Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

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Porter, Edith; Bevins, Charles L.; DiRosario, Julianne; Becknell, Brian; Wang, Huanyu

2012-01-01

Background The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects. Methodology/Principal Findings Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection. Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility. PMID:22359618

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

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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.

HUMAN GLOMERULAR VOLUME QUANTIFICATIONDURING THE AGING PROCESS

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Dejan Zdravković

2004-12-01

Full Text Available Kidney function is directly related to the changes of renal tissue, especially glomeruli, which is particularly distinct during the aging process. The impossibility of kidney function substitution points to the need for glomerular morphologic and functional characteristics estimation during the aging process.Human cadaveric kidney tissue samples were used as material during research. Age of cadavers ranged from 20 to 70 years and they were classified according to the scheme: I (20–29; II (30–39; III (40–49; IV (50–59; V (60–69 i VI (older than 70. After the routine histologic preparation of the renal tissue the slices were analized stereologicaly under the light microscope with projection screen (Reichert Visopan with 40 x lens magnification. M42 test system was used and 100, by unbased method selected glomeruli, were analyzed.Average glomerular capillary network volume shows significant increase (p< 0,001 as far as to the age of 50 years in regard to the age of 20 to 29 years. This parameter shows insignificant decrease after the age of 50 until the age of 70 years. This decrease was significant after the age of 70 years in regard to the period of the 20 to 29 (p< 0,05 and the period of 40 to 49 years (p<0,01.

Cycloxygenase-2 is expressed in vasculature of normal and ischemic adult human kidney and is colocalized with vascular prostaglandin E2 EP4 receptors

DEFF Research Database (Denmark)

Therland, Karina L; Stubbe, Jane; Thiesson, Helle C

2004-01-01

The study was performed to elucidate the distribution and cellular localization of cyclooxygenase (COX)-2 in human kidney and to address localization of downstream targets for COX-derived prostanoids. Cortex and outer and inner medulla tissue were obtained from control kidneys (cancer specimens),...... feature encountered in human kidneys at all ages, whereas COX-2 was seen in macula densa only in fetal kidney. Vascular COX-2 activity in human kidney and extrarenal tissues may support blood flow and affect vascular wall-blood interaction....

Proteomic study on gender differences in aging kidney of mice

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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.

Reduction in podocyte SIRT1 accelerates kidney injury in aging mice.

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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.

The Kidney in Aging: Physiological Changes and Pathological Implications.

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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.

Optical coherence tomography of the living human kidney

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Peter M. Andrews

2014-03-01

Full Text Available Acute tubular necrosis (ATN induced by ischemia is the most common insult to donor kidneys destined for transplantation. ATN results from swelling and subsequent damage to cells lining the kidney tubules. In this study, we demonstrate the capability of optical coherence tomography (OCT to image the renal microstructures of living human donor kidneys and potentially provide a measure to determine the extent of ATN. We also found that Doppler-based OCT (i.e., DOCT reveals renal blood flow dynamics that is another major factor which could relate to post-transplant renal function. All OCT/DOCT observations were performed in a noninvasive, sterile and timely manner on intact human kidneys both prior to (ex vivo and following (in vivo their transplantation. Our results indicate that this imaging model provides transplant surgeons with an objective visualization of the transplant kidneys prior and immediately post transplantation.

The Expression Changes of Inflammasomes in the Aging Rat Kidneys.

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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.

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.

Emerging role of autophagy in kidney function, diseases and aging

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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

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants

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Danica Ryan

2018-01-01

Interpretation: These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.

Changes of the glomerular size during the human fetal kidney development

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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

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

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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.

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

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

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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

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

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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

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

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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.

An Assessment of Urinary Biomarkers in a Series of Declined Human Kidneys Measured During ex-vivo Normothermic Kidney Perfusion

OpenAIRE

Hosgood, Sarah Anne; Nicholson, Michael Lennard

2016-01-01

BACKGROUND: The measurement of urinary biomarkers during ex-vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys. METHODS: Fifty six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based ...

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; 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.

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

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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.

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

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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.

Low vascularization of the nephrogenic zone of the fetal kidney suggests a major role for hypoxia in human nephrogenesis.

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Gerosa, C; Fanni, D; Faa, A; Van Eyken, P; Ravarino, A; Fanos, V; Faa, G

2017-09-01

CD31 reactivity is generally utilized as a marker of endothelial cells. CD31 immunoreactivity in the developing human kidney revealed that fetal glomerular capillary endothelial cells change their immunohistochemical phenotype during maturation. The aim of this study was to analyze CD31 reactivity in the fetal human kidney in the different stages of intrauterine development: We observed different distribution of CD31-reactive vascular progenitors in the different areas of the developing kidney. In particular, the nephrogenic zone and the renal capsule were characterized by a scarcity of CD31-reactive cells at all gestational ages. These data suggest the hypothesis that nephrogenesis does not need high oxygen levels and confirms a major role of hypoxia in nephrogenesis.

Triglycerides in the Human Kidney Cortex: Relationship with Body Size

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Bobulescu, Ion Alexandru; Lotan, Yair; Zhang, Jianning; Rosenthal, Tara R.; Rogers, John T.; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W.

2014-01-01

Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis. PMID:25170827

Incidence and mortality of kidney cancers, and human development index in Asia; a matter of concern.

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Arabsalmani, Masoumeh; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Hadadian, Fatemeh; Towhidi, Farhad; Vafaee, Kamran; Salehiniya, Hamid

2017-01-01

The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. This ecological study was based on GLOBOCAN data Asia for assessment the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its details that include life expectancy at birth, mean years of schooling and gross national income (GNI) per capita. We use of correlation bivariate method for assessment the correlation between ASIR and ASMR with HDI and its components. A total of 121 099 kidney cancer cases were recorded in Asian countries in 2012.Overall, 80 080 cases (66.12%) were males. Sex ratio was 1.95. The three countries with the highest number of new patients were china (66 466 cases), Japan (16 830 cases), India(9658 cases), respectively. Positive correlation were seen between HDI and ASIR of kidney cancer 0.655 ( P = 0.001), and HDI and ASMR of kidney cancer 0.285 ( P = 0.055). A positive relationship between ASIR and the HDI was seen. The relationship is due to risk factors in countries with high development such as older age, smoking, hypertension, obesity, and diet. However, ASMR showed no significant relationship with HDI.

Molecular events in matrix protein metabolism in the aging kidney

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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

[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.

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.

Reconstruction and Analysis of Human Kidney-Specific Metabolic Network Based on Omics Data

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Ai-Di Zhang

2013-01-01

Full Text Available With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases.

Comparison of human and automatic segmentations of kidneys from CT images

International Nuclear Information System (INIS)

Rao, Manjori; Stough, Joshua; Chi, Y.-Y.; Muller, Keith; Tracton, Gregg; Pizer, Stephen M.; Chaney, Edward L.

2005-01-01

Purpose: A controlled observer study was conducted to compare a method for automatic image segmentation with conventional user-guided segmentation of right and left kidneys from planning computerized tomographic (CT) images. Methods and materials: Deformable shape models called m-reps were used to automatically segment right and left kidneys from 12 target CT images, and the results were compared with careful manual segmentations performed by two human experts. M-rep models were trained based on manual segmentations from a collection of images that did not include the targets. Segmentation using m-reps began with interactive initialization to position the kidney model over the target kidney in the image data. Fully automatic segmentation proceeded through two stages at successively smaller spatial scales. At the first stage, a global similarity transformation of the kidney model was computed to position the model closer to the target kidney. The similarity transformation was followed by large-scale deformations based on principal geodesic analysis (PGA). During the second stage, the medial atoms comprising the m-rep model were deformed one by one. This procedure was iterated until no changes were observed. The transformations and deformations at both stages were driven by optimizing an objective function with two terms. One term penalized the currently deformed m-rep by an amount proportional to its deviation from the mean m-rep derived from PGA of the training segmentations. The second term computed a model-to-image match term based on the goodness of match of the trained intensity template for the currently deformed m-rep with the corresponding intensity data in the target image. Human and m-rep segmentations were compared using quantitative metrics provided in a toolset called Valmet. Metrics reported in this article include (1) percent volume overlap; (2) mean surface distance between two segmentations; and (3) maximum surface separation (Hausdorff distance

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.

Shift of galectin-3 expression in the human kidney during development

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Clara Gerosa

2013-06-01

Full Text Available Galectin-3 (Gal-3 is a member of the lectin family, including 14 mammalian galectins, and has been shown to be involved in the many biological processes. In fact it has been reported to be expressed during human nephrogenesis, in the ureteric bud tips and in the medullary regions. In 11 developing human kidney the immunoexpression of Gal-3 was studied. Previously observations on Gal-3 expression in collecting ducts were confirmed and a wild variable reactivity was detected among the range from 20 to 36 weeks of gestational age considered. Between the early and late phases of gestation two phases have been identified: the first, from 20 up to 26 weeks of gestation, with a strong reactivity and the second, from 30 to 36 weeks, with a decrease in Gal-3 expression. This finding clearly indicates a major role for Gal-3 in early human nephrogenesis ending around the 30th week of gestation. In conclusion, Gal-3 apparently plays a role in kidney development at different check points, participating both to ureteric bud proliferation and to differentiation of structures originating from the metanephric mesenchyme. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

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

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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.

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.)

Urinary acylcarnitines are altered in human kidney cancer.

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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.

Metaplasia of the parietal layer of Bowman's capsule. A histopathological survey of the human kidney

OpenAIRE

Haensly, William E.; Lee, J.C.

1986-01-01

Human kidney sections taken at autopsy were examined to determine the incidence of metaplasia of the Bowman's parietal epithelium. Autopsy records were consulted to determine if there was any correlation between clinical disease, histopathological changes in organ systems and metaplasia of Bowman's capsule. The sections represented both sexes in 9 age groups from 2 to 87 years. The sections were fixed in neutral formalin, embedded in paraffin, sectioned at 6 pm...

Morphometrical study of the human kidney. Radiodiagnosis and patological anatomy applications

International Nuclear Information System (INIS)

Sampaio, J.B.; Lacerda, C.A.M. de

1987-01-01

A morphometrical estimate was made on 100 human kidneys obtained by necropsies. The results of the renal measurements showed the averages of 11.06cm long, 6.24cm wide for the superior pole, 5.42cm wide for the inferior pole, 3.26cm thickness, and 119.48g weight. The left kidney presented a greater lenght, greater width, greater thickness and greater weight than the kidney. The statistical analysis of the correlation between several indices is presented. (author) [pt

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

Human renin biosynthesis and secretion in normal and ischemic kidneys

International Nuclear Information System (INIS)

Pratt, R.E.; Carleton, J.E.; Richie, J.P.; Heusser, C.; Dzau, V.J.

1987-01-01

The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing or prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time

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

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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.

Kidney Problems

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... 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, ...

Regenerative Medicine, Disease Modelling, and Drug Discovery in Human Pluripotent Stem Cell-Derived Kidney Tissue

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Navin Gupta

2017-08-01

Full Text Available The multitude of research clarifying critical factors in embryonic organ development has been instrumental in human stem cell research. Mammalian organogenesis serves as the archetype for directed differentiation protocols, subdividing the process into a series of distinct intermediate stages that can be chemically induced and monitored for the expression of stage-specific markers. Significant advances over the past few years include established directed differentiation protocols of human embryonic stem cells and human induced pluripotent stem cells (hiPSC into human kidney organoids in vitro. Human kidney tissue in vitro simulates the in vivo response when subjected to nephrotoxins, providing a novel screening platform during drug discovery to facilitate identification of lead candidates, reduce developmental expenditures, and reduce future rates of drug-induced acute kidney injury. Patient-derived hiPSC, which bear naturally occurring DNA mutations, may allow for modelling of human genetic diseases to enable determination of pathological mechanisms and screening for novel therapeutics. In addition, recent advances in genome editing with clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 enable the generation of specific mutations to study genetic disease, with non-mutated lines serving as an ideal isogenic control. The growing population of patients with end-stage kidney disease is a worldwide healthcare problem, with high morbidity and mortality rates, that warrants the discovery of novel forms of renal replacement therapy. Coupling the outlined advances in hiPSC research with innovative bioengineering techniques, such as decellularised kidney and three-dimensional printed scaffolds, may contribute to the development of bioengineered transplantable human kidney tissue as a means of renal replacement therapy.

Identification of differential gene expression patterns in human arteries from patients with chronic kidney disease

DEFF Research Database (Denmark)

Stubbe, Jane; Skov, Vibe; Thiesson, Helle Charlotte

2018-01-01

BACKGROUND: Uremia accelerates atherosclerosis but little is known about affected pathways in human vasculature. This study aimed to identify differentially expressed arterial transcripts in patients with chronic kidney disease (CKD) Methods: Global mRNA expression was estimated by microarray...... hybridization in iliac arteries (n=14) from renal transplant recipients and compared with renal arteries from healthy living kidney donors (n=19) in study 1. Study 2 compared non-atherosclerotic internal mammary arteries (IMA) from five patients with elevated plasma creatinine levels and age and gender matched...... controls with normal levels. Western blotting and immunohistochemistry for selected proteins was performed on a subset of study 1 samples. RESULTS: 15 gene transcripts with fold changes (FC)>1.05 were significantly different between the two groups in study 1, with false discovery rates (FDR) of

Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality.

Science.gov (United States)

Greiman, Alyssa K; Rosoff, James S; Prasad, Sandip M

2017-12-01

To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development. We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI). Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5-2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R 2 = 0.78), prostate (regression coefficient -1.56, R 2 = 0.85), kidney (regression coefficient -1.34, R 2 = 0.74), and bladder cancer (regression coefficient -1.01, R 2 = 0.80). While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

The association of the human development index with global kidney cancer incidence and mortality.

Science.gov (United States)

Patel, Amit R; Prasad, Sandip M; Shih, Ya-Chen Tina; Eggener, Scott E

2012-06-01

We describe contemporary worldwide age standardized incidence and mortality rates for kidney cancer, and their association with social and economic development metrics. We obtained gender specific, age standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2008 database. We compared the mortality-to-incidence ratio on the national and regional levels in males and females, and assessed the association with the development level of each country using the United Nations Human Development Index. The age standardized incidence rate varied twentyfold worldwide with the highest rate in North America, and the lowest in Africa and South Central Asia (11.8 vs 1.2 and 1.0/100,000 individuals, respectively). The geographic distribution of the age standardized mortality rate was similar to that of the age standardized incidence rate with the highest rates in Europe and North America (3.1 and 2.6/100,000 individuals, respectively) and the lowest rates in Asian and African regions (0.6 to 1.5). Age standardized incidence and mortality rates were 4.5 and 2.8 times higher, respectively, in more developed countries than in developing countries. However, the mortality-to-incidence ratio was highest in Africa and Asia, and lowest in North America (0.6 to 0.8 vs 0.2/100,000 individuals). There was a strong inverse relationship between the Human Development Index and the mortality-to-incidence ratio (regression coefficient -0.79, p<0.0001). Kidney cancer incidence and mortality rates vary widely throughout the world while the mortality-to-incidence ratio is highest in less developed nations. These observations suggest significant health care disparities and may reflect differences in risk factors, health care access, quality of care, diagnostic modalities and treatment options available. Future research should assess whether the mortality-to-incidence ratio decreases with increasing development. Copyright © 2012 American Urological

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.

Mapping of Carboxypeptidase M in Normal Human Kidney and Renal Cell Carcinoma

Science.gov (United States)

Denis, Catherine J.; Van Acker, Nathalie; De Schepper, Stefanie; De Bie, Martine; Andries, Luc; Fransen, Erik; Hendriks, Dirk; Kockx, Mark M.

2013-01-01

Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney. PMID:23172796

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.

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.

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.

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.

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.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

Science.gov (United States)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

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...

Agonist-induced desensitization of human β3-adrenoceptors expressed in human embryonic kidney cells

NARCIS (Netherlands)

Michel-Reher, Martina B.; Michel, Martin C.

2013-01-01

β3-Adrenoceptors are resistant to agonist-induced desensitization in some cell types but susceptible in others including transfected human embryonic kidney (HEK) cells. Therefore, we have studied cellular and molecular changes involved in agonist-induced β3-adrenoceptor desensitization in HEK cells.

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

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.

Metaplasia of the parietal layer of Bowman's capsule in the human kidney. Incidence in alcoholic liver disease and hypertension

OpenAIRE

Haensly, William E.

1988-01-01

This report is the second of two surveys to determine the incidence of metaplasia of Bowman's parietal epithelium in the human kidney. Human kidney sections obtained at autopsy at the Department of Pathology, University of Texas Medical Branch, Galveston, Texas, were examined with the light microscope. The kidneys were fixed in neutral formalin, sectioned at 6 pm and stained with hematoxylin and eosin. Autopsy records were consulted after kidney section exa...

Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders.

Science.gov (United States)

Lazzeri, Elena; Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura; Romagnani, Paola

2015-08-01

The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. Copyright © 2015 by the American Society of Nephrology.

Critical concentrations of cadmium in human liver and kidney measured by prompt-gamma neutron activation

International Nuclear Information System (INIS)

Cohn, S.H.; Vartsky, D.; Yasumura, S.; Zanzi, I.; Ellis, K.J.

1979-01-01

Few data exist on Cd metabolism in human beings. In particular, data are needed on the role of parameters such as age, sex, weight, diet, smoking habits, and state of health. Prompt-gamma neutron activation analysis (PGNAA) provides the only currently available means for measuring in vivo levels of liver and kidney Cd. The method employs an 85 Ci, 235 Pu,Be neutron source and a gamma ray detection system consisting of two Ge(Li) detector. The dose delivered to the liver and left kidney is 666 mrem (detection limit is 1.4 μg/g Cd in the liver and 2.0 mg Cd for one kidney). Absolute levels of Cd in the kidney and concentrations of Cd in the liver were measured in vivo in twenty healthy adult males using 238 Pu,Be neutron sources. Organ Cd levels of smokers were significantly elevated above those of nonsmokers. Biological half-time for Cd in the body was estimated to be 15.7 yr. Cigarette smoking was estimated to result in the absorption of 1.9 μg of Cd per pack. No relationship was bound between body stores of Cd (liver and kidney) and Cd or β-microglobulin levels in urine and blood. Currently the above neutron activation facility is being mounted on a 34-ft mobile trailer unit. This unit will be used to monitor levels of Cd in industrial workers. It is anticipated that critically important data, particularly on industrially exposed workers, will provide a better basis for determining critical concentrations and for the setting or revision of standards for industrial and environmental Cd pollution

Measurement of uranium in human teeth and kidney stones with the fission track technique

International Nuclear Information System (INIS)

Vartanian, R.

1986-01-01

The measurement of uranium in human teeth and in kidney stones was carried out using the fission track activation technique. In this determination 2759 and 2205 absolute counts of tracks for teeth samples and 1689 tracks for kidney stone samples were performed, respectively. The results are as follows: xsub(tooth) (1)=(0.227+-0.006) ppm, xsub(tooth) (2)=(0.143+-0.007) ppm and xsub(kidney)=(0.568+-0.020) ppm. The experimental method is described and the results are discussed. (author)

Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

Energy Technology Data Exchange (ETDEWEB)

Duangtum, Natapol [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Junking, Mutita; Sawasdee, Nunghathai [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Cheunsuchon, Boonyarit [Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Limjindaporn, Thawornchai, E-mail: limjindaporn@yahoo.com [Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai, E-mail: grpye@mahidol.ac.th [Medical Molecular Biology Unit, Office for Research and Development Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand)

2011-09-16

Highlights: {yields} Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). {yields} The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. {yields} The co-localization between kAE and KIF3B was detected in human kidney tissues. {yields} A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. {yields} KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of {alpha}-intercalated cells of the kidney collecting duct leads to the defect of the Cl{sup -}/HCO{sub 3}{sup -} exchange and the failure of proton (H{sup +}) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney {alpha}-intercalated cells.

Human kidney anion exchanger 1 interacts with kinesin family member 3B (KIF3B)

International Nuclear Information System (INIS)

Duangtum, Natapol; Junking, Mutita; Sawasdee, Nunghathai; Cheunsuchon, Boonyarit; Limjindaporn, Thawornchai; Yenchitsomanus, Pa-thai

2011-01-01

Highlights: → Impaired trafficking of kAE1 causes distal renal tubular acidosis (dRTA). → The interaction between kAE1 and kinesin family member 3B (KIF3B) is reported. → The co-localization between kAE and KIF3B was detected in human kidney tissues. → A marked reduction of kAE1 on the cell membrane was observed when KIF3B was knockdown. → KFI3B plays an important role in trafficking of kAE1 to the plasma membrane. -- Abstract: Impaired trafficking of human kidney anion exchanger 1 (kAE1) to the basolateral membrane of α-intercalated cells of the kidney collecting duct leads to the defect of the Cl - /HCO 3 - exchange and the failure of proton (H + ) secretion at the apical membrane of these cells, causing distal renal tubular acidosis (dRTA). In the sorting process, kAE1 interacts with AP-1 mu1A, a subunit of AP-1A adaptor complex. However, it is not known whether kAE1 interacts with motor proteins in its trafficking process to the plasma membrane or not. We report here that kAE1 interacts with kinesin family member 3B (KIF3B) in kidney cells and a dileucine motif at the carboxyl terminus of kAE1 contributes to this interaction. We have also demonstrated that kAE1 co-localizes with KIF3B in human kidney tissues and the suppression of endogenous KIF3B in HEK293T cells by small interfering RNA (siRNA) decreases membrane localization of kAE1 but increases its intracellular accumulation. All results suggest that KIF3B is involved in the trafficking of kAE1 to the plasma membrane of human kidney α-intercalated cells.

The Use of Starfish in the Regenaration of Human Kidney. Fact or Fiction?

Directory of Open Access Journals (Sweden)

Mehdi Mahmudpour

2016-11-01

Full Text Available With performing the first kidney transplantations in 1950s and 1960s, medical science hopes were raised to find out proper ways for treatment of End Stage Renal Disease or dialysis patients. But regarding to immunologic bases of transplantation and the use of immunosuppressant medicines and their side effects, patients may encounter to severe and inevitable side effects that sometimes may even lead to death. Therefore, in recent years, medical sciences in convergence with technology, pursue a new kind of approach so called "regenerative medicine"; however this method has its own challenges and complexities. But regarding to potential regenerative abilities of aquatic animals such as starfish, it may be possible to overcome on some of these challenges. The results of recent studies on evolutionary processes of human kidney and development and regeneration in starfish and, and presence of path and common cytokines among these processes proves this claim. This article presents some evidences that imply on practical usage of starfish in human kidney regeneration.

Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

Science.gov (United States)

Nicoletto, Bruna Bellincanta; Pedrollo, Elis Forcellini; Carpes, Larissa Salomoni; Coloretti, Natália Gomes; Krolikowski, Thaiana Cirino; Souza, Gabriela Corrêa; Gonçalves, Luiz Felipe Santos; Manfro, Roberto Ceratti; Canani, Luis Henrique

2018-01-01

The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; pProgranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

Model experiment of in vivo synchrotron X-ray diffraction of human kidney stones

Energy Technology Data Exchange (ETDEWEB)

Ancharov, A.I. [Institute of Solid State Chemistry and Mechanochemistry SB RAS, Novosibirsk (Russian Federation)]. E-mail: ancharov@mail.ru; Potapov, S.S. [Institute of Mineralogy UB RAS, Miass (Russian Federation); Moiseenko, T.N. [The State Regional Clinical Hospital, Novosibirsk (Russian Federation); Feofilov, I.V. [The State Regional Clinical Hospital, Novosibirsk (Russian Federation); Nizovskii, A.I. [Boreskov Institute of Catalysis SB RAS, Novosibirsk (Russian Federation)

2007-05-21

The diffraction of synchrotron radiation (SR) was used to explore the phase composition of kidney stones placed into a specific object phantom, which imitated the human body. As an imitation of the patient breath, the kidney stone was moved vertically and rotated to an angle of 15{sup o} during the recording of the X-ray pattern. It was shown that rotation and displacement did not distort the X-ray pattern.

Model experiment of in vivo synchrotron X-ray diffraction of human kidney stones

International Nuclear Information System (INIS)

Ancharov, A.I.; Potapov, S.S.; Moiseenko, T.N.; Feofilov, I.V.; Nizovskii, A.I.

2007-01-01

The diffraction of synchrotron radiation (SR) was used to explore the phase composition of kidney stones placed into a specific object phantom, which imitated the human body. As an imitation of the patient breath, the kidney stone was moved vertically and rotated to an angle of 15 o during the recording of the X-ray pattern. It was shown that rotation and displacement did not distort the X-ray pattern

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

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.

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

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

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.

The epithelial sodium channel γ-subunit is processed proteolytically in human kidney

DEFF Research Database (Denmark)

Langkilde, Rikke Zachar; Skjødt, Karsten; Marcussen, Niels

2015-01-01

The epithelial sodium channel (ENaC) of the kidney is necessary for extracellular volume homeostasis and normal arterial BP. Activity of ENaC is enhanced by proteolytic cleavage of the gamma-subunit and putative release of a 43-amino acid inhibitory tract from the gamma-subunit ectodomain. We......ENaC was detected consistently only in tissue from patients with proteinuria and observed in collecting ducts. In conclusion, human kidney gammaENaC is subject to proteolytic cleavage, yielding fragments compatible with furin cleavage, and proteinuria is associated with cleavage at the putative prostasin...

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

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

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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.

Incidence and mortality of kidney cancers, and human development index in Asia; a matter of concern

OpenAIRE

Arabsalmani, Masoumeh; Mohammadian-Hafshejani, Abdollah; Ghoncheh, Mahshid; Hadadian, Fatemeh; Towhidi, Farhad; Vafaee, Kamran; Salehiniya, Hamid

2016-01-01

Background The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. Objectives This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. ...

The senile kidney

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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.

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.

Kidney disease and aging: A reciprocal relation.

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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.

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.

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.

Blood cleaner on-chip design for artificial human kidney manipulation

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Suwanpayak N

2011-05-01

Full Text Available N Suwanpayak1, MA Jalil2, MS Aziz3, FD Ismail3, J Ali3, PP Yupapin11Nanoscale Science and Engineering Research Alliance (N'SERA, Advanced Research Center for Photonics, Faculty of Science, King Mongkut's Institute of Technology, Ladkrabang, Bangkok, Thailand; 2Ibnu Sina Institute of Fundamental Science Studies (IIS, 3Institute of Advanced Photonics Science, Nanotechnology Research Alliance, Universiti Teknologi Malaysia, Johor Bahru, MalaysiaAbstract: A novel design of a blood cleaner on-chip using an optical waveguide known as a PANDA ring resonator is proposed. By controlling some suitable parameters, the optical vortices (gradient optical fields/wells can be generated and used to form the trapping tools in the same way as optical tweezers. In operation, the trapping force is formed by the combination between the gradient field and scattering photons by using the intense optical vortices generated within the PANDA ring resonator. This can be used for blood waste trapping and moves dynamically within the blood cleaner on-chip system (artificial kidney, and is performed within the wavelength routers. Finally, the blood quality test is exploited by the external probe before sending to the destination. The advantage of the proposed kidney on-chip system is that the unwanted substances can be trapped and filtered from the artificial kidney, which can be available for blood cleaning applications.Keywords: optical trapping, blood dialysis, blood cleaner, human kidney manipulation

Human Heredity and Health (H3) in Africa Kidney Disease Research Network: A Focus on Methods in Sub-Saharan Africa.

Science.gov (United States)

Osafo, Charlotte; Raji, Yemi Raheem; Burke, David; Tayo, Bamidele O; Tiffin, Nicki; Moxey-Mims, Marva M; Rasooly, Rebekah S; Kimmel, Paul L; Ojo, Akinlolu; Adu, Dwomoa; Parekh, Rulan S

2015-12-07

CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa. Copyright © 2015 by the American Society of Nephrology.

[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.

Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina.

Science.gov (United States)

Mossoba, Miriam E; Flynn, Thomas J; Vohra, Sanah; Wiesenfeld, Paddy L; Sprando, Robert L

2015-12-01

Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems.

Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine.

Science.gov (United States)

Stumvoll, M; Chintalapudi, U; Perriello, G; Welle, S; Gutierrez, O; Gerich, J

1995-11-01

Despite ample evidence that the kidney can both produce and use appreciable amounts of glucose, the human kidney is generally regarded as playing a minor role in glucose homeostasis. This view is based on measurements of arteriorenal vein glucose concentrations indicating little or no net release of glucose. However, inferences from net balance measurements do not take into consideration the simultaneous release and uptake of glucose by the kidney. Therefore, to assess the contribution of release and uptake of glucose by the human kidney to overall entry and removal of plasma glucose, we used a combination of balance and isotope techniques to measure renal glucose net balance, fractional extraction, uptake and release as well as overall plasma glucose appearance and disposal in 10 normal volunteers under basal postabsorptive conditions and during a 3-h epinephrine infusion. In the basal postabsorptive state, there was small but significant net output of glucose by the kidney (66 +/- 22 mumol.min-1, P = 0.016). However, since renal glucose fractional extraction averaged 2.9 +/- 0.3%, there was considerable renal glucose uptake (2.3 +/- 0.2 mumol.kg-1.min-1) which accounted for 20.2 +/- 1.7% of systemic glucose disposal (11.4 +/- 0.5 mumol.kg-1.min-1). Renal glucose release (3.2 +/- 0.2 mumol.kg-1.min-1) accounted for 27.8 +/- 2.1% of systemic glucose appearance (11.4 +/- 0.5 mumol.kg-1.min-1). Epinephrine infusion, which increased plasma epinephrine to levels observed during hypoglycemia (3722 +/- 453 pmol/liter) increased renal glucose release nearly twofold (5.2 +/- 0.5 vs 2.8 +/- 0.1 mol.kg-1.min-1, P = 0.01) so that at the end of the infusion, renal glucose release accounted for 40.3 +/- 5.5% of systemic glucose appearance and essentially all of the increase in systemic glucose appearance. These observations suggest an important role for the human kidney in glucose homeostasis.

Urea and impairment of the Gut-Kidney axis in Chronic Kidney Disease.

Science.gov (United States)

Di Iorio, Biagio Raffaele; Marzocco, Stefania; Nardone, Luca; Sirico, Marilisa; De Simone, Emanuele; Di Natale, Gabriella; Di Micco, Lucia

2017-12-05

Gut microbiota can be considered a real organ coordinating health and wellness of our body. It is made of more than 100 trillions of microorganisms, thus about 3 times higher than the number of human body cells and more than 150 times than human genes containing 1000 different microbe species. It has been described a symbiotic relationship between gut and kidney, confirmed by several observations. This is a bi-directional relation with a mutual influence, even when kidney disease occurs, and consequent alterations of intestinal microbiota and production of uremic toxins, that in turn worsens kidney disease and its progression. Our review analyzes the components of gut-kidney axis and relative clinical consequences. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

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.

Non-invasive determination of metabolite concentrations in human transplanted kidney in vivo by 31P MR spectroscopy

International Nuclear Information System (INIS)

Kugel, H.; Wittsack, H.J.; Wenzel, F.; Heindel, W.; Lackner, K.; Stippel, D.

2000-01-01

To investigate concentrations of phosphorus-containing metabolites in human transplanted kidney in vivo by quantitative 31 P MR spectroscopy (MRS) using surface coils and to compare the obtained values with previous data. Material and Methods: In 5 patients with well-functioning transplanted kidneys, 31 P spectra were obtained with the three-dimensional localization image-selected in vivo spectroscopy technique applying a protocol for quantitative spectroscopy using surface coils. Relaxation corrected signal intensities determined by time domain fitting were used to derive absolute molar concentrations for phosphate-containing metabolites. Results: Little or no phosphocreatine in all spectra verified the absence of muscle contamination, confirming proper volume localization. The mean concentrations in the transplanted kidneys were as follows: ATP 1.60±0.26 mmol/l, PDE 2.14±0.91 mmol/l, Pi 0.66±0.25 mmol/l, PME 2.32±0.50 mmol/l. These values are consistent with previously reported values determined by other techniques. Conclusion: The non-invasive determination of absolute metabolite concentrations in human kidney using MRS supplements the use of signal intensity ratios to detect pathologic changes in the energy metabolism of transplanted kidneys

APOPTOSIS DURING HUMAN FETAL KIDNEY DEVELOPMENT

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Rade Čukuranović

2005-01-01

Full Text Available Kidney morphogenesis is a complex and stepwise process. The formation of mature kidney in mammals is preceded by two primitive embryonic kidneys known as pronephros and mesonephros. Metanephros develops as a result of reciprocal inductive interactions between two primordial mesodermal derivates: ureteric bud, an epithelial outgrowth of the Wolffian duct, and metanephric blastema, a group of mesenchymal cells. The ureteric bud induces the metanephric mesenchyme to differentiate and form nephrons, whilst the metanephric mesenchyme induces the ureteric bud to grow and branch to form collecting ducts. The nephron goes through four developmental stages, which are described as: 1 vesicle, 2 comma-shaped and S-shaped stages, 3 developing capillary loop, and finally 4 maturing glomerulus. Apoptosis (programmed cell death is a predominant form of physiological cell death, by which organism eliminate unwanted or damaged cells. It is the major component of normal development and disease. Apoptosis is the result of series of biochemical processes happening in certain order in a dying cell, among which the most important is activation of enzyme families called caspases which influence different cell components. Apoptosis is characterized by membrane blebbing, shrinkage of the cell, nuclear fragmentation and chromatin condensation. Organelles are preserved almost intact. Cell surface molecules change. A variety of physiological and pathological stimuli can initiate apoptosis. They act via receptor mechanisms, through biochemical agents, or cause DNA and cell membrane damage. Apoptosis is an important component of fetal development. It is thought that apoptosis is the one of the main regulatory events involved in kidney morphogenesis, considering that among great number of developed cells, only a few of them are involved in the developing program by escaping apoptosis. In any period during kidney development about 3 to 5%of cells are apoptotic. Thorough

A Selection of Constitutional Perspectives on Human Kidney Sales ...

African Journals Online (AJOL)

There are thousands of desperate people globally who need a kidney for transplantation. The number of people who require a kidney transplant continues to escalate faster than the number of kidneys available for a transplant. The specific focus of this article is to determine whether the payment of kidney donors could be ...

Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

Directory of Open Access Journals (Sweden)

Bruna Bellincanta Nicoletto

Full Text Available The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown.To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation.Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays.Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; p<0.01 and increased at one year (53.15 ± 2.55 ng/mL; p<0.01 vs. three months, remaining significantly lower than before transplantation (p<0.01 (pover time<0.01. At one year after transplantation, there was a significant increase in body mass index, trunk fat and waist circumference compared to immediate period after transplantation. Progranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin.Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

Accumulation of long-chain glycosphingolipids during aging is prevented by caloric restriction.

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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

Human podocyte depletion in association with older age and hypertension.

Science.gov (United States)

Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F

2016-04-01

Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.

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,

Pakistan's kidney trade: an overview of the 2007 'Transplantation of Human Organs and Human Tissue Ordinance.' To what extent will it curb the trade?

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Raza, Mohsen; Skordis-Worrall, Jolene

2012-01-01

Pakistan has the unenviable reputation for being one of the world's leading 'transplant tourism' destinations, largely the buying and selling of kidneys from its impoverished population to rich international patients. After nearly two decades of pressure to formally prohibit the trade, the Government of Pakistan promulgated the 'Transplantation of Human Organs and Human Tissue Ordinance' (THOTO) in 2007. This was then passed by Senate and enshrined in law in March 2010. This paper gives a brief overview of the organ trade within Pakistan and analyses the criteria of THOTO in banning the widespread practise. It then goes on to answer: 'To what extent will THOTO succeed in curbing Pakistan's kidney trade?' This is aided by the use of a comparative case study looking at India's failed organ trade legislation. This paper concludes THOTO has set a strong basis for curbing Pakistan's kidney trade. However, for this to be successfully achieved, it needs to be implemented with strong and sustained political will, strict and efficient enforcement as well as effective monitoring and evaluation. Efforts are needed to tackle both 'supply' and 'demand' factors of Pakistan's kidney trade, with developed countries also having a responsibility to reduce the flow of citizens travelling to Pakistan to purchase a kidney.

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

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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.

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

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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.

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

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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.

Strong human leukocyte antigen matching effect in nonsensitized kidney recipients with high pretransplant soluble CD30.

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Süsal, Caner; Pelzl, Steffen; Opelz, Gerhard

2003-10-27

The influence of human leukocyte antigen (HLA) matching on graft survival is greater in patients with preformed lymphocytotoxic antibodies than in nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft outcome independently of presensitization status. The impact of HLA compatibility on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric kidney recipients in relation to the pretransplant serum sCD30 content. Although HLA compatibility influenced graft outcome only marginally in nonsensitized recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong HLA matching effect was observed in nonsensitized recipients with high sCD30 (at 3 years: PsCD30 benefit from an HLA well-matched kidney. Patients should be tested for sCD30 while on the waiting list for a kidney transplant, and HLA well-matched kidneys should be allocated to patients with high sCD30.

Tensin3 is a negative regulator of cell migration and all four Tensin family members are downregulated in human kidney cancer.

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Danuta Martuszewska

Full Text Available The Tensin family of intracellular proteins (Tensin1, -2, -3 and -4 are thought to act as links between the extracellular matrix and the cytoskeleton, and thereby mediate signaling for cell shape and motility. Dysregulation of Tensin expression has previously been implicated in human cancer. Here, we have for the first time evaluated the significance of all four Tensins in a study of human renal cell carcinoma (RCC, as well as probed the biological function of Tensin3.Expression of Tensin2 and Tensin3 at mRNA and protein levels was largely absent in a panel of diverse human cancer cell lines. Quantitative RT-PCR analysis revealed mRNA expression of all four Tensin genes to be significantly downregulated in human kidney tumors (50-100% reduction versus normal kidney cortex; P<0.001. Furthermore, the mRNA expressions of Tensins mostly correlated positively with each other and negatively with tumor grade, but not tumor size. Immunohistochemical analysis revealed Tensin3 to be present in the cytoplasm of tubular epithelium in normal human kidney sections, whilst expression was weaker or absent in 41% of kidney tumors. A subset of tumor sections showed a preferential plasma membrane expression of Tensin3, which in clear cell RCC patients was correlated with longer survival. Stable expression of Tensin3 in HEK 293 cells markedly inhibited both cell migration and matrix invasion, a function independent of putative phosphatase activity in Tensin3. Conversely, siRNA knockdown of endogenous Tensin3 in human cancer cells significantly increased their migration.Our findings indicate that the Tensins may represent a novel group of metastasis suppressors in the kidney, the loss of which leads to greater tumor cell motility and consequent metastasis. Moreover, tumorigenesis in the human kidney may be facilitated by a general downregulation of Tensins. Therefore, anti-metastatic therapies may benefit from restoring or preserving Tensin expression in primary

Age difference in deposition of plutonium in organs of rats and the estimation of distribution in humans

Energy Technology Data Exchange (ETDEWEB)

Fukuda, Satoshi; Iida, Haruzo [National Inst. of Radiological Sciences, Chiba (Japan)

2000-05-01

Differences in plutonium distribution in various organs, particularly the bones, of rats injected at different ages were examined in order to aid in estimating plutonium distribution in humans. Comparisons were made between rats and humans based on the bone histomorphometric and mineral density data. Male and female rats of three ages (3, 12, and 24 months old), respectively, received an injection of plutonium nitrate by two dose modalities; a fixed amount of plutonium without regard to age, sex, or body weight; per g of body weight. The rats were killed 2 weeks after the injection of plutonium. The amounts of plutonium deposited in the organs varied without regard to the body or organ weight; those in the skeleton increased from 3 to 12 months, reaching a peak at 12 months, but then decreased, along with the age-related changes in the bone surface, volume, and mineral density. Those in the liver, spleen and kidney decreased despite the body weight gain with age in both sexes. Age-related differences in the deposition of plutonium in humans were estimated based on the bone data characteristics obtained from the histomorphometry and bone mineral density for corresponding of ages between rats and humans. The results indicate that age is the most important factor in estimating the distribution of plutonium deposition in the early period after plutonium exposure, and that body or organ weight is not always a useful indicator, particularly in the aged. (author)

Characterization of human kidney stones using micro-PIXE and RBS: A comparative study between two different populations

International Nuclear Information System (INIS)

Pineda-Vargas, C.A.; Eisa, M.E.M.; Rodgers, A.L.

2009-01-01

The micro-PIXE and RBS techniques are used to investigate the matrix as well as the trace elemental composition of calcium-rich human tissues on a microscopic scale. This paper deals with the spatial distribution of trace metals in hard human tissues such as kidney stone concretions, undertaken at the nuclear microprobe (NMP) facility. Relevant information about ion beam techniques used for material characterization will be discussed. Mapping correlation between different trace metals to extract information related to micro-regions composition will be illustrated with an application using proton energies of 1.5 and 3.0 MeV and applied to a comparative study for human kidney stone concretions nucleation region analysis from two different population groups (Sudan and South Africa)

Outcomes of Kidney Transplantations Under the Philippine Health Insurance Corporation's Type Z Benefit Package at the National Kidney and Transplant Institute, Philippines.

Science.gov (United States)

Pamugas, G E P; Arakama, M-H I; Danguilan, R A; Ledesma, D

2016-04-01

Under the Universal Health Care Program of the Department of Health, the Philippine Health Insurance Corporation (PHIC) launched the Case Type Z benefit package for kidney transplantation, providing the largest amount (USD $13,300.00) for any single medical procedure. The objective of this study was to describe under the PHIC Case Type Z Benefit Package for kidney transplantation at the National Kidney and Transplant Institute and kidney transplantation outcomes under this package. Included in the benefit were standard risk recipients between 10 and 70 years of age with at least 1 human leukocyte antigen (HLA) DR match with the donor, panel-reactive antibody (PRA) less than 20%, and absence of donor-specific antibody (DSA). Previous transplantations, malignancy, hepatitis B and C, human immunodeficiency virus (HIV) positivity, cytomegalovirus (CMV) R-/D+, congestive heart failure, and liver cirrhosis were exclusion criteria. Patients were evaluated by a medical social worker according to their family's financial status. Since June 2012, a total of 261 patients have received the benefit, with 44 under service, 37 with fixed co-pay and 180 with variable co-pay. Of the living donor kidney transplants, 98% had immediate graft function, with 2.3% (6/261) acute rejection rates at 1 year. The total cost of hospitalization was within the benefit for living donor kidney transplants (less than USD 8000.00) but exceeded it in all cases of deceased donor kidney transplants. The successful use of and excellent outcomes under the Case Type Z benefit demonstrated how collaboration among government agencies, health care providers, and pharmaceutical companies could result in a program that improved the access to health care for Filipino patients with end-stage renal disease. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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.

Ultrasonography of polycystic kidney

International Nuclear Information System (INIS)

Oh, Seung Chul; Cho, Seung Gi; Lee, Kwan Seh; Kim, Kun Sang

1980-01-01

Polycystic disease is defined as a heritable disorder with diffuse involvement of both kidneys. The term 'Polycystic disease' comprises at least two separate, genetically different disease-one with an onset typically in childhood (infantile polycystic disease) and the other with an onset typically in adulthood (adult polycystic disease). Adult polycystic kidney disease is the most common form of cystic kidney disease in humans. Ultrasonography is a very useful noninvasive diagnostic modality in the patient with clinically suspected renal diseases as well as screening test. 14 cases of ultrasonography in patient with polycystic kidney were reviewed. All cases show unilateral or bilateral enlarged kidneys. 7 cases reveal kidneys and liver replaced by multiple cysts of varing size. Screening ultrasonography for a familial tree is reported

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

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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.

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

Prolonged CT urography in duplex kidney.

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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.

Prevalence of high-risk human papillomavirus cervical infection in female kidney graft recipients: an observational study.

Science.gov (United States)

Pietrzak, Bronislawa; Mazanowska, Natalia; Ekiel, Alicja M; Durlik, Magdalena; Martirosian, Gayane; Wielgos, Mirosław; Kaminski, Pawel

2012-06-18

Immunosuppressive therapy protects the transplanted organ but predisposes the recipient to chronic infections and malignancies. Transplant patients are at risk of cervical intraepithelial neoplasia (CIN) and cervical cancer resulting from an impaired immune response in the case of primary infection or of reactivation of a latent infection with human papillomavirus of high oncogenic potential (HR-HPV). The aim of this study was to assess the prevalence of HR-HPV cervical infections and CIN in 60 female kidney graft recipients of reproductive age in comparison to that in healthy controls. Cervical swabs were analyzed for the presence of HR-HPV DNA. HR-HPV-positive women remained under strict observation and were re-examined after 24 months for the presence of transforming HR-HPV infection by testing for HR-HPV E6/E7 mRNA. All the HR-HPV-positive patients were scheduled for further diagnostic tests including exfoliative cytology, colposcopy and cervical biopsy. The prevalence of HR-HPV did not differ significantly between the study group and the healthy controls (18% vs 25%, p = 0.37). There was no correlation between HR-HPV presence and the immunosuppresive regimen, underlying disease, graft function or time interval from transplantation. A higher prevalence of HR-HPV was observed in females who had had ≥ 2 sexual partners in the past. Among HR-HPV-positive patients, two cases of CIN2+ were diagnosed in each group. In the course of follow-up, transforming HR-HPV infections were detected in two kidney recipients and in one healthy female. Histologic examination confirmed another two cases of CIN2+ developing in the cervical canal. Female kidney graft recipients of reproductive age are as exposed to HR-HPV infection as are healthy individuals. Tests detecting the presence of HR-HPV E6/E7 mRNA offer a novel diagnostic opportunity in those patients, especially in those cases where lesions have developed in the cervical canal.

Prevalence of high-risk human papillomavirus cervical infection in female kidney graft recipients: an observational study

Directory of Open Access Journals (Sweden)

Pietrzak Bronislawa

2012-06-01

Full Text Available Abstract Background Immunosuppressive therapy protects the transplanted organ but predisposes the recipient to chronic infections and malignancies. Transplant patients are at risk of cervical intraepithelial neoplasia (CIN and cervical cancer resulting from an impaired immune response in the case of primary infection or of reactivation of a latent infection with human papillomavirus of high oncogenic potential (HR-HPV. Methods The aim of this study was to assess the prevalence of HR-HPV cervical infections and CIN in 60 female kidney graft recipients of reproductive age in comparison to that in healthy controls. Cervical swabs were analyzed for the presence of HR-HPV DNA. HR-HPV-positive women remained under strict observation and were re-examined after 24 months for the presence of transforming HR-HPV infection by testing for HR-HPV E6/E7 mRNA. All the HR-HPV-positive patients were scheduled for further diagnostic tests including exfoliative cytology, colposcopy and cervical biopsy. Results The prevalence of HR-HPV did not differ significantly between the study group and the healthy controls (18% vs 25%, p = 0.37. There was no correlation between HR-HPV presence and the immunosuppresive regimen, underlying disease, graft function or time interval from transplantation. A higher prevalence of HR-HPV was observed in females who had had ≥2 sexual partners in the past. Among HR-HPV-positive patients, two cases of CIN2+ were diagnosed in each group. In the course of follow-up, transforming HR-HPV infections were detected in two kidney recipients and in one healthy female. Histologic examination confirmed another two cases of CIN2+ developing in the cervical canal. Conclusions Female kidney graft recipients of reproductive age are as exposed to HR-HPV infection as are healthy individuals. Tests detecting the presence of HR-HPV E6/E7 mRNA offer a novel diagnostic opportunity in those patients, especially in those cases where lesions have

The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

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Lee, Yu Qi; Collins, Clare E.; Gordon, Adrienne; Rae, Kym M.; Pringle, Kirsty G.

2018-01-01

The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3), folate and vitamin B12 (n = 2), iron (n = 1), vitamin D (n = 1), total energy (n = 2) and protein (n = 1). Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater. PMID:29466283

Drugs to foster kidney regeneration in experimental animals and humans.

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Gagliardini, Elena; Benigni, Ariela

2014-01-01

The incidence of kidney diseases is increasing worldwide and they are emerging as a major public health problem. Once mostly considered inexorable, renal disease progression can now be halted and lesions can even regress with drugs such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type I receptor blockers, indicating the possibility of kidney repair. The discovery of renal progenitor cells lining the Bowman capsule of adult rat and human kidneys has shed light on the mechanism of repair by ACEi. Parietal progenitors are a reservoir of cells that contribute to podocyte turnover in physiological conditions. In the early phases of renal disease these progenitors migrate chaotically and subsequently proliferate, accumulating in Bowman's space. The abnormal behavior of parietal progenitors is sustained by the activation of CXCR4 receptors in response to an increased production of the chemokine SDF-1 by podocytes activated by the inflammatory environment. Ang II, via the AT1 receptor, also contributes to progenitor cell proliferation. The CXCR4/SDF-1 and Ang II/AT1 receptor pathogenic pathways both pave the way for lesion formation and subsequent sclerosis. ACEi normalize the CXCR4 and AT1 receptor expression on progenitors, limiting their proliferation, concomitant with the regression of hyperplastic lesions in animals, and in a patient with crescentic glomerulopathy. Understanding the molecular and cellular determinants of regeneration triggered by renoprotective drugs will reveal novel pathways that might be challenged or targeted by pharmacological therapy. © 2014 S. Karger AG, Basel.

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

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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

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.

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.

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)

Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

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Cruz, Nelly M.; Song, Xuewen; Czerniecki, Stefan M.; Gulieva, Ramila E.; Churchill, Angela J.; Kim, Yong Kyun; Winston, Kosuke; Tran, Linh M.; Diaz, Marco A.; Fu, Hongxia; Finn, Laura S.; Pei, York; Himmelfarb, Jonathan; Freedman, Benjamin S.

2017-11-01

Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

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

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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.

Biodemography of human ageing

DEFF Research Database (Denmark)

Vaupel, James W

2010-01-01

Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...

The Relationship between Maternal Nutrition during Pregnancy and Offspring Kidney Structure and Function in Humans: A Systematic Review

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Yu Qi Lee

2018-02-01

Full Text Available The intrauterine environment is critical for fetal growth and organ development. Evidence from animal models indicates that the developing kidney is vulnerable to suboptimal maternal nutrition and changes in health status. However, evidence from human studies are yet to be synthesised. Therefore, the aim of the current study was to systematically review current research on the relationship between maternal nutrition during pregnancy and offspring kidney structure and function in humans. A search of five databases identified 9501 articles, of which three experimental and seven observational studies met the inclusion criteria. Nutrients reviewed to date included vitamin A (n = 3, folate and vitamin B12 (n = 2, iron (n = 1, vitamin D (n = 1, total energy (n = 2 and protein (n = 1. Seven studies were assessed as being of “positive” and three of “neutral” quality. A variety of populations were studied, with limited studies investigating maternal nutrition during pregnancy, while measurements of offspring kidney outcomes were diverse across studies. There was a lack of consistency in the timing of follow-up for offspring kidney structure and/or function assessments, thus limiting comparability between studies. Deficiencies in maternal folate, vitamin A, and total energy during pregnancy were associated with detrimental impacts on kidney structure and function, measured by kidney volume, proteinuria, eGFRcystC and mean creatinine clearance in the offspring. Additional experimental and longitudinal prospective studies are warranted to confirm this relationship, especially in Indigenous populations where the risk of renal disease is greater.

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

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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.

Validation of an LC-MS/MS method to measure tacrolimus in rat kidney and liver tissue and its application to human kidney biopsies.

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Noll, Benjamin D; Coller, Janet K; Somogyi, Andrew A; Morris, Raymond G; Russ, Graeme R; Hesselink, Dennis A; Van Gelder, Teun; Sallustio, Benedetta C

2013-10-01

Tacrolimus (TAC) has a narrow therapeutic index and high interindividual and intraindividual pharmacokinetic variability, necessitating therapeutic drug monitoring to individualize dosage. Recent evidence suggests that intragraft TAC concentrations may better predict transplant outcomes. This study aimed to develop a method for the quantification of TAC in small biopsy-sized samples of rat kidney and liver tissue, which could be applied to clinical biopsy samples from kidney transplant recipients. Kidneys and livers were harvested from Mrp2-deficient TR- Wistar rats administered TAC (4 mg·kg·d for 14 days, n = 8) or vehicle (n = 10). Tissue samples (0.20-1.00 mg of dry weight) were solubilized enzymatically and underwent liquid-liquid extraction before analysis by liquid chromatography tandem mass spectrometry method. TAC-free tissue was used in the calibrator and quality control samples. Analyte detection was accomplished using positive electrospray ionization (TAC: m/z 821.5 → 768.6; internal standard ascomycin m/z 809.3 → 756.4). Calibration curves (0.04-2.6 μg/L) were linear (R > 0.99, n = 10), with interday and intraday calibrator coefficients of variation and bias <17% at the lower limit of quantification and <15% at all other concentrations (n = 6-10). Extraction efficiencies for TAC and ascomycin were approximately 70%, and matrix effects were minimal. Rat kidney TAC concentrations were higher (range 109-190 pg/mg tissue) than those in the liver (range 22-53 pg/mg of tissue), with median tissue/blood concentrations ratios of 72.0 and 17.6, respectively. In 2 transplant patients, kidney TAC concentrations ranged from 119 to 285 pg/mg of tissue and were approximately 20 times higher than whole blood trough TAC concentrations. The method displayed precision and accuracy suitable for application to TAC measurement in human kidney biopsy tissue.

Perspectives of Older Kidney Transplant Recipients on Kidney Transplantation.

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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

Kidney biomimicry--a rediscovered scientific field that could provide hope to patients with kidney disease.

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Stenvinkel, Peter; Johnson, Richard J

2013-11-01

Most studies on kidney disease have relied on classic experimental studies in mice and rats or clinical studies in humans. From such studies much understanding of the physiology and pathophysiology of kidney disease has been obtained. However, breakthroughs in the prevention and treatment of kidney diseases have been relatively few, and new approaches to fight kidney disease are needed. Here we discuss kidney biomimicry as a new approach to understand kidney disease. Examples are given of how various animals have developed ways to prevent or respond to kidney failure, how to protect themselves from hypoxia or oxidative stress and from the scourge of hyperglycemia. We suggest that investigation of evolutionary biology and comparative physiology might provide new insights for the prevention and treatment of kidney disease. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

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

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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.

[Gene transfer-induced human heme oxygenase-1 over-expression protects kidney from ischemia-reperfusion injury in rats].

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Lü, Jin-xing; Yan, Chun-yin; Pu, Jin-xian; Hou, Jian-quan; Yuan, He-xing; Ping, Ji-gen

2010-12-14

To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (PhHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

Acute Kidney Injury in the Elderly

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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

Prevalence and clinical and laboratory characteristics of kidney disease in anti-retroviral-naive human immunodeficiency virus-infected patients in South-South Nigeria

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U H Okafor

2016-01-01

Full Text Available Since the emergence of acquired immune deficiency syndrome (AIDS about three decades ago, several renal disorders have been reported as common complications of human immunodeficiency virus (HIV infection. These renal disorders result from diverse etiologies. The aim of this cross-sectional study was to determine the prevalence and clinical and laboratory characteristics of anti-retroviral-naοve HIV-infected patients with impaired kidney disorder in South-South Nigeria. This study was conducted on patients presenting at the University of Benin Teaching Hospital, Benin City in South-South Nigeria for six months. The patients′ demographic data and clinical, hematological and biochemical parameters were assessed. Their glomerular filtration rate (GFR was calculated and the protein excretion was assessed from the protein- creatinine ratio. Data were analyzed using statistical software program SPSS version 15.0. Threehundred and eighty-three patients with a mean age of 35.39 ± 8.78 years and a male: female ratio of 1:1 were studied; 53.3% had evidence of kidney disorder. The main clinical features in patients with kidney disorder were evidence of fluid retention, urinary symptoms, pallor and encephalopathy. The mean systolic and diastolic blood pressures were 115.33 ± 17.17 and 72.33 ± 14.31 mm Hg, respectively. The mean estimated GFR was 52.5 mL/min/1.73 m 2 . Patients with kidney disorder had higher proteinuria (P = 0.001, lower mean CD4 cell count and packed cell volume (P = 0.019 and 0.001, respectively. Kidney disorder is a common complication in HIV-infected patients, and they have clinical and laboratory anomalies. Screening of HIV/AIDS patients at the time of diagnosis will facilitate early diagnosis of kidney disorders in them.

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

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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.

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.

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...

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

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Tilahun Alelign

2018-01-01

Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

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Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

2018-01-01

Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

In vivo sodium ({sup 23}Na) imaging of the human kidneys at 7 T: Preliminary results

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Haneder, Stefan [University Medical Center Mannheim, Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); Medical University of Vienna/Vienna General Hospital, Department of Biomedical Imaging and Image-guided Therapy, Department of Radiology, Vienna (Austria); Juras, Vladimir; Trattnig, Siegfried; Zbyn, Stefan [Medical University of Vienna/Vienna General Hospital, Department of Biomedical Imaging and Image-guided Therapy, Department of Radiology, Vienna (Austria); Michaely, Henrik J.; Schoenberg, Stefan O. [University Medical Center Mannheim, Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, Mannheim (Germany); Deligianni, Xeni; Bieri, Oliver [University of Basel Hospital, Department of Radiology, Division of Radiological Physics, Basel (Switzerland)

2014-02-15

To evaluate the feasibility of in vivo {sup 23}Na imaging of the corticomedullary {sup 23}Na gradient and to measure {sup 23}Na transverse relaxation times (T2*) in human kidneys. In this prospective, IRB-approved study, eight healthy volunteers (4 female, 4 male; mean age 29.4 ± 3.6 years) were examined on a 7-T whole-body MR system using a {sup 23}Na-only spine-array coil. For morphological {sup 23}Na-MRI, a 3D gradient echo (GRE) sequence with a variable echo time scheme (vTE) was used. T2* times were calculated using a multiecho 3D vTE-GRE approach. {sup 23}Na signal-to-noise ratios (SNR) were given on a pixel-by-pixel basis for a 20-mm section from the cortex in the direction of the medulla. T2* maps were calculated by fitting the {sup 23}Na signal decay monoexponentially on a pixel-by-pixel basis, using least squares fit. Mean corticomedullary {sup 23}Na-SNR increased from the cortex (32.2 ± 5.6) towards the medulla (85.7 ± 16.0). The SNR increase ranged interindividually from 57.2 % to 66.3 %. Mean {sup 23}Na-T2* relaxation times differed statistically significantly (P < 0.001) between the cortex (17.9 ± 0.8 ms) and medulla (20.6 ± 1.0 ms). The aim of this study was to evaluate the feasibility of in vivo {sup 23}Na MRI of the corticomedullary {sup 23}Na gradient and to measure the {sup 23}Na T2* relaxation times of human kidneys at 7 T. (orig.)

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.

Do You Have Symptoms of a Kidney Stone?

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... Or, the stone will be removed with treatment. Dogs, Cats, and Kidney Stones Humans aren't the only ones affected by kidney and bladder stones. Dogs, cats, and other animals can also have kidney ...

Chronic kidney disease in HIV patients

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Bakri, S.; Rasyid, H.; Kasim, H.; Katu, S.

2018-03-01

Chronic kidney disease (CKD) is a health problem in human immunodeficiency virus (HIV) population. Prediction of CKD in HIV patients needsto have done. This study aimis to identify the prevalence of CKD in HIV patients.Thisis a cross-sectional studyofmale and female, age 18-60 years old, diagnosedHIVat Wahidin Sudirohusodo & Hasanuddin University Hospital Makassar. Diagnosed as CKD if estimated glomerular filtration rate (eGFR) HIV patients included in the analyses. Distribution of CKD, showed 3 (3.5%) subjects with eGFRHIV populations in Makassar is still quite low.

Finite element modeling of the human kidney for probabilistic occupant models: Statistical shape analysis and mesh morphing.

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Yates, Keegan M; Untaroiu, Costin D

2018-04-16

Statistical shape analysis was conducted on 15 pairs (left and right) of human kidneys. It was shown that the left and right kidney were significantly different in size and shape. In addition, several common modes of kidney variation were identified using statistical shape analysis. Semi-automatic mesh morphing techniques have been developed to efficiently create subject specific meshes from a template mesh with a similar geometry. Subject specific meshes as well as probabilistic kidney meshes were created from a template mesh. Mesh quality remained about the same as the template mesh while only taking a fraction of the time to create the mesh from scratch or morph with manually identified landmarks. This technique can help enhance the quality of information gathered from experimental testing with subject specific meshes as well as help to more efficiently predict injury by creating models with the mean shape as well as models at the extremes for each principal component. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adaptive regulation of taurine and beta-alanine uptake in a human kidney cell line from the proximal tubule

DEFF Research Database (Denmark)

Jessen, H; Jacobsen, Christian

1997-01-01

1. The underlying mechanisms involved in the adaptive regulation of beta-amino acid uptake in the human proximal tubule were examined by use of an immortalized human embryonic kidney epithelial cell line (IHKE). 2. The results indicated that the adaptive response to maintain whole-body taurine...

The challenges of human population ageing

DEFF Research Database (Denmark)

Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid

2015-01-01

The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical...... of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20-21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create 'age-friendly' societies and promote 'ageing...

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

Immune System and Kidney Transplantation.

Science.gov (United States)

Shrestha, Badri Man

2017-01-01

The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

Renal water molecular diffusion characteristics in healthy native kidneys: assessment with diffusion tensor MR imaging.

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Zhenfeng Zheng

Full Text Available BACKGROUND: To explore the characteristics of diffusion tensor imaging (DTI and magnetic resonance (MR imaging in healthy native kidneys. METHODS: Seventy-three patients without chronic kidney disease underwent DTI-MRI with spin echo-echo planar (SE-EPI sequences accompanied by an array spatial sensitivity encoding technique (ASSET. Cortical and medullary mean, axial and radial diffusivity (MD, AD and RD, fractional anisotropy (FA and primary, secondary and tertiary eigenvalues (λ1, λ2, λ3 were analysed in both kidneys and in different genders. RESULTS: Cortical MD, λ2, λ3, and RD values were higher than corresponding medullary values. The cortical FA value was lower than the medullary FA value. Medullary λ1 and RD values in the left kidney were lower than in the right kidney. Medullary λ2, and λ3 values in women were higher than those in men. Medullary FA values in women were lower than those in men. Medullary FA (r = 0.351, P = 0.002 and λ1 (r = 0.277, P = 0.018 positively correlated with eGFR. Medullary FA (r = -0.25, P = 0.033 negatively correlated with age. CONCLUSIONS: Renal water molecular diffusion differences exist in human kidneys and genders. Age and eGFR correlate with medullary FA and primary eigenvalue.

Laser Capture Microdissection and Multiplex-Tandem PCR Analysis of Proximal Tubular Epithelial Cell Signaling in Human Kidney Disease

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Wilkinson, Ray; Wang, Xiangju; Kassianos, Andrew J.; Zuryn, Steven; Roper, Kathrein E.; Osborne, Andrew; Sampangi, Sandeep; Francis, Leo; Raghunath, Vishwas; Healy, Helen

2014-01-01

Interstitial fibrosis, a histological process common to many kidney diseases, is the precursor state to end stage kidney disease, a devastating and costly outcome for the patient and the health system. Fibrosis is historically associated with chronic kidney disease (CKD) but emerging evidence is now linking many forms of acute kidney disease (AKD) with the development of CKD. Indeed, we and others have observed at least some degree of fibrosis in up to 50% of clinically defined cases of AKD. Epithelial cells of the proximal tubule (PTEC) are central in the development of kidney interstitial fibrosis. We combine the novel techniques of laser capture microdissection and multiplex-tandem PCR to identify and quantitate “real time” gene transcription profiles of purified PTEC isolated from human kidney biopsies that describe signaling pathways associated with this pathological fibrotic process. Our results: (i) confirm previous in-vitro and animal model studies; kidney injury molecule-1 is up-regulated in patients with acute tubular injury, inflammation, neutrophil infiltration and a range of chronic disease diagnoses, (ii) provide data to inform treatment; complement component 3 expression correlates with inflammation and acute tubular injury, (iii) identify potential new biomarkers; proline 4-hydroxylase transcription is down-regulated and vimentin is up-regulated across kidney diseases, (iv) describe previously unrecognized feedback mechanisms within PTEC; Smad-3 is down-regulated in many kidney diseases suggesting a possible negative feedback loop for TGF-β in the disease state, whilst tight junction protein-1 is up-regulated in many kidney diseases, suggesting feedback interactions with vimentin expression. These data demonstrate that the combined techniques of laser capture microdissection and multiplex-tandem PCR have the power to study molecular signaling within single cell populations derived from clinically sourced tissue. PMID:24475278

Fetal first trimester growth is not associated with kidney outcomes in childhood.

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Bakker, Hanneke; Gaillard, Romy; Hofman, Albert; Reiss, Irwin K; Steegers, Eric A P; Jaddoe, Vincent W V

2017-04-01

Impaired fetal growth is associated with increased risks of kidney diseases in later life. Because human development rates are highest during the first trimester, this trimester may be a particularly critical period for kidney outcomes. We have therefore examined the association of fetal first trimester growth with kidney outcomes in childhood. This study was embedded in a prospective population-based cohort study among 1176 pregnant women and their children. We used fetal first trimester crown-length as the growth measure among mothers with a regular menstrual cycle and a known first day of the last menstrual period. At the childhood age of 6 (median 5.7-6.8) years, we measured combined kidney volume, microalbuminuria and estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C concentrations. No consistent associations of fetal first trimester crown-rump length with childhood combined kidney volume, eGFR and microalbuminuria were observed. Compared to children with a fetal first trimester crown-rump length in the highest quintile, those in the lowest quintile had a larger childhood combined kidney volume (difference 5.32 cm 3 , 95 % confidence interval 1.06 to 9.57), but no differences in kidney function. Our results do not support the hypothesis that fetal first trimester growth restriction affects kidney size and function in childhood. Further studies are needed to focus on critical periods in early life for kidney function and disease in later life.

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...

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

Global trends and challenges in deceased donor kidney allocation.

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Wu, Diana A; Watson, Christopher J; Bradley, J Andrew; Johnson, Rachel J; Forsythe, John L; Oniscu, Gabriel C

2017-06-01

Worldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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

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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

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

Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

Science.gov (United States)

Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

2018-03-01

Cotton rat ( Sigmodon hispidus) is a useful experimental rodent for the study of human infectious diseases. We previously clarified that cotton rats, particularly females, developed chronic kidney disease characterized by cystic lesions, inflammation, and fibrosis. The present study investigated female-associated factors for chronic kidney disease development in cotton rats. Notably, female cotton rats developed separation of the pelvic symphysis and hypertrophy in the vaginal parts of the cervix with age, which strongly associated with pyometra. The development of pyometra closely associated with the deterioration of renal dysfunction or immunological abnormalities was indicated by blood urea nitrogen and serum creatinine or spleen weight and serum albumin/globulin ratio, respectively. These parameters for renal dysfunction and immunological abnormalities were statistically correlated. These phenotypes found in the female reproductive organs were completely inhibited by ovariectomy. Further, the female cotton rats with pyometra tended to show more severe chronic kidney disease phenotypes and immunological abnormalities than those without pyometra; these changes were inhibited in ovariectomized cotton rats. With regard to renal histopathology, cystic lesions, inflammation, and fibrosis were ameliorated by ovariectomy. Notably, the immunostaining intensity of estrogen receptor α and estrogen receptor β were weak in the healthy kidneys, but both estrogen receptors were strongly induced in the renal tubules showing cystic changes. In conclusion, the close correlations among female reproductive organ-associated abnormalities, immunological abnormalities, and renal dysfunction characterize the chronic kidney disease features of female cotton rats. Thus, the cotton rat is a unique rodent model to elucidate the pathological crosstalk between chronic kidney disease and sex-related factors. Impact statement The increasing number of elderly individuals in the overall

Dual roles for coactivator activator and its counterbalancing isoform coactivator modulator in human kidney cell tumorigenesis.

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Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y; Tsai, Ming-Jer; O'Malley, Bert W

2008-10-01

Coactivator activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein, we show that CoAA is a dual-function coregulator that inhibits G(1)-S transition in human kidney cells and suppresses anchorage-independent growth and xenograft tumor formation. Suppression occurs in part by down-regulating c-myc and its downstream effectors ccnd1 and skp2 and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, coactivator modulator (CoAM), antagonizes CoAA-induced G(1)-S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma compared with normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice isoform. This is, thus far, the only example of a nuclear receptor coregulator involved in suppression of kidney cancer and suggests potentially significant new roles for coregulators in renal cancer biology.

Dual roles for CoAA and its counterbalancing isoform CoAM in human kidney cell tumorigenesis

Science.gov (United States)

Kang, Yun Kyoung; Schiff, Rachel; Ko, Lan; Wang, Tao; Tsai, Sophia Y.; Tsai, Ming-Jer; W. O’Malley, Bert

2008-01-01

Co-Activator Activator (CoAA) has been reported to be a coactivator that regulates steroid receptor-mediated transcription and alternative RNA splicing. Herein we show that CoAA is a dual-function coregulator that inhibits G1/S transition in human kidney cells and suppresses anchorage independent growth and xenograft tumor formation. Suppression occurs in part by downregulating c-myc and its downstream effectors ccnd1 and skp2, and causing accumulation of p27/Kip1 protein. In this cellular setting, CoAA directly represses the proto-oncogene, c-myc by recruiting HDAC3 protein and decreasing both the acetylation of histone H3 and the presence of RNA polymerase II on the c-myc promoter. Interestingly, a splicing isoform of CoAA, Coactivator Modulator (CoAM), antagonizes CoAA-induced G1/S transition and growth inhibition by negatively regulating the mRNA levels of the endogenous CoAA isoform. In addition, we found that expression of CoAA protein is significantly decreased in human renal cell carcinoma as compared to normal kidney. Our study presents evidence that CoAA is a potential tumor suppressor in renal carcinoma and that CoAM is a counterbalancing splice-isoform. This is so far the only example of a nuclear receptor coregulator involved in suppression of kidney cancer, and suggests potentially significant new roles for coregulators in renal cancer biology. PMID:18829545

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.

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.

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

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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.

Urinary C-type natriuretic peptide excretion: a potential novel biomarker for renal fibrosis during aging.

Science.gov (United States)

Sangaralingham, S Jeson; Heublein, Denise M; Grande, Joseph P; Cataliotti, Alessandro; Rule, Andrew D; McKie, Paul M; Martin, Fernando L; Burnett, John C

2011-11-01

Renal aging is characterized by structural changes in the kidney including fibrosis, which contributes to the increased risk of kidney and cardiac failure in the elderly. Studies involving healthy kidney donors demonstrated subclinical age-related nephropathy on renal biopsy that was not detected by standard diagnostic tests. Thus there is a high-priority need for novel noninvasive biomarkers to detect the presence of preclinical age-associated renal structural and functional changes. C-type natriuretic peptide (CNP) possesses renoprotective properties and is present in the kidney; however, its modulation during aging remains undefined. We assessed circulating and urinary CNP in a Fischer rat model of experimental aging and also determined renal structural and functional adaptations to the aging process. Histological and electron microscopic analysis demonstrated significant renal fibrosis, glomerular basement membrane thickening, and mesangial matrix expansion with aging. While plasma CNP levels progressively declined with aging, urinary CNP excretion increased, along with the ratio of urinary to plasma CNP, which preceded significant elevations in proteinuria and blood pressure. Also, CNP immunoreactivity was increased in the distal and proximal tubules in both the aging rat and aging human kidneys. Our findings provide evidence that urinary CNP and its ratio to plasma CNP may represent a novel biomarker for early age-mediated renal structural alterations, particularly fibrosis. Thus urinary CNP could potentially aid in identifying subjects with preclinical structural changes before the onset of symptoms and disease, allowing for the initiation of strategies designed to prevent the progression of chronic kidney disease particularly in the aging population.

Four decades of kidney transplantation in Cuba.

Science.gov (United States)

Alfonzo, Jorge P

2013-01-01

This article describes the background, beginnings, development, evolution and outcomes of kidney transplantation in Cuba. Nephrology as a medical specialty in Cuba began in 1962 and was formalized in 1966. Conditions were created to implement renal replacement therapy (including transplants), bring nephrology care to the entire country and train human resources who would assume this responsibility, making Cuba one of the first countries with a comprehensive program for renal patient care. After three unsuccessful cadaveric-donor kidney transplantations in 1968-69, the ensuing history of kidney transplantation can be summarized in the following three stages. 1970-1975: In January 1970, cadaveric-donor kidney transplantation began at the Nephrology Institute. That year, 17 kidney transplantations were performed; four of these patients lived with functional kidneys for 15-25 years; 10-year graft survival was 23.5% (Kaplan-Meier survival curve); HLA typing began in 1974. By December 1975, 170 grafts had been done in three hospitals. 1976-1985: Seven transplantation centers performed 893 grafts during this period. HLA-DR typing was introduced in 1976 and the National Histocompatibility Laboratory Network was founded in 1978. The first related living-donor kidney transplantation was done in 1979. 1986-2011: The National Kidney Transplantation Coordinating Center and the National Kidney Transplantation Program were created in 1986; the first combined kidney-pancreas transplantation was performed the same year. In 1990, cyclosporine and the Cuban monoclonal antibody IOR-T3 were introduced for immunosuppression to prevent rejection, as were other Cuban products (hepatitis B vaccine and recombinant human erythropoietin) for transplant patients. By December 2011, the cumulative number of transplants was 4636 (384 from related living donors). With over 40 years of experience, kidney transplantation is now well established in Cuba; it is free and universally accessible, on the

Persistent anemia in a kidney transplant recipient with parvovirus B19 infection

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Abbas Pakkyara

2017-01-01

Full Text Available Anemia after kidney transplant is not uncommon. This paper reports a case of unexplained anemia in a kidney transplant recipient that persisted for more than two months, and that did not respond to recombinant human erythropoietin treatment but was successfully treated after diagnosing Parvovirus B19 (ParvoV B19 infection. A middle-aged male underwent living-unrelated kidney transplantation from Pakistan in April 2015. He was on triple immuno-suppression therapy consisting of prednisolone, tacrolimus, and mycophenolate mofetil. He presented with anemia which persisted for more than two months that did not improve with Darbepoetin alpha and required blood transfusions. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts characteristic of a ParvoV B19 infection. The serum was highly positive for ParvoV B19 DNA polymerase chain reaction. The anemia resolved completely three weeks after the administration of intravenous immunoglobulin. ParvoV B19 infection should be considered in the differential diagnosis of kidney transplant recipients who present with anemia associated with a low reticulocyte count.

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

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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.

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

Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

Directory of Open Access Journals (Sweden)

Jonas Ahlstedt

2015-12-01

Full Text Available Peptide receptor radionuclide therapy (PRRT has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

Organ slices as an in vitro test system for drug metabolism in human liver, lung and kidney

NARCIS (Netherlands)

Olinga, Peter; de Jager, M.H; Meijer, D.K F; Groothuis, Geny; Merema, M.T.

1999-01-01

Metabolism of xenobiotics occurs mainly in the liver, but in addition, the lungs and kidneys may contribute considerably. The choice of the animal species during drug development as a predictive model for the human condition is often inadequate due to large interspecies differences. Therefore, a

Transgenic Xenopus laevis Line for In Vivo Labeling of Nephrons within the Kidney

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Mark E. Corkins

2018-04-01

Full Text Available Xenopus laevis embryos are an established model for studying kidney development. The nephron structure and genetic pathways that regulate nephrogenesis are conserved between Xenopus and humans, allowing for the study of human disease-causing genes. Xenopus embryos are also amenable to large-scale screening, but studies of kidney disease-related genes have been impeded because assessment of kidney development has largely been limited to examining fixed embryos. To overcome this problem, we have generated a transgenic line that labels the kidney. We characterize this cdh17:eGFP line, showing green fluorescent protein (GFP expression in the pronephric and mesonephric kidneys and colocalization with known kidney markers. We also demonstrate the feasibility of live imaging of embryonic kidney development and the use of cdh17:eGFP as a kidney marker for secretion assays. Additionally, we develop a new methodology to isolate and identify kidney cells for primary culture. We also use morpholino knockdown of essential kidney development genes to establish that GFP expression enables observation of phenotypes, previously only described in fixed embryos. Taken together, this transgenic line will enable primary kidney cell culture and live imaging of pronephric and mesonephric kidney development. It will also provide a simple means for high-throughput screening of putative human kidney disease-causing genes.

Transgenic expression of human heme oxygenase-1 in pigs confers resistance against xenograft rejection during ex vivo perfusion of porcine kidneys.

Science.gov (United States)

Petersen, Björn; Ramackers, Wolf; Lucas-Hahn, Andrea; Lemme, Erika; Hassel, Petra; Queisser, Anna-Lisa; Herrmann, Doris; Barg-Kues, Brigitte; Carnwath, Joseph W; Klose, Johannes; Tiede, Andreas; Friedrich, Lars; Baars, Wiebke; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

2011-01-01

The major immunological hurdle to successful porcine-to-human xenotransplantation is the acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and perturbation of coagulation. Heme oxygenase-1 (HO-1) and its derivatives have anti-apoptotic, anti-inflammatory effects and protect against reactive oxygen species, rendering HO-1 a promising molecule to control AVR. Here, we report the production and characterization of pigs transgenic for human heme oxygenase-1 (hHO-1) and demonstrate significant protection in porcine kidneys against xenograft rejection in ex vivo perfusion with human blood and transgenic porcine aortic endothelial cells (PAEC) in a TNF-α-mediated apoptosis assay. Transgenic and non-transgenic PAEC were tested in a TNF-α-mediated apoptosis assay. Expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was measured by real-time PCR. hHO-1 transgenic porcine kidneys were perfused with pooled and diluted human AB blood in an ex vivo perfusion circuit. MHC class-II up-regulation after induction with IFN-γ was compared between wild-type and hHO-1 transgenic PAEC. Cloned hHO-1 transgenic pigs expressed hHO-1 in heart, kidney, liver, and in cultured ECs and fibroblasts. hHO-1 transgenic PAEC were protected against TNF-α-mediated apoptosis. Real-time PCR revealed reduced expression of adhesion molecules like ICAM-1, VCAM-1, and E-selectin. These effects could be abrogated by the incubation of transgenic PAECs with the specific HO-1 inhibitor zinc protoporphorine IX (Zn(II)PPIX, 20 μm). IFN-γ induced up-regulation of MHC class-II molecules was significantly reduced in PAECs from hHO-1 transgenic pigs. hHO-1 transgenic porcine kidneys could successfully be perfused with diluted human AB-pooled blood for a maximum of 240 min (with and without C1 inh), while in wild-type kidneys, blood flow ceased after ∼60 min. Elevated levels of d-Dimer and TAT were detected, but no significant consumption of fibrinogen and

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.

The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells

International Nuclear Information System (INIS)

O'Neill, Frank J.; Greenlee, John E.; Carney, Helen

2003-01-01

Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

The challenges of human population ageing

Science.gov (United States)

Sander, Miriam; Oxlund, Bjarke; Jespersen, Astrid; Krasnik, Allan; Mortensen, Erik Lykke; Westendorp, Rudi Gerardus Johannes; Rasmussen, Lene Juel

2015-01-01

The 20th century saw an unprecedented increase in average human lifespan as well as a rapid decline in human fertility in many countries of the world. The accompanying worldwide change in demographics of human populations is linked to unanticipated and unprecedented economic, cultural, medical, social, public health and public policy challenges, whose full implications on a societal level are only just beginning to be fully appreciated. Some of these implications are discussed in this commentary, an outcome of Cultures of Health and Ageing, a conference co-sponsored by the University of Copenhagen (UCPH) and the Center for Healthy Ageing at UCPH, which took place on 20–21 June 2014 in Copenhagen, Denmark. Questions discussed here include the following: what is driving age-structural change in human populations? how can we create ‘age-friendly’ societies and promote ‘ageing-in-community’? what tools will effectively promote social engagement and prevent social detachment among older individuals? is there a risk that further extension of human lifespan would be a greater burden to the individual and to society than is warranted by the potential benefit of longer life? PMID:25452294

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.

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

Science.gov (United States)

Czerniecki, Stefan M; Cruz, Nelly M; Harder, Jennifer L; Menon, Rajasree; Annis, James; Otto, Edgar A; Gulieva, Ramila E; Islas, Laura V; Kim, Yong Kyun; Tran, Linh M; Martins, Timothy J; Pippin, Jeffrey W; Fu, Hongxia; Kretzler, Matthias; Shankland, Stuart J; Himmelfarb, Jonathan; Moon, Randall T; Paragas, Neal; Freedman, Benjamin S

2018-05-15

Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening. Copyright © 2018 Elsevier Inc. All rights reserved.

The kidneys in the Bible: what happened?

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Eknoyan, Garabed

2005-12-01

The kidneys, always used in the plural (kelayot), are mentioned more than 30 times in the Bible. In the Pentateuch, the kidneys are cited 11 times in the detailed instructions given for the sacrificial offering of animals at the altar. Whereas those instructions were for purification ceremonies at the Temple, sacrificial offerings were made subsequently in seeking divine intervention for the relief of medical problems. In the books of the Bible that follow the Pentateuch, mostly in Jeremiah and Psalms, the human kidneys are cited figuratively as the site of temperament, emotions, prudence, vigor, and wisdom. In five instances, they are mentioned as the organs examined by God to judge an individual. They are cited either before or after but always in conjunction with the heart as mirrors of the psyche of the person examined. There is also reference to the kidneys as the site of divine punishment for misdemeanors, committed or perceived, particularly in the book of Job, whose suffering and ailments are legendary. In the first vernacular versions of the Bible in English, the translators elected to use the term "reins" instead of kidneys in differentiating the metaphoric uses of human kidneys from that of their mention as anatomic organs of sacrificial animals burned at the altar. This initial effort at linguistic purity or gentility has progressed further in recent versions of the Bible, in which the reins are now replaced by the soul or the mind. The erosion may have begun in the centuries that followed the writing of the Bible, when recognition of the kidneys as excretory organs deprived them of the ancient aura of mysterious organs hidden deep in the body but accessible to the look of God. At approximately the same time, Greek analytical philosophy argued that the brain, which is never mentioned in the Bible, was the most divine and sacred part of the body. This argument gained ground in the past century, when the functions of the brain were elucidated, and

PATHOMORPHOLOGY OF ZERO BIOPSIES OF DONOR KIDNEYS

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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. 

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.

Balanced steady state free precession for arterial spin labeling MRI: Initial experience for blood flow mapping in human brain, retina, and kidney.

Science.gov (United States)

Park, Sung-Hong; Wang, Danny J J; Duong, Timothy Q

2013-09-01

We implemented pseudo-continuous ASL (pCASL) with 2D and 3D balanced steady state free precession (bSSFP) readout for mapping blood flow in the human brain, retina, and kidney, free of distortion and signal dropout, which are typically observed in the most commonly used echo-planar imaging acquisition. High resolution functional brain imaging in the human visual cortex was feasible with 3D bSSFP pCASL. Blood flow of the human retina could be imaged with pCASL and bSSFP in conjunction with a phase cycling approach to suppress the banding artifacts associated with bSSFP. Furthermore, bSSFP based pCASL enabled us to map renal blood flow within a single breath hold. Control and test-retest experiments suggested that the measured blood flow values in retina and kidney were reliable. Because there is no specific imaging tool for mapping human retina blood flow and the standard contrast agent technique for mapping renal blood flow can cause problems for patients with kidney dysfunction, bSSFP based pCASL may provide a useful tool for the diagnosis of retinal and renal diseases and can complement existing imaging techniques. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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.

Wnt Signaling in Kidney Development and Disease.

Science.gov (United States)

Wang, Yongping; Zhou, Chengji J; Liu, Youhua

2018-01-01

Wnt signal cascade is an evolutionarily conserved, developmental pathway that regulates embryogenesis, injury repair, and pathogenesis of human diseases. It is well established that Wnt ligands transmit their signal via canonical, β-catenin-dependent and noncanonical, β-catenin-independent mechanisms. Mounting evidence has revealed that Wnt signaling plays a key role in controlling early nephrogenesis and is implicated in the development of various kidney disorders. Dysregulations of Wnt expression cause a variety of developmental abnormalities and human diseases, such as congenital anomalies of the kidney and urinary tract, cystic kidney, and renal carcinoma. Multiple Wnt ligands, their receptors, and transcriptional targets are upregulated during nephron formation, which is crucial for mediating the reciprocal interaction between primordial tissues of ureteric bud and metanephric mesenchyme. Renal cysts are also associated with disrupted Wnt signaling. In addition, Wnt components are important players in renal tumorigenesis. Activation of Wnt/β-catenin is instrumental for tubular repair and regeneration after acute kidney injury. However, sustained activation of this signal cascade is linked to chronic kidney diseases and renal fibrosis in patients and experimental animal models. Mechanistically, Wnt signaling controls a diverse array of biologic processes, such as cell cycle progression, cell polarity and migration, cilia biology, and activation of renin-angiotensin system. In this chapter, we have reviewed recent findings that implicate Wnt signaling in kidney development and diseases. Targeting this signaling may hold promise for future treatment of kidney disorders in patients. Copyright © 2018 Elsevier Inc. All rights reserved.

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

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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.

Renal cancer in recipients of kidney transplant

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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.

New biomarkers of acute kidney injury

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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

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...

Ethics, Justice and the Sale of Kidneys for Transplantation Purposes

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M Slabbert

2010-08-01

Full Text Available Living kidney donor transplantations are complex; add to that financial compensation to the donor and one enters an ethical maze. Debates on whether the buying and selling of kidneys should be allowed are mainly between utilitarians, deontologists and virtue ethicists as legal transplants are more common in the Western world. The pros and cons of each theory in relation to the sale of human organs are analysed, after which the foundational principles for all bio-ethical judgments; beneficence, non-maleficence, autonomy and justice are also scrutinised in seeking to justify the sale of human kidneys for transplantation purposes in a country with a human rights culture.

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

The role of SIRT1 in diabetic kidney disease

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Rabi eYacoub

2014-10-01

Full Text Available Sirtuins (SIRTs are members of the silent information regulator 2 (Sir2 family. In mammals, of the seven known SIRTs, SIRT1 function is most studied and has been shown to regulate wide range of cellular functions that affect metabolic homeostasis and aging. SIRT1 exerts anti-apoptotic, anti-oxidative, and anti-inflammatory effects against cellular injury, and protects the cells through the regulation of mitochondrial biogenesis, autophagy, and metabolism in response to the cellular energy and redox status. SIRT1 also promotes vasodilation and protects vascular tissues. In humans and animal models with diabetic kidney disease, its expression tends to be decreased in renal cells, and increased expression of SIRT1 was found to play a renal protective role in animal models with diabetic kidney disease. In this review we discuss the role and potential mechanisms by which SIRT1 protects against DKD.

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...

Overexpression of esterase D in kidney from trisomy 13 fetuses

Energy Technology Data Exchange (ETDEWEB)

Loughna, S.; Moore, G. (Institute of Obstetrics and Gynaecology, London (United Kingdom)); Gau, G.; Blunt, S. (Cytogenetics Lab., London (United Kingdom)); Nicolaides, K. (King' s College School of Medicine and Dentistry, London (United Kingdom))

1993-10-01

Human trisomy 13 (Patau syndrome) occurs in approximately 1 in 5,000 live births. It is compatible with life, but prolonged survival is rare. Anomalies often involve the urogenital, cardiac, craniofacial, and central nervous systems. It is possible that these abnormalities may be due to the overexpression of developmentally important genes on chromosome 13. The expression of esterase D (localized to chromosome 13q14.11) has been investigated in both muscle and kidney from trisomy 13 fetuses and has been compared with normal age- and sex-matched fetal tissues, by using northern analysis. More than a twofold increase in expression of esterase D was found in the kidney of two trisomy 13 fetuses, with normal levels in a third. Overexpression was not seen in the muscle tissues from these fetuses. 34 refs., 3 figs., 2 tabs.

Novel treatment strategies for chronic kidney disease: insights from the animal kingdom.

Science.gov (United States)

Stenvinkel, Peter; Painer, Johanna; Kuro-O, Makoto; Lanaspa, Miguel; Arnold, Walter; Ruf, Thomas; Shiels, Paul G; Johnson, Richard J

2018-04-01

Many of the >2 million animal species that inhabit Earth have developed survival mechanisms that aid in the prevention of obesity, kidney disease, starvation, dehydration and vascular ageing; however, some animals remain susceptible to these complications. Domestic and captive wild felids, for example, show susceptibility to chronic kidney disease (CKD), potentially linked to the high protein intake of these animals. By contrast, naked mole rats are a model of longevity and are protected from extreme environmental conditions through mechanisms that provide resistance to oxidative stress. Biomimetic studies suggest that the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) offers protection in extreme environmental conditions and promotes longevity in the animal kingdom. Similarly, during months of fasting, immobilization and anuria, hibernating bears are protected from muscle wasting, azotaemia, thrombotic complications, organ damage and osteoporosis - features that are often associated with CKD. Improved understanding of the susceptibility and protective mechanisms of these animals and others could provide insights into novel strategies to prevent and treat several human diseases, such as CKD and ageing-associated complications. An integrated collaboration between nephrologists and experts from other fields, such as veterinarians, zoologists, biologists, anthropologists and ecologists, could introduce a novel approach for improving human health and help nephrologists to find novel treatment strategies for CKD.

Preservation of beta cell function in adult human pancreatic islets for several months in vitro

DEFF Research Database (Denmark)

Brunstedt, J; Andersson, A; Frimodt-Møller, C

1979-01-01

Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more tha...... technique presents a valuable tool for studying chronic effects of metabolites and hormones on islet function, as well as for islet storage prior to transplantation into humans.......Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more than...

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.

Prognosis of Dialysed Patients after Kidney Transplant Failure

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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.

Human mesenchymal stem cells alter macrophage phenotype and promote regeneration via homing to the kidney following ischemia-reperfusion injury

NARCIS (Netherlands)

Wise, Andrea F; Williams, Timothy M; Kiewiet, Mensiena B G; Payne, Natalie L; Siatskas, Christopher; Samuel, Chrishan S; Ricardo, Sharon D

2014-01-01

Mesenchymal stem cells (MSCs) ameliorate injury and accelerate repair in many organs, including the kidney, although the reparative mechanisms and interaction with macrophages have not been elucidated. This study investigated the reparative potential of human bone marrow-derived MSCs and traced

Kidneys From α1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With Human Blood.

Science.gov (United States)

Ahrens, Hellen E; Petersen, Björn; Ramackers, Wolf; Petkov, Stoyan; Herrmann, Doris; Hauschild-Quintern, Janet; Lucas-Hahn, Andrea; Hassel, Petra; Ziegler, Maren; Baars, Wiebke; Bergmann, Sabine; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

2015-07-01

Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a (51)Chromium release assay and by ex vivo kidney perfusions with human blood. Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation.

42 CFR 410.48 - Kidney disease education services.

Science.gov (United States)

2010-10-01

... 410.48 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... on how the kidneys work and what happens when the kidneys fail. (ii) Understanding if remaining... outcomes assessments serve to assess the program's effectiveness in meeting the communication needs of...

Amino acid sequence and posttranslational modifications of human factor VIIa from plasma and transfected baby hamster kidney cells

International Nuclear Information System (INIS)

Thim, L.; Bjoern, S.; Christensen, M.; Nicolaisen, E.M.; Lund-Hansen, T.; Pedersen, A.H.; Hedner, U.

1988-01-01

Blood coagulation factor VII is a vitamin K dependent glycoprotein which in its activated form, factor VII a , participates in the coagulation process by activating factor X and/or factor IX in the presence of Ca 2+ and tissue factor. Three types of potential posttranslational modifications exist in the human factor VII a molecule, namely, 10 γ-carboxylated, N-terminally located glutamic acid residues, 1 β-hydroxylated aspartic acid residue, and 2 N-glycosylated asparagine residues. In the present study, the amino acid sequence and posttranslational modifications of recombinant factor VII a as purified from the culture medium of a transfected baby hamster kidney cell line have been compared to human plasma factor VII a . By use of HPLC, amino acid analysis, peptide mapping, and automated Edman degradation, the protein backbone of recombinant factor VII a was found to be identical with human factor VII a . Asparagine residues 145 and 322 were found to be fully N-glycosylated in human plasma factor VII a . In the recombinant factor VII a , asparagine residue 322 was fully glycosylated whereas asparagine residue 145 was only partially (approximately 66%) glycosylated. Besides minor differences in the sialic acid and fucose contents, the overall carbohydrate compositions were nearly identical in recombinant factor VII a and human plasma factor VII a . These results show that factor VII a as produced in the transfected baby hamster kidney cells is very similar to human plasma factor VII a and that this cell line thus might represent an alternative source for human factor VII a

Prevalence and predictors of chronic kidney disease in newly diagnosed human immunodeficiency virus patients in Owerri, Nigeria

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E N Anyabolu

2016-01-01

Full Text Available Human immunodeficiency virus (HIV infection is a common cause of chronic kidney disease (CKD in Sub-Saharan Africa. This study aims at identifying the prevalence and predictors of CKD in newly diagnosed HIV patients in Owerri, South East Nigeria. This was a cross-sectional study consisting of 393 newly diagnosed HIV-seropositive subjects and 136 age- and sex-matched seronegative subjects as controls. CKD was defined as 24-hour urine protein (24-HUP ≥0.3 g and/or glomerular filtration rate (GFR < 60 ml/min. Subjects were recruited from the HIV clinic and the Medical Outpatient Department of Federal Medical Centre, Owerri. Clinical and anthropometric data were collected. Relevant investigations were performed, including HIV screening and relevant urine and blood investigations. The mean age of the HIV subjects was 38.84 ± 10.65 years. CKD was present in 86 (22.9% HIV subjects and 11 (8.l % controls. Low waist circumference (WC, high serum creatinine, high spot urine protein/creatinine ratio (SUPCR, high 24-HUP/creatinine Ratio (24-HUPCR, high 24-HUP/osmolality Ratio (24-HUPOR predicted CKD in HIV subjects. CKD prevalence is high (22.9% among newly diagnosed HIV patients in South East Nigeria. The predictors of CKD included WC, serum creatinine, SUPCR, 24-HUPCR, and 24-HUPOR.

Expression of the vitamin D receptor, 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase in the human kidney and renal clear cell cancer

DEFF Research Database (Denmark)

Blomberg Jensen, Martin; Andersen, Claus B.; Nielsen, John E

2010-01-01

The vitamin D receptor (VDR), CYP27B1 and CYP24A1 are expressed in the human kidney, but the segmental expression of the 25-hydroxylases is unknown. A comprehensive analysis of CYP2R1, CYP27A1, CYP27B1, VDR and CYP24A1 expression in normal kidney and renal clear cell cancer (CCc) would reveal...

Human factors: A major issue in plant aging

International Nuclear Information System (INIS)

Widrig, R.D.

1985-01-01

Humans play a significant role in the effects of aging on safe and reliable operation of nuclear power plants. These human issues may be more important than the issues of materials and component degradation with age. Human actions can accelerate or decelerate physical aging of a plant. And an aging plant can have a significant negative impact on staff quality and performance. The purpose of this paper is to provide some insights into the nature of these human factors issues and their relationship to plant aging. An early awareness of these issues facilitates timely action to at least mitigate these problems before they become insurmountable

Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray

OpenAIRE

Higgins, John P.T.; Wang, Lingli; Kambham, Neeraja; Montgomery, Kelli; Mason, Veronica; Vogelmann, Stefanie U.; Lemley, Kevin V.; Brown, Patrick O.; Brooks, James D.; van de Rijn, Matt

2004-01-01

The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied g...

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

Increasing access to kidney transplantation in countries with limited resources: the Indian experience with kidney paired donation.

Science.gov (United States)

Kute, Vivek B; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Engineer, Divyesh P; Modi, Pranjal R; Shah, Veena R; Trivedi, Hargovind L

2014-10-01

According to the Indian chronic kidney disease registry, in 2010 only 2% of end stage kidney disease patients were managed with kidney transplantation, 37% were managed with dialysis and 61% were treated conservatively without renal replacement therapy. In countries like India, where a well-organized deceased donor kidney transplantation program is not available, living donor kidney transplantation is the major source of organs for kidney transplantation. The most common reason to decline a donor for directed living donation is ABO incompatibility, which eliminates up to one third of the potential living donor pool. Because access to transplantation with human leukocyte antigen (HLA)-desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end stage kidney disease patients. KPD is a rapidly growing and cost-effective living donor kidney transplantation strategy for patients who are incompatible with their healthy, willing living donor. In principle, KPD is feasible for any centre that performs living donor kidney transplantation. In transplant centres with a large living donor kidney transplantation program KPD does not require extra infrastructure, decreases waiting time, avoids transplant tourism and prevents commercial trafficking. Although KPD is still underutilized in India, it has been performed more frequently in recent times. To substantially increase donor pool and transplant rates, transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy. © 2014 Asian Pacific Society of Nephrology.

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

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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

Frailty in elderly people with chronic kidney disease

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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.

Animal and human models to understand ageing.

Science.gov (United States)

Lees, Hayley; Walters, Hannah; Cox, Lynne S

2016-11-01

Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney.

Science.gov (United States)

Minuth, Will W

2018-01-01

While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches. © 2017 S. Karger AG, Basel.

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.

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.)

New kidney physiopathology concepts acquired from a quantitative kidney function examination: the 197Hg uptake test

International Nuclear Information System (INIS)

Raynaud, C.; Ricard, S.; Knipper, M.

1976-01-01

The kidney function of 331 ureter obstruction cases, of which 112 unilateral, was studied by the radioactive Hg renal uptake test. The results obtained call for the following remarks: kidneys deprived of activity by a chronic ureteral obstacle retain a minimal function representing about a quarter the normal value, which seems not to improve after removal of the obstacle. Apart from these cases, conservation surgery in unilateral ureter obstructions is followed by a significant kidney function improvement on the operated side in more than one case in three. In 43% of ureter obstructions considered as unilateral the functional value of both kidneys is impaired. The main features of human compensatory kidney hypertrophy are beginning to emerge: it develops on the less affected kidney and it settles in and regresses slowly. Moreover the results reported show that it adapts to keep the total function at a fixed value in a given subject. Five exceptions to this rule however developed a compensatory hypertrophy significantly higher than expected after surgery, as through a new limit had been established after the operation. These exceptional cases are very interesting from both a practical and theoretical viewpoint [fr

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.

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.

Renal denervation and hypertension - The need to investigate unintended effects and neural control of the human kidney.

Science.gov (United States)

Grisk, Olaf

2017-05-01

Increased renal sympathetic nerve activity (RSNA) is present in human and experimental forms of arterial hypertension. Experimental denervation studies showed that renal nerves contribute to the development of hypertension. Clinical trials provided equivocal results on the antihypertensive efficacy of renal denervation in patients spurring discussions on technical aspects of renal denervation and further research on the role of renal nerves for the regulation of kidney function as well as the pathophysiology of hypertension. This review summarizes recent findings on adrenoceptor expression and function in the human kidney, adrenoceptor-dependent regulation of sodium chloride transport in the distal nephron, experimental data on chronic RSNA and the development of high arterial pressure and consequences of renal denervation that may limit its antihypertensive efficacy. Future research needs to reduce the gap between our knowledge on neural control of renal function in animals vs. humans to facilitate translation of experimental animal data to humans. More experimental studies on the temporal relationship between RSNA and arterial pressure in the chronic setting are needed to better define the pathogenetic role of heightened RSNA in different forms of arterial hypertension in order to improve the rational basis for renal denervation in antihypertensive therapy. Finally, research on unintended consequences of renal denervation including but not limited to reinnervation and denervation supersensitivity needs to be intensified to further assess the potential of renal denervation to slow the progression of renal disease and hypertension. Copyright © 2016 Elsevier B.V. All rights reserved.

Analysis of elements in human blood of patients with chronic kidney disease using neutron activation analysis

International Nuclear Information System (INIS)

Metairon, S.; Zamboni, C.B.; Kovacs, L.; Genezini, F.A.; Santos, N.F.; Vilela, E.C.

2009-01-01

Neutron activation analysis has been used to determine Br, Ca, Cl, K, Mg and Na concentrations in whole blood of patients with chronic kidney disease (CKD) as well as in whole blood of normal individuals (control group). The dependence of the elements concentration in function of sex, age, time and type of treatment were investigated. The similarities and differences between healthy individuals and CKD are discussed. (author)

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.

Developmental immunolocalization of the Klotho protein in mouse kidney epithelial cells

Directory of Open Access Journals (Sweden)

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.

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...

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.

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.

Human accumulation of mercury in Greenland

DEFF Research Database (Denmark)

Johansen, Poul; Mulvad, Gert; Pedersen, Henning Sloth

2007-01-01

In the Arctic, the traditional diet exposes its people to a high intake of mercury especially from marine mammals. To determine whether the mercury is accumulated in humans, we analyzed autopsy samples of liver, kidney and spleen from adult ethnic Greenlanders who died between 1990 and 1994 from...... a wide range of causes, natural and violent. Liver, kidney and spleen samples from between 33 and 71 case subjects were analyzed for total mercury and methylmercury, and liver samples also for selenium. Metal levels in men and women did not differ and were not related to age except in one case, i.......e. for total mercury in liver, where a significant declining concentration with age was observed. The highest total mercury levels were found in kidney followed by liver and spleen. Methylmercury followed the same pattern, but levels were much lower, constituting only 19% of the total mercury concentration...

Human accumulation of mercury in Greenland

DEFF Research Database (Denmark)

Johansen, P.; Mulvad, G.; Pedersen, H. S.

2007-01-01

a wide range of causes, natural and violent. Liver, kidney and spleen samples from between 33 and 71 case subjects were analyzed for total mercury and methylmercury, and liver samples also for selenium. Metal levels in men and women did not differ and were not related to age except in one case, i......In the Arctic, the traditional diet exposes its people to a high intake of mercury especially from marine mammals. To determine whether the mercury is accumulated in humans, we analyzed autopsy samples of liver, kidney and spleen from adult ethnic Greenlanders who died between 1990 and 1994 from.......e. for total mercury in liver, where a significant declining concentration with age was observed. The highest total mercury levels were found in kidney followed by liver and spleen. Methylmercury followed the same pattern, but levels were much lower, constituting only 19% of the total mercury concentration...

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 - ...

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....

Hypotension during endotoxemia in aged humans

DEFF Research Database (Denmark)

Krabbe, Karen Suarez; Kemp, Helle Bruunsgaard; Qvist, Jesper

2001-01-01

BACKGROUND: and objective The aim of this study was to determine possible age-associated differences in human blood pressure regulation during an immunological challenge in healthy subjects. METHODS: Eight healthy young volunteers (median age 24 yr) and nine healthy elderly volunteers (median age...

Human Ageing Genomic Resources: new and updated databases

Science.gov (United States)

Tacutu, Robi; Thornton, Daniel; Johnson, Emily; Budovsky, Arie; Barardo, Diogo; Craig, Thomas; Diana, Eugene; Lehmann, Gilad; Toren, Dmitri; Wang, Jingwei; Fraifeld, Vadim E

2018-01-01

Abstract In spite of a growing body of research and data, human ageing remains a poorly understood process. Over 10 years ago we developed the Human Ageing Genomic Resources (HAGR), a collection of databases and tools for studying the biology and genetics of ageing. Here, we present HAGR’s main functionalities, highlighting new additions and improvements. HAGR consists of six core databases: (i) the GenAge database of ageing-related genes, in turn composed of a dataset of >300 human ageing-related genes and a dataset with >2000 genes associated with ageing or longevity in model organisms; (ii) the AnAge database of animal ageing and longevity, featuring >4000 species; (iii) the GenDR database with >200 genes associated with the life-extending effects of dietary restriction; (iv) the LongevityMap database of human genetic association studies of longevity with >500 entries; (v) the DrugAge database with >400 ageing or longevity-associated drugs or compounds; (vi) the CellAge database with >200 genes associated with cell senescence. All our databases are manually curated by experts and regularly updated to ensure a high quality data. Cross-links across our databases and to external resources help researchers locate and integrate relevant information. HAGR is freely available online (http://genomics.senescence.info/). PMID:29121237

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.

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.

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...

Biological psychological and social determinants of old age: Bio-psycho-social aspects of human aging

Directory of Open Access Journals (Sweden)

Małgorzata Dziechciaż

2014-11-01

Full Text Available Biological psychological and social determinants of old age: Bio-psycho-social aspects of human aging. The aging of humans is a physiological and dynamic process ongoing with time. In accordance with most gerontologists’ assertions it starts in the fourth decade of life and leads to death. The process of human aging is complex and individualized, occurs in the biological, psychological and social sphere. Biological aging is characterized by progressive age-changes in metabolism and physicochemical properties of cells, leading to impaired self-regulation, regeneration, and to structural changes and functional tissues and organs. It is a natural and irreversible process which can run as successful aging, typical or pathological. Biological changes that occur with age in the human body affect mood, attitude to the environment, physical condition and social activity, and designate the place of seniors in the family and society. Psychical ageing refers to human awareness and his adaptability to the ageing process. Among adaptation attitudes we can differentiate: constructive, dependence, hostile towards others and towards self attitudes. With progressed age, difficulties with adjustment to the new situation are increasing, adverse changes in the cognitive and intellectual sphere take place, perception process involutes, perceived sensations and information received is lowered, and thinking processes change. Social ageing is limited to the role of an old person is culturally conditioned and may change as customs change. Social ageing refers to how a human being perceives the ageing process and how society sees it.

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

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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.

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.

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.

Association between Residential Proximity to PERC Dry Cleaning Establishments and Kidney Cancer in New York City

Directory of Open Access Journals (Sweden)

Jing Ma

2009-01-01

Full Text Available Perchloroethylene (PERC is commonly used as a dry cleaning solvent and is believed to be a human carcinogen, with occupational exposure resulting in elevated rates of kidney cancer. Living near a dry cleaning facility using PERC has been demonstrated to increase the risk of PERC exposure throughout the building where the dry cleaning is conducted, and in nearby buildings. We designed this study to test the hypothesis that living in an area where there are many PERC dry cleaners increases PERC exposure and the risk of kidney cancer. We matched the diagnosis of kidney cancer from hospitalization discharge data in New York City for the years 1994–2004 by zip code of patient residence to the zip code density of dry cleaners using PERC, as a surrogate for residential exposure. We controlled for age, race, gender, and median household income. We found a significant association between the density of PERC dry cleaning establishments and the rate of hospital discharges that include a diagnosis of kidney cancer among persons 45 years of age and older living in New York City. The rate ratio increased by 10 to 27% for the populations in zip codes with higher density of PERC dry cleaners. Because our exposure assessment is inexact, we are likely underestimating the real association between exposure to PERC and rates of kidney cancer. Our results support the hypothesis that living near a dry cleaning facility using PERC increases the risk of PERC exposure and of developing kidney cancer. To our knowledge, this study is the first to demonstrate an association between residential PERC exposure and cancer risk.

Association between Residential Proximity to PERC Dry Cleaning Establishments and Kidney Cancer in New York City

International Nuclear Information System (INIS)

Ma, J.; Lessner, L.; Lessner, L.; Carpenter, D.O.; Schreiber, J.

2010-01-01

Perchloroethylene (PERC) is commonly used as a dry cleaning solvent and is believed to be a human carcinogen, with occupational exposure resulting in elevated rates of kidney cancer. Living near a dry cleaning facility using PERC has been demonstrated to increase the risk of PERC exposure throughout the building where the dry cleaning is conducted, and in nearby buildings. We designed this study to test the hypothesis that living in an area where there are many PERC dry cleaners increases PERC exposure and the risk of kidney cancer. We matched the diagnosis of kidney cancer from hospitalization discharge data in New York City for the years 1994-2004 by zip code of patient residence to the zip code density of dry cleaners using PERC, as a surrogate for residential exposure. We controlled for age, race, gender, and median household income. We found a significant association between the density of PERC dry cleaning establishments and the rate of hospital discharges that include a diagnosis of kidney cancer among persons 45 years of age and older living in New York City. The rate ratio increased by 10 to 27% for the populations in zip codes with higher density of PERC dry cleaners. Because our exposure assessment is inexact, we are likely underestimating the real association between exposure to PERC and rates of kidney cancer. Our results support the hypothesis that living near a dry cleaning facility using PERC increases the risk of PERC exposure and of developing kidney cancer. To our knowledge, this study is the first to demonstrate an association between residential PERC exposure and cancer risk.

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

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

A human cytochrome P-450 is recognized by anti-liver/kidney microsome antibodies in autoimmune chronic hepatitis.

Science.gov (United States)

Kiffel, L; Loeper, J; Homberg, J C; Leroux, J P

1989-02-28

1- Anti-liver/kidney microsome autoantibodies type 1 (anti-LKM1), observed in some children with chronic active hepatitis, were used to isolate their antigen in human liver microsomes. A protein, called P-LKM1 was thus purified. This protein was recognized by a rabbit antiserum directed against the related human cytochromes P-450 bufI and P-450 bufII. 2- A human liver microsomal protein immunoprecipitated with anti-LKM1 sera was also recognized by anti cytochromes P-450 bufI/II antibodies. 3- Anti-LKM1 antibodies potently inhibited microsomal bufuralol 1'-hydroxylation. These results displayed the possible identity between cytochrome P-450 bufI/II and LKM1 antigen.

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.

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)

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...

Cloning and expression of a human kidney cDNA for an α2-adrenergic receptor subtype

International Nuclear Information System (INIS)

Regan, J.W.; Kobilka, T.S.; Yang-Feng, T.L.; Caron, M.G.; Lefkowitz, R.J.; Kobilka, B.K.

1988-01-01

An α 2 -adrenergic receptor subtype has been cloned from a human kidney cDNA library using the gene for the human platelet α 2 -adrenergic receptor as a probe. The deduced amino acid sequence resembles the human platelet α 2 -adrenergic receptor and is consistent with the structure of other members of he family of guanine nucleotide-binding protein-coupled receptors. The cDNA was expressed in a mammalian cell line (COS-7), and the α 2 -adrenergic ligand [ 3 H]rauwolscine was bound. Competition curve analysis with a variety of adrenergic ligands suggests that this cDNA clone represents the α 2 B-adrenergic receptor. The gene for this receptor is on human chromosome 4, whereas the gene for the human platelet α 2 -adrenergic receptor (α 2 A) lies on chromosome 10. This ability to express the receptor in mammalian cells, free of other adrenergic receptor subtypes, should help in developing more selective α-adrenergic ligands

Molecular aging and rejuvenation of human muscle stem cells

DEFF Research Database (Denmark)

Carlson, Morgan E; Suetta, Charlotte; Conboy, Michael J

2009-01-01

. Our findings establish key evolutionarily conserved mechanisms of human stem cell aging. We find that satellite cells are maintained in aged human skeletal muscle, but fail to activate in response to muscle attrition, due to diminished activation of Notch compounded by elevated transforming growth...... factor beta (TGF-beta)/phospho Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling declines in human muscle with age, and is important for activating Notch in human muscle stem cells. This molecular......Very little remains known about the regulation of human organ stem cells (in general, and during the aging process), and most previous data were collected in short-lived rodents. We examined whether stem cell aging in rodents could be extrapolated to genetically and environmentally variable humans...

Recent developments in epigenetics of acute and chronic kidney diseases.

Science.gov (United States)

Reddy, Marpadga A; Natarajan, Rama

2015-08-01

The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies.

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%.

Behaviour of trace element concentration in human organs in dependence of age and environment

International Nuclear Information System (INIS)

Persigehl, M.; Schicha, H.; Kasperek, K.; Feinendegen, L.E.; Kernforschungsanlage Juelich G.m.b.H.

1977-01-01

To study the behaviour of trace elements in dependence of age and environment, samples of skin, lung, heart, aorta, kidney, liver and brain were assayed for concentrations of Fe, Zn, Rb, Co, Cr, Se, Sc, Sb, Cs, Al and partly Eu. All samples were dried at 100 deg C for two days. Instrumental neutron-activation analysis was used to determine the element concentrations. The neutron flux was 5 x 10 13 n cm -2 sec -1 . After decay of the short lived radioisotopes, the Al-concentration was measured following a second irradiation of 1 minute and directly comparing with a standard sample. Nearly all element concentrations changed with processing age, but they showed no clear correlation to either parameter assessed. The non-essential elements Se, Sb and Sc were increasingly concentrated in all organs except the skin. Comparing lung samples of patients from highly industrialized regions with those of lesser industrialization, the elements Sc, Al, Sb, Eu and Co were accumulated by a factor of 10 to 100. Thus the concentrations of trace elements in human organism also depend on the degree of industrialization. (T.G.)

The bovine kidney as an experimental model in urology: external gross anatomy.

Science.gov (United States)

Carvalho, Francismar S; Bagetti Filho, Hélio J S; Henry, Robert W; Pereira-Sampaio, Marco A

2009-01-01

The objective of this work was to obtain and record detailed and accurate measurements of the bovine kidney and to compare these new data with findings in humans. Thirty-eight bovine kidneys were used. The total number of lobes, along with the number of lobes located in the cranial polar, caudal polar and hilar regions, were recorded. Several measurements of the kidneys were made and evaluated. The hilar region presents the greatest length (mean of 76.87 mm) of the 3 renal regions of the kidney. The large area of the bovine renal hilus could make access to hilar structures easier than in the human kidney. The coefficient of variation for renal length was small (8.14%), while the coefficient of variation for the lobar number was high (26.82%). The number of renal lobes ranged from 13 to 35, with a mean of 20.62. The hilar region presents the highest number of lobes, while the cranial pole presents the lowest. The number of lobes in the cranial and caudal poles increases with the width of these regions. This is different from the hilar region, in which the lobar number increases with the length of the hilus. These data indicate that the adult bovine kidney can be used as a model for certain urologic procedures, but researchers must be aware that there are some major differences between the adult bovine kidney and the human kidney, as indicated by the data reported in this paper. (c) 2008 S. Karger AG, Basel.

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.

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

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...

Four-Way Kidney Exchange Transplant With Desensitization Increases Access to Living-Donor Kidney Transplant: First Report From India.

Science.gov (United States)

Kute, Vivek B; Patel, Himanshu V; Shah, Pankaj R; Modi, Pranjal R; Shah, Veena R; Kasat, Govind S; Patil, Mayur V; Patel, Jaydeep C; Kumar, Deepak P; Trivedi, Hargovind L

2017-09-26

This study reports our experience of the first 4-way kidney exchange transplant combined with desensitization in India, which allows increased access to living-donor kidney transplant for sensitized patients. Four-way kidney exchange transplant procedures were approved by the ethics committee of our institution and the Organ Transplantation Authorization Committee of state governments of India (as per the Transplantation of Human Organs Act of India). The protocols conformed to Declaration of Istanbul principles and the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from patients, donors, and their guardians. In April 2016, our transplant team completed simultaneous 4-way kidney exchange transplant procedures without any medical (rejection and infections) or surgical complications. Reasons for being included for kidney exchange transplant were ABO incom-patible (2 recipients) and sensitization (2 recipients). All 4 recipients had stable graft function with no proteinuria and donor-specific antibody at 11-month follow-up on standard triple immunosup-pression. Patient and graft survival rates were both 100%. To the best of our knowledge, this is the first single-center report of 4-way kidney exchange transplant combined with desensitization from India. This procedure has the potential to expand living-donor kidney transplant in disadvantaged groups (eg, sensitized patients). Recipients who are hard to match due to high panel reactive antibody and difficult to desensitize due to strong donor-specific antibodies can receive a transplant with a combination of kidney exchange and desensitization. Our study suggests that 4-way kidney exchange transplant can be performed in developing countries (India) similar to that shown in programs in developed countries with team work, kidney exchange registry, and counseling.

Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

Science.gov (United States)

Sagrinati, Costanza; Netti, Giuseppe Stefano; Mazzinghi, Benedetta; Lazzeri, Elena; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Meini, Claudia; Gacci, Mauro; Squecco, Roberta; Carini, Marco; Gesualdo, Loreto; Francini, Fabio; Maggi, Enrico; Annunziato, Francesco; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

2006-09-01

Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

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 ...

JURIDICAL ANALYSIS OF LEGISLATION RELATED TO THE CRIME OF TRADE IN HUMAN ORGANS FOR THE BENEFIT OF THE KIDNEY ORGAN TRANSPLANT (Comparative Studies Between Indonesia with Philippines

Directory of Open Access Journals (Sweden)

Benny Situmorang

2016-06-01

Full Text Available In accordance with organ transplant’s evolve especially the kidneys it is necessary to rule out specific health legislation  in dealing with transplantation  of human body’s  organs  to prevent  human  trafficking  of human  organs.  The approaches used is the approach of legislation and comparisons to provide an overview of the regulation of transplantation of human body’s organs in Indonesia, and to know the comparison with other countries that have specific rules on transplants. The result is that the regulations in Indonesia does not have rules on organ transplants from living non-related organ donation and found no legal protection againts the donor. Keywords: Organ   transplant,   kidney   transplant,   human   trafficking,   health legislation.

Localization of Mg2+-sensing shark kidney calcium receptor SKCaR in kidney of spiny dogfish, Squalus acanthias.

Science.gov (United States)

Hentschel, Hartmut; Nearing, Jacqueline; Harris, H William; Betka, Marlies; Baum, Michelle; Hebert, Steven C; Elger, Marlies

2003-09-01

We recently cloned a homologue of the bovine parathyroid calcium receptor from the kidney of a spiny dogfish (Squalus acanthias) and termed this new protein SKCaR. SKCaR senses alterations in extracellular Mg2+ after its expression in human embryonic kidney cells (Nearing J, Betka M, Quinn S, Hentschel H, Elger M, Baum M, Bai M, Chattopadyhay N, Brown E, Hebert S, and Harris HW. Proc Natl Acad. Sci USA 99: 9231-9236, 2002). In this report, we used light and electron microscopic immunocytochemical techniques to study the distribution of SKCaR in dogfish kidney. SKCaR antiserum bound to the apical membranes of shark kidney epithelial cells in the following tubular segments: proximal tubules (PIa and PIIb), late distal tubule, and collecting tubule/collecting duct as well as diffusely labeled cells of early distal tubule. The highly specific distribution of SKCaR in mesial tissue as well as lateral countercurrent bundles of dogfish kidney is compatible with a role for SKCaR to sense local tubular Mg2+ concentrations. This highly specific distribution of SKCaR protein in dogfish kidney could possibly work in concert with the powerful Mg2+ secretory system present in the PIIa segment of elasmobranch fish kidney to affect recycling of Mg2+ from putative Mg2+-sensing/Mg2+-reabsorbing segments. These data provide support for the possible existence of Mg2+ cycling in elasmobranch kidney in a manner analogous to that described for mammals.

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 ...

Evolutionary trade-offs in kidney injury and repair.

Science.gov (United States)

Lei, Yutian; Anders, Hans-Joachim

2017-11-01

Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.

Contextual reminders fail to trigger memory reconsolidation in aged rats and aged humans.

Science.gov (United States)

Jones, Bethany J; Pest, Stacey M; Vargas, Iliana M; Glisky, Elizabeth L; Fellous, Jean-Marc

2015-04-01

There is strong evidence that hippocampal memory returns to a labile state upon reactivation, initiating a reconsolidation process that restabilizes it and allows for its updating. Normal aging is associated with deficits in episodic memory processes. However, the effects of aging on memory reconsolidation and its neural substrate remain largely unknown, and an animal model is lacking. In this study we investigated the effects of aging on context-dependent reconsolidation using an episodic set-learning task in humans and an analogous set-learning spatial task in rats. In both tasks, young and older subjects learned a set of objects (humans) or feeder locations (rats; Set 1) in Context A on Day 1. On Day 2, a different set (Set 2) was learned in either Context A (Reminder condition) or Context B (No Reminder condition). On Day 3, subjects were instructed (humans) or cued (rats) to recall Set 1. Young rats and humans in the Reminder condition falsely recalled significantly more items from Set 2 than those in the No Reminder condition, suggesting that the reminder context triggered a reactivation of Set 1 on Day 2 and allowed the integration of Set 2 items into Set 1. In both species, older subjects displayed a different pattern of results than young subjects. In aged rats, there was no difference between conditions in the level of falsely recalled Set 2 items (intrusions). Older humans in the No Reminder condition made significantly more intrusions than those in the Reminder condition. Follow-up control experiments in aged rats suggested that intrusions in older animals reflected general interference, independent of context manipulations. We conclude that contextual reminders are not sufficient to trigger memory updating in aged rats or aged humans, unlike in younger individuals. Future studies using this animal model should further our understanding of the role of the hippocampus in memory maintenance and updating during normal aging. Copyright © 2015 Elsevier Inc

Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

Science.gov (United States)

Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

1989-03-15

Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

[Early human transplants: 60th anniversary of the first successful kidney transplants].

Science.gov (United States)

Gentili, Marc E

2015-11-01

First kidney transplant attempts begin with the 20th century: improving vascular sutures, understanding the phenomena of rejection or tolerance, then progress in HLA groups enable early success in the second half of the century. Definition of brain death, use of corticosteroids, radiotherapy and prime immunosuppressors promote the development of transplants. Discover of cyclosporine in the 1980s, and legislative developments augur a new era. Many advances are arising: use of stem cells from the donor, enhancement of Maastricht 3 donor or living donation. Finally organ transplantation remains an immense human adventure, but also scientific and ethic. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

A New UK 2006 National Kidney Allocation Scheme for deceased heart-beating donor kidneys.

Science.gov (United States)

Johnson, Rachel J; Fuggle, Susan V; Mumford, Lisa; Bradley, J Andrew; Forsythe, John L R; Rudge, Chris J

2010-02-27

In 2004, it was agreed that a new allocation scheme for kidneys from deceased heart-beating donors was required in the United Kingdom to address observed inequities in access to transplant. The 2006 National Kidney Allocation Scheme (2006 NKAS) was developed to meet agreed objectives and preparatory work included a review of the criteria for human leukocyte antigen (HLA) matching and simulation evidence about the effectiveness of alternative schemes. ALGORITHM FOR 2006 NKAS: The 2006 NKAS gives absolute priority to all 000 HLA-A, -B, -DR-mismatched patients and well-matched pediatric patients (inequity of access will take a number of years to address fully.

Phosphate-a poison for humans?

Science.gov (United States)

Komaba, Hirotaka; Fukagawa, Masafumi

2016-10-01

Maintenance of phosphate balance is essential for life, and mammals have developed a sophisticated system to regulate phosphate homeostasis over the course of evolution. However, due to the dependence of phosphate elimination on the kidney, humans with decreased kidney function are likely to be in a positive phosphate balance. Phosphate excess has been well recognized as a critical factor in the pathogenesis of mineral and bone disorders associated with chronic kidney disease, but recent investigations have also uncovered toxic effects of phosphate on the cardiovascular system and the aging process. Compelling evidence also suggests that increased fibroblastic growth factor 23 and parathyroid hormone levels in response to a positive phosphate balance contribute to adverse clinical outcomes. These insights support the current practice of managing serum phosphate in patients with advanced chronic kidney disease, although definitive evidence of these effects is lacking. Given the potential toxicity of excess phosphate, the general population may also be viewed as a target for phosphate management. However, the widespread implementation of dietary phosphate intervention in the general population may not be warranted due to the limited impact of increased phosphate intake on mineral metabolism and clinical outcomes. Nonetheless, the increasing incidence of kidney disease or injury in our aging society emphasizes the potential importance of this issue. Further work is needed to more completely characterize phosphate toxicity and to establish the optimal therapeutic strategy for managing phosphate in patients with chronic kidney disease and in the general population. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Human Growth Hormone (HGH): Does It Slow Aging?

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Healthy Lifestyle Healthy aging Human growth hormone is described by some as the key to slowing the aging process. Before you sign up, get the ... slowdown has triggered an interest in using synthetic human growth hormone (HGH) as a way to stave ...

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

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...

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

Kidney stone matrix proteins ameliorate calcium oxalate monohydrate induced apoptotic injury to renal epithelial cells.

Science.gov (United States)

Narula, Shifa; Tandon, Simran; Singh, Shrawan Kumar; Tandon, Chanderdeep

2016-11-01

Kidney stone formation is a highly prevalent disease, affecting 8-10% of the human population worldwide. Proteins are the major constituents of human kidney stone's organic matrix and considered to play critical role in the pathogenesis of disease but their mechanism of modulation still needs to be explicated. Therefore, in this study we investigated the effect of human kidney stone matrix proteins on the calcium oxalate monohydrate (COM) mediated cellular injury. The renal epithelial cells (MDCK) were exposed to 200μg/ml COM crystals to induce injury. The effect of proteins isolated from human kidney stone was studied on COM injured cells. The alterations in cell-crystal interactions were examined by phase contrast, polarizing, fluorescence and scanning electron microscopy. Moreover, its effect on the extent of COM induced cell injury, was quantified by flow cytometric analysis. Our study indicated the antilithiatic potential of human kidney stone proteins on COM injured MDCK cells. Flow cytometric analysis and fluorescence imaging ascertained that matrix proteins decreased the extent of apoptotic injury caused by COM crystals on MDCK cells. Moreover, the electron microscopic studies of MDCK cells revealed that matrix proteins caused significant dissolution of COM crystals, indicating cytoprotection against the impact of calcium oxalate injury. The present study gives insights into the mechanism implied by urinary proteins to restrain the pathogenesis of kidney stone disease. This will provide a better understanding of the formation of kidney stones which can be useful for the proper management of the disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Diabetic kidney disease: a report from an ADA Consensus Conference.

Science.gov (United States)

Tuttle, Katherine R; Bakris, George L; Bilous, Rudolf W; Chiang, Jane L; de Boer, Ian H; Goldstein-Fuchs, Jordi; Hirsch, Irl B; Kalantar-Zadeh, Kamyar; Narva, Andrew S; Navaneethan, Sankar D; Neumiller, Joshua J; Patel, Uptal D; Ratner, Robert E; Whaley-Connell, Adam T; Molitch, Mark E

2014-10-01

The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in type 2 diabetes. This overall increase in the number of people with diabetes has had a major impact on development of diabetic kidney disease (DKD), one of the most frequent complications of both types of diabetes. DKD is the leading cause of end-stage renal disease (ESRD), accounting for approximately 50% of cases in the developed world. Although incidence rates for ESRD attributable to DKD have recently stabilized, these rates continue to rise in high-risk groups such as middle-aged African Americans, Native Americans, and Hispanics. The costs of care for people with DKD are extraordinarily high. In the Medicare population alone, DKD-related expenditures among this mostly older group were nearly $25 billion in 2011. Due to the high human and societal costs, the Consensus Conference on Chronic Kidney Disease and Diabetes was convened by the American Diabetes Association in collaboration with the American Society of Nephrology and the National Kidney Foundation to appraise issues regarding patient management, highlighting current practices and new directions. Major topic areas in DKD included (1) identification and monitoring, (2) cardiovascular disease and management of dyslipidemia, (3) hypertension and use of renin-angiotensin-aldosterone system blockade and mineralocorticoid receptor blockade, (4) glycemia measurement, hypoglycemia, and drug therapies, (5) nutrition and general care in advanced-stage chronic kidney disease, (6) children and adolescents, and (7) multidisciplinary approaches and medical home models for health care delivery. This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD. Copyright © 2014 American Diabetes Association and the National Kidney Foundation. Published by Elsevier Inc

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 ...

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.

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

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

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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.

Creating computer aided 3D model of spleen and kidney based based on Visible Human Project

International Nuclear Information System (INIS)

Aldur, Muhammad M.

2005-01-01

To investigate the efficacy of computer aided 3-dimensional (3D) reconstruction technique on visualization and modeling of gross anatomical structures with an affordable methodology applied on the spleen and kidney. From The Visible Human Project Dataset cryosection images, developed by the National Library of Medicine, the spleen and kidney sections were preferred to be used due to their highly distinct contours. The software used for the reconstruction were Surf Driver 3.5.3 for Mac and Cinema 4D X L version 7.1 for Mac OS X. This study was carried out in May 2004 at the Department of Anatomy, Hacettepe University, Ankara, Turkey. As a result of this study, it is determined that these 2 programs could be effectively used both for 3D modeling of the mentioned organs and volumetric analyses on these models. It is also seen that it is possible to hold the physical models of these gross anatomical digital ones with stereolithography technique by means of the data exchange file format provided by the program and present such images as anaglyph. Surf Driver 3.5.3 for Mac OS and Cinema 4 DXL version 7.1 for Mac OS X can be used effectively for reconstruction of gross anatomical structures from serial parallel sections with distinct contours such as spleen and kidney and the animation of models. These software constitute a highly effective way of getting volumetric calculations, spatial relations and morphometrical measurements of reconstructed structures. (author)

Percutaneous nephrolithotomy in patients with a solitary kidney

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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

Living donor risk model for predicting kidney allograft and patient survival in an emerging economy.

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Zafar, Mirza Naqi; Wong, Germaine; Aziz, Tahir; Abbas, Khawar; Adibul Hasan Rizvi, S

2018-03-01

Living donor kidney is the main source of donor organs in low to middle income countries. We aimed to develop a living donor risk model that predicts graft and patient survival in an emerging economy. We used data from the Sindh Institute of Urology and Transplantation (SIUT) database (n = 2283 recipients and n = 2283 living kidney donors, transplanted between 1993 and 2009) and conducted Cox proportional hazard analyses to develop a composite score that predicts graft and patient survivals. Donor factors age, creatinine clearance, nephron dose (estimated by donor/recipient body weight ratio) and human leukocyte antigen (HLA) match were included in the living donor risk model. The adjusted hazard ratios (HRs) for graft failures among those who received a kidney with living donor scores (reference to donor score of zero) of 1, 2, 3 and 4 were 1.14 (95%CI: 0.94-1.39), 1.24 (95%CI:1.03-1.49), 1.25 (95%CI:1.03-1.51) and 1.36 (95%CI:1.08-1.72) (P-value for trend =0.05). Similar findings were observed for patient survival. Similar to findings in high income countries, our study suggests that donor characteristics such as age, nephron dose, creatinine clearance and HLA match are important factors that determine the long-term patient and graft survival in low income countries. However, other crucial but undefined factors may play a role in determining the overall risk of graft failure and mortality in living kidney donor transplant recipients. © 2016 Asian Pacific Society of Nephrology.

Phosphorus Regulation in Chronic Kidney Disease.

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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.

Kidney pain (image)

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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 ...

Effect of socio-demographic factors on endogenous biomarkers (cystatin C and creatinine) among elderly chronic kidney disease patients: a cross-sectional study.

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Khan, Irfanullah; Khan, Amer Hayat; Adnan, Azreen Syazril; Sulaiman, Syed Azhar Syed; Hamzah, Azhar Bin Amir; Ahmed, Nafees; Khan, Amjad

2018-06-01

Creatinine is normally used to evaluate kidney function among elderly patients in clinical practice, which has been reported to be affected by socio-demographic factors like BMI and age. Cystatin C a newly introduced biomarker may be more efficient in identifying kidney function in obese and aged CKD patients. The aim of the current study was to assess the effect of BMI on endogenous biomarkers (cystatin C and creatinine) among elderly CKD patients in Malaysia, a first such study in the country. The current study was conducted at the Hospital University Sains Malaysia, Kelantan. A total of 300 elderly Malay participants ≥ 65 years, with CKD, were taken in study. Demographic data, blood pressure, weight, and height were documented. Serum creatinine was assayed by Chemistry Analyzer Model Architect-C8000 (Jaffe Method), while serum cystatin C was examined by Human cystatin C ELISA kit (Sigma-Aldrich) using Thermo Scientific Varioskan Flash ELISA reader. The study participants were divided into three groups on the basis of age. There was a statistically significant difference at the p value C levels were observed on the basis of patient's age and BMI. Cystatin C is not related to BMI and age among elderly chronic kidney disease patients. The study clearly evaluates the role of serum cystatin C as a good competitor of creatinine among the elderly CKD patients.

High mortality in diabetic recipients of high KDPI deceased donor kidneys.

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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.

[Kidney transplantation epidemiology in France].

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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

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

Gene expression in the aging human brain: an overview.

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Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

2016-03-01

The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

International Nuclear Information System (INIS)

Barregard, Lars; Bergström, Göran; Fagerberg, Björn

2014-01-01

Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

Cadmium, type 2 diabetes, and kidney damage in a cohort of middle-aged women

Energy Technology Data Exchange (ETDEWEB)

Barregard, Lars, E-mail: lars.barregard@amm.gu.se [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg P.O. Box 414, SE-405 30 Gothenburg (Sweden); Bergström, Göran, E-mail: goran.bergstrom@wlab.gu.se [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg (Sweden); Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg (Sweden); Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, SE-405 30 Gothenburg (Sweden); Department of Molecular and Clinical Medicine, University of Gothenburg, SE-405 30 Gothenburg (Sweden)

2014-11-15

Background: It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim: To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods: All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results: The mean B-Cd (n=590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P=0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P=0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT

Nutrition modulation of human aging: The calorie restriction paradigm.

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Das, Sai Krupa; Balasubramanian, Priya; Weerasekara, Yasoma K

2017-11-05

Globally, the aging population is growing rapidly, creating an urgent need to attenuate age-related health conditions, including metabolic disease and disability. A promising strategy for healthy aging based on consistently positive results from studies with a variety of species, including non-human primates (NHP), is calorie restriction (CR), or the restriction of energy intake while maintaining intake of essential nutrients. The burgeoning evidence for this approach in humans is reviewed and the major study to date to address this question, CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy), is described. CALERIE findings indicate the feasibility of CR in non-obese humans, confirm observations in NHP, and are consistent with improvements in disease risk reduction and potential anti-aging effects. Finally, the mechanisms of CR in humans are reviewed which sums up the fact that evolutionarily conserved mechanisms mediate the anti-aging effects of CR. Overall, the prospect for further research in both NHP and humans is highly encouraging. Copyright © 2017 Elsevier B.V. All rights reserved.

Perfusion of tumor-bearing kidneys as a model for scintigraphic screening of monoclonal antibodies

International Nuclear Information System (INIS)

van Dijk, J.; Oosterwijk, E.; van Kroonenburgh, M.J.; Jonas, U.; Fleuren, G.J.; Pauwels, E.K.; Warnaar, S.O.

1988-01-01

Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with /sup 99m/Tc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo

Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.

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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.

Kidney damage in extracorporeal shock wave lithotripsy: a numerical approach for different shock profiles.

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Weinberg, Kerstin; Ortiz, Michael

2009-08-01

In shock-wave lithotripsy--a medical procedure to fragment kidney stones--the patient is subjected to hypersonic waves focused at the kidney stone. Although this procedure is widely applied, the physics behind this medical treatment, in particular the question of how the injuries to the surrounding kidney tissue arise, is still under investigation. To contribute to the solution of this problem, two- and three-dimensional numerical simulations of a human kidney under shock-wave loading are presented. For this purpose a constitutive model of the bio-mechanical system kidney is introduced, which is able to map large visco-elastic deformations and, in particular, material damage. The specific phenomena of cavitation induced oscillating bubbles is modeled here as an evolution of spherical pores within the soft kidney tissue. By means of large scale finite element simulations, we study the shock-wave propagation into the kidney tissue, adapt unknown material parameters and analyze the resulting stress states. The simulations predict localized damage in the human kidney in the same regions as observed in animal experiments. Furthermore, the numerical results suggest that in first instance the pressure amplitude of the shock wave impulse (and not so much its exact time-pressure profile) is responsible for damaging the kidney tissue.

Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance.

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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.

Dog kidney: anatomical relationships between intrarenal arteries and kidney collecting system.

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Marques-Sampaio, Beatriz P S; Pereira-Sampaio, Marco A; Henry, Robert W; Favorito, Luciano A; Sampaio, Francisco J B

2007-08-01

The detailed findings of canine intrarenal anatomy (collecting system and arteries) are presented. Ninety-five three-dimensional endocasts of the kidney collecting system together with the intrarenal arteries were prepared using standard injection-corrosion techniques and were studied. A single renal artery was observed in 88.4% of the casts. The renal artery divided into a dorsal and a ventral branch. Using the branching pattern of the ventral and dorsal divisions of the renal artery, the vessels were classified in type I or type II. Type I presented a cranial and a caudal artery, whereas type II presented a mesorenal and a caudal artery. Cranial branches of dorsal and ventral arteries supplied the cranial pole in 90.5% of the specimens. Caudal branches of the dorsal and the ventral divisions of the renal artery irrigated both the caudal pole and the mid-zone of the kidney in 95.8% and 98.9% of the cases, respectively. In all casts, caudal branches of both dorsal and ventral arteries supplied the caudal pole. Therefore, the caudal branches of the ventral and dorsal divisions of the renal artery are of utmost importance in the kidney arterial supply. Although many results of renal and intrarenal anatomy in dogs may not be completely transposed to humans, the anatomical relationship between arteries and the collecting system in the cranial pole of the dog kidney is similar to those in man. This fact supports the use of the dog as an animal model for urologic procedures at the cranial pole. (c) 2007 Wiley-Liss, Inc.

The concept of ageing in evolutionary algorithms: Discussion and inspirations for human ageing.

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Dimopoulos, Christos; Papageorgis, Panagiotis; Boustras, George; Efstathiades, Christodoulos

2017-04-01

This paper discusses the concept of ageing as this applies to the operation of Evolutionary Algorithms, and examines its relationship to the concept of ageing as this is understood for human beings. Evolutionary Algorithms constitute a family of search algorithms which base their operation on an analogy from the evolution of species in nature. The paper initially provides the necessary knowledge on the operation of Evolutionary Algorithms, focusing on the use of ageing strategies during the implementation of the evolutionary process. Background knowledge on the concept of ageing, as this is defined scientifically for biological systems, is subsequently presented. Based on this information, the paper provides a comparison between the two ageing concepts, and discusses the philosophical inspirations which can be drawn for human ageing based on the operation of Evolutionary Algorithms. Copyright © 2017 Elsevier B.V. All rights reserved.

Mammalian target of rapamycin inhibition in polycystic kidney disease: From bench to bedside

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Hyun-Jung Kim

2012-09-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common life-threatening hereditary disease in the USA resulting in chronic kidney disease and the need for dialysis and transplantation. Approximately 85% of cases of ADPKD are caused by a mutation in the Pkd1 gene that encodes polycystin-1, a large membrane receptor. The Pkd1 gene mutation results in abnormal proliferation in tubular epithelial cells, which plays a crucial role in cyst development and/or growth in PKD. Activation of the proliferative mammalian target of rapamycin (mTOR signaling pathway has been demonstrated in polycystic kidneys from rodents and humans. mTOR inhibition with sirolimus or everolimus decreases cysts in most animal models of PKD including Pkd1 and Pkd2 gene deficient orthologous models of human disease. On the basis of animal studies, human studies were undertaken. Two large randomized clinical trials published in the New England Journal of Medicine of everolimus or sirolimus in ADPKD patients were very unimpressive and associated with a high side-effect profile. Possible reasons for the unimpressive nature of the human studies include their short duration, the high drop-out rate, suboptimal dosing, lack of randomization of “fast” and “slow progressors” and the lack of correlation between kidney size and kidney function in ADPKD. The future of mTOR inhibition in ADPKD is discussed.

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.

Science.gov (United States)

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.

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.

Tetracycline Reduces Kidney Damage Induced by Loxosceles Spider Venom

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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.

RLIP76 Targeted Therapy for Kidney Cancer.

Science.gov (United States)

Singhal, Sharad S; Singhal, Jyotsana; Figarola, James; Horne, David; Awasthi, Sanjay

2015-10-01

Despite recent improvements in chemotherapeutic approaches to treating kidney cancer, this malignancy remains deadly if not found and removed at an early stage of the disease. Kidney cancer is highly drug-resistant, which may at least partially result from high expression of transporter proteins in the cell membranes of kidney cells. Although these transporter proteins can contribute to drug-resistance, targeting proteins from the ATP-binding cassette transporter family has not been effective in reversing drug-resistance in kidney cancer. Recent studies have identified RLIP76 as a key stress-defense protein that protects normal cells from damage caused by stress conditions, including heat, ultra-violet light, X-irradiation, and oxidant/electrophilic toxic chemicals, and is crucial for protecting cancer cells from apoptosis. RLIP76 is the predominant glutathione-electrophile-conjugate (GS-E) transporter in cells, and inhibiting it with antibodies or through siRNA or antisense causes apoptosis in many cancer cell types. To date, blocking of RLIP76, either alone or in combination with chemotherapeutic drugs, as a therapeutic strategy for kidney cancer has not yet been evaluated in human clinical trials, although there is considerable potential for RLIP76 to be developed as a therapeutic agent for kidney cancer. In the present review, we discuss the mechanisms underlying apoptosis caused by RLIP76 depletion, the role of RLIP76 in clathrin-dependent endocytosis deficiency, and the feasibility of RLIP76-targeted therapy for kidney cancer.

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 ...

DNA methylation and healthy human aging.

Science.gov (United States)

Jones, Meaghan J; Goodman, Sarah J; Kobor, Michael S

2015-12-01

The process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next-generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site-specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age-related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining 'epigenetic age' for human health and outline some important caveats to existing and future studies. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Advanced glycation end-products (AGEs accumulation in skin: relations with chronic kidney disease-mineral and bone disorder

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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.

Environmental cadmium and zinc concentrations in liver and kidney of European hare from different Serbian regions

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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.

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.

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...

Contemporary views on human aging and longevity

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Chmielewski Piotr

2016-06-01

Full Text Available Aging is currently stimulating intense interest of both researchers and the general public. In developed countries, the average life expectancy has increased by roughly 30 years within the last century, and human senescence has been delayed by around a decade. Although aging is arguably the most familiar aspect of human biology, its proximate and ultimate causes have not been elucidated fully and understood yet. Nowadays there are two main approaches to the ultimate causes of aging. These are deterministic and stochastic models. The proximate theories constitute a distinct group of explanations. They focus on mechanistic causes of aging. In this view, there is no reason to believe that there is only one biological mechanism responsible for aging. The aging process is highly complex and results from an accumulation of random molecular damage. Currently, the disposable soma theory (DST, proposed by Thomas Kirkwood, is the most influential and coherent line of reasoning in biogerontology. This model does not postulate any particular mechanism underpinning somatic defense. Therefore, it is compatible with various models, including mechanistic and evolutionary explanations. Recently, however, an interesting theory of hyper-function of mTOR as a more direct cause of aging has been formulated by Mikhail Blagosklonny, offering an entirely different approach to numerous problems and paradoxes in current biogerontology. In this view, aging is quasi-programmed, which means that it is an aimless continuation of developmental growth. This mTOR-centric model allows the prediction of completely new relationships. The aim of this article is to present and compare the views of both parties in the dispute, based on the results of some recent experimental studies, and the contemporary knowledge of selected major aspects of human aging and longevity

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.

Do glutathione levels decline in aging human brain?

Science.gov (United States)

Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Kidney biopsy

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... 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 ...

Fetal first trimester growth is not associated with kidney outcomes in childhood

NARCIS (Netherlands)

H. Bakker (Hanneke); R. Gaillard (Romy); A. Hofman (Albert); I.K.M. Reiss (Irwin); E.A.P. Steegers (Eric); V.W.V. Jaddoe (Vincent)

2017-01-01

textabstractBackground: Impaired fetal growth is associated with increased risks of kidney diseases in later life. Because human development rates are highest during the first trimester, this trimester may be a particularly critical period for kidney outcomes. We have therefore examined the

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

Outcome of recipients of human leukocyte antigen incompatible kidney transplants who underwent desensitization at King Fahad Specialist Hospital, Dammam, Saudi Arabia

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Mohammed Abdulrahim Idris

2017-01-01

Full Text Available In patients whom are highly sensitized immunologically, the benefit of kidney transplantation can be extended to this population through the utilization of organs from human leukocyte antigen incompatible (HLAi donors. This retrospective observational study was designed to identify the incidence and predictors of acute antibody-mediated rejection/acute cellular rejection (AMR/ACR in our kidney recipients from living kidney donors (sensitized and those with low immunologic risk. This single-center study has been conducted at King Fahad Specialist Hospital, Dammam (KFSH-D, Saudi Arabia; during the period of September 2008- August 2013. All eligible recipients of living donor kidneys during the study period were included (n = 213 in the study. Over 60% of patients in the study were females. Thirty of the 213 kidneys were from HLAi donors. During the follow-up period (median follow-up time = 16 months; 3–27 months, the incidence rate of ACR among HLA compatible (HLAc and HLAi groups was 22.2% and 16.7%, respectively (P >0.05. The incidence rate of AMR was 2.6% in HLAc group and 16.7%in the HLAi group (P<0.05. The significantly higher incidence of AMR in HLAi group can be explained by the presence of the donor-specific antibodies in weak titers. These results are consistent with studies from similar populations in published literature. However, the relatively small number and short duration of the study are considered, and longer follow-up of this population will be needed for conclusions on the sustainability of our findings.

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

[Can man live with a pig kidney?].

Science.gov (United States)

Valentin, J F; Lebranchu, Y; Nivet, H

1999-01-01

The transplantation of organs from one species to another introduces a question of compatibility not seen in allotransplantation, the ability of a kidney to perform its physiological function in the new host environment. It has been assumed that an allotransplanted organ will function normally if is not rejected; ample experience supports this assumption. This luxury will not exist in the field of xenotransplantation, where the issues of comparative physiology will assume great importance. From many standpoints, the pig kidney seems an ideal donor for xenotransplantation. They are of similar size and have remarkably similar internal anatomy. Even if the immunological problems could be overcome, there is almost no direct experimental evidence to answer the question of whether or not a pig kidney can function in a human body.

Src family kinases in chronic kidney disease.

Science.gov (United States)

Wang, Jun; Zhuang, Shougang

2017-09-01

Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved. Copyright © 2017 the American Physiological Society.

CADMIUM ACCUMULATION IN HORSE MUSCLE, LIVER AND KIDNEY SLAUGHTERED IN BARI

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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.

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)

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...

Appraisal of the porcine kidney autotransplantation model

NARCIS (Netherlands)

Post, Ivo C. J. H.; Dirkes, Marcel C.; Heger, Michal; van Loon, Johannes P. A. M.; Swildens, Bas; Huijzer, Goos M.; van Gulik, Thomas M.

2012-01-01

Animal models are extensively used for transplantation related research, especially kidney transplantation. Porcine autotransplantation models are considered to be favorable regarding translatability to the human setting. The key determinants for translatability of the model are discussed,

Analysis of kidney stones by PIXE and RBS techniques

Energy Technology Data Exchange (ETDEWEB)

Alkofai, M M [Physics Dept., Yarmouk University, Irbid, (Jordan); Hallak, A B [Research Institute, King Fahd University of Petroleum and Minerals, Dhahran 31261, (Saudi Arabia)

1995-10-01

Human kidney stones were analyzed by PIXE and RBS techniques using 2 MeV He{sup ++} beam. The stones were found to contain the elements: C, N, O, F, Na, Mg, Si, P, S, Cl, K, Ca, Fe and Br. Results obtained by PIXE agree with the results obtained by RBS within experimental errors. A Mechanism for the formation of the kidney stones is suggested. 3 figs., 1 tab.

Analysis of kidney stones by PIXE and RBS techniques

International Nuclear Information System (INIS)

Alkofai, M.M.; Hallak, A.B.

1995-01-01

Human kidney stones were analyzed by PIXE and RBS techniques using 2 MeV He ++ beam. The stones were found to contain the elements: C, N, O, F, Na, Mg, Si, P, S, Cl, K, Ca, Fe and Br. Results obtained by PIXE agree with the results obtained by RBS within experimental errors. A Mechanism for the formation of the kidney stones is suggested. 3 figs., 1 tab

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

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 ...

Aging and human sexual behavior: biocultural perspectives - a mini-review.

Science.gov (United States)

Gray, Peter B; Garcia, Justin R

2012-01-01

In this mini-review, we consider an evolutionary biocultural perspective on human aging and sexuality. An evolutionary approach to senescence highlights the energetic trade-offs between fertility and mortality. By comparing humans to other primates, we situate human senescence as an evolutionary process, with shifts in postreproductive sexual behavior in this light. Age-related declines in sexual behavior are typical for humans but also highly contingent on the sociocultural context within which aging individuals express their sexuality. We briefly review some of the most comprehensive studies of aging and sexual behavior, both from the USA and cross-culturally. We frame these patterns with respect to the long-term relationships within which human sexual behavior typically occurs. Because sexuality is typically expressed within pair-bonds, sexual behavior sometimes declines in both members of a couple with age, but also exhibits sex-specific effects that have their roots in evolved sex differences. Copyright © 2012 S. Karger AG, Basel.

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.

[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.

Derivation of a Predictive Model for Graft Loss Following Acute Kidney Injury in Kidney Transplant Recipients.

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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

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

Directory of Open Access Journals (Sweden)

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.

Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

International Nuclear Information System (INIS)

Al-Kafaji, Ghada; Malik, Afshan N.

2010-01-01

During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as μ-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 ± 50 vs 147 ± 54, p < 0.05), and hearts (1583 ± 277 vs 191 ± 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 ± 37 vs 18 ± 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

Hyperglycemia induces elevated expression of thyroid hormone binding protein in vivo in kidney and heart and in vitro in mesangial cells

Energy Technology Data Exchange (ETDEWEB)

Al-Kafaji, Ghada [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom); Malik, Afshan N., E-mail: afshan.malik@kcl.ac.uk [Diabetes Research Group, Division of Reproduction and Endocrinology, King' s College London (United Kingdom)

2010-01-22

During a search for glucose-regulated abundant mRNAs in the diabetic rat kidney, we cloned thyroid hormone binding protein (THBP), also known as {mu}-crystallin or CRYM. The aim of this study was to investigate the effect of hyperglycemia/high glucose on the expression of THBP. THBP mRNA copy numbers were determined in kidneys and hearts of diabetic GK rats vs normoglycemic Wistar rats, and in human mesangial cells (HMCs) exposed to high glucose using real-time qPCR, and THBP protein levels were measured by Western blotting and immunofluorescence. Intracellular ROS was measured in THBP transfected cells using DCF fluorescence. Hyperglycemia significantly increased THBP mRNA in GK rat kidneys (326 {+-} 50 vs 147 {+-} 54, p < 0.05), and hearts (1583 {+-} 277 vs 191 {+-} 63, p < 0.05). Moreover, the levels of THBP mRNA increased with age and hyperglycemia in GK rat kidneys, whereas in normoglycemic Wistar rat kidneys there was a decline with age. High glucose significantly increased THBP mRNA (92 {+-} 37 vs 18 {+-} 4, p < 0.005), and protein in HMCs. The expression of THBP as a fusion protein in transfected HMCs resulted in reduction of glucose-induced intracellular ROS. We have shown that THBP mRNA is increased in diabetic kidney and heart, is regulated by high glucose in renal cells, and appears to attenuate glucose-induced intracellular ROS. These data suggest that THBP may be involved in the cellular pathways activated in response to glucose. This is the first report linking hyperglycemia with THBP and suggests that the role of THBP in diabetic complications should be further investigated.

The seroprevalence of Parvovirus B19 among kidney transplant recipients: a single-center study.

Science.gov (United States)

Khameneh, Zakieh Rostamzadeh; Sepehrvand, Nariman; Sohrabi, Vahid; Ghasemzadeh, Nazafarin

2014-01-01

Parvovirus B19 is a DNA virus that is responsible for causing several diseases in humans. Parvovirus B19-induced persistent anemia is one of its manifestations that is relatively common in transplant recipients. This study was aimed to investigate the seroprevalence of parvovirus B19 among kidney transplant recipients. Ninety-one transplant recipients were selected randomly and were investigated for several variables including age, gender, educational status, history of hemodialysis (HD), history of blood transfusion and immunosuppressive therapy. Two milliliters of blood samples were collected via venipuncture and evaluated for anti-Parvovirus B19 IgG antibody using enzyme-linked immunosorbent assay. All recipients were anemic, with 72.5% of them suffering from severe anemia (Hb ≤ 11 in men and ≤ 10 in women). Sixty-three patients (69.2%) were seropositive for Parvovirus B19. There was no significant difference in age, sex, educational status, history of blood transfusion, history of HD and immunosuppressive therapy between seropositive and seronegative groups. The seroprevalence of Parvovirus B19 was relatively high in kidney transplant recipients in Urmia, Iran. Our study failed to find a correlation between the severity of anemia and the seropositivity of Parvovirus B19.

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.

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

MicroRNAs as potential therapeutic targets in kidney disease

Science.gov (United States)

Gomez, Ivan G; Grafals, Monica; Portilla, Didier; Duffield, Jeremy S

2014-01-01

One cornerstone of Chronic Kidney Disease (CKD) is fibrosis, as kidneys are susceptible due to their high vascularity and predisposition to ischemia. Presently, only therapies targeting the angiotensin receptor are used in clinical practice to retard the progression of CKD. Thus, there is a pressing need for new therapies designed to treat the damaged kidney. Several independent laboratories have identified a number of microRNAs that are dysregulated in human and animal models of CKD. We will explore the evidence suggesting that by blocking the activity of such dysregulated microRNAs, new therapeutics could be developed to treat the progression of CKD. PMID:23660218

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

Human leukocyte antigen in the allocation of kidneys from cadaveric donors in the United States.

Science.gov (United States)

Ting, Alan; Edwards, Leah Bennett

2004-02-27

Minorities wait longer for a cadaveric donor kidney transplant than whites. For example, the median waiting time to transplant for candidates listed from 1997 to 1998 was 874 days for whites, 1,493 days for blacks, 1,281 days for Hispanics, 1,491 days for Asians, and 1,466 days for others. The current allocation algorithm has been criticized as contributing to decreased access to transplants for racial minorities. There are two levels in the current algorithm: The first is mandatory national sharing between donors and patients with zero human leukocyte antigen (HLA)-A, B, and DR mismatches. The second occurs if there are no candidates and local placement is accomplished based on an algorithm with an HLA component that assigns seven, five, and two points to zero, one, and two HLA-B and DR mismatches, respectively. An analysis of the data shows that a higher percentage of white recipients (21%) received zero antigen mismatched kidneys compared with other races: blacks (7%), Hispanics (14%), and Asians (7%). Whites also received the highest percentage of kidneys with zero B and DR mismatches and one B and DR mismatch compared with the other races. These data indicate that the current algorithm favors whites over minorities, and it is most likely that giving points for HLA-B matching is a strong contributory factor. To address this inequity, the Organ Procurement and Transplantation Network and United Network for Organ Sharing Board of Directors approved a recommendation in November 2002 to change the HLA points to award two points for zero DR mismatches and one point for one DR mismatch. Obviously it will take some time to gather sufficient data to allow meaningful analysis of the effect of the policy change.

A human protein interaction network shows conservation of aging processes between human and invertebrate species.

Directory of Open Access Journals (Sweden)

Russell Bell

2009-03-01

Full Text Available We have mapped a protein interaction network of human homologs of proteins that modify longevity in invertebrate species. This network is derived from a proteome-scale human protein interaction Core Network generated through unbiased high-throughput yeast two-hybrid searches. The longevity network is composed of 175 human homologs of proteins known to confer increased longevity through loss of function in yeast, nematode, or fly, and 2,163 additional human proteins that interact with these homologs. Overall, the network consists of 3,271 binary interactions among 2,338 unique proteins. A comparison of the average node degree of the human longevity homologs with random sets of proteins in the Core Network indicates that human homologs of longevity proteins are highly connected hubs with a mean node degree of 18.8 partners. Shortest path length analysis shows that proteins in this network are significantly more connected than would be expected by chance. To examine the relationship of this network to human aging phenotypes, we compared the genes encoding longevity network proteins to genes known to be changed transcriptionally during aging in human muscle. In the case of both the longevity protein homologs and their interactors, we observed enrichments for differentially expressed genes in the network. To determine whether homologs of human longevity interacting proteins can modulate life span in invertebrates, homologs of 18 human FRAP1 interacting proteins showing significant changes in human aging muscle were tested for effects on nematode life span using RNAi. Of 18 genes tested, 33% extended life span when knocked-down in Caenorhabditis elegans. These observations indicate that a broad class of longevity genes identified in invertebrate models of aging have relevance to human aging. They also indicate that the longevity protein interaction network presented here is enriched for novel conserved longevity proteins.

Ex-vivo machine perfusion for kidney preservation.

Science.gov (United States)

Hamar, Matyas; Selzner, Markus

2018-06-01

Machine perfusion is a novel strategy to decrease preservation injury, improve graft assessment, and increase organ acceptance for transplantation. This review summarizes the current advances in ex-vivo machine-based kidney preservation technologies over the last year. Ex-vivo perfusion technologies, such as hypothermic and normothermic machine perfusion and controlled oxygenated rewarming, have gained high interest in the field of organ preservation. Keeping kidney grafts functionally and metabolically active during the preservation period offers a unique chance for viability assessment, reconditioning, and organ repair. Normothermic ex-vivo kidney perfusion has been recently translated into clinical practice. Preclinical results suggest that prolonged warm perfusion appears superior than a brief end-ischemic reconditioning in terms of renal function and injury. An established standardized protocol for continuous warm perfusion is still not available for human grafts. Ex-vivo machine perfusion represents a superior organ preservation method over static cold storage. There is still an urgent need for the optimization of the perfusion fluid and machine technology and to identify the optimal indication in kidney transplantation. Recent research is focusing on graft assessment and therapeutic strategies.

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 ...

76 FR 11501 - National Institute of Diabetes and Digestive and Kidney Diseases

Science.gov (United States)

2011-03-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Amended Notice of Meeting Notice is hereby given of a change in the meeting of the National Institute of Diabetes and Digestive and Kidney Diseases Special Emphasis...

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

CMV induces HERV-K and HERV-W expression in kidney transplant recipients.

Science.gov (United States)

Bergallo, Massimiliano; Galliano, Ilaria; Montanari, Paola; Gambarino, Stefano; Mareschi, Katia; Ferro, Francesca; Fagioli, Franca; Tovo, Pier-Angelo; Ravanini, Paolo

2015-07-01

Human endogenous retrovirus (HERVs) constitute approximately 8% of the human genome. Induction of HERV transcription is possible under certain circumstances, and may have a possible role in some pathological conditions. The aim of this study was to evaluate HERV-K and -W pol gene expression in kidney transplant recipients and to investigate the possible relationship between HERVs gene expression and CMV infection in these patients. Thirty-three samples of kidney transplant patients and twenty healthy blood donors were used to analyze, HERV-K and -W pol gene RNA expression by relative quantitative relative Real-Time PCR. We demonstrated that HERVs pol gene expression levels were higher in kidney transplant recipients than in healthy subjects. Moreover, HERV-K and -W pol gene expression was significantly higher in the group of kidney transplant recipients with high CMV viral load than in the groups with no or moderate CMV viral load. Our data suggest that CMV may facilitate in vivo HERV activation. Published by Elsevier B.V.

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 ...

Urinary endotrophin predicts disease progression in patients with chronic kidney disease

DEFF Research Database (Denmark)

Rasmussen, Daniel Guldager Kring; Fenton, Anthony; Jesky, Mark

2017-01-01

Renal fibrosis is the central pathogenic process in progression of chronic kidney disease (CKD). Collagen type VI (COL VI) is upregulated in renal fibrosis. Endotrophin is released from COL VI and promotes pleiotropic pro-fibrotic effects. Kidney disease severity varies considerably and accurate...... information regarding CKD progression may improve clinical decisions. We tested the hypothesis that urinary endotrophin derived during COL VI deposition in fibrotic human kidneys is a marker for progression of CKD in the Renal Impairment in Secondary Care (RIISC) cohort, a prospective observational study...... of 499 CKD patients. Endotrophin localised to areas of increased COL VI deposition in fibrotic kidneys but was not present in histologically normal kidneys. The third and fourth quartiles of urinary endotrophin:creatinine ratio (ECR) were independently associated with one-year disease progression after...

Induction of antigen-specific antibody response in human pheripheral blood lymphocytes in vitro by a dog kidney cell vaccine against rabies virus (DKCV).

NARCIS (Netherlands)

F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert); H.G. Loggen; R.H.J. Bakker (Roland); J.A.A.M. van Asten (Jack); J.G. Kreeftenberg; P. van der Marel; G. van Steenis (Bert)

1983-01-01

textabstractIn the present report an in vitro method for obtaining a secondary human antibody response to a dog kidney cell vaccine against rabies virus (DKCV) is described. Cultures of peripheral blood mononuclear cells from normal rabies-immune and nonimmune donors were stimulated in vitro by

Added sugars drive chronic kidney disease and its consequences: A comprehensive review

Directory of Open Access Journals (Sweden)

James J. DiNicolantonio

2016-06-01

Full Text Available The consumption of added sugars (e.g. sucrose [table sugar] and high-fructose corn syrup over the last 200 years has increased exponentially and parallels the increased prevalence of chronic kidney disease (CKD. Data for animals and humans suggest that the consumption of added sugars leads to kidney damage and related metabolic derangements that increase cardiovascular risk. Importantly, the consumption of added sugars has been found to induce insulin resistance and increase uric acid in humans, both of which increase the conversion of glucose to fructose (i.e. fructogenesis via the polyol pathway. The polyol pathway has recently been implicated in the contribution and progression of kidney damage, suggesting that even glucose can be toxic to the kidney via its endogenous transformation into fructose in the proximal tubule. Consuming added fructose has been shown to induce insulin resistance, which can lead to hyperglycaemia, oxidative stress, inflammation and the activation of the immune system, all of which can synergistically contribute to kidney damage. CKD guidelines should stress a reduction in the consumption of added sugars as a means to prevent and treat CKD as well as reduce CKD–related morbidity and mortality.

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

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.

Kidney deformation and intraprocedural registration: a study of elements of image-guided kidney surgery.

Science.gov (United States)

Altamar, Hernan O; Ong, Rowena E; Glisson, Courtenay L; Viprakasit, Davis P; Miga, Michael I; Herrell, Stanley Duke; Galloway, Robert L

2011-03-01

Central to any image-guided surgical procedure is the alignment of image and physical coordinate spaces, or registration. We explored the task of registration in the kidney through in vivo and ex vivo porcine animal models and a human study of minimally invasive kidney surgery. A set of (n = 6) ex vivo porcine kidney models was utilized to study the effect of perfusion and loss of turgor caused by incision. Computed tomography (CT) and laser range scanner localizations of the porcine kidneys were performed before and after renal vessel clamping and after capsular incision. The da Vinci robotic surgery system was used for kidney surface acquisition and registration during robot-assisted laparoscopic partial nephrectomy. The surgeon acquired the physical surface data points with a tracked robotic instrument. These data points were aligned to preoperative CT for surface-based registrations. In addition, two biomechanical elastic computer models (isotropic and anisotropic) were constructed to simulate deformations in one of the kidneys to assess predictive capabilities. The mean displacement at the surface fiducials (glass beads) in six porcine kidneys was 4.4 ± 2.1 mm (range 3.4-6.7 mm), with a maximum displacement range of 6.1 to 11.2 mm. Surface-based registrations using the da Vinci robotic instrument in robot-assisted laparoscopic partial nephrectomy yielded mean and standard deviation closest point distances of 1.4 and 1.1 mm. With respect to computer model predictive capability, the target registration error was on average 6.7 mm without using the model and 3.2 mm with using the model. The maximum target error reduced from 11.4 to 6.2 mm. The anisotropic biomechanical model yielded better performance but was not statistically better. An initial point-based alignment followed by an iterative closest point registration is a feasible method of registering preoperative image (CT) space to intraoperative physical (robot) space. Although rigid registration provides

Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology.

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Hu, Jianwen; Han, Jizhong; Li, Haoran; Zhang, Xian; Liu, Lan Lan; Chen, Fei; Zeng, Bin

2018-01-01

Mammalian cells, e.g., CHO, BHK, HEK293, HT-1080, and NS0 cells, represent important manufacturing platforms in bioengineering. They are widely used for the production of recombinant therapeutic proteins, vaccines, anticancer agents, and other clinically relevant drugs. HEK293 (human embryonic kidney 293) cells and their derived cell lines provide an attractive heterologous system for the development of recombinant proteins or adenovirus productions, not least due to their human-like posttranslational modification of protein molecules to provide the desired biological activity. Secondly, they also exhibit high transfection efficiency yielding high-quality recombinant proteins. They are easy to maintain and express with high fidelity membrane proteins, such as ion channels and transporters, and thus are attractive for structural biology and electrophysiology studies. In this article, we review the literature on HEK293 cells regarding their origins but also stress their advancements into the different cell lines engineered and discuss some significant aspects which make them versatile systems for biopharmaceutical manufacturing, drug screening, structural biology research, and electrophysiology applications. © 2018 S. Karger AG, Basel.

Renal function and carotid atherosclerosis in adults with no known kidney disease.

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Buscemi, S; Geraci, G; Massenti, F M; Buscemi, C; Costa, F; D'Orio, C; Rosafio, G; Buscemi, C; Maniaci, V; Parrinello, G

2017-03-01

A high prevalence of atherosclerotic lesions characterizes patients with chronic kidney disease, though there is little data on the relationship between kidney function and atherosclerotic changes in the healthy population or in people with no known renal impairment. The aim of our study was to analyze, in a comprehensive general population with no known kidney disease, the relationship between renal function and subclinical carotid atherosclerotic damage. A general real-life population of 611 participants (233 males and 378 females; age ≥18 years) with no known kidney failure was selected for the study. The glomerular filtration rate (GFR) was estimated according to the CKD-EPI equation. Carotid intima-media thickness (c-IMT) and plaques were assessed by duplex Doppler ultrasonography of the carotid vessels. The main laboratory and metabolic parameters were evaluated in all participants. When we divided the overall study population into tertiles according to GFR values (I tertile 99 ml/min/1.73 m 2 ), the c-IMT mean values and the prevalence of carotid plaques decreased with the increasing tertile of GFR. On univariate analysis, c-IMT was significantly correlated with eGFR (r = -0.33; p < 0.001), serum creatinine (r = 0.17; p < 0.001), and other variables such as age, systolic blood pressure, waist circumference, fasting or random glycemia, and glycated hemoglobin (HbA 1 c). On multiple regression analysis, serum creatinine was associated with c-IMT (β = 0.069; p = 0.017), independent of other covariates. Our study seems to suggest the importance of early identification of people with near normal or mildly decreased renal function due to its association with carotid atherosclerosis. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights

Medication use and kidney cancer risk: A population-based study.

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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.

Frailty, Disability and Physical Exercise in the Aging Process and in Chronic Kidney Disease

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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.

Kidney stem cells in development, regeneration and cancer.

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Dziedzic, Klaudyna; Pleniceanu, Oren; Dekel, Benjamin

2014-12-01

The generation of nephrons during development depends on differentiation via a mesenchymal to epithelial transition (MET) of self-renewing, tissue-specific stem cells confined to a specific anatomic niche of the nephrogenic cortex. These cells may transform to generate oncogenic stem cells and drive pediatric renal cancer. Once nephron epithelia are formed the view of post-MET tissue renal growth and maintenance by adult tissue-specific epithelial stem cells becomes controversial. Recently, genetic lineage tracing that followed clonal evolution of single kidney cells showed that the need for new cells is constantly driven by fate-restricted unipotent clonal expansions in varying kidney segments arguing against a multipotent adult stem cell model. Lineage-restriction was similarly maintained in kidney organoids grown in culture. Importantly, kidney cells in which Wnt was activated were traced to give significant clonal progeny indicating a clonogenic hierarchy. In vivo nephron epithelia may be endowed with the capacity akin to that of unipotent epithelial stem/progenitor such that under specific stimuli can clonally expand/self renew by local proliferation of mature differentiated cells. Finding ways to ex vivo preserve and expand the observed in vivo kidney-forming capacity inherent to both the fetal and adult kidneys is crucial for taking renal regenerative medicine forward. Some of the strategies used to achieve this are sorting human fetal nephron stem/progenitor cells, growing adult nephrospheres or reprogramming differentiated kidney cells toward expandable renal progenitors. Copyright © 2014. Published by Elsevier Ltd.

Effect of Immigration Status on Outcomes in Pediatric Kidney Transplant Recipients.

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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.

Relationship between intracranial aneurysms and the severity of autosomal dominant polycystic kidney disease.

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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.

A2 to B Blood Type Incompatible Deceased Donor Kidney Transplantation in a Recipient Infected with the Human Immunodeficiency Virus: A Case Report.

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Forbes, R C; DeMers, A; Concepcion, B P; Moore, D R; Schaefer, H M; Shaffer, D

With the introduction of the Kidney Allocation System in the United States in December 2014, transplant centers can list eligible B blood type recipients for A2 organ offers. There have been no prior reports of ABO incompatible A2 to B deceased donor kidney transplantation in human immunodeficiency virus-positive (HIV+) recipients to guide clinicians on enrolling or performing A2 to B transplantations in HIV+ candidates. We are the first to report a case of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results. We describe an HIV+ 39-year-old African American man with end-stage renal disease who underwent A2 to B blood type incompatible deceased donor kidney transplantation. Prior to transplantation, he had an undetectable HIV viral load. The patient was unsensitized, with his most recent anti-A titer data being 1:2 IgG and 1:32 IgG/IgM. Induction therapy of basiliximab and methylprednisolone was followed by a postoperative regimen of plasma exchange, intravenous immunoglobulin, and rituximab with maintenance on tacrolimus, mycophenolate mofetil, and prednisone. He had delayed graft function without rejection on allograft biopsy. Nadir serum creatinine was 2.0 mg/dL. He continued to have an undetectable viral load on the same antiretroviral therapy adjusted for renal function. To our knowledge, this is the first report of A2 to B deceased donor kidney transplantation in an HIV+ recipient with good intermediate-term results, suggesting that A2 donor kidneys may be considered for transplantation into HIV+ B-blood type wait list candidates. Published by Elsevier Inc.

Pathogenesis of age-related bone loss in humans.

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Khosla, Sundeep

2013-10-01

Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD.

One-year enzyme-linked immunosorbent assay follow-up of human interleukin for Da cells/leukemia inhibitory factor in blood and urine of 22 kidney transplant recipients.

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Morel, D; Taupin, J L; Combe, C; Potaux, L; Gualde, N; Moreau, J F

1994-12-15

The cytokine human interleukin for Da cells/leukemia inhibitory factor (HILDA/LIF) exerts multiple biological effects in vitro. In mice, high circulating levels of HILDA/LIF induce a wide range of pathophysiological events, some of them closely involved with immunological and inflammatory responses. Using a sandwich ELISA recognizing the natural human HILDA/LIF molecule with a threshold of 50 pg/ml in urine and 150 pg/ml in plasma, we monitored the urine and plasma HILDA/LIF levels of 22 patients in their first year after a kidney transplant. HILDA/LIF urine excretion is increased during acute rejection, and infections also trigger heavy HILDA/LIF plasma concentrations or urine excretion. In addition, this study raises the question of HILDA/LIF involvement in post-kidney-transplant phenomena such as hypercalcemia, osteoporosis, or the reversal of anemia.

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 ...

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

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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.

Smoking and risk of kidney failure in the Singapore Chinese health study.

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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.

Injury - kidney and ureter

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... 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 ...

Renal Tissue Oxygenation in Essential Hypertension and Chronic Kidney Disease

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Menno Pruijm

2013-01-01

Full Text Available Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI, detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD. In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

Dietary sodium in chronic kidney disease: a comprehensive approach.

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Wright, Julie A; Cavanaugh, Kerri L

2010-01-01

Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake.

Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo.

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Shao, Y; He, T; Fisher, G J; Voorhees, J J; Quan, T

2017-02-01

Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. Sun-protected buttock skin (76 ± 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human skin

Human factors: a major issue in plant aging

International Nuclear Information System (INIS)

Widrig, R.D.

1985-07-01

Human factors issues will be of great significance in the safe and reliable operation of aging nuclear power plants, and they may be more important than materials/component-type issues. Human actions can accelerate or decelerate te physical aging process. And an aging plant can have significant negative implications on staff performance and actions. Some examples include difficulties in attracting and retaining good managers, financial decisions based on a short and uncertain remaining plant life, difficulties in replacing retiring staff, increased maintenance complexity, and increased burden on training. These problems can be dealt with more effectively by early recognition and a well conceived mitigation effort

Predicting human age using regional morphometry and inter-regional morphological similarity

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Wang, Xun-Heng; Li, Lihua

2016-03-01

The goal of this study is predicting human age using neuro-metrics derived from structural MRI, as well as investigating the relationships between age and predictive neuro-metrics. To this end, a cohort of healthy subjects were recruited from 1000 Functional Connectomes Project. The ages of the participations were ranging from 7 to 83 (36.17+/-20.46). The structural MRI for each subject was preprocessed using FreeSurfer, resulting in regional cortical thickness, mean curvature, regional volume and regional surface area for 148 anatomical parcellations. The individual age was predicted from the combination of regional and inter-regional neuro-metrics. The prediction accuracy is r = 0.835, p Pearson correlation coefficient between predicted ages and actual ages. Moreover, the LASSO linear regression also found certain predictive features, most of which were inter-regional features. The turning-point of the developmental trajectories in human brain was around 40 years old based on regional cortical thickness. In conclusion, structural MRI could be potential biomarkers for the aging in human brain. The human age could be successfully predicted from the combination of regional morphometry and inter-regional morphological similarity. The inter-regional measures could be beneficial to investigating human brain connectome.

Study of rat kidney transamidinase structure and regulation with monoclonal antibodies and the purification and characterization of human kidney transamidinase

International Nuclear Information System (INIS)

Gross, M.D.

1985-01-01

The isolation of monoclonal antibodies to transamidinase made possible the development of an immunosorbent inhibition assay for transamidinase protein using a 125 I-labeled monoclonal antibody. This assay is a more direct measurement of transamidinase protein than the determination of the amount of polyclonal antibody required to precipitate the transamidinase activities. Rats were fed diets supplemented with creatine and/or glycine, and the amounts of transamidinase protein were determined with the assay using the monoclonal antibody. The transamidinase activities of kidneys from the rats fed the various supplemented diets ranged from 10 to 40% of the control values, whereas, the amounts of transamidinase protein were, in all instances no lower than 66% of the control values. Purified homogeneous rat kidney transamidinase and rat kidney supernatants were subjected to isoelectric focussing and four to five fractions of the enzyme were obtained. Polyclonal antibodies, but not the monoclonal antibodies were found by Western blotting experiments to recognize all the forms of the enzyme obtained by the isoelectric focussing. The author concluded that the monoclonal antibodies recognized forms of the enzyme that changed very little in amount, relative to the alterations in enzyme activities, when rats were fed a diet containing creatine

[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

An integrative analysis of DNA methylation and RNA-Seq data for human heart, kidney and liver

Directory of Open Access Journals (Sweden)

Xie Linglin

2011-12-01

Full Text Available Abstract Background Many groups, including our own, have proposed the use of DNA methylation profiles as biomarkers for various disease states. While much research has been done identifying DNA methylation signatures in cancer vs. normal etc., we still lack sufficient knowledge of the role that differential methylation plays during normal cellular differentiation and tissue specification. We also need thorough, genome level studies to determine the meaning of methylation of individual CpG dinucleotides in terms of gene expression. Results In this study, we have used (insert statistical method here to compile unique DNA methylation signatures from normal human heart, lung, and kidney using the Illumina Infinium 27 K methylation arraysand compared those to gene expression by RNA sequencing. We have identified unique signatures of global DNA methylation for human heart, kidney and liver, and showed that DNA methylation data can be used to correctly classify various tissues. It indicates that DNA methylation reflects tissue specificity and may play an important role in tissue differentiation. The integrative analysis of methylation and RNA-Seq data showed that gene methylation and its transcriptional levels were comprehensively correlated. The location of methylation markers in terms of distance to transcription start site and CpG island showed no effects on the regulation of gene expression by DNA methylation in normal tissues. Conclusions This study showed that an integrative analysis of methylation array and RNA-Seq data can be utilized to discover the global regulation of gene expression by DNA methylation and suggests that DNA methylation plays an important role in normal tissue differentiation via modulation of gene expression.

Proteomics and aging : studying the influence of aging on endothelial cells and human plasma

NARCIS (Netherlands)

Eman, M.R.

2007-01-01

In general, human aging is considered one of the most complex and less-well understood process in biology. In this thesis the possibilities of proteomics technology in the field of aging were explored. The complexity of the aging process was supposed to accompanied by relatively subtle proteome

Different techniques of vessel reconstruction during kidney transplantation

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Tomić Aleksandar

2015-01-01

Full Text Available Background/Aim. Multiple renal arteries (MRAs represent a surgical challenge by the difficulty in performing anastomoses, bleeding and stenosis. MRAs should be preserved and special attention should be paid to accessory polar arteries. All renal arteries (RAs must be reconstructed and prepared for safe anastomosis. The paper decribed the different techniques of vessel reconstruction during kidney transplantation including important steps within recovery of organs, preparation and implantation. Methods. In a 16-year period (1996-2012 of kidney transplantation in the Military Medical Academy, Belgrade, a total of 310 living donors and 44 human cadaver kidney transplantations were performed, of which 28 (8% kidneys had two or more RAs. Results. All the transplanted kidneys had immediate function. We repaired 20 cases of donor kidneys with 2 arteries, 4 cases with three RAs, one case with 4 RAs, one case with 4 RAs and renal vein reconstruction, one case with 3 arteries and additional polytetrafluoroethylene (PTFE graft reconstruction, one case with transected renal artery and reconstruction with 5 cm long deceased donor external iliac artery. There were no major complications and graft failure. At a minimum of 1-year follow-up, all the patients showed normal renal function. Conclusion. Donor kidney transplantation on a contralateral side and “end-to-end” anastomosis of the renal artery to the internal iliac artery (IIA is our standard procedure with satisfactory results. Renal artery reconstruction and anastomosis with IIA is a safe and highly efficient procedure and kidneys with MRAs are not contraindicated for transplantation. A surgical team should be fully competent to remove cadaveric abdominal organs to avoid accidental injuries of organs vessels.