Cicero, A; Reece, L J; Roth, A E; Ekwenna, O; Fumo, D E; Krawiec, K D; Kopke, J E; Jain, S; Tan, M; Paloyo, S R

    2017-03-01

    Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  7. Smoking and risk of kidney failure in the Singapore Chinese health study.

    Directory of Open Access Journals (Sweden)

    Aizhen Jin

    Full Text Available The relationship between smoking and risk of kidney failure, especially in people of Chinese origin, is not clear. We analyzed data from the Singapore Chinese Health Study to investigate whether smoking increases the risk of kidney failure.The Singapore Chinese Health Study is a population-based cohort of 63,257 Chinese adults enrolled between 1993 and 1998. Information on smoking status was collected at baseline. Incidence of kidney failure was identified via record linkage with the nationwide Singapore Renal Registry until 2008. Kidney failure was defined by one of the following: 1 serum creatinine level of more than or equal to 500 µmol/l (5.7 mg/dl, 2 estimated glomerular filtration rate of less than 15 ml/min/1.73 m(2, 3 undergoing hemodialysis or peritoneal dialysis, 4 undergone kidney transplantation. Cox proportional hazard regression analysis was performed for the outcome of kidney failure after adjusting for age, education, dialect, herbal medications, body mass index, sex, physician-diagnosed hypertension and diabetes mellitus.The mean age of subjects was 55.6 years at baseline, and 44% were men. Overall 30.6% were ever smokers (current or former at baseline. A total of 674 incident cases of kidney failure occurred during a median follow-up of 13.3 years. Among men, smokers had a significant increase in the adjusted risk of kidney failure [hazard ratio (HR: 1.29; 95% CI: 1.02-1.64] compared to never smokers. There was a strong dose-dependent association between number of years of smoking and kidney failure, (p for trend = 0.011. The risk decreased with prolonged cessation (quitting ≥10 years since baseline. The number of women smokers was too few for conclusive relationship.Information on baseline kidney function was not available.Cigarette smoking is associated with increased risk of kidney failure among Chinese men. The risk appears to be dose- and duration-dependent and modifiable after long duration of cessation.

  8. Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease

    Science.gov (United States)

    Koppe, Laetitia; Nyam, Elsa; Vivot, Kevin; Manning Fox, Jocelyn E.; Dai, Xiao-Qing; Nguyen, Bich N.; Attané, Camille; Moullé, Valentine S.; MacDonald, Patrick E.; Ghislain, Julien

    2016-01-01

    Disorders of glucose homeostasis are common in chronic kidney disease (CKD) and are associated with increased mortality, but the mechanisms of impaired insulin secretion in this disease remain unclear. Here, we tested the hypothesis that defective insulin secretion in CKD is caused by a direct effect of urea on pancreatic β cells. In a murine model in which CKD is induced by 5/6 nephrectomy (CKD mice), we observed defects in glucose-stimulated insulin secretion in vivo and in isolated islets. Similarly, insulin secretion was impaired in normal mouse and human islets that were cultured with disease-relevant concentrations of urea and in islets from normal mice treated orally with urea for 3 weeks. In CKD mouse islets as well as urea-exposed normal islets, we observed an increase in oxidative stress and protein O-GlcNAcylation. Protein O-GlcNAcylation was also observed in pancreatic sections from CKD patients. Impairment of insulin secretion in both CKD mouse and urea-exposed islets was associated with reduced glucose utilization and activity of phosphofructokinase 1 (PFK-1), which could be reversed by inhibiting O-GlcNAcylation. Inhibition of O-GlcNAcylation also restored insulin secretion in both mouse models. These results suggest that insulin secretory defects associated with CKD arise from elevated circulating levels of urea that increase islet protein O-GlcNAcylation and impair glycolysis. PMID:27525435

  9. Injury - kidney and ureter

    Science.gov (United States)

    ... kidney; Ureteral injury; Pre-renal failure - injury, Post-renal failure - injury; Kidney obstruction - injury Images Kidney anatomy Kidney - blood and urine flow References Molitoris BA. Acute kidney injury. In: Goldman ...

  10. High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

    OpenAIRE

    Malinouski, Mikalai; Kehr, Sebastian; Finney, Lydia; Vogt, Stefan; Carlson, Bradley A.; Seravalli, Javier; Jin, Richard; Handy, Diane E.; Park, Thomas J.; Loscalzo, Joseph; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2012-01-01

    Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distributio...

  11. [Acute kidney injury

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; van Heurn, L.W.; Snoeijs, M.G.

    2012-01-01

    - 'Acute kidney injury' is modern terminology for a sudden decline in kidney function, and is defined by the RIFLE classification (RIFLE is an acronym for Risk, Injury, Failure, Loss and End-stage kidney disease).- Acute kidney injury occurs as a result of the combination of reduced perfusion in the

  12. Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia.

    Science.gov (United States)

    Penning, Marlies; Chua, Jamie S; van Kooten, Cees; Zandbergen, Malu; Buurma, Aletta; Schutte, Joke; Bruijn, Jan Anthonie; Khankin, Eliyahu V; Bloemenkamp, Kitty; Karumanchi, S Ananth; Baelde, Hans

    2015-07-01

    A growing body of evidence suggests that complement dysregulation plays a role in the pathogenesis of preeclampsia. The kidney is one of the major organs affected in preeclampsia. Because the kidney is highly susceptible to complement activation, we hypothesized that preeclampsia is associated with renal complement activation. We performed a nationwide search for renal autopsy material in the Netherlands using a computerized database (PALGA). Renal tissue was obtained from 11 women with preeclampsia, 25 pregnant controls, and 14 nonpregnant controls with hypertension. The samples were immunostained for C4d, C1q, mannose-binding lectin, properdin, C3d, C5b-9, IgA, IgG, and IgM. Preeclampsia was significantly associated with renal C4d-a stable marker of complement activation-and the classical pathway marker C1q. In addition, the prevalence of IgM was significantly higher in the kidneys of the preeclamptic women. No other complement markers studied differed between the groups. Our findings in human samples were validated using a soluble fms-like tyrosine kinase 1 mouse model of preeclampsia. The kidneys in the soluble fms-like tyrosine kinase 1-injected mice had significantly more C4 deposits than the control mice. The association between preeclampsia and renal C4d, C1q, and IgM levels suggests that the classical complement pathway is involved in the renal injury in preeclampsia. Moreover, our finding that soluble fms-like tyrosine kinase 1-injected mice develop excess C4 deposits indicates that angiogenic dysregulation may play a role in complement activation within the kidney. We suggest that inhibiting complement activation may be beneficial for preventing the renal manifestations of preeclampsia. © 2015 American Heart Association, Inc.

  13. Ultrasound findings in dual kidney transplantation.

    Science.gov (United States)

    Damasio, M B; Cittadini, G; Rolla, D; Massarino, F; Stagnaro, N; Gherzi, M; Paoletti, E; Derchi, L E

    2013-02-01

    This study was done to analyse colour Doppler ultrasound (CDUS) findings in patients with dual kidney transplantation (DKT) and to compare renal volume and resistive index (RI) values between DKT and single kidney transplantation (SKT). We reviewed the clinical and imaging findings [30 CDUS, five magnetic resonance (MR) and one computed tomography (CT) examination] in 30 patients with DKT (23 men and seven women; median age 65 years; range 55-82). Three patients had clinical signs of graft malfunction. Renal volumes and RI were compared with those of 14 SKT patients and comparable levels of renal function. Three patients had graft dysfunction: one had chronic rejection and two had pathologies involving one kidney only (one encrusted pyeloureteritis of a left graft and one occluded main artery of a left graft). Asymptomatic unilateral pathologies were seen in six cases. In asymptomatic DKT patients, no significant differences in length, volume, cortical echogenicity and RI between the two kidneys were observed; DKTs were smaller (median volume 116.7 vs. 171.6 cc) and had higher RIs (0.76 vs. 0.68) (pDKT, allowing detection of clinically unsuspected unilateral diseases. At comparable levels of renal function, DKT patients had higher RI and lower volumes than SKT patients.

  14. Dual Kidney Transplantation: A Review of Past and Prospect for Future.

    Science.gov (United States)

    Khalil, Muhammad Abdul Mabood; Tan, Jackson; Khan, Taqi F Toufeeq; Khalil, Muhammad Ashhad Ullah; Azmat, Rabeea

    2017-01-01

    Kidney transplantation (KT) is one of the treatment options for patients with chronic kidney disease. The number of patients waiting for kidney transplantation is growing day by day. Various strategies have been put in place to expand the donor pool. Extended criteria donors are now accepted more frequently. Increasing number of elderly donors with age > 60 years, history of diabetes or hypertension, and clinical proteinuria are accepted as donor. Dual kidney transplantation (DKT) is also more frequently done and experience with this technique is slowly building up. DKT not only helps to reduce the number of patients on waiting list but also limits unnecessary discard of viable organs. Surgical complications of DKT are comparable to single kidney transplantation (SKT). Patient and graft survivals are also promising. This review article provides a summary of evidence available in the literature.

  15. Dietary Cadmium Intake and Its Effects on Kidneys

    Directory of Open Access Journals (Sweden)

    Soisungwan Satarug

    2018-03-01

    Full Text Available Cadmium (Cd is a food-chain contaminant that has high rates of soil-to-plant transference. This phenomenon makes dietary Cd intake unavoidable. Although long-term Cd intake impacts many organ systems, the kidney has long been considered to be a critical target of its toxicity. This review addresses how measurements of Cd intake levels and its effects on kidneys have traditionally been made. These measurements underpin the derivation of our current toxicity threshold limit and tolerable intake levels for Cd. The metal transporters that mediate absorption of Cd in the gastrointestinal tract are summarized together with glomerular filtration of Cd and its sequestration by the kidneys. The contribution of age differences, gender, and smoking status to Cd accumulation in lungs, liver, and kidneys are highlighted. The basis for use of urinary Cd excretion to reflect body burden is discussed together with the use of urinary N-acetyl-β-d-glucosaminidase (NAG and β2-microglobulin (β2-MG levels to quantify its toxicity. The associations of Cd with the development of chronic kidney disease and hypertension, reduced weight gain, and zinc reabsorption are highlighted. In addition, the review addresses how urinary Cd threshold levels have been derived from human population data and their utility as a warning sign of impending kidney malfunction.

  16. Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II

    Science.gov (United States)

    Gleitz, Hélène F. E.; O’Leary, Claire; Holley, Rebecca J.

    2017-01-01

    Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this. Therapeutic efficacy and subsequent validation can be assessed using a variety of outcome measures that are translatable to clinical practice, such as behavioural measures. We sought to consolidate current knowledge of the cognitive, skeletal and motor abnormalities present in the MPS II mouse model by performing time course behavioural examinations of working memory, anxiety, activity levels, sociability and coordination and balance, up to 8 months of age. Cognitive decline associated with alterations in spatial working memory is detectable at 8 months of age in MPS II mice using spontaneous alternation, together with an altered response to novel environments and anxiolytic behaviour in the open-field. Coordination and balance on the accelerating rotarod were also significantly worse at 8 months, and may be associated with skeletal changes seen in MPS II mice. We demonstrate that the progressive nature of MPS II disease is also seen in the mouse model, and that cognitive and motor differences are detectable at 8 months of age using spontaneous alternation, the accelerating rotarod and the open-field tests. This study establishes neurological, motor and skeletal measures for use in pre-clinical studies to develop therapeutic approaches in MPS II. PMID:28207863

  17. Infants with prenatally diagnosed kidney anomalies have an increased risk of urinary tract infections

    DEFF Research Database (Denmark)

    Rasmussen, Maria; Sunde, Lone; Andersen, René F

    2017-01-01

    AIM: This study estimated the urinary tract infection (UTI) risk in a nationwide cohort of infants prenatally diagnosed with parenchymal kidney anomalies compared with a comparison cohort. METHODS: A Danish population-based nationwide cohort of foetuses diagnosed with parenchymal kidney anomalies...... between 2007 and 2012 had previously been identified. These were compared with foetuses without kidney anomalies who were prenatally scanned the same year. Live born infants were followed from birth until the diagnosis of UTI, emigration, death or two years of age. Cumulative incidences of UTIs were...... computed. Mortality was estimated using the Kaplan-Meier method. RESULTS: We identified 412 foetuses with parenchymal kidney anomalies out of 362 069 who underwent ultrasound scans and 277 were born alive. The overall risk of a UTI before the age of two years was 19%, and it was 14% among infants without...

  18. Recovery of aging-related size increase of skin epithelial cells: in vivo mouse and in vitro human study.

    Directory of Open Access Journals (Sweden)

    Igor Sokolov

    Full Text Available The size increase of skin epithelial cells during aging is well-known. Here we demonstrate that treatment of aging cells with cytochalasin B substantially decreases cell size. This decrease was demonstrated on a mouse model and on human skin cells in vitro. Six nude mice were treated by topical application of cytochalasin B on skin of the dorsal left midsection for 140 days (the right side served as control for placebo treatment. An average decrease in cell size of 56±16% resulted. A reduction of cell size was also observed on primary human skin epithelial cells of different in vitro age (passages from 1 to 8. A cell strain obtained from a pool of 6 human subjects was treated with cytochalasin B in vitro for 12 hours. We observed a decrease in cell size that became statistically significant and reached 20-40% for cells of older passage (6-8 passages whereas no substantial change was observed for younger cells. These results may be important for understanding the aging processes, and for cosmetic treatment of aging skin.

  19. Age-dependent variations of zinc-65 metabolism in LACA mice

    International Nuclear Information System (INIS)

    He Liusheng; Yan Xiaoshan; Wu Dechang

    1991-01-01

    Mice were gavaged with zinc-65 solution, 8.6-19.3 kBq per mouse, and the whole-body retention and organ content of zinc-65 measured at diffe-rent times afterwards. The age-dependence of the fractional absorption of zinc-65 from the gastrointestinal tract (f 1 ) endogenous faecal excretion fraction of zinc-65 (EFEF), tissue distribution and whole-body retention were determined. f 1 values obtained were 0.86 ±0.15, 0.64±0.11, 0.52±0.07 and 0.39±0.02 in suckling, adolescent, young adult and older mice, respectively. The EFEF values determined were 0.083±0.008, 0.099±0.004, 0.122±0.018 and 0.144±0.005 of intraperitoneally injected zinc-65 was in suckling, adolescent, young adult and older mice at administration. Zinc-65 mainly distributed in the liver, muscle, lung, kidney and bone. In some tissues, there was an inverse relationship between relative content of gavaged zinc-65 and animal's age at administration. The whole-body biological half-lives of zinc-65 increased with animal age. (author)

  20. Pharmacokinetics of WR-1065 in mouse tissue following treatment with WR-2721

    International Nuclear Information System (INIS)

    Utley, J.F.; Seaver, N.; Newton, G.L.; Fahey, R.C.

    1984-01-01

    Levels of reduced glutathione (GSH) and N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065) were measured in tissues of Balb/c mouse bearing EMT 6 tumors at time intervals ranging from 5 min to 48 hr after i.v. injection of S-2-(3-aminopropylamino)ethyl phosphorothioate (WR-2721) at 500 mg per kg. In all tissues examined (liver, kidney, lung, heart, muscle, brain, tumor, spleen, and salivary gland), maximal WR-1065 levels occurred 5-15 min after injection, with levels in liver, kidney, lung, and salivary gland exceeding one μmole per gm. The post-maximum decline in WR-1065 varied markedly with tissue, lung exhibiting a 6-fold drop by 30 min and salivary gland falling only 15% after 3 hr. In a mouse treated with carbon-14 labeled WR-2721 it was found after 15 min that WR-1065 accounted for over half of the total drug in all tissues except tumor, where it accounted for a third of the total drug. There was no evidence that GSH levels were substantially altered by WR-2721 treatment. The results provide the first direct evidence supporting the widely held view that WR-2721 treatment results in intracellular WR-1065 and they demonstrate that high levels of WR-1065 occur very soon after i.v. injection

  1. Evaluation of {sup 123}I-orthoiodohippurate single kidney clearance rate by renal sequential scintigraphy in a large cohort of likely normal subjects aged between 0 and 18 years

    Energy Technology Data Exchange (ETDEWEB)

    Imperiale, Alessio; Olianti, Catia; Comis, Giannetto; Cava, Giuseppe la [University of Florence, Nuclear Medicine Unit, Department of Clinical Pathophysiology, Florence (Italy)

    2006-12-15

    Age-related values of{sup 123}I-orthoiodohippurate (OIH) single kidney clearance rate (Cl) were estimated in a large cohort of likely normal children aged between 0 and 18 years. Among 4,111 children examined in the past 10 years, 917 were selected with the following inclusion criteria: (a) mild ultrasonographic hydronephrosis with right differential renal function (DRF) <53% and >47% (498 pts), (b) known or suspected urinary tract infection with normal ultrasound, serum creatinine and DMSA and DRF <53% and >47% (419 pts).{sup 123}I-OIH-Cl was assessed using a validated gamma camera method. Children were divided into 21 age classes: from 0 to 2 years, eight 3-month classes; from 2 to 14 years, twelve 1-year classes; from 14 to 18 years, one 4-year class. Cl, plotted against age, was fitted using an increasing function (y = a - be - cx). Mean{sup 123}I-OIH-Cl of 1,834 kidneys was 306{+-}22 ml/min/1.73 m{sup 2} BSA. Mean{sup 123}I-OIH-Cl of the right and left kidneys was 307{+-}23 and 305{+-}22 ml/min/1.73 m{sup 2} BSA, respectively (p<0.002). The best-fitting{sup 123}I-OIH-Cl growing function was: Cl=311-230e-0.69 x Age (months).{sup 123}I-OIH-Cl improved progressively starting from birth, reaching 96% and 98% of the mature value at 1 and 1.5 years, respectively.{sup 123}I-OIH-Cl at birth (age=0) was 81 ml/min/1.73 m{sup 2} BSA. After 18.6 days of life, the renal function had doubled its starting value, and it reached a plateau of 311 ml/min/1.73 m{sup 2} BSA at 2 years. This work represents a systematic evaluation of ERPF by a gamma camera method in a large cohort of selected likely normal paediatric subjects. (orig.)

  2. The Relationship Between Pulmonary Emphysema and Kidney Function in Smokers

    Science.gov (United States)

    Chandra, Divay; Stamm, Jason A.; Palevsky, Paul M.; Leader, Joseph K.; Fuhrman, Carl R.; Zhang, Yingze; Bon, Jessica; Duncan, Steven R.; Branch, Robert A.; Weissfeld, Joel; Gur, David; Gladwin, Mark T.

    2012-01-01

    Background: It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV1. Methods: Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. Results: The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m2. Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m2 (P = .01), independent of airflow obstruction (FEV1), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV1 or quantitative CT scan measures of airway dimension. Conclusions: More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV1. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation. PMID:22459775

  3. Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

    Science.gov (United States)

    Nguyen, Kevin A; Syed, Jamil S; Espenschied, Carin R; LaDuca, Holly; Bhagat, Ansh M; Suarez-Sarmiento, Alfredo; O'Rourke, Timothy K; Brierley, Karina L; Hofstatter, Erin W; Shuch, Brian

    2017-11-15

    Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P kidney cancer. Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. A Soft Computing Approach to Kidney Diseases Evaluation.

    Science.gov (United States)

    Neves, José; Martins, M Rosário; Vilhena, João; Neves, João; Gomes, Sabino; Abelha, António; Machado, José; Vicente, Henrique

    2015-10-01

    Kidney renal failure means that one's kidney have unexpectedly stopped functioning, i.e., once chronic disease is exposed, the presence or degree of kidney dysfunction and its progression must be assessed, and the underlying syndrome has to be diagnosed. Although the patient's history and physical examination may denote good practice, some key information has to be obtained from valuation of the glomerular filtration rate, and the analysis of serum biomarkers. Indeed, chronic kidney sickness depicts anomalous kidney function and/or its makeup, i.e., there is evidence that treatment may avoid or delay its progression, either by reducing and prevent the development of some associated complications, namely hypertension, obesity, diabetes mellitus, and cardiovascular complications. Acute kidney injury appears abruptly, with a rapid deterioration of the renal function, but is often reversible if it is recognized early and treated promptly. In both situations, i.e., acute kidney injury and chronic kidney disease, an early intervention can significantly improve the prognosis. The assessment of these pathologies is therefore mandatory, although it is hard to do it with traditional methodologies and existing tools for problem solving. Hence, in this work, we will focus on the development of a hybrid decision support system, in terms of its knowledge representation and reasoning procedures based on Logic Programming, that will allow one to consider incomplete, unknown, and even contradictory information, complemented with an approach to computing centered on Artificial Neural Networks, in order to weigh the Degree-of-Confidence that one has on such a happening. The present study involved 558 patients with an age average of 51.7 years and the chronic kidney disease was observed in 175 cases. The dataset comprise twenty four variables, grouped into five main categories. The proposed model showed a good performance in the diagnosis of chronic kidney disease, since the

  5. Identifying potential kidney donors using social networking web sites.

    Science.gov (United States)

    Chang, Alexander; Anderson, Emily E; Turner, Hang T; Shoham, David; Hou, Susan H; Grams, Morgan

    2013-01-01

    Social networking sites like Facebook may be a powerful tool for increasing rates of live kidney donation. They allow for wide dissemination of information and discussion and could lessen anxiety associated with a face-to-face request for donation. However, sparse data exist on the use of social media for this purpose. We searched Facebook, the most popular social networking site, for publicly available English-language pages seeking kidney donors for a specific individual, abstracting information on the potential recipient, characteristics of the page itself, and whether potential donors were tested. In the 91 pages meeting inclusion criteria, the mean age of potential recipients was 37 (range: 2-69); 88% were US residents. Other posted information included the individual's photograph (76%), blood type (64%), cause of kidney disease (43%), and location (71%). Thirty-two percent of pages reported having potential donors tested, and 10% reported receiving a live-donor kidney transplant. Those reporting donor testing shared more potential recipient characteristics, provided more information about transplantation, and had higher page traffic. Facebook is already being used to identify potential kidney donors. Future studies should focus on how to safely, ethically, and effectively use social networking sites to inform potential donors and potentially expand live kidney donation. © 2013 John Wiley & Sons A/S.

  6. Normal standards for kidney length as measured with US in premature infants

    International Nuclear Information System (INIS)

    Schlesinger, A.E.; Hedlund, G.L.; Pierson, W.P.; Null, D.M.

    1986-01-01

    In order to develop normal standards for kidney length in premature infants, the authors measured kidney length by US imaging in 39 (to date) premature infants less than 72 hours old and without known renal disease. Kidney length was compared with four different parameters of body size, including gestational age, birth weight, birth length, and body surface area. Similar standards have been generated previously for normal renal length as measured by US imaging in full-term infants and older children. These standards have proven utility in cases of congenital and acquired disorders that abnormally increase or decrease renal size. Scatter plots of kidney length versus body weight and kidney length versus body surface area conformed well to a logarithmic distribution, with a high correlation coefficient and close-fitting 95% confidence limits (SEE = 2.05)

  7. Acute kidney failure

    Science.gov (United States)

    ... Renal failure - acute; ARF; Kidney injury - acute Images Kidney anatomy References Devarajan P. Biomarkers for assessment of renal function during acute kidney injury. In: Alpern RJ, Moe OW, Caplan M, ...

  8. Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

    Science.gov (United States)

    Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

    2017-01-01

    Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

  9. HYPERTENSION AND OBESITY AND THE RISK OF KIDNEY CANCER IN TWO LARGE COHORTS OF US MEN AND WOMEN

    Science.gov (United States)

    Sanfilippo, Kristen M.; McTigue, Kathleen M.; Fidler, Christian J.; Neaton, James D.; Chang, Yuefang; Fried, Linda F.; Liu, Simin; Kuller, Lewis H.

    2014-01-01

    Kidney cancer incidence is increasing globally. Reasons for this rise are unclear, but could relate to obesity and hypertension. We analyzed longitudinal relationships between hypertension and obesity and kidney cancer incidence in 156,774 participants of the Women’s Health Initiative (WHI) clinical trials and observational studies over 10.8 years. In addition, we examined the impact of blood pressure (BP) on kidney cancer deaths over 25 years among the 353,340 men screened for the Multiple Risk Factor Intervention Trial (MRFIT). In the WHI, systolic SBP was categorized in 6 groups from 160 mmHg and body mass index (BMI) was categorized using standard criteria. In age-adjusted analyses, kidney cancer risk increased across SBP categories (p-value for trend kidney cancer. In the MRFIT sample, there were 906 deaths after an average of 25 years of follow-up attributed to kidney cancer amongst the 353,340 participants aged 35–57 years at screening. The risk of death from kidney cancer increased in a dose-response fashion with increasing SBP (HR=1.87 for SBP>160 versus kidney cancer, and whether specific drug therapies for hypertension can reduce kidney cancer risk. PMID:24637660

  10. Poor embryo development in post-ovulatory in vivo-aged mouse oocytes is associated with mitochondrial dysfunction, but mitochondrial transfer from somatic cells is not sufficient for rejuvenation.

    Science.gov (United States)

    Igarashi, Hideki; Takahashi, Toshifumi; Abe, Hiroyuki; Nakano, Hiroshi; Nakajima, Osamu; Nagase, Satoru

    2016-10-01

    Does in vivo aging of mouse oocytes affect mitochondrial function? Mitochondrial function was impaired in post-ovulatory in vivo-aged mouse oocytes and microinjection of somatic cell mitochondria did not rescue poor fertilization and embryonic development rates. The mechanisms underlying the decline in oocyte quality associated with oocyte aging remain unknown, although studies have suggested that the decline is regulated by mitochondrial dysfunction. However, only a limited number of studies have provided direct evidence implicating mitochondrial dysfunction in oocyte quality during the aging of oocytes. We used post-ovulatory, in vivo-aged mouse oocytes as a model for studying low-quality oocytes in oocyte aging. Superovulated oocytes released from the oviduct at 14 h and 20-24 h post-hCG injection were designated as 'fresh' and 'aged' oocytes, respectively. Membrane potentials and oxygen consumption in single oocytes were evaluated as measures of mitochondrial function in fresh and aged oocytes. Mitochondrial transcriptional factor A (TFAM) expression levels were examined by western blotting, and colocalization of mitochondria and TFAM was analyzed by measuring immunofluorescence in fresh and aged oocytes. IVF and blastocyst formation rates were calculated after oocyte microinjection with mitochondria derived from liver cells. The average mitochondrial membrane potential in fresh oocytes was significantly higher than that in aged oocytes (P transfer of cytosolic factors or cellular organelles, such as the endoplasmic reticulum or mitochondria, from specific cell types. This study was supported by Grants-in-Aid for General Science Research to Toshifumi Takahashi (No. 25462550) and Hideki Igarashi (No. 26462474). The funding source played no role in study design in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The authors have no conflict of interest to disclose.

  11. Cadmium and the kidney.

    OpenAIRE

    Friberg, L

    1984-01-01

    The paper is a review of certain aspects of importance of cadmium and the kidney regarding the assessment of risks and understanding of mechanisms of action. The review discusses the following topics: history and etiology of cadmium-induced kidney dysfunction and related disorders; cadmium metabolism, metallothionein and kidney dysfunction; cadmium in urine as indicator of body burden, exposure and kidney dysfunction; cadmium levels in kidney and liver as indicators of kidney dysfunction; cha...

  12. Aged garlic extract modulates the oxidative modifications induced by γ-rays in mouse bone marrow and erythrocytes cells

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Elshamy, E.; Sallam, M.H.

    2006-01-01

    Gamma-ray generate hydroxyl radicals in cells and induce cellular DNA damage which leads to genotoxicity and chromosomes aberrations. The radioprotective and therapeutic efficacy of aged garlic extract (AGE) was investigated with micronucleus method as a reliable method for the detection of chromosomes damage induced by chemical and radiation. The frequency of micronuclei found in bone marrow erythroblast cells of the Protected and treated groups with 1.0 ml/20 g body wt/day for 10 consecutive days were significantly much lower than that of the exposed groups to γ-irradiation without protection or treatment. In addition, the enzyme activities of mouse erythrocyte antioxidant defense mechanism: superoxide dismutase (SOD), glutathione peroxidase (GSH-P x ) and glutathione reductase (GSH-R) were markedly decreased after irradiation while in protected and treated groups with Age showed significant increase but did not reach the control level except for Gash-R activity of protected group

  13. Kidney transplant in diabetic patients: modalities, indications and results

    Directory of Open Access Journals (Sweden)

    Rangel Érika B

    2009-08-01

    Full Text Available Abstract Background Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy. Conclusion Type 1 and 2 diabetic patients present higher survival rates after transplant in comparison to the dialysis therapy, although the prevalence of cardiovascular events and infectious complications remain higher than in the general population.

  14. High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

    Science.gov (United States)

    Malinouski, Mikalai; Kehr, Sebastian; Finney, Lydia; Vogt, Stefan; Carlson, Bradley A.; Seravalli, Javier; Jin, Richard; Handy, Diane E.; Park, Thomas J.; Loscalzo, Joseph; Hatfield, Dolph L.

    2012-01-01

    Abstract Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA[Ser]Sec and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. Innovation: We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. Conclusion: XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution. Antioxid. Redox Signal. 16, 185–192. PMID:21854231

  15. Accumulation of long-chain glycosphingolipids during aging is prevented by caloric restriction.

    Directory of Open Access Journals (Sweden)

    María José Hernández-Corbacho

    Full Text Available Chronic kidney disease and end-stage renal disease are major causes of morbidity and mortality that are seen far more commonly in the aged population. Interestingly, kidney function declines during aging even in the absence of underlying renal disease. Declining renal function has been associated with age-related cellular damage and dysfunction with reports of increased levels of apoptosis, necrosis, and inflammation in the aged kidney. Bioactive sphingolipids have been shown to regulate these same cellular processes, and have also been suggested to play a role in aging and cellular senescence.We hypothesized that alterations in kidney sphingolipids play a role in the declining kidney function that occurs during aging. To begin to address this, the sphingolipid profile was measured in young (3 mo, middle aged (9 mo and old (17 mo C57BL/6 male mice. Interestingly, while modest changes in ceramides and sphingoid bases were evident in kidneys from older mice, the most dramatic elevations were seen in long-chain hexosylceramides (HexCer and lactosylceramides (LacCer, with C14- and C16-lactosylceramides elevated as much as 8 and 12-fold, respectively. Increases in long-chain LacCers during aging are not exclusive to the kidney, as they also occur in the liver and brain. Importantly, caloric restriction, previously shown to prevent the declining kidney function seen in aging, inhibits accumulation of long-chain HexCer/LacCers and prevents the age-associated elevation of enzymes involved in their synthesis. Additionally, long-chain LacCers are also significantly elevated in human fibroblasts isolated from elderly individuals.This study demonstrates accumulation of the glycosphingolipids HexCer and LacCer in several different organs in rodents and humans during aging. In addition, data demonstrate that HexCer and LacCer metabolism is regulated by caloric restriction. Taken together, data suggest that HexCer/LacCers are important mediators of cellular

  16. Histopathologic Findings of Potential Kidney Donors With Asymptomatic Microscopic Hematuria: Impact on Donation.

    Science.gov (United States)

    Hassan, E A; Ali, T Z; Abdulbaki, A; Ibrahim, I A; Almanae, H M; Aleid, H A

    2017-10-01

    Isolated microscopic hematuria (IMH) is not uncommon in potential kidney donors. The aim was to study the kidney biopsy findings of potential kidney donors with IMH and the impact of the histopathologic diagnoses on the decision to accept or decline such donors from kidney donation. In this retrospective study, all the potential kidney donors with IMH were identified from the medical records of patients who underwent kidney biopsies between January 2010 and December 2016. Forty-five such individuals were identified. The mean age of these potential donors was 32.6 years and 76% were male. All of them had normal blood pressure and no significant proteinuria. Seventeen (38%) biopsies showed histopathologic abnormalities; thin basement membrane disease (n = 13; 28%) was the most common cause followed by immunoglobulin (Ig)A nephropathy (n = 4; 9%). Donors with abnormal biopsy findings were excluded from donation. However, 62% of the potential donors had normal kidney biopsy findings and were accepted for kidney donation. IMH justifies extensive work-up including kidney biopsy to identify donors who may have underlying significant glomerular pathology excluding them from kidney donation. On the other hand, kidney biopsy also helps in accepting the donors if it does not show significant abnormality. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. SIRT1 signalling protects mouse oocytes against oxidative stress and is deregulated during aging.

    Science.gov (United States)

    Di Emidio, Giovanna; Falone, Stefano; Vitti, Maurizio; D'Alessandro, Anna Maria; Vento, Marilena; Di Pietro, Cinzia; Amicarelli, Fernanda; Tatone, Carla

    2014-09-01

    Is SIRT1 involved in the oxidative stress (OS) response in mouse oocytes? SIRT1 plays a pivotal role in the adaptive response of mouse germinal vesicle (GV) oocytes to OS and promotes a signalling cascade leading to up-regulation of the MnSod gene. OS is known to continuously threaten acquisition and maintenance of oocyte developmental potential during in vivo processes and in vitro manipulations. Previous studies in somatic cells have provided strong evidence for the role of SIRT1 as a sensor of the cell redox state and a protector against OS and aging. GV oocytes obtained from young (4-8 weeks) and reproductively old (48-52 weeks) CD1 mice were blocked in the prophase stage by 0.5 µM cilostamide. Groups of 30 oocytes were exposed to 25 µM H2O2 and processed following different times for the analysis of intracellular localization of SIRT1 and FOXO3A, and evaluation of Sirt1, miRNA-132, FoxO3a and MnSod gene expression. Another set of oocytes was cultured in the presence or absence of the SIRT1-specific inhibitor Ex527, and exposed to H2O2 in order to assess the involvement of SIRT1 in the activation of a FoxO3a-MnSod axis and ROS detoxification. In the last part of this study, GV oocytes were maturated in vitro in the presence of different Ex527 concentrations (0, 2.5, 5, 10, 20 µM) and assessed for maturation rates following 16 h. Effects of Ex527 on spindle morphology and ROS levels were also evaluated. SIRT1 and FOXO3A intracellular distribution in response to OS was investigated by immunocytochemistry. Real-time RT-PCR was employed to analyse Sirt1, miR-132, FoxO3a and MnSod gene expression. Reactive oxygen species (ROS) production was evaluated by in vivo measurement of carboxy-H2DCF diacetate labelling. Spindle and chromosomal distribution in in vitro matured oocytes were analysed by immunocytochemistry and DNA fluorescent labelling, respectively. Specific changes in the intracellular localization of SIRT1 and up-regulation of Sirt1 gene were detected in

  18. Skin autofluorescence as a measure of advanced glycation endproduct deposition: a novel risk marker in chronic kidney disease.

    Science.gov (United States)

    Smit, Andries J; Gerrits, Esther G

    2010-11-01

    Skin autofluorescence (SAF) is a new method to noninvasively assess accumulation of advanced glycation endproducts (AGEs) in a tissue with low turnover. Recent progress in the clinical application of SAF as a risk marker for diabetic nephropathy as well as cardiovascular disease in nondiabetic end-stage kidney disease, less advanced chronic kidney disease, and renal transplant recipients is reviewed. Experimental studies highlight the fundamental role of the interaction of AGEs with the receptor for AGEs (RAGEs), also called the AGE-RAGE axis, in the pathogenesis of vascular and chronic kidney disease. SAF predicts (cardiovascular) mortality in renal failure and also chronic renal transplant dysfunction. Long-term follow-up results from the Diabetes Control and Complications Trial and UK Prospective Diabetes Study suggest that AGE accumulation is a key carrier of metabolic memory and oxidative stress. Short-term intervention studies in diabetic nephropathy with thiamine, benfotiamine and angiotensin-receptor blockers aimed at reducing AGE formation have reported mixed results. SAF is a noninvasive marker of AGE accumulation in a tissue with low turnover, and thereby of metabolic memory and oxidative stress. SAF independently predicts cardiovascular and renal risk in diabetes, as well as in chronic kidney disease. Further long-term studies are required to assess the potential benefits of interventions to reduce AGE accumulation.

  19. Rhabdomyosarcoma of the kidney

    Directory of Open Access Journals (Sweden)

    Alaa Samkari

    2018-05-01

    Full Text Available Rhabdomyosarcoma is considered the most common soft tissue sarcoma arising in patients younger than 15 years old, accounting for 5%–10% of childhood solid tumors. Sarcoma of the kidney represents 1% of all primary renal malignancies. Primary renal rhabdomyosarcoma is a very rare entity with limited number of cases reported in the literature. In this paper we present two cases of primary renal rhabdomyosarcoma in pediatric patients. The two tumors involved the renal parenchyma and occurred in 2-year-old girl and 6-year-old boy, respectively. Histopathology examination and immunohistochemistry studies confirm the diagnosis of embryonal rhabdomyosarcoma with pleomorphic component, and pleomorphic rhabdomyosarcoma, respectively. Both cases are treated with chemotherapy and show a good response with no evidence of recurrence or metastasis. The aim of this paper is to expand the differential diagnosis of primary mesenchymal kidney tumors in pediatric age group. Keywords: Rhabdomyosarcoma, Renal neoplasm, Pediatric, Oncology

  20. The risk factors for diabetes mellitus after kidney transplantation

    International Nuclear Information System (INIS)

    Effat Razeghi; Monireh Amerian; Peimaneh Heydarian

    2010-01-01

    Post-transplant diabetes mellitus (PTDM) is an adverse complication of kidney transplantation, associated with decreased graft and patient survival. We investigated the risk factors for PTDM and their relation to graft rejection in our kidney transplant recipients. We prospectively included 109 consecutive first kidney transplant recipients transplanted at the Sina Hospital in Tehran from June 2003 to May 2004. Patients were excluded if they had diabetes at the time of transplantation either as the cause of kidney failure or as a comorbidity. PTDM was defined by fasting blood sugar =126 mg/dL or random blood sugar =200 mg/dL on two occasions and the need for insulin therapy and/or oral hypoglycemic drugs for at least two weeks. Thirty non-diabetic transplant recipients were diagnosed as having PTDM during the six month followup period after transplantation. Sixty non-PTDM controls, matched for age, sex and immun suppressive regimen, and transplanted as closely as possible to the PTDM cases, were randomly selected. The risk factors for PTDM were investigated in these 90 transplant recipients. Age older than 50 years (P = 0.04), history of hypertension (P = 0.02), polycystic kidney disease (P = 0.015), duration on dialysis more than one year (P < 0.0001), family history of diabetes mellitus (P < 0.0001), mean daily dose of prednisolone =15 mg/day (P < 0.0001) and cyclosporine =240 mg/day (P < 0.0001) were all more in the PTDM group. Also, the mean serum triglycerides was higher (P = 0.019) and there was an increased risk of graft rejection (P < 0.0001) in the PTDM group (Author).

  1. Role of cytosolic NADP+-dependent isocitrate dehydrogenase in ischemia-reperfusion injury in mouse kidney

    OpenAIRE

    Kim, Jinu; Kim, Ki Young; Jang, Hee-Seong; Yoshida, Takumi; Tsuchiya, Ken; Nitta, Kosaku; Park, Jeen-Woo; Bonventre, Joseph V.; Park, Kwon Moo

    2008-01-01

    Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expressio...

  2. Diabetic Kidney Problems

    Science.gov (United States)

    ... too high. Over time, this can damage your kidneys. Your kidneys clean your blood. If they are damaged, waste ... in your blood instead of leaving your body. Kidney damage from diabetes is called diabetic nephropathy. It ...

  3. Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study.

    Science.gov (United States)

    Jing, Jiaojiao; Kielstein, Jan T; Schultheiss, Ulla T; Sitter, Thomas; Titze, Stephanie I; Schaeffner, Elke S; McAdams-DeMarco, Mara; Kronenberg, Florian; Eckardt, Kai-Uwe; Köttgen, Anna

    2015-04-01

    Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. Data from 5085 CKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  4. Neurocognitive functions of pediatric kidney transplant recipients.

    Science.gov (United States)

    Molnar-Varga, Marta; Novak, Marta; Szabo, Attila J; Kelen, Kata; Streja, Elani; Remport, Adam; Mucsi, Istvan; Molnar, Miklos Z; Reusz, Gyorgy

    2016-09-01

    End-stage renal disease (ESRD) in children is associated with impaired neurocognitive function and development. However, data on factors associated with neurocognitive dysfunctions in children with kidney transplants are limited. We conducted a cross-sectional analysis comparing cognitive functions (using the Woodcock-Johnson International Edition, WJIE) in 35 kidney transplant and 35 healthy control children. Data on laboratory measurements, comorbidities, and social characteristics were collected. Transplant children had significantly worse scores on the intelligence quotient (IQ) test compared with controls [Full Scale IQ score 85 (26) vs 107 (10), p 9 months) were associated with lower test scores. Age-standardized duration of hospitalization was inversely correlated with IQ (r = -0.46, p <0.01) and was an independent significant predictor (Beta = -0.38, p = 0.02) of IQ scores in transplanted children. Child kidney transplant recipients have neurocognitive function impairments that are associated with markers of socioeconomic status (SES) and factors related to disease severity.

  5. Awareness and attitude to deceased kidney donation among health-care workers in Sokoto, Nigeria.

    Science.gov (United States)

    Agwu, Ngwobia Peter; Awosan, Kehinde Joseph; Ukwuani, Solomon Ifeanyi; Oyibo, Emmanuel Ugbede; Makusidi, Muhammad Aliyu; Ajala, Rotimi Abiodun

    2018-01-01

    Access to renal replacement therapy by the increasing population of patients with end-stage kidney disease across Sub-Saharan Africa, including Nigeria, has become a major public health challenge. Although deceased kidney donation constitutes a viable source, its uptake by patients is contingent on its acceptance by health-care workers. The aim of this study is to assess the awareness and attitude to deceased kidney donation among health-care workers in Sokoto, Nigeria. A cross-sectional study was conducted among 470 staff of Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria (attending a 1-week seminar), selected by universal sampling. Data were collected with a set of pretested, self-administered, and semi-structured questionnaire. The mean age of the respondents was 34.1 ± 7.8 years, and most of them (77.7%) were aged donation, only about half (51.9%) were willing to accept deceased kidney donation. Furthermore, 43.4% were willing to give consent to donate deceased relative's kidney, and 26.1% were willing to carry an organ donation card. Predictors of willingness to accept deceased kidney donation were male sex, being a medical doctor or laboratory scientist and being a Moslem (Odds ratio >2, P donation is crucial to promoting its acceptance among them.

  6. Functional recovery in the irradiated kidney following removal of the contralateral unirradiated kidney

    International Nuclear Information System (INIS)

    Robbins, M.E.C.; Hopewell, J.W.; Golding, S.J.

    1986-01-01

    Radiation-induced damage to one kidney in the pig causes a fall in total renal function; this would be recognised and lead to a compensatory response in the unirradiated kidney. The presence of the unirradiated contralateral kidney may effectively prevent the irradiated kidney from expressing any potential for repair and/or recovery of function. If this were true then the question would obviously arise, does the irradiated kidney retain some capacity for recovery? In order to answer this question, the contralateral unirradiated kidney was removed from pigs 26 weeks after the irradiation of the other kidney. The subsequent response of the irradiated kidney to nephrectomy was assessed in terms of the changes in renal size and haemodynamics, i.e. GFR and effective renal plasma flow (ERPF). (Auth.)

  7. Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-analysis

    NARCIS (Netherlands)

    Tangri, N.; Grams, M.E.; Levey, A.S.; Coresh, J.; Appel, L.J.; Astor, B.C.; Chodick, G.; Collins, A.J.; Djurdjev, O.; Elley, C.R.; Evans, M.; Garg, A.X.; Hallan, S.I.; Inker, L.A.; Ito, S.; Jee, S.H.; Kovesdy, C.P.; Kronenberg, F.; Heerspink, H.J.; Marks, A.; Nadkarni, G.N.; Navaneethan, S.D.; Nelson, R.G.; Titze, S.; Sarnak, M.J.; Stengel, B.; Woodward, M.; Iseki, K.; Wetzels, J.F.M.; et al.,

    2016-01-01

    IMPORTANCE: Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously

  8. Risk for cancer in living kidney donors and recipients.

    Science.gov (United States)

    Wang, Min; Zhang, Huai; Zhou, Dan; Qiao, Yong-Chao; Pan, Yan-Hong; Wang, Yan-Chao; Zhao, Hai-Lu

    2018-03-01

    Malignancy following renal transplantation remains inconsistent with the reported safety of kidney donation during the long-term follow-up. We conducted searches of the published literature which included healthy participants, recipients, living kidney donors (LKDs), and the availability of outcome data for malignancy. Eight from 938 potentially relevant studies were analyzed by means of fixed-effects model or random-effects model, as appropriately. In 48,950 participants, the follow-up range was 18 months to 20 years, and the mean age of the subjects was approximately 41 years. The incidence rate with 95% confidence interval (CI) for malignancy after kidney transplantation was 0.03 (0.01-0.05) in recipients and 0.03 (0.1-0.07) in LKDs, giving a pooled incidence rate of 0.03 (95% CI 0.02-0.04). LKDs contrasted nondonors by the overall odds ratio and 95% CI for total cancer of 2.80 (2.69-2.92). Kidney transplantation was associated with an increased risk of cancer during a long-term follow-up. Long-term risk for cancer in LKDs and kidney recipients should be monitored.

  9. Medullary Sponge Kidney

    Science.gov (United States)

    ... UTI removing any kidney stones Curing an Existing Urinary Tract Infection To treat a UTI , the health care provider ... UTIs and kidney stones. Medications to Prevent Future Urinary Tract Infections and Kidney Stones Health care providers may prescribe ...

  10. En bloc kidney transplantation: ultrasonography assessment

    International Nuclear Information System (INIS)

    Arenal, F.; Ganado, T.; Merino, M.S.; Contreras, E.; Hernandez, J.; Prats, D.

    1997-01-01

    The objective of our study is to assess the utility of ultrasonography in the study of the complications associated with en bloc kidney transplantation. Twenty-three recipients of double transplants from donors under the age of 3 years were studied. Ultrasound (mode B: pulsed Doppler and color Doppler) was performed within the first three postoperative days and was repeated at 6 and 12 months. The morphology of the graft and renal blood flow were assessed, and the indices of pulsatility, resistance and acceleration were measured. Four patients required graft explanation: three due to massive hemorrhagic infarction and one due to venous thrombosis. Vascular complications were detected in five transplants (21.7%), urological complications in four (17.4%) and medical complications in two (8.7%). The most common vascular complication was unilateral renal artery stenosis. Color Doppler ultrasound diagnosed all the medical and urological complications and three of the five cases of vascular pathology (60%). Renal size was seen to be increased during the first postoperative year. The ultrasonographic study is more difficult to perform in en bloc kidney transplantation than in single kidney grafting: however, given its marked sensitivity in the detection of postransplantation complications. Doppler ultrasound is the imaging technique of choice in the determination of the cause of deteriorated kidney function. (Author) 15 refs

  11. Smaller kidney size at birth in South Asians: findings from the Born in Bradford birth cohort study.

    Science.gov (United States)

    Roderick, Paul J; Jeffrey, Robin F; Yuen, Ho M; Godfrey, Keith M; West, Jane; Wright, John

    2016-03-01

    Rates of advanced chronic kidney disease and renal replacement therapy are higher in South Asian than in white British populations. Low birth weight is also more frequent in South Asian populations and has been associated with increased risks of kidney disease, perhaps due to a reduced nephron endowment. Using ultrasound scans at 34 weeks of gestation, we measured fetal kidney dimensions (transverse and anteroposterior diameters, length and circumference) and derived volume in a random sample of 872 white British and 715 South Asian participants in the Born in Bradford cohort study. Kidney measurements were compared between ethnic groups. Birth weight for gestational age at 40 weeks was 200 g less in South Asian babies compared with white British babies. The mean kidney volume for gestational age was 16% lower in South Asian than in white British babies [8.79 versus 10.45 cm(3), difference 1.66 cm(3) (95% confidence interval 1.40-1.93, P < 0.001)]. The difference was robust after adjustment for maternal age, socio-economic factors, marital status, body mass index, smoking and alcohol use in pregnancy, parity, baby's gender and birth weight for gestational age [adjusted difference 1.38 cm(3) (0.97-1.84), P < 0.001]. There were smaller reductions in other fetal measures. South Asian babies have smaller kidneys compared with white British babies, even after adjusting for potential confounders including birth weight. This finding may contribute to increased risks of adult kidney disease in South Asian populations. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. Changes of the glomerular size during the human fetal kidney development

    Directory of Open Access Journals (Sweden)

    Daković-Bjelaković Marija

    2006-01-01

    Full Text Available Introduction. Newborns adaptation on postnatal conditions includes significant morphological and functional renal changes. Every kidney contains a constant number of nephrons, at the end of the nephrogenesis period, which extends from week 8 to 34 of gestation. Mature juxtamedullary nephrons possess higher filtration capacity than primitive superficial nephrons, which have insufficient vascularization. Objective. The objective of the study was to calculate an average glomerular diameter in cortical zones of the kidney during development, to define periods of their most intensive growth, and to record differences of glomerular size between different cortical zones. METHOD A total of 30 human fetal kidneys aged from IV to X lunar months were analyzed. Stereological methods were used for calculating the average glomerular diameter in superficial, intermediate and juxtamedullary zone of the kidney cortex. Results. Glomeruli in the superficial cortical zone had the lowest average diameter. The average glomerular diameter continually increased from IV lunar month (0.057±0.004 mm to X lunar month (0.082±0.004 mm, with highly significant correlation with gestational age (r=0.755; p<0.01. The average glomerular diameter in the intermediate zone increased from 0.081±0.004 mm (IV lunar month to 0.096±0.004 mm (X lunar month with low linear correlation with gestational age (r=0.161. Juxtamedullary glomeruli were the biggest ones. Their average diameter, during the IV LM ranged from 0.093±0.006 mm to 0.101±0.004 mm. In the newborns (X lunar month, juxtamedullary glomeruli had spherical structures with an average diameter of 0.103±0.004 mm, and low negative correlation (r=-0.032 with gestational age. In the IV and V lunar months of gestation, there was significant difference (p<0.01; p<0.05 between the average glomerular diameter in the different zones of the kidney cortex. Conclusion. Superficial glomeruli had the smallest diameter, while

  13. Kidney Stones (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Kidney Stones KidsHealth / For Parents / Kidney Stones What's in ... other treatments to help remove the stones. How Kidney Stones Form It's the kidneys' job to remove ...

  14. Effects of bisphenol A on the metabolisms of active oxygen species in mouse tissues

    International Nuclear Information System (INIS)

    Kabuto, H.; Hasuike, S.; Minagawa, N.; Shishibori, T.

    2003-01-01

    We investigated the modifications in endogenous antioxidant capacity, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, oxidative stress index, reduced glutathione (GSH), glutathione disulfide (GSSG), and thiobarbituric acid-reactive substance (TBARS) in the brain, liver, kidney, and testes of mice under bisphenol A (BPA), an endocrine disrupter, treated for 5 days. BPA was administrated intraperitoneally at doses of 25 and 50 mg/kg/day. The TBARS levels were not affected by BPA administrations. The SOD activities increased and the catalase activities decreased in the liver after BPA administration. The GPx activity decreased in the kidney. The levels of GSH+GSSG increased in the brain, kidney, liver, and testes, while, the levels of GSH decreased in the testes. SOD converts superoxide into hydrogen peroxide, and catalase and GPx convert hydrogen peroxide into hydrogen oxide. Our results suggest that the injection of BPA induces overproduction of hydrogen peroxide in the mouse organs. Hydrogen peroxide is easily converted to hydroxy radical. The decrease of GSH and the increase of GSSG may be caused by the hydroxy radical. BPA may show its toxicity by increasing hydrogen peroxide

  15. Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal Mass.

    Science.gov (United States)

    Nguyen, Kevin A; Syed, Jamil S; Shuch, Brian

    2017-05-01

    The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Chronic Kidney Disease

    Science.gov (United States)

    You have two kidneys, each about the size of your fist. Their main job is to filter your blood. They remove wastes and ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  17. Upper gastrointestinal alterations in kidney transplant candidates.

    Science.gov (United States)

    Homse Netto, João Pedro; Pinheiro, João Pedro Sant'Anna; Ferrari, Mariana Lopes; Soares, Mirella Tizziani; Silveira, Rogério Augusto Gomes; Maioli, Mariana Espiga; Delfino, Vinicius Daher Alvares

    2018-05-14

    The incidence of gastrointestinal disorders among patients with chronic kidney disease (CKD) is high, despite the lack of a good correlation between endoscopic findings and symptoms. Many services thus perform upper gastrointestinal (UGI) endoscopy on kidney transplant candidates. This study aims to describe the alterations seen on the upper endoscopies of 96 kidney-transplant candidates seen from 2014 to 2015. Ninety-six CKD patients underwent upper endoscopic examination as part of the preparation to receive kidney grafts. The data collected from the patients' medical records were charted on Microsoft Office Excel 2016 and presented descriptively. Mean values, medians, interquartile ranges and 95% confidence intervals of the clinic and epidemiological variables were calculated. Possible associations between endoscopic findings and infection by H. pylori were studied. Males accounted for 54.17% of the 96 patients included in the study. Median age and time on dialysis were 50 years and 50 months, respectively. The most frequent upper endoscopy finding was enanthematous pangastritis (57.30%), followed by erosive esophagitis (30.20%). Gastric intestinal metaplasia and peptic ulcer were found in 8.33% and 7.30% of the patients, respectively. H. pylori tests were positive in 49 patients, and H. pylori infection was correlated only with non-erosive esophagitis (P = 0.046). Abnormal upper endoscopy findings were detected in all studied patients. This study suggested that upper endoscopy is a valid procedure for kidney transplant candidates. However, prospective studies are needed to shed more light on this matter.

  18. Kidneys and Urinary Tract

    Science.gov (United States)

    ... Videos for Educators Search English Español Kidneys and Urinary Tract KidsHealth / For Teens / Kidneys and Urinary Tract What's ... a sign of diabetes . What the Kidneys and Urinary Tract Do Although the two kidneys work together to ...

  19. Uncompensated polyuria in a mouse model of Bartter's syndrome

    Science.gov (United States)

    Takahashi, Nobuyuki; Chernavvsky, Daniel R.; Gomez, R. Ariel; Igarashi, Peter; Gitelman, Hillel J.; Smithies, Oliver

    2000-01-01

    We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2−/− pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of −/− pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued −/− adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the −/− adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney. PMID:10779555

  20. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: kvbenede@vub.ac.be [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: lvgrunsv@vub.ac.be [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)

    2013-09-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  1. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    International Nuclear Information System (INIS)

    Van Beneden, Katrien; Geers, Caroline; Pauwels, Marina; Mannaerts, Inge; Wissing, Karl M.; Van den Branden, Christiane; Grunsven, Leo A. van

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation

  2. Radiation carcinogenesis in mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, Ryo; Niwa, Ohtsura

    2006-01-01

    Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

  3. Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary

    Directory of Open Access Journals (Sweden)

    Longo Dan L

    2008-06-01

    Full Text Available Abstract Background The aging of reproductive organs is not only a major social issue, but of special interest in aging research. A long-standing view of 'immortal germ line versus mortal soma' poses an important question of whether the reproductive tissues age in similar ways to the somatic tissues. As a first step to understand this phenomenon, we examine global changes in gene expression patterns by DNA microarrays in ovaries and testes of C57BL/6 mice at 1, 6, 16, and 24 months of age. In addition, we compared a group of mice on ad libitum (AL feeding with a group on lifespan-extending 40% calorie restriction (CR. Results We found that gene expression changes occurred in aging gonads, but were generally different from those in somatic organs during aging. For example, only two functional categories of genes previously associated with aging in muscle, kidney, and brain were confirmed in ovary: genes associated with complement activation were upregulated, and genes associated with mitochondrial electron transport were downregulated. The bulk of the changes in gonads were mostly related to gonad-specific functions. Ovaries showed extensive gene expression changes with age, especially in the period when ovulation ceases (from 6 to 16 months, whereas testes showed only limited age-related changes. The same trend was seen for the effects of CR: CR-mediated reversal of age-associated gene expression changes, reported in somatic organs previously, was limited to a small number of genes in gonads. Instead, in both ovary and testis, CR caused small and mostly gonad-specific effects: suppression of ovulation in ovary and activation of testis-specific genes in testis. Conclusion Overall, the results are consistent with unique modes of aging and its modification by CR in testis and ovary.

  4. (LBP) extraction technology and its anti-aging effect

    African Journals Online (AJOL)

    The objective of the study was to optimise the LBP extraction technology and to study the anti-aging effect of LBP by establishing D-gal aging mouse model. Orthogonal design was used to study the extraction technology. The experimental aging mouse model was formed by continuous injection of D-gal, and the anti-aging ...

  5. Ultrasonography of the Kidney

    DEFF Research Database (Denmark)

    Lindskov Hansen, Kristoffer; Nielsen, Michael Bachmann; Ewertsen, Caroline

    2016-01-01

    Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most pathological changes in the kidneys are distinguishable with ultrasound. In this pictorial review, the most common findings in renal ultrasound...

  6. Does hypertension remain after kidney transplantation?

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand

    2015-05-01

    Full Text Available Hypertension is a common complication of kidney transplantation with the prevalence of 80%. Studies in adults have shown a high prevalence of hypertension (HTN in the first three months of transplantation while this rate is reduced to 50- 60% at the end of the first year. HTN remains as a major risk factor for cardiovascular diseases, lower graft survival rates and poor function of transplanted kidney in adults and children. In this retrospective study, medical records of 400 kidney transplantation patients of Sina Hospital were evaluated. Patients were followed monthly for the 1st year, every two months in the 2nd year and every three months after that. In this study 244 (61% patients were male. Mean ± SD age of recipients was 39.3 ± 13.8 years. In most patients (40.8% the cause of end-stage renal disease (ESRD was unknown followed by HTN (26.3%. A total of 166 (41.5% patients had been hypertensive before transplantation and 234 (58.5% had normal blood pressure. Among these 234 individuals, 94 (40.2% developed post-transplantation HTN. On the other hand, among 166 pre-transplant hypertensive patients, 86 patients (56.8% remained hypertensive after transplantation. Totally 180 (45% patients had post-transplantation HTN and 220 patients (55% didn't develop HTN. Based on the findings, the incidence of post-transplantation hypertension is high, and kidney transplantation does not lead to remission of hypertension. On the other hand, hypertension is one of the main causes of ESRD. Thus, early screening of hypertension can prevent kidney damage and reduce further problems in renal transplant recipients.

  7. Generation of a tenascin-C-CreER2 knockin mouse line for conditional DNA recombination in renal medullary interstitial cells.

    Directory of Open Access Journals (Sweden)

    Wenjuan He

    Full Text Available Renal medullary interstitial cells (RMIC are specialized fibroblast-like cells that exert important functions in maintaining body fluid homeostasis and systemic blood pressure. Here, we generated a RMIC specific tenascin-C promoter driven inducible CreER2 knockin mouse line with an EGFP reporter. Similar as endogenous tenascin-C expression, the reporter EGFP expression in the tenascin-C-CreER2(+/- mice was observed in the inner medulla of the kidney, and co-localized with COX2 but not with AQP2 or AQP1, suggesting selective expression in RMICs. After recombination (tenascin-C-CreER2(+/-/ROSA26-lacZ(+/- mice + tamoxifen, β-gal activity was restricted to the cells in the inner medulla of the kidney, and didn't co-localize with AQP2, consistent with selective Cre recombinase activity in RMICs. Cre activity was not obvious in other major organs or without tamoxifen treatment. This inducible RMIC specific Cre mouse line should therefore provide a novel tool to manipulate genes of interest in RMICs.

  8. Revisiting double kidney transplantation: two kidneys provide better graft survival than one.

    Science.gov (United States)

    Cruzado, J M; Fernandez, L; Riera, L; Bestard, O; Carrera, M; Torras, J; Gil Vernet, S; Melilli, E; Ngango, L; Grinyó, J M

    2011-01-01

    Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our "Dual Kidney Transplant program." Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our "old for old" renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the "old for old" program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Kidneys at Higher Risk of Discard: Expanding the Role of Dual Kidney Transplantation

    Science.gov (United States)

    Tanriover, B.; Mohan, S.; Cohen, D. J.; Radhakrishnan, J.; Nickolas, T. L.; Stone, P. W.; Tsapepas, D. S.; Crew, R. J.; Dube, G. K.; Sandoval, P. R.; Samstein, B.; Dogan, E.; Gaston, R. S.; Tanriover, J. N.; Ratner, L. E.; Hardy, M. A.

    2014-01-01

    Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI) >85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (90%). Kidneys with KDPI >90% were associated with increased odds of discard (OR = 1.99, 95% CI 1.74–2.29) compared to ones with KDPI 90% were associated with lower overall allograft failure (HR = 0.74, 95% CI 0.62–0.89) and better patient survival (HR = 0.79, 95% CI 0.64–0.98) compared to single ECD kidneys with KDPI >90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile. PMID:24472195

  10. Acute kidney injury in children with heart failure: any relationship to ...

    African Journals Online (AJOL)

    Materials and Method : Prospective study of cohort of children with heart failure were studied. Heart failure was defined using heart rate for age, respiratory rate for age and tender hepatomegaly. Acute kidney injury was based on absolute serum creatinine level > 0.5 mg/dl on admission. Age, gender, and out come we r e ...

  11. Concordance of outcomes of pairs of kidneys transplanted into different recipients.

    LENUS (Irish Health Repository)

    Traynor, Carol

    2012-09-01

    Kidney transplant outcomes are influenced by donor characteristics, including age and gender. Additional donor factors, both genetic and environmental, also influence graft outcome. We aim to assess the strength of donor factors in determining kidney transplant outcomes by comparing paired kidneys from a single donor transplanted into different recipients. We conducted a retrospective cohort study of outcomes of pairs of deceased donor kidneys transplanted in our centre between 1992 and 2008. We examined the relationship within pairs for eGFR at 1 year and at 5 years post-transplant using Spearman\\'s Correlation and the concordance of pairs of transplant kidneys with respect to the occurrence of acute rejection and delayed graft function (DGF). A total of 652 recipient pairs were analysed. Spearman\\'s correlation for eGFR was 0.36 at 1 year and 0.36 at 5 years post-transplant. The incidence of DGF was 11%. The odds ratio of DGF occurring if the contralateral kidney had DGF was 5.99 (95% CI, 3.19-11.25). There is a significant degree of relationship within pairs of kidneys transplanted from the same donor for serum creatinine at 1 year and 5 years post-transplant and also for the occurrence of delayed graft function.

  12. In vitro and in vivo transdermal delivery capacity of quantum dots through mouse skin

    International Nuclear Information System (INIS)

    Chu Maoquan; Wu Qiang; Wang Jiaxu; Hou Shengke; Miao Yi; Peng Jinliang; Sun Ye

    2007-01-01

    CdTe quantum dots (QDs) with red fluorescence have been used to study their transdermal delivery capacity through mouse skin. The results showed that the QDs could permeate through skin, either separated from or still attached to live mice. Although the fluorescence emitted by the QDs could only be found in the skin and muscle cells located under the mouse skins coated with QDs, an inductive coupled plasma atomic emission spectrometry (ICP-AES) study indicated that the main organs, such as the heart, liver, spleen, lung, kidney and brain, all contained a significant quantity of Cd atoms. Moreover, these Cd atoms could remain in vivo for at least one week. As a control, the concentration of Cd atoms in normal mice not coated with QDs was very low

  13. [Chronic kidney disease in Primary Health Care: prevalence and associated risk factors].

    Science.gov (United States)

    Salvador González, Betlem; Rodríguez Pascual, Mercedes; Ruipérez Guijarro, Laura; Ferré González, Antonia; Cunillera Puertolas, Oriol; Rodríguez Latre, Luisa M

    2015-04-01

    To determine the prevalence of chronic kidney disease and associated risk factors in subjects over 60 years of age, as well as its staging by determining the glomerular filtration rate (GFR). Cross-sectional observational study. Primary Health Care. Patients≥60 years of age who were seen in 40 Primary Health Care centres with serum creatinine measured in a central laboratory between January 1 and December 31, 2010. kidney transplant, home care. Social-demographic and anthropometric data, cardiovascular risk factors, and diseases established according to electronic clinical records. Serum creatinine was measured using standardised Jaffe kinetic method, and GFR estimated with MDRD-4-IDMS and CKD-EPI. A total of 97,665 subjects (57.3% women, median age 70.0 years [Q1: 65.0, Q3: 77.0]). GFR-MDRD prevalence<60=15.1% (16.6% in women, 13.2% in men; P<.001) and increased with age. Multivariate analysis showed a positive association between GFR-MDRD<60 and age (OR=1.74; 95% CI 1.70 to 1.77), hypertension (OR=2.18; 95% CI 2.08 to 2.30), heart failure (OR=2.03; 95% CI 1.83 to 2.25), atrial fibrillation (OR=1.57; 95% CI 1.41 to 1.76), ischaemic heart disease (OR=1.40; 95% CI 1.30 to 1.50), peripheral arterial disease (OR=1.31; 95% CI 1.09 to 1.57), dyslipidaemia (OR=1.28; 95% CI 1.23 to 1.33), diabetes (OR=1.26; 95% CI 1.17 to 1.34), and stroke (OR=1.17; 95% CI 1.09 to 1.25). The GFR-CKD-EPI model showed an increase in OR with age and male sex, that became significant as a chronic kidney disease risk factor. Chronic kidney disease has considerable prevalence in subjects≥60 years seen in Primary Health Care, more in women, and increasing with age. Hypertension, more than diabetes, was the main associated cardiovascular risk factor. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. Acute kidney injury in the cancer patient.

    Science.gov (United States)

    Campbell, G Adam; Hu, Daniel; Okusa, Mark D

    2014-01-01

    Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  15. Imaging of solid kidney tumours in children

    International Nuclear Information System (INIS)

    Hugosson, C.; Nyman, R.; Jacobsson, B.; Jorulf, H.; Sackey, K.; McDonald, P.

    1995-01-01

    Eighteen children aged 6 months to 12 years with 20 solid renal tumours; 13 Wilms' tumours (WT), 2 clear cell sarcomas of the kidney, 1 malignant rhabdoid tumour of the kidney and 2 cases of bilateral nephroblastomatosis with Wilms' tumour underwent evaluation with US, CT and MR imaging. Contrast-enhanced CT and non-enhanced MR were equally accurate in determining the size and origin of the tumour but were unreliable in separation of stages I, II and III. US could only accurately assess the size of the tumours. MR characteristics varied somewhat between WTs and non-WTs but contrast-enhanced MR imaging might be useful for separation of WTs from nephroblastomatosis. (orig.)

  16. Polyamine metabolism in the kidneys of castrated and testosterone-treated mice after administration of methylglyoxal bis(guanylhydrazone).

    Science.gov (United States)

    Henningsson, S; Persson, L; Rosengren, E

    1979-02-01

    The effects of methylglyoxal bis(guanylhydrazone) on S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) activity were studied in the mouse kidney stimulated to growth by testosterone administration. The drug was found a potent inhibitor of the enzyme in vitrol Administration of methylglyoxal bis(guanylhydrazone) in vivo resulted in a transient inhibition followed by a strong enhancement of the enzyme activity. Dialysis of the kidney extract, to remove remaining methylglyoxal bis(guanylhydrazone), revealed a great and rapid increase in the activity of S-adenosyl-L-methionine decarboxylase. Injections of testosterone to castrated mice resulted in a marked increase in kidney weight and an accumulation of renal putrescine, spermidine and spermine. These effects of testosterone could not be blocked by simultaneous injections of methylglyoxal bis(guanylhydrazone). It appears that due to secondary effects by which the inhibition of methylglyoxal bis(guanylhydrazone) on S-adenosyl-L-methionine decarboxylase activity is circumvented the inhibitor seems to be of uncertain value in attempts to decrease selectively the in vivo levels of polyamines.

  17. Aging-associated renal disease in mice is fructokinase dependent.

    Science.gov (United States)

    Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J

    2016-10-01

    Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.

  18. Kidney Cancer

    Science.gov (United States)

    ... kind of kidney cancer called Wilms' tumor. The incidence of kidney cancer seems to be increasing. One ... doesn't go away Loss of appetite Unexplained weight loss Tiredness Fever, which usually comes and goes ( ...

  19. Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

    Science.gov (United States)

    Falkevall, Annelie; Mehlem, Annika; Palombo, Isolde; Heller Sahlgren, Benjamin; Ebarasi, Lwaki; He, Liqun; Ytterberg, A Jimmy; Olauson, Hannes; Axelsson, Jonas; Sundelin, Birgitta; Patrakka, Jaakko; Scotney, Pierre; Nash, Andrew; Eriksson, Ulf

    2017-03-07

    Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population.

    Science.gov (United States)

    Liu, Dong-Wei; Wan, Jia; Liu, Zhang-Suo; Wang, Pei; Cheng, Gen-Yang; Shi, Xue-Zhong

    2013-04-01

    Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD. A total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, dyslipidemia and albuminuria/reduced eGFR. Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively. Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.

  1. Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

    Science.gov (United States)

    Bansal, Nisha; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen; Lima, Joao; Kramer, Holly; Shlipak, Michael; Bibbins-Domingo, Kirsten

    2016-02-01

    Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Observational study. We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year 25. eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). LVMI measured at year 25. We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n = 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n = 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (β coefficient, 1.48; 95% CI, 0.11-2.83; P = 0.03) after adjustment for confounders. There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated

  2. A simplified donor risk index for predicting outcome after deceased donor kidney transplantation.

    Science.gov (United States)

    Watson, Christopher J E; Johnson, Rachel J; Birch, Rhiannon; Collett, Dave; Bradley, J Andrew

    2012-02-15

    We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, Pinformed consent.

  3. Aging and low-grade inflammation reduce renal function in middle-aged and older adults in Japan and the USA.

    Science.gov (United States)

    Costello-White, Reagan; Ryff, Carol D; Coe, Christopher L

    2015-08-01

    The objective of this study was to investigate the effects of low-grade inflammation on age-related changes in glomerular filtration rate (GFR) in middle-aged and older white Americans, African-Americans, and Japanese adults. Serum creatinine, C-reactive protein (CRP), and interleukin-6 (IL-6) levels were determined for 1570 adult participants in two surveys of aging in the USA and Japan (N = 1188 and 382, respectively). Kidney function declined with age in both countries and was associated with IL-6 and CRP. IL-6 and CRP also influenced the extent of the arithmetic bias when calculating the GFR using the chronic kidney disease epidemiology (CKD-EPI) formula with just serum creatinine. Younger African-Americans initially had the highest GFR but showed a steep age-related decrement that was associated with elevated inflammation. Japanese adults had the lowest average GFR but evinced a large effect of increased inflammatory activity when over 70 years of age. Importantly, our results also indicate that low-grade inflammation is important to consider when evaluating kidney function solely from serum creatinine.

  4. [Hispanic American kidney patients in the age of online social networks: content analysis of postings, 2010 - 2012].

    Science.gov (United States)

    Mercado-Martínez, Francisco J; Urias-Vázquez, Jorge E

    2014-01-01

    Describe the use of online social networks by people with chronic kidney disease, their caregivers, and family members, living in Hispanic American countries, and identify the most frequent topics and subtopics in their postings. A qualitative study was conducted of postings by chronic kidney patients, their caregivers, and family members, living in Hispanic America, on five social networks: Blogger, Facebook, Twitter, WordPress, and YouTube, from 2010 to 2012. The internal search engines of each network were used with medical and lay terms in Spanish: chronic kidney disease, renal failure, peritoneal dialysis, hemodialysis, renal transplant, renal patient, nephropathy, and kidney patients association. An analysis was carried out of the thematic content of 1 846 postings on Facebook, Blogger, and WordPress. A total of 162 social network accounts were identified (97 individuals and 65 groups); the majority was in Mexico (46), with others in Argentina, Chile, Colombia, and Peru (44 accounts). The most frequent topics were exchange of information (46.0%), descriptions of experiences as patients (17.9%), support (15.6%), descriptions of experiences with health services (8.5%), interaction with peers (3.5%), and promotion of behavior change (3.4%). Chronic kidney patients living in Hispanic America use online social networks to inform and to be informed, describe their experiences with the disease and health services, and as a support mechanism. This produces knowledge that is different from and complementary to knowledge conveyed by health professionals. There is a pressing need to promote studies of the opportunities that these technologies offer in the Americas, a region characterized by enormous social inequality.

  5. Kidney Failure

    Science.gov (United States)

    Healthy kidneys clean your blood by removing excess fluid, minerals, and wastes. They also make hormones that keep your ... strong and your blood healthy. But if the kidneys are damaged, they don't work properly. Harmful ...

  6. The characteristics and mortality risk factors for acute kidney injury in different age groups in China-a cross sectional study.

    Science.gov (United States)

    Wei, Qing; Liu, Hong; Tu, Yan-; Tang, Ri-Ning; Wang, Yan-Li; Pan, Ming-Ming; Liu, Bi-Cheng

    2016-10-01

    Age is an independent risk factor for acute kidney injury (AKI). The causes and outcomes of AKI in children, middle-aged, and older patients are different. The objective of this country-based study was to identify the characteristics and mortality factors for AKI in different age groups in China. Using data from 374,286 adult patients (≥18 years) admitted to 44 study hospitals, we investigated the characteristics and mortality risk factors for AKI in four different age groups: 18-39 years of age, 40-59 years of age, 60-79 years of age, and ≥80 years of age. The identification criteria for AKI included the 2012 KDIGO AKI definition and an expanded criterion. The country-based survey included 7604 AKI patients (7604/374,286, 2.03%). The proportions of AKI in the four age groups were 11.52%, 30.79%, 41.03%, and 16.66%, respectively. In any age group, the patients with AKI stage 1 were the majority (43.4%, 42.4%, 46.4%, and 52.2%, respectively), and the most common classification of AKI was pre-renal AKI (44.3%, 51.3%, 52.3%, and 56.4%, respectively). The higher AKI peak stage occurred for the in-hospital mortality factors for AKI in all age groups; except for the AKI stage 2 patients in the 18-39 age group. The characteristics and mortality factors for AKI vary by age in China. Elderly patients were the primary population with AKI, and the most common type of AKI was pre-renal AKI. Special caution should be taken to the old population in hospitalized patients to prevent the pre-renal AKI.

  7. Marital Status and Return to Work After Living Kidney Donation.

    Science.gov (United States)

    Frech, Adrianne; Natale, Ginny; Hayes, Don; Tumin, Dmitry

    2018-01-01

    Living kidney donation is safe and effective, but patients in need of a transplant continue to outnumber donors. Disincentives to living donation include lost income, risk of job loss, perioperative complications, and unreimbursed medical expenses. This study uses US registry and follow-up data on living kidney donors from 2013 to 2015 to identify social predictors of return to work across gender following living kidney donation. Using logistic regression, we find that predictors of return to work following living kidney donation differ for women and men. Among women, age, education, smoking status, and procedure type are associated with return to work. Among men, education, procedure type, and hospital readmission within 6 weeks postdonation are associated with return to work. Notably, single and divorced men are less likely to return to work compared to married men (odds ratio [OR] for single men 0.51, 95% confidence interval [CI], 0.37-0.69, P donation.

  8. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    Science.gov (United States)

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  9. Stereoselective formation of a cholesterol ester conjugate from fenvalerate by mouse microsomal carboxyesterase(s).

    Science.gov (United States)

    Miyamoto, J; Kaneko, H; Takamatsu, Y

    1986-06-01

    In accordance with in vivo findings, of the four chiral isomers of fenvalerate (S-5602 Sumicidin, Pydrin, [RS]-alpha-cyano-3-phenoxybenzyl [RS]-2-(4-chlorophenyl)isovalerate), only the [2R, alpha S]-isomer (B-isomer) yielded cholesteryl [2R]-2-(4-chlorophenyl)isovalerate (CPIA-cholesterol ester) in the in vitro study using several tissue homogenates of mice, rats, dogs, and monkeys. There were species differences in the extent of CPIA-cholesterol-ester formation, with mouse tissues showing relatively higher activity than those of other animals. The kidney, brain, and spleen of mice showed relatively higher capacities to form this ester compared to other tissues, and the enzyme activity was mainly localized in microsomal fractions. The CPIA-cholesterol ester did not seem to be produced by three known biosynthetic pathways of endogenous cholesterol esters--acyl-CoA:cholesterol O-acyltransferase (ACAT), lecithin:cholesterol O-acyltransferase (LCAT), and cholesterol esterase. Carboxyesterase(s) of mouse kidney microsomes solubilized by digitonin hydrolyzed only the B alpha-isomer of fenvalerate, yielding CPIA, whereas they yielded the corresponding cholesterol ester in the presence of artificial liposomes containing cholesterol. Thus, it appears that the stereoselective formation of the CPIA-cholesterol ester results from the stereoselective formation of the CPIA-carboxyesterase complex only from the B alpha-isomer, which subsequently undergoes cleavage by cholesterol to yield the CPIA-cholesterol ester.

  10. The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease

    Science.gov (United States)

    2016-10-01

    shown that two parent compounds, 11B-dichloro and 11B- dipropyl, are effective in preventing and delaying cyst growth in two different orthologous mouse...polycystic kidney disease (PKD). In collaboration with the Essigmann lab at MIT, we have shown that two parent compounds, 11B-dichloro and 11B-dipropyl, are...cultured at the permissible temperature (33 °C), then re-plated at 37 °C, in the absence of interferon gamma, conditions in which turn off the large T

  11. Effect of furosemide and dietary sodium on kidney and plasma big and small renin

    International Nuclear Information System (INIS)

    Iwao, H.; Michelakis, A.M.

    1981-01-01

    Renin was found in mouse plasma in high-molecular-weight forms (big big renin, big renin) and a low-molecular-weight form (small renin). They were measuerd by a radioimmunoassay procedure for the direct measurement of renin. In the kidney, 89% of total renin was small renin and the rest was big big and big renin. This distribution pattern of renins was not changed when the kideny tissue was homogenized in the presence of protease inhibitors. Low-sodium or high-sodium diets changed renal renin content, but not the distribution pattern of renins in the kidney. Acute stimulation of renin release by furosemide increased small renin but not big big and big renin in plasma. However, dietary sodium depletion for 2 weeks significantly increased big big, big, and small renin in plasma of mice with or without submaxillary glands. In contrast, high-sodium intake significantly decreased big big, big, and small renin in plasma of mice with or without submaxillary glands

  12. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

    Directory of Open Access Journals (Sweden)

    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  13. Expanded criteria donor kidneys for younger recipients: acceptable outcomes.

    Science.gov (United States)

    Goplani, K R; Kute, V B; Vanikar, A V; Shah, P R; Gumber, M R; Patel, H V; Modi, P R; Trivedi, H L

    2010-12-01

    European senior programme (ESP) is well known for acceptable outcomes using expanded criteria donor (ECD) kidneys from donors older than 65 years for recipients older than 65 years. The incidence of end-stage renal disease (ESRD) is 229/million in India with a mean age of 45 years. We performed a retrospective analysis of transplantation of ECD versus standard criteria donor (SCD) kidneys into younger recipients. Forty-three ECD transplantations among 158 deceased donor organ transplantation (DDOT) were performed between January 2006 and December 2009. Among 43 transplantation from 30 donors, 14 were dual kidney transplantations (DKT) performed based upon biopsy evaluation. All recipients received thymoglobulin (rATG) induction followed by immunosuppression with a steroid, mycophenolate mofetil (MMF), and a calcineurin inhibitor. Statistical analysis used chi-square test and unpaired Student t test. Kaplan-Meier curves were used for survival analysis. For ECD the mean donor age was 64 ± 11 years. Cerebrovascular accidents (CVA) were the cause of death among 60% of donors, 73.13% of whom were hypertensive and 23.13% diabetic. Mean DKT donor age was 75 ± 9.17 years versus 60 ± 8.0 years for single kidney transplantation (SKT). Mean recipient age of DKT versus SKT was 44 ± 12.4 years versus 43 ± 14 years. Mean serum creatinine (SCr; mg/dL) of SKT patients was 1.64 ± 0.75 versus 1.68 ± 0.46 in DKT. Mean follow-up was 455 ± 352 days. Mean SCr of 43 ECD recipients of mean age, 43.4 ± 14.2 years was 1.61 ± 0.61 mg/dL. Among 43 recipients, 23.25% were diabetic, 41.86% displayed delayed graft function (DGF), and 23.25% experienced biopsy-proven acute rejection (BPAR). Patient survival rate was 72.09% and graft survival rate was 67.44%. For SCD transplantations (n = 115), the mean donor age was 36 ± 14 years and recipient mean age was 32.8 ± 14.07 years. Mean SCr was 1.32 ± 0.46 mg/dL with 26.95% recipients displaying DGF, whereas 20.86% had BPAR. In the SCD

  14. Gender Disparity in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Naghibi Orode

    2008-01-01

    Full Text Available Gender discrimination in benefiting from medical treatment is a worldwide pro-blem. Kidney transplantation, as the ideal treatment for patients with end-stage renal disease (ESRD, is not an exception. Considering the unique kidney donation patterns and different family styles in the Middle East, studying this problem in Iran seemed justifiable and necessary. In addition to comparing the numbers of female and male recipients, which has been done in other similar studies, considering the critical effect of waiting time on the outcome, we assessed and compared the waiting times also. The data of age, gender, nationality, donor type and waiting time before transplantation of 1426 (61.85% male, 38.14% female recipients who underwent transplantation in Imam Reza Hospital in the northeast of Iran from 1990 to 2003, was analyzed. Recipients were categorised into three groups based on donation patterns: those receiving kidney from live unrelated, live related and cadaver donors. The number of patients in each group was 1057 (61.96% male, 38.03% female, 232 (67.24% male, 32.75% female and 137 (51.82% male, 48.17% female respectively. The mean overall waiting time was 708 days. Comparing waiting time of male and female recipients in each of these groups did not show significant difference. In all categories of donors, females were less likely than males to be recipients. Furthermore, waiting time for females was longer than males when receiving kidney from sisters and children. For spousal donations, males were recipients more frequently than females although female recipients in this group waited less than their male counterparts to receive the kidney. Generally, our results are in accordance with results of similar researches. In all three mentioned groups, males com-prised the majority while the waiting time does not show significant difference between genders. We suggest some reasons for this phenomenon, of which the two main ones are: fewer females

  15. Comment: Kidney exchange to overcome financial barriers to kidney transplantation

    OpenAIRE

    Baines, L.S.; Jindal, R.M.

    2017-01-01

    Rees et al. have shown the feasibility of global kidney exchange (GKE) to overcome financial cost and address the current shortage of organs for transplantation. Wiseman and Gill, question their interpretation of definition of "financial incompatibility". The authors1 do not factor in the well documented cognitive and emotional aspects of kidney transplantation. Particularly, relevant to kidney transplantation is how patients calculate risk and the emotional turmoil characterised by anxiety a...

  16. Kidney Stones

    Science.gov (United States)

    ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ...

  17. Kidney Cancer

    Science.gov (United States)

    You have two kidneys. They are fist-sized organs on either side of your backbone above your waist. The tubes inside filter and ... blood, taking out waste products and making urine. Kidney cancer forms in the lining of tiny tubes ...

  18. Effect of thymectomy and splenectomy on the course of x-ray induced progressive intercapillary glomerulosclerosis in the mouse kidney

    Energy Technology Data Exchange (ETDEWEB)

    Guttman, P H

    1967-01-01

    Whole body neonatal irradiation (450 rads) of Swiss-Webster mice resulted in progressive intercapillary glomerulosclerosis (IGS). Neonatal thymectomy potentiated the effect of irradiation. Removal of the spleen at 18 days markedly reduced the effect of irradiation on the kidney when combined with thymectomy at birth. In the presence of an intact thymus, splenectomy had no effect on the course of radiation induced IGS. Germinal center formation and plasma cell infiltration were observed in the thymus of splenectomized-irradiated mice. The possible role of immunity in the pathogenesis of late effects of x-ray on the kidney is considered in the light of these findings.

  19. Gout after living kidney donation: Correlations with demographic traits and renal complications

    Science.gov (United States)

    Lam, Ngan N.; Garg, Amit X.; Segev, Dorry L.; Schnitzler, Mark A.; Xiao, Huiling; Axelrod, David; Brennan, Daniel C.; Kasiske, Bertram L.; Tuttle-Newhall, Janet E.; Lentine, Krista L.

    2015-01-01

    Background The demographic and clinical correlates of gout after living kidney donation are not well described. Methods Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared rates of renal diagnoses among donors with and without gout, matched 1:3 by age, sex, and race. Results The study sample of 4,650 donors included 13.1% African-Americans. By seven years, African-Americans were almost twice as likely to develop gout as Caucasian donors (4.4% vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval, CI, 1.0–3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86, 95% CI 0.66–1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5–107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1–11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2–4.2). Conclusion Donor subgroups at increased risk of gout include African-Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment. PMID:25896309

  20. Megalin-mediated specific uptake of chitosan/siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing.

    Science.gov (United States)

    Gao, Shan; Hein, San; Dagnæs-Hansen, Frederik; Weyer, Kathrin; Yang, Chuanxu; Nielsen, Rikke; Christensen, Erik I; Fenton, Robert A; Kjems, Jørgen

    2014-01-01

    RNAi-based strategies provide a great therapeutic potential for treatment of various human diseases including kidney disorders, but face the challenge of in vivo delivery and specific targeting. The chitosan delivery system has previously been shown to target siRNA specifically to the kidneys in mice when administered intravenously. Here we confirm by 2D and 3D bioimaging that chitosan formulated siRNA is retained in the kidney for more than 48 hours where it accumulates in proximal tubule epithelial cells (PTECs), a process that was strongly dependent on the molecular weight of chitosan. Chitosan/siRNA nanoparticles, administered to chimeric mice with conditional knockout of the megalin gene, distributed almost exclusively in cells that expressed megalin, implying that the chitosan/siRNA particle uptake was mediated by a megalin-dependent endocytotic pathway. Knockdown of the water channel aquaporin 1 (AQP1) by up to 50% in PTECs was achieved utilizing the systemic i.v. delivery of chitosan/AQP1 siRNA in mice. In conclusion, specific targeting PTECs with the chitosan nanoparticle system may prove to be a useful strategy for knockdown of specific genes in PTECs, and provides a potential therapeutic strategy for treating various kidney diseases.