Sample records for attenuates kidney fibrogenesis

  1. Inflammatory PAF Receptor Signaling Initiates Hedgehog Signaling and Kidney Fibrogenesis During Ethanol Consumption.

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    Calivarathan Latchoumycandane

    Full Text Available Acute inflammation either resolves or proceeds to fibrotic repair that replaces functional tissue. Pro-fibrotic hedgehog signaling and induction of its Gli transcription factor in pericytes induces fibrosis in kidney, but molecular instructions connecting inflammation to fibrosis are opaque. We show acute kidney inflammation resulting from chronic ingestion of the common xenobiotic ethanol initiates Gli1 transcription and hedgehog synthesis in kidney pericytes, and promotes renal fibrosis. Ethanol ingestion stimulated transcription of TGF-ß, collagens I and IV, and alpha-smooth muscle actin with accumulation of these proteins. This was accompanied by deposition of extracellular fibrils. Ethanol catabolism by CYP2E1 in kidney generates local reactive oxygen species that oxidize cellular phospholipids to phospholipid products that activate the Platelet-activating Factor receptor (PTAFR for inflammatory phospholipids. Genetically deleting this ptafr locus abolished accumulation of mRNA for TGF-ß, collagen IV, and α-smooth muscle actin. Loss of PTAFR also abolished ethanol-stimulated Sonic (Shh and Indian hedgehog (Ihh expression, and abolished transcription and accumulation of Gli1. Shh induced in pericytes and Ihh in tubules escaped to urine of ethanol-fed mice. Neutrophil myeloperoxidase (MPO is required for ethanol-induced kidney inflammation, and Shh was not present in kidney or urine of mpo-/- mice. Shh also was present in urine of patients with acute kidney injury, but not in normal individuals or those with fibrotic liver cirrhosis We conclude neither endogenous PTAFR signaling nor CYP2E1-generated radicals alone are sufficient to initiate hedgehog signaling, but instead PTAFR-dependent neutrophil infiltration with myeloperoxidase activation is necessary to initiate ethanol-induced fibrosis in kidney. We also show fibrogenic mediators escape to urine, defining a new class of urinary mechanistic biomarkers of fibrogenesis for an organ not

  2. Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector. (United States)

    Xu, Jing; Li, Pei-Xue; Wu, Jun; Gao, Yi-Jun; Yin, Meng-Xin; Lin, Ye; Yang, Ming; Chen, Dong-Ping; Sun, Hai-Peng; Liu, Zeng-Bo; Gu, Xiang-Chen; Huang, Hong-Ling; Fu, Li-Li; Hu, Hui-Min; He, Liang-Liang; Wu, Wen-Qing; Fei, Zhao-Liang; Ji, Hong-Bin; Zhang, Lei; Mei, Chang-Lin


    Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.

  3. Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing. (United States)

    Wang, Lin-Lin; Zhao, Rui; Li, Jiao-Yong; Li, Shan-Shan; Liu, Min; Wang, Meng; Zhang, Meng-Zhou; Dong, Wen-Wen; Jiang, Shu-Kun; Zhang, Miao; Tian, Zhi-Ling; Liu, Chang-Sheng; Guan, Da-Wei


    Previous studies showed that cannabinoid 2 (CB2) receptor is expressed in multiple effector cells during skin wound healing. Meanwhile, its functional involvement in inflammation, fibrosis, and cell proliferation in other organs and skin diseases implied CB2 receptor might also regulate skin wound healing. To verify this hypothesis, mice excisional wounds were created and treated with highly selective CB2 receptor agonist GP1a (1-(2,4-dichlorophenyl)-6-methyl- N-piperidin-1-yl-4H-indeno[1,2-c]pyrazole-3-carboxamide) and antagonist AM630 ([6-iodo-2- methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone) respectively. The inflammatory infiltration, cytokine expression, fibrogenesis, and wound re-epithelialization were analyzed. After CB2 receptor activation, neutrophil and macrophage infiltrations were reduced, and expressions of monocyte chemotactic protein (MCP)-1, stromal cell-derived factor (SDF)-1, Interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)-A were decreased. Keratinocyte proliferation and migration were enhanced. Wound re-epithelialization was accelerated. Fibroblast accumulation and fibroblast-to-myofibroblast transformation were attenuated, and expression of pro-collagen I was decreased. Furthermore, HaCaT cells in vitro were treated with GP1a or AM630, which revealed that CB2 receptor activation promoted keratinocyte migration by inducing the epithelial to mesenchymal transition. These results, taken together, indicate that activating CB2 receptor could ameliorate wound healing by reducing inflammation, accelerating re-epithelialization, and attenuating scar formation. Thus, CB2 receptor agonist might be a novel perspective for skin wound therapy.

  4. Myeloid cell-derived HIF attenuates inflammation in UUO-induced kidney injury (United States)

    Kobayashi, Hanako; Gilbert, Victoria; Liu, Qingdu; Kapitsinou, Pinelopi P.; Unger, Travis L.; Rha, Jennifer; Rivella, Stefano; Schlöndorff, Detlef; Haase, Volker H.


    Renal fibrosis and inflammation are associated with hypoxia, and tissue pO2 plays a central role in modulating the progression of chronic kidney disease. Key mediators of cellular adaptation to hypoxia are hypoxia-inducible factor (HIF)-1 and -2. In the kidney they are expressed in a cell type-specific manner; to what degree activation of each homolog modulates renal fibrogenesis and inflammation has not been established. To address this issue, we used Cre-loxP recombination to activate or to delete both Hif-1 and Hif-2 either globally or cell type-specifically in myeloid cells. Global activation of Hif suppressed inflammation and fibrogenesis in mice subjected to unilateral ureteral obstruction, while activation of Hif in myeloid cells suppressed inflammation only. Suppression of inflammatory cell infiltration was associated with down-regulation of CC chemokine receptors in renal macrophages. Conversely, global deletion or myeloid-specific inactivation of Hif promoted inflammation. Furthermore, prolonged hypoxia suppressed the expression of multiple inflammatory molecules in non-injured kidneys. Collectively, we provide experimental evidence that hypoxia and/or myeloid cell-specific HIF activation attenuates renal inflammation associated with chronic kidney injury. PMID:22490864

  5. Myeloid cell-derived hypoxia-inducible factor attenuates inflammation in unilateral ureteral obstruction-induced kidney injury. (United States)

    Kobayashi, Hanako; Gilbert, Victoria; Liu, Qingdu; Kapitsinou, Pinelopi P; Unger, Travis L; Rha, Jennifer; Rivella, Stefano; Schlöndorff, Detlef; Haase, Volker H


    Renal fibrosis and inflammation are associated with hypoxia, and tissue pO(2) plays a central role in modulating the progression of chronic kidney disease. Key mediators of cellular adaptation to hypoxia are hypoxia-inducible factor (HIF)-1 and -2. In the kidney, they are expressed in a cell type-specific manner; to what degree activation of each homolog modulates renal fibrogenesis and inflammation has not been established. To address this issue, we used Cre-loxP recombination to activate or to delete both Hif-1 and Hif-2 either globally or cell type specifically in myeloid cells. Global activation of Hif suppressed inflammation and fibrogenesis in mice subjected to unilateral ureteral obstruction, whereas activation of Hif in myeloid cells suppressed inflammation only. Suppression of inflammatory cell infiltration was associated with downregulation of CC chemokine receptors in renal macrophages. Conversely, global deletion or myeloid-specific inactivation of Hif promoted inflammation. Furthermore, prolonged hypoxia suppressed the expression of multiple inflammatory molecules in noninjured kidneys. Collectively, we provide experimental evidence that hypoxia and/or myeloid cell-specific HIF activation attenuates renal inflammation associated with chronic kidney injury.

  6. Lack of the matricellular protein SPARC (secreted protein, acidic and rich in cysteine attenuates liver fibrogenesis in mice.

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    Catalina Atorrasagasti

    Full Text Available INTRODUCTION: Secreted Protein, Acidic and Rich in Cysteine (SPARC is a matricellular protein involved in many biological processes and found over-expressed in cirrhotic livers. By mean of a genetic approach we herein provide evidence from different in vivo liver disease models suggesting a profibrogenic role for SPARC. METHODS: Two in vivo models of liver fibrosis, based on TAA administration and bile duct ligation, were developed on SPARC wild-type (SPARC(+/+ and knock-out (SPARC(-/- mice. Hepatic SPARC expression was analyzed by qPCR. Fibrosis was assessed by Sirius Red staining, and the maturation state of collagen fibers was analyzed using polarized light. Necroinflammatory activity was evaluated by applying the Knodell score and liver inflammatory infiltration was characterized by immunohistochemistry. Hepatic stellate cell activation was assessed by α-SMA immunohistochemistry. In addition, pro-fibrogenic genes and inflammatory cytokines were measured by qPCR and/or ELISA. Liver gene expression profile was analyzed in SPARC(-/- and SPARC(+/+ mice using Affymetrix Mouse Gene ST 1.0 array. RESULTS: SPARC expression was found induced in fibrotic livers of mouse and human. SPARC(-/- mice showed a reduction in the degree of inflammation, mainly CD4+ cells, and fibrosis. Consistently, collagen deposits and mRNA expression levels were decreased in SPARC(-/- mice when compared to SPARC(+/+ mice; in addition, MMP-2 expression was increased in SPARC(-/- mice. A reduction in the number of activated myofibroblasts was observed. Moreover, TGF-β1 expression levels were down-regulated in the liver as well as in the serum of TAA-treated knock-out animals. Ingenuity Pathway Analysis (IPA analysis suggested several gene networks which might involve protective mechanisms of SPARC deficiency against liver fibrogenesis and a better established machinery to repair DNA and detoxify from external chemical stimuli. CONCLUSIONS: Overall our data suggest that

  7. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

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    Malaviya, Rama; Venosa, Alessandro [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Hall, LeRoy [Drug Safety Sciences, Johnson and Johnson, Raritan, NJ 08869 (United States); Gow, Andrew J. [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sinko, Patrick J. [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)


    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  8. ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-β1, PDGF-BB, NF-κB and MMP-2,9

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    Xu Li; Ying Meng; Xi-Shan Yang; Ling-Fei Mi; Shao-Xi Cai


    AIM: Angiotensin Ⅱ has pro-fibrotic function in the liver.Blockade of the renin-angiotensin-aldosterone-system (RAAS) attenuates hepatic fibrosis. The aim of the present study was to determine the mechanism of angiotensinconverting enzyme inhibitor (ACEI) on the progression of rat hepatic fibrosis.METHODS: Forty male Wistar rats were divided into three groups. Model group (Mo): The rats were injected subcutaneously with 40% of CCl4 0.25 mL/100 g. Perindopril group (Pe): The rats were injected subcutaneously with administrated. Control group (Nc): the rats were treated with olive oil only. After 4 and 6 wk, the rats were killed.The liver sections were stained with Masson. The protein expressions of AT1R, TGF-β1 and PDGF-BB were examined by Western blot. Nuclear factor κB (NF-κB) DNA binding activity was examined by EMSA (Electrophoretic gel mobility shift assay). Matrix metalloproteinase-2,9(MMP-2,9) activity was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radioimmunoassays.RESULTS: Using Western blot, we clearly provided direct evidence for the expression of AT1R in liver. The expression was up-regulated when fibrogenesis occurred. Perindopril treatment significantly reduced mean fibrosis score,protein levels of AT1R, TGF-β1 and PDGF-BB, serum levels of HA and LN, and the activity of MMP-2,9. NF-κB DNA binding activity markedly increased in model group, perindopril treatment considerably reduced NF-κB DNA binding activity.CONCLUSION: Perindopril attenuates CCl4-induced hepatic fibrogenesis of rat by inhibiting TGF-β1, PDGF-BB,NF-κB and MMP-2,9.

  9. Liver fibrogenesis and genetic factors. (United States)

    Boursier, Jérôme; Louvet, Alexandre


    Chronic liver diseases lead to the accumulation of fibrosis in the liver with eventual progression to cirrhosis and its complications. However, there is a wide range of inter-individual variation in the liver fibrogenesis process, thus posing a challenge to physicians to identify patients with poor prognosis. As demographic and environmental factors only account for a small portion of fibrogenesis variability, host genetic factors have been suggested as playing an important role. Due to technical limitations, the first genetic studies were restricted to the evaluation of candidate genes having a known or supposed function in liver fibrogenesis. Recently, technological improvements have made it possible to study the whole human genome in a single scan. Genome-wide association studies have considerably heightened the interest in genetics as part of the study of liver fibrogenesis through their identification of previously unsuspected genes that are statistically associated with liver fibrosis. It is thus possible to determine new diagnostic or prognostic genetic markers for the management of patients with chronic liver diseases. Moreover, functional analyses of these genes may provide new insights into the pathophysiology of liver fibrogenesis.


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    Md. Abdul Hye Khan


    Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  11. Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury. (United States)

    Khan, Abdul Hye; Falck, John R; Manthati, Vijaya L; Campbell, William B; Imig, John D


    Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10 mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

  12. Omega-3 Polyunsaturated Fatty Acids Attenuate Fibroblast Activation and Kidney Fibrosis Involving MTORC2 Signaling Suppression (United States)

    Zeng, Zhifeng; Yang, Haiyuan; Wang, Ying; Ren, Jiafa; Dai, Yifan; Dai, Chunsun


    Epidemiologic studies showed the correlation between the deficiency of omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the progression of chronic kidney diseases (CKD), however, the role and mechanisms for n-3 PUFAs in protecting against kidney fibrosis remain obscure. In this study, NRK-49F cells, a rat kidney interstitial fibroblast cell line, were stimulated with TGFβ1. A Caenorhabditis elegans fat-1 transgenic mouse model in which n-3 PUFAs are endogenously produced from n-6 PUFAs owing to the expression of n-3 fatty acid desaturase were deployed. Docosahexaenoic acid (DHA), one member of n-3 PUFAs family, could suppress TGFβ1-induced fibroblast activation at a dose and time dependent manner. Additionally, DHA could largely inhibit TGFβ1-stimulated Akt but not S6 or Smad3 phosphorylation at a time dependent manner. To decipher the role for n-3 PUFAs in protecting against kidney fibrosis, fat-1 transgenic mice were operated with unilateral ureter obstruction (UUO). Compared to the wild types, fat-1 transgenics developed much less kidney fibrosis and inflammatory cell accumulation accompanied by less p-Akt (Ser473), p-Akt (Thr308), p-S6 and p-Smad3 in kidney tissues at day 7 after UUO. Thus, n-3 PUFAs can attenuate fibroblast activation and kidney fibrosis, which may be associated with the inhibition of mTORC2 signaling. PMID:28393852

  13. Experimental inhibition of porcupine-mediated Wnt O-acylation attenuates kidney fibrosis. (United States)

    Madan, Babita; Patel, Mehul B; Zhang, Jiandong; Bunte, Ralph M; Rudemiller, Nathan P; Griffiths, Robert; Virshup, David M; Crowley, Steven D


    Activated Wnt signaling is critical in the pathogenesis of renal fibrosis, a final common pathway for most forms of chronic kidney disease. Therapeutic intervention by inhibition of individual Wnts or downstream Wnt/β-catenin signaling has been proposed, but these approaches do not interrupt the functions of all Wnts nor block non-canonical Wnt signaling pathways. Alternatively, an orally bioavailable small molecule, Wnt-C59, blocks the catalytic activity of the Wnt-acyl transferase porcupine, and thereby prevents secretion of all Wnt isoforms. We found that inhibiting porcupine dramatically attenuates kidney fibrosis in the murine unilateral ureteral obstruction model. Wnt-C59 treatment similarly blunts collagen mRNA expression in the obstructed kidney. Consistent with its actions to broadly arrest Wnt signaling, porcupine inhibition reduces expression of Wnt target genes and bolsters nuclear exclusion of β-catenin in the kidney following ureteral obstruction. Importantly, prevention of Wnt secretion by Wnt-C59 blunts expression of inflammatory cytokines in the obstructed kidney that otherwise provoke a positive feedback loop of Wnt expression in collagen-producing fibroblasts and epithelial cells. Thus, therapeutic targeting of porcupine abrogates kidney fibrosis not only by overcoming the redundancy of individual Wnt isoforms but also by preventing upstream cytokine-induced Wnt generation. These findings reveal a novel therapeutic maneuver to protect the kidney from fibrosis by interrupting a pathogenic crosstalk loop between locally generated inflammatory cytokines and the Wnt/β-catenin signaling pathway.

  14. Plant recombinant erythropoietin attenuates inflammatory kidney cell injury. (United States)

    Conley, Andrew J; Mohib, Kanishka; Jevnikar, Anthony M; Brandle, Jim E


    Human erythropoietin (EPO) is a pleiotropic cytokine with remarkable tissue-protective activities in addition to its well-established role in red blood cell production. Unfortunately, conventional mammalian cell cultures are unlikely to meet the anticipated market demands for recombinant EPO because of limited capacity and high production costs. Plant expression systems may address these limitations to enable practical, cost-effective delivery of EPO in tissue injury prevention therapeutics. In this study, we produced human EPO in tobacco and demonstrated that plant-derived EPO had tissue-protective activity. Our results indicated that targeting to the endoplasmic reticulum (ER) provided the highest accumulation levels of EPO, with a yield approaching 0.05% of total soluble protein in tobacco leaves. The codon optimization of the human EPO gene for plant expression had no clear advantage; furthermore, the human EPO signal peptide performed better than a tobacco signal peptide. In addition, we found that glycosylation was essential for the stability of plant recombinant EPO, whereas the presence of an elastin-like polypeptide fusion had a limited positive impact on the level of EPO accumulation. Confocal microscopy showed that apoplast and ER-targeted EPO were correctly localized, and N-glycan analysis demonstrated that complex plant glycans existed on apoplast-targeted EPO, but not on ER-targeted EPO. Importantly, plant-derived EPO had enhanced receptor-binding affinity and was able to protect kidney epithelial cells from cytokine-induced death in vitro. These findings demonstrate that tobacco plants may be an attractive alternative for the production of large amounts of biologically active EPO.

  15. Tyrosol attenuates ischemia-reperfusion-induced kidney injury via inhibition of inducible nitric oxide synthase. (United States)

    Wang, Pengqi; Zhu, Qingjun; Wu, Nan; Siow, Yaw L; Aukema, Harold; O, Karmin


    Tyrosol is a natural phenolic antioxidant compound. Oxidative stress represents one of the important mechanisms underlying ischemia-reperfusion-induced kidney injury. The aim of this study was to investigate the effect of tyrosol against ischemia-reperfusion-induced acute kidney injury. The left kidney of Sprague-Dawley rats was subjected to 45 min of ischemia followed by reperfusion for 6 h. Ischemia-reperfusion caused an increase in peroxynitrite formation and lipid peroxidation. The level of nitric oxide (NO) metabolites and the mRNA of inducible nitric oxide synthase (iNOS) were elevated in ischemia-reperfused kidneys. Administration of tyrosol (100 mg/kg body weight) to rats prior to the induction of ischemia significantly reduced peroxynitrite formation, lipid peroxidation, and the level of NO metabolites. Tyrosol administration also attenuated ischemia-reperfusion-induced NF-κB activation and iNOS expression. Such a treatment improved kidney function. Results suggest that tyrosol may have a protective effect against acute kidney injury through inhibition of iNOS-mediated oxidative stress.

  16. Akt1-mediated fast/glycolytic skeletal muscle growth attenuates renal damage in experimental kidney disease. (United States)

    Hanatani, Shinsuke; Izumiya, Yasuhiro; Araki, Satoshi; Rokutanda, Taku; Kimura, Yuichi; Walsh, Kenneth; Ogawa, Hisao


    Muscle wasting is frequently observed in patients with kidney disease, and low muscle strength is associated with poor outcomes in these patients. However, little is known about the effects of skeletal muscle growth per se on kidney diseases. In this study, we utilized a skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mouse model that promotes the growth of functional skeletal muscle independent of exercise to investigate the effects of muscle growth on kidney diseases. Seven days after Akt1 activation in skeletal muscle, renal injury was induced by unilateral ureteral obstruction (UUO) in Akt1 TG and wild-type (WT) control mice. The expression of atrogin-1, an atrophy-inducing gene in skeletal muscle, was upregulated 7 days after UUO in WT mice but not in Akt1 TG mice. UUO-induced renal interstitial fibrosis, tubular injury, apoptosis, and increased expression of inflammatory, fibrosis-related, and adhesion molecule genes were significantly diminished in Akt1 TG mice compared with WT mice. An increase in the activating phosphorylation of eNOS in the kidney accompanied the attenuation of renal damage by myogenic Akt1 activation. Treatment with the NOS inhibitor L-NAME abolished the protective effect of skeletal muscle Akt activation on obstructive kidney disease. In conclusion, Akt1-mediated muscle growth reduces renal damage in a model of obstructive kidney disease. This improvement appears to be mediated by an increase in eNOS signaling in the kidney. Our data support the concept that loss of muscle mass during kidney disease can contribute to renal failure, and maintaining muscle mass may improve clinical outcome.

  17. RACK1-mediated translation control promotes liver fibrogenesis

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    Liu, Min; Peng, Peike; Wang, Jiajun [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Wang, Lan; Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai 200032 (China); Jia, Dongwei, E-mail: [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Ruan, Yuanyuan, E-mail: [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032 (China); Institute of Biomedical Science, Fudan University, Shanghai 200032 (China)


    Activation of quiescent hepatic stellate cells (HSCs) is the central event of liver fibrosis. The translational machinery is an optimized molecular network that affects cellular homoeostasis and diseases, whereas the role of protein translation in HSCs activation and liver fibrosis is little defined. Our previous report suggests that up-regulation of receptor for activated C-kinase 1(RACK1) in HSCs is critical for liver fibrogenesis. In this study, we found that RACK1 promoted macrophage conditioned medium (MCM)-induced assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. RACK1 enhanced the translation and expression of pro-fibrogenic factors collagen 1α1, snail and cyclin E1 induced by MCM. Administration of PP242 or knock-down of eIF4E suppressed RACK1-stimulated collagen 1α1 production, proliferation and migration in primary HSCs. In addition, depletion of eIF4E attenuated thioacetamide (TAA)-induced liver fibrosis in vivo. Our data suggest that RACK1-mediated stimulation of cap-dependent translation plays crucial roles in HSCs activation and liver fibrogenesis, and targeting translation initiation could be a promising strategy for the treatment of liver fibrosis. - Highlights: • RACK1 induces the assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. • RACK1 stimulates the translation of collagen 1α1, snail and cyclin E1 in HSCs. • RACK1 promotes HSCs activation via cap-mediated translation. • Depletion of eIF4E suppresses liver fibrogenesis in vivo.

  18. Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism

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    Mario Negrette-Guzmán


    Full Text Available It has been shown that curcumin (CUR, a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM- induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2-related factor 2 (Nrf2 nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

  19. Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism. (United States)

    Negrette-Guzmán, Mario; García-Niño, Wylly Ramsés; Tapia, Edilia; Zazueta, Cecilia; Huerta-Yepez, Sara; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Aparicio-Trejo, Omar Emiliano; Madero, Magdalena; Pedraza-Chaverri, José


    It has been shown that curcumin (CUR), a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM-) induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2)-related factor 2 (Nrf2) nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h) during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day) was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

  20. Cinnabar Induces Renal Inflammation and Fibrogenesis in Rats

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    Ying Wang


    Full Text Available The purpose of this study was to investigate whether cinnabar causes renal inflammation and fibrosis in rats. Rats were dosed orally with cinnabar (1 g/kg/day for 8 weeks or 12 weeks. The control rats were treated with solvent (5% carboxymethylcellulose solution over the same time periods, respectively. Renal mercury (RHg, urinary mercury (UHg, serum creatinine (SCr, urine kidney injury molecule 1 (KIM-1, renal pathology, and renal mediators were examined. At both 8 weeks and 12 weeks, RHg, UHg, and urine KIM-1 were significantly higher in the cinnabar group than in the control group, although SCr was unchanged. Kidney lesions in the cinnabar-treated rats occurred mainly in the tubules and interstitium, including vacuolization, protein casts, infiltration of inflammatory cells, and slight increase in interstitial collagen. In addition, mild mesangial proliferation was observed in glomeruli. Moreover, the expression of inflammatory and fibrogenic mediators was upregulated in the cinnabar group. In conclusion, cinnabar may cause kidney damage due to the accumulation of mercury, and renal inflammation and slight fibrogenesis may occur in rats. In the clinic, the potential risk of renal injury due to the prolonged consumption of cinnabar should be considered even though the agent is relatively nontoxic.

  1. Silencing of Histone Deacetylase 9 Expression in Podocytes Attenuates Kidney Injury in Diabetic Nephropathy (United States)

    Liu, Feng; Zong, Ming; Wen, Xiaofei; Li, Xuezhu; Wang, Jun; Wang, Yi; Jiang, Wei; Li, Xiaojun; Guo, Zhongliang; Qi, Hualin


    Podocyte dysfunction is important in the onset and development of diabetic nephropathy (DN). Histone deacetylases (HDACs) have been recently proved to play critical roles in the pathogenesis of DN. As one subtype of the class IIa HDACs, HDAC9 is capable to repress/de-repress their target genes in tumor, inflammation, atherosclerosis and metabolic diseases. In the present study, we investigate whether HDAC9 is involved in the pathophysiologic process of DN, especially the podocyte injury. Firstly, we explored the expression patterns and localization of HDAC9 and found that HDAC9 expression was significantly up-regulated in high glucose (HG)-treated mouse podocytes, as well as kidney tissues from diabetic db/db mice and patients with DN. Secondly, knockdown of HDAC9 in mouse podocytes significantly suppressed HG-induced reactive oxygen species (ROS) generation, cell apoptosis and inflammation through JAK2/STAT3 pathway and reduced the podocytes injury by decreasing the expression levels of Nephrin and Podocin. Moreover, in diabetic db/db mice, silencing of HDAC9 attenuated the glomerulosclerosis, inflammatory cytokine release, podocyte apoptosis and renal injury. Collectively, these data indicate that HDAC9 may be involved in the process of DN, especially podocyte injury. Our study suggest that inhibition of HDAC9 may have a therapeutic potential in DN treatment. PMID:27633396

  2. TGF-β: Titan of Lung Fibrogenesis. (United States)

    Yue, Xinping; Shan, Bin; Lasky, Joseph A


    Pulmonary fibrosis is characterized by epithelial cell injury, accumulation of myofibroblasts, and excessive deposition of collagen and other extracellular matrix elements, leading to loss of pulmonary function. Studies in both humans and animal models strongly suggest that TGF-β1 plays a pivotal role in the pathogenesis of pulmonary fibrosis. This review will first give an overview of TGF-β signaling and the effects of its inhibition on lung fibrogenesis. This overview includes information on TGF-β signal transduction pathways, the importance of TGF-β in the accumulation of myofibroblasts, the role of TGF-β in epithelial injury and apoptosis, the role of TGF-β in extracellular matrix remodeling, and the effects of inhibiting TGF-β signaling in animal models of lung fibrosis. Subsequently this review will highlight recent advances in two areas of particular interest to our research group: (1) TGF-β and proteoglycans; (2) TGF-β and histone deacetylases. Although our understanding of the role of TGF-β and its mechanisms of action in lung fibrogenesis has increased dramatically in recent years, there is still much to be learned about this important molecule, especially how TGF-β function is modulated in vivo, and its complex interactions with other factors expressed during lung injury and repair. Research in these areas will help identify novel therapeutic targets for the treatment of pulmonary fibrosis that will hopefully improve the prognosis of this devastating illness.

  3. Eriodictyol attenuates cisplatin-induced kidney injury by inhibiting oxidative stress and inflammation. (United States)

    Li, Cheng-zhen; Jin, Hai-hong; Sun, Hong-xin; Zhang, Zhong-zhe; Zheng, Jia-xin; Li, Shu-hua; Han, Seong-ho


    Eriodictyol, a flavonoid present in citrus fruits, has been reported to have antioxidant and anti-inflammatory effects. In this study, the protective effects of eriodictyol on cisplatin (CP)-induced kidney injury were detected. CP-induced kidney injury model was established by administration of CP (20mg/kg). The results showed that treatment of eriodictyol inhibited the production of blood urea nitrogen (BUN), creatinine, MDA, TBARS, reactive oxygen species (ROS), as well as the production of TNF-α, and IL-1β in kidney tissues induced by CP. Eriodictyol also up-regulated the activities of SOD, CAT, and GSH-PX decreased by CP. Furthermore, eriodictyol was found to up-regulate the expression of Nrf2/HO-1 and inhibited CP-induced NF-κB activation in kidney tissues. In conclusion, eriodictyol protected against CP-induced kidney injury through activating Nrf2 and inhibiting NF-κB activation.

  4. Fibrogenesis and carcinoid tumor - a case report

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    Eduardo Fonseca Alves Filho


    Full Text Available Carcinoid tumors are rare. They may appear in the entire gastrointestinal and respiratory tracts, with single or multiple occurrences. Prognosis is dependent on the size and location. Symptoms may appear in carcinoid syndrome, related to active substances, especially serotonin. One important aspect associated with these tumors and usually ignored is fibrogenesis. This is a case report of a patient with carcinoid tumor of the terminal ileum, treated by laparoscopy, associated with fat and fibrosis infiltration.Tumores carcinoides são pouco frequentes, podem surgir em todo o trato gastrointestinal e respiratório, podem ser únicos ou múltiplos. O prognóstico depende do tamanho e da localização do tumor. Podem ocorrer sintomas relacionados à síndrome carcinoide, decorrente da produção de substâncias ativas, em especial serotonina. Um aspecto comumente ignorado associado a estes tumores é a estimulação da fibrogênese. Relatamos um caso de tumor carcinoide de íleo, tratado por videolaparoscopia, associado à infiltração fibroadiposa.

  5. Betanin attenuates oxidative stress and inflammatory reaction in kidney of paraquat-treated rat. (United States)

    Tan, Dehong; Wang, Yiheng; Bai, Bing; Yang, Xuelian; Han, Junyan


    The effects of natural pigment betanin on oxidative stress and inflammation in kidney of paraquat-treated rat were investigated. Paraquat was injected intraperitoneally into rats to induce renal damage. The rats were randomly divided into four groups: a control group, a paraquat group, and two paraquat groups that were treated with betanin at 25 and 100 mg/kg/d three days before and two days after paraquat administration. Treatment with betanin alleviated the paraquat-incurred acute kidney injury, evidenced by histological improvement, reduced serum and urine markers for kidney injury. Betanin antagonized the paraquat-induced inflammation, indicated by reduced expression of inducible nitric oxide synthase and cyclooxygenase, blunted activation of nuclear factor kappa B, and diminished lysosomal protease activities. Betanin also decreased oxidative stress elicited by paraquat. In conclusion, betanin may have a protective effect against paraquat-induced acute kidney damage. The mechanisms of the protection appear to be the inhibition of oxidative stress and inflammation.

  6. Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury. (United States)

    Mami, Iadh; Bouvier, Nicolas; El Karoui, Khalil; Gallazzini, Morgan; Rabant, Marion; Laurent-Puig, Pierre; Li, Shuping; Tharaux, Pierre-Louis; Beaune, Philippe; Thervet, Eric; Chevet, Eric; Hu, Guo-Fu; Pallet, Nicolas


    Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney disease and aging, but the molecular bases underlying the biologic outcomes on the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a ribonuclease that promotes cellular adaptation under stress but its contribution to ER stress signaling remains elusive. In this study, we investigated the ANG-mediated contribution to the signaling and biologic outcomes of ER stress in kidney injury. ANG expression was significantly higher in samples from injured human kidneys than in samples from normal human kidneys, and in mouse and rat kidneys, ANG expression was specifically induced under ER stress. In human renal epithelial cells, ER stress induced ANG expression in a manner dependent on the activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER stress through induction of stress granules and inhibition of translation. Moreover, the severity of renal lesions induced by ER stress was dramatically greater in ANG knockout mice (Ang(-/-)) mice than in wild-type mice. These results indicate that ANG is a critical mediator of tissue adaptation to kidney injury and reveal a physiologically relevant ER stress-mediated adaptive translational control mechanism.

  7. Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease.

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    Yanling Zhang

    Full Text Available Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2 leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally nephrectomised rats, a model of progressive chronic kidney disease (CKD that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.

  8. Endoglin haploinsufficiency attenuates radiation-induced deterioration of kidney function in mice

    NARCIS (Netherlands)

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.


    Background and Purpose: Endoglin is a transforming growth receptor beta (TGF-beta) co-receptor, which plays a crucial role in the development of late normal tissue damage. Mice with halved endoglin levels (Eng(+/-) mice) develop less inflammation, vascular damage and fibrosis after kidney irradiatio

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

    DEFF Research Database (Denmark)

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


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

  10. Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication (United States)

    Xu, Jia-jun; Zhen, Jian-tao; Tang, Li; Lin, Qing-ming


    BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury (AKI) in rats with paraquat intoxication. METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group (n=8), paraquat group (n=8) and Xuebijing-treated group (n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing (8 mL/kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-inflammatory cytokines mRNA levels in kidney were assayed using real-time RT-PCR. RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group (Pparaquat group (Pparaquat group (Pparaquat poisoning by suppressing inflammatory response. PMID:28123623

  11. Adenovirus-mediated interteukin-13 gene therapy attenuates acute kidney allograft injury

    NARCIS (Netherlands)

    Sandovici, Maria; Deelmani, Leo E.; van Goor, Harry; Helfrich, Wijnand; de Zeeuw, Dick; Henning, Robert H.


    Background Kidney transplantation is possible by virtue of systemic immunosuppression, which is in turn accompanied by serious side effects. The search for novel therapeutic agents and strategies is ongoing. Here we investigate the effects of adenovirus-mediated gene therapy with interleukin (IL)-13

  12. Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

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    Meliana Riwanto

    Full Text Available Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD. Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect" plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+, a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1 in cystic kidneys of Cy/+ rats compared with wild-type (+/+ rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day for 5 weeks resulted in significantly lower kidney weights (-27% and 2-kidney/total-body-weight ratios (-20% and decreased renal cyst index (-48% compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min, BUN (0.69±0.26 vs 0.40±0.10 ml/min and uric acid (0.38±0.20 vs 0.21±0.10 ml/min, and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD.

  13. Attenuation of cellular antioxidant defense mechanisms in kidney of rats intoxicated with carbofuran. (United States)

    Kaur, Bhupindervir; Khera, Alka; Sandhir, Rajat


    Carbofuran, an anticholinestrase carbamate, is commonly used as an insecticide. Its toxic effect on kidney is less established. The present study was designed to investigate the effect of carbofuran on kidneys and to understand the mechanism involved in its nephrotoxicity. Male Wistar rats were divided into two groups of eight animals each; control animals received sunflower oil (vehicle) and carbofuran exposed animals were treated with carbofuran (1 mg/kg body weight) orally for 28 days. At the end of the treatment, significant increase was observed in urea and creatinine levels in serum along with the inhibition of acetylcholinesterase, suggesting nephrotoxicity. The antioxidant defense system of animals treated with carbofuran was altered in terms of increased lipid peroxidation, reduced glutathione, and total thiols and decreased activity of antioxidant enzymes (superoxide dismutase and catalase). The results indicate that carbofuran is nephrotoxic and increased oxidative stress appears to be involved in its nephrotoxic effects.

  14. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion. (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling


    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  15. Mortality and kidney histopathology of Chinook salmon Oncorhynchus tshawytscha exposed to virulent and attenuated Renibacterium salmoninarum strains (United States)

    O'Farrell, Caroline L.; Elliott, Diane G.; Landolt, Marsha L.


    An isolate of Renibacterium salmoninarum (strain MT 239) exhibiting reduced virulence in rainbow trout Oncorhynchus mykiss was tested for its ability to cause bacterial kidney disease (BKD) in chinook salmon Oncorhynchus tshawytscha, a salmonid species more susceptible to BKD. Juvenile chinook salmon were exposed to either 33209, the American Type Culture Collection type strain of R. salmoninarum, or to MT 239, by an intraperitoneal injection of 1 x 10(3) or 1 x 10(6) bacteria fish(-1), or by a 24 h immersion in 1 x 10(5) or 1 x 10(7) bacteria ml(-1). For 22 wk fish were held in 12 degrees C water and monitored for mortality. Fish were sampled periodically for histological examination of kidney tissues. In contrast to fish exposed to the high dose of strain 33209 by either injection or immersion, none of the fish exposed to strain MT 239 by either route exhibited gross clinical signs or histopathological changes indicative of BKD. However, the MT 239 strain was detected by the direct fluorescent antibody technique in 4 fish that died up to 11 wk after the injection challenge and in 5 fish that died up to 20 wk after the immersion challenge. Viable MT 239 was isolated in culture from 3 fish that died up to 13 wk after the immersion challenge. Total mortality in groups injected with the high dose of strain MT 239 (12%) was also significantly lower (p < 0.05) than mortality in groups injected with strain 33209 (73 %). These data indicate that the attenuated virulence observed with MT 239 in rainbow trout also occurs in a salmonid species highly susceptible to BKD. The reasons for the attenuated virulence of MT 239 were not determined but may be related to the reduced levels of the putative virulence protein p57 associated with this strain.

  16. Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

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    Li Gao


    Full Text Available Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.

  17. Fatty liver associated with metabolic derangement in patients with chronic kidney disease: A controlled attenuation parameter study

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    Chang-Yun Yoon


    Full Text Available Background: Hepatic steatosis measured with controlled attenuation parameter (CAP using transient elastography predicts metabolic syndrome in the general population. We investigated whether CAP predicted metabolic syndrome in chronic kidney disease patients. Methods: CAP was measured with transient elastography in 465 predialysis chronic kidney disease patients (mean age, 57.5 years. Results: The median CAP value was 239 (202–274 dB/m. In 195 (41.9% patients with metabolic syndrome, diabetes mellitus was more prevalent (105 [53.8%] vs. 71 [26.3%], P < 0.001, with significantly increased urine albumin-to-creatinine ratio (184 [38–706] vs. 56 [16–408] mg/g Cr, P = 0.003, high sensitivity C-reactive protein levels (5.4 [1.4–28.2] vs. 1.7 [0.6–9.9] mg/L, P < 0.001, and CAP (248 [210–302] vs. 226 [196–259] dB/m, P < 0.001. In multiple linear regression analysis, CAP was independently related to body mass index (β = 0.742, P < 0.001, triglyceride levels (β = 2.034, P < 0.001, estimated glomerular filtration rate (β = 0.316, P = 0.001, serum albumin (β = 1.386, P < 0.001, alanine aminotransferase (β = 0.064, P = 0.029, and total bilirubin (β = −0.881, P = 0.009. In multiple logistic regression analysis, increased CAP was independently associated with increased metabolic syndrome risk (per 10 dB/m increase; odds ratio, 1.093; 95% confidence interval, 1.009–1.183; P = 0.029 even after adjusting for multiple confounding factors. Conclusion: Increased CAP measured with transient elastography significantly correlated with and could predict increased metabolic syndrome risk in chronic kidney disease patients.

  18. Transcriptional profiles of multiple genes in the anterior kidney of channel catfish vaccinated with an attenuated Aeromonas hydrophila. (United States)

    Mu, Xingjiang; Pridgeon, Julia W; Klesius, Phillip H


    A total of 22 uniquely expressed sequence tags (ESTs) were identified from channel catfish anterior kidney subtractive cDNA library at 12 h post vaccination with an attenuated Aeromonas hydrophila (AL09-71 N+R). Of the 22 ESTs, six were confirmed to be significantly (P < 0.05) induced by the vaccination. Of 88 channel catfish genes selected from literature, 14 were found to be significantly (P < 0.05) upregulated by the vaccination. The transcriptional levels of the total 20 genes induced by the vaccination were then compared to that induced by the virulent parent A. hydrophila (AL09-71) at different time points. At 3 h post vaccination (hpv) or infection (hpi), Na(+)/K(+) ATPase α subunit was upregulated the most. At 6 and 12 hpv or hpi, hepcidin and interleukin-1β were induced the highest. At 24 hpv or hpi, hepcidin was upregulated the most, followed by lysozyme c. At 48 hpi, lysozyme c and hepcidin were significantly induced. When vaccinated fish were challenged by AL09-71, relative percent of survival of vaccinated fish were 100% at 14 days post vaccination (dpv). Transcriptional levels of toll-like receptor 5 and hepcidin were significantly upregulated in vaccinated fish at 14 dpv. Taken together, our results suggest that vaccination with attenuated A. hydrophila mimics infection by live bacteria, inducing multiple immune genes in channel catfish.

  19. SIRT1/3 Activation by Resveratrol Attenuates Acute Kidney Injury in a Septic Rat Model (United States)

    Xu, Siqi; Wei, Siwei; Dai, Xingui


    Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI. PMID:28003866

  20. Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria (United States)

    Mohammed-Ali, Zahraa; Lu, Chao; Marway, Mandeep K.; Carlisle, Rachel E.; Ask, Kjetil; Lukic, Dusan; Krepinsky, Joan C.; Dickhout, Jeffrey G.


    Endoplasmic reticulum (ER) stress is implicated in chronic kidney disease (CKD) development in patients and in animal models. Here we show that ER stress inhibition through 4-phenylbutyric acid (4-PBA) administration decreases blood pressure, albuminuria, and tubular casts in an angiotensin II/deoxycorticosterone acetate/salt murine model of CKD. Lower albuminuria in 4-PBA-treated mice was associated with higher levels of cubilin protein in renal tissue membrane fractions. 4-PBA decreased renal interstitial fibrosis, renal CD3+ T-cell and macrophage infiltration, mRNA expression of TGFβ1, Wnt signaling molecules, and ER stress-induced pro-inflammatory genes. CHOP deficient mice that underwent this model of CKD developed hypertension comparable to wild type mice, but had less albuminuria and tubular casts. CHOP deficiency resulted in higher nephrin levels and decreased glomerulosclerosis compared to wild type mice; this effect was accompanied by lower macrophage infiltration and fibrosis. Our findings portray ER stress inhibition as a means to alleviate hypertensive CKD by preserving glomerular barrier integrity and tubular function. These results demonstrate ER stress modulation as a novel target for preserving renal function in hypertensive CKD. PMID:28148966

  1. Olmesartan attenuates tacrolimus-induced biochemical and ultrastructural changes in rat kidney tissue. (United States)

    Al-Harbi, Naif O; Imam, Faisal; Al-Harbi, Mohammed M; Iqbal, Muzaffar; Nadeem, Ahmed; Sayed-Ahmed, Mohammed M; Alabidy, Ali D; Almukhallafi, Ali F


    Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in organ transplantation, but its use is limited due to its marked nephrotoxicity. The present study investigated the effect of olmesartan (angiotensin receptor blocker) on tacrolimus-induced nephrotoxicity in rats. A total of 24 rats were divided into four groups, which included control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. Tacrolimus significantly increased BUN and creatinine level. Treatment with olmesartan reversed tacrolimus-induced changes in the biochemical markers (BUN and creatinine) of nephrotoxicity. Tacrolimus significantly decreased GSH level and catalase activity while increasing MDA level. Olmesartan also attenuated the effects of tacrolimus on MDA, GSH, and catalase. In tacrolimus group histological examination showed marked changes in renal tubule, mitochondria, and podocyte processes. Histopathological and ultrastructural studies showed that treatment with olmesartan prevented tacrolimus-induced renal damage. These results suggest that olmesartan has protective effects on tacrolimus-induced nephrotoxicity, implying that RAS might be playing role in tacrolimus-induced nephrotoxicity.

  2. Olmesartan Attenuates Tacrolimus-Induced Biochemical and Ultrastructural Changes in Rat Kidney Tissue

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    Naif O. Al-Harbi


    Full Text Available Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in organ transplantation, but its use is limited due to its marked nephrotoxicity. The present study investigated the effect of olmesartan (angiotensin receptor blocker on tacrolimus-induced nephrotoxicity in rats. A total of 24 rats were divided into four groups, which included control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups. Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. Tacrolimus significantly increased BUN and creatinine level. Treatment with olmesartan reversed tacrolimus-induced changes in the biochemical markers (BUN and creatinine of nephrotoxicity. Tacrolimus significantly decreased GSH level and catalase activity while increasing MDA level. Olmesartan also attenuated the effects of tacrolimus on MDA, GSH, and catalase. In tacrolimus group histological examination showed marked changes in renal tubule, mitochondria, and podocyte processes. Histopathological and ultrastructural studies showed that treatment with olmesartan prevented tacrolimus-induced renal damage. These results suggest that olmesartan has protective effects on tacrolimus-induced nephrotoxicity, implying that RAS might be playing role in tacrolimus-induced nephrotoxicity.

  3. Impact of D-pinitol on the attenuation of proinflammatory cytokines, hyperglycemia-mediated oxidative stress and protection of kidney tissue ultrastructure in streptozotocin-induced diabetic rats. (United States)

    Sivakumar, Selvaraj; Palsamy, Periyasamy; Subramanian, Sorimuthu Pillai


    Oxidative stress plays a crucial role in the progression and development of diabetes and its complications due to chronic hyperglycemia. The present study was aimed to investigate the kidney tissue protective nature of d-pinitol, a cyclitol present in soybean, by assessing the key markers of hyperglycemia-mediated oxidative stress, proinflammatory cytokines and ultrastructural alterations in streptozotocin-induced diabetic rats. Oral administration of d-pinitol (50mg/kg body weight/day) for 30 days to diabetic group of rats showed a significant elevation in the level of total protein and significant decline in the levels of blood urea, serum uric acid, creatinine and advanced glycation endproducts (AGEs) and kidney proinflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, NF-kappaB p65 subunit and nitrite. Further, d-pinitol administration elicited a significant attenuation in the activities of kidney enzymatic antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) and the levels of kidney non-enzymatic antioxidants such as vitamin E, vitamin C and reduced glutathione (GSH) in the diabetic group of rats, with a concomitant decline in the levels of kidney lipid peroxides, hydroperoxides and protein carbonyls. The histological and ultrastructural observations on the kidney tissues also confirmed the renoprotective nature of d-pinitol. Thus the present study demonstrated the renoprotective nature of d-pinitol by attenuating the hyperglycemia-mediated proinflammatory cytokines and antioxidant competence in kidney tissues of streptozotocin-induced diabetic rats.

  4. Exercise attenuates renal dysfunction with preservation of myocardial function in chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Rafael da Silva Luiz

    Full Text Available Previous studies have suggested that exercise improves renal and cardiac functions in patients with chronic kidney disease. The aim of this study was to evaluate the effects of long-term aerobic swimming exercise with overload on renal and cardiac function in rats with 5/6 nefrectomy (5/6Nx. Eight Wistar rats were placed into 4 groups: Control (C, Control+Exercise (E, Sedentary 5/6Nx (NxS and 5/6Nx+Exercise (NxE. The rats were subjected to swimming exercise sessions with overload for 30 min five days per week for five weeks. Exercise reduced the effect of 5/6Nx on creatinine clearance compared to the NxS group. In addition, exercise minimized the increase in mean proteinuria compared to the NxS group (96.9±10.0 vs. 51.4±9.9 mg/24 h; p<0.05. Blood pressure was higher in the NxS and NxE groups compared to the C and E groups (216±4 and 178±3 vs. 123±2 and 124±2 mm Hg, p<0.05. In the 200 glomeruli that were evaluated, the NxS group had a higher sclerosis index than did the NxE group (16% vs. 2%, p<0.05. Echocardiography demonstrated a higher anterior wall of the left ventricle (LV in diastole in the NxS group compared with the C, E and NxE groups. The NxS group also had a higher LV posterior wall in diastole and systole compared with the E group. The developed isometric tension in Lmax of the heart papillary muscle was lower in the NxS group compared with the C, E and NxE groups. These results suggested that exercise in 5/6Nx animals might reduce the progression of renal disease and lessen the cardiovascular impact of a reduction in renal mass.

  5. Pyrroloquinoline-quinone suppresses liver fibrogenesis in mice.

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    Dongwei Jia

    Full Text Available Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injuries, and its progression toward cirrhosis is the major cause of liver-related morbidity and mortality worldwide. However, anti-fibrotic treatment remains an unconquered area for drug development. Accumulating evidence indicate that oxidative stress plays a critical role in liver fibrogenesis. In this study, we found that PQQ, a natural anti-oxidant present in a wide variety of human foods, exerted potent anti-fibrotic and ROS-scavenging activity in Balb/C mouse models of liver fibrosis. The antioxidant activity of PQQ was involved in the modulation of multiple steps during liver fibrogenesis, including chronic liver injury, hepatic inflammation, as well as activation of hepatic stellate cells and production of extracellular matrix. PQQ also suppressed the up-regulation of RACK1 in activated HSCs in vivo and in vitro. Our data suggest that PQQ suppresses oxidative stress and liver fibrogenesis in mice, and provide rationale for the clinical application of PQQ in the prevention and treatment of liver fibrosis.

  6. Redox mechanisms in hepatic chronic wound healing and fibrogenesis

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    Novo Erica


    Full Text Available Abstract Reactive oxygen species (ROS generated within cells or, more generally, in a tissue environment, may easily turn into a source of cell and tissue injury. Aerobic organisms have developed evolutionarily conserved mechanisms and strategies to carefully control the generation of ROS and other oxidative stress-related radical or non-radical reactive intermediates (that is, to maintain redox homeostasis, as well as to 'make use' of these molecules under physiological conditions as tools to modulate signal transduction, gene expression and cellular functional responses (that is, redox signalling. However, a derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, can play a significant role in the pathogenesis of major human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis. This review has been designed to first offer a critical introduction to current knowledge in the field of redox research in order to introduce readers to the complexity of redox signalling and redox homeostasis. This will include ready-to-use key information and concepts on ROS, free radicals and oxidative stress-related reactive intermediates and reactions, sources of ROS in mammalian cells and tissues, antioxidant defences, redox sensors and, more generally, the major principles of redox signalling and redox-dependent transcriptional regulation of mammalian cells. This information will serve as a basis of knowledge to introduce the role of ROS and other oxidative stress-related intermediates in contributing to essential events, such as the induction of cell death, the perpetuation of chronic inflammatory responses, fibrogenesis and much more, with a major focus on hepatic chronic wound healing and liver fibrogenesis.

  7. Eplerenone attenuates pulse wave reflection in chronic kidney disease stage 3-4--a randomized controlled study.

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    Lene Boesby

    Full Text Available BACKGROUND: Patients with chronic kidney disease (CKD have high cardiovascular mortality and morbidity associated with increased arterial stiffness. Plasma aldosterone levels are increased in CKD, and aldosterone has been found to increase vascular inflammation and fibrosis. It was hypothesized that aldosterone receptor inhibition with eplerenone could reduce arterial stiffness in CKD stage 3-4. STUDY DESIGN: The design was randomized, open, parallel group. Measurements of arterial stiffness markers were undertaken at weeks 1 and 24. INTERVENTION: 24 weeks of add-on treatment with 25-50 mg eplerenone or standard medication. OUTCOMES: Primary outcome parameter was carotid-femoral pulse wave velocity (cfPWV. Secondary outcomes were augmentation index (AIx, ambulatory arterial stiffness index (AASI and urinary albumin excretion. RESULTS: Fifty-four CKD patients (mean eGFR 36 mL/min/1.73 m(2, SD 11 were randomized. Forty-six patients completed the trial. The mean difference in cfPWV changes between groups was 0.1 m/s (95%CI: -1.0, 1.3, P = 0.8. The mean difference in AIx changes between groups was 4.4% (0.1, 8.6, P = 0.04. AASI was unchanged in both groups. The ratio of change in urinary albumin excretion in the eplerenone group compared to the control was 0.61 (0.37, 1.01, P = 0.05. Four patients were withdrawn from the eplerenone group including three because of possible side effects; one was withdrawn from the control group. Mild hyperkalemia was seen on three occasions and was easily managed. LIMITATIONS: The full planned number of patients was not attained. The duration of the trial may have been too short to obtain full effect of eplerenone on the arteries. CONCLUSIONS: Add-on treatment with eplerenone in CKD stage 3-4 did not significantly reduce cfPWV. There may be beneficial vascular effects leading to attenuated pulse wave reflection. Treatment was well-tolerated. TRIAL REGISTRATION: ClinicalTrials.govNCT01100203.

  8. Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease. (United States)

    Chintagari, Narendranath Reddy; Nguyen, Julia; Belcher, John D; Vercellotti, Gregory M; Alayash, Abdu I


    Sickle cell disease (SCD), a hereditary hemolytic disorder is characterized by chronic hemolysis, oxidative stress, vaso-occlusion and end-organ damage. Hemolysis releases toxic cell-free hemoglobin (Hb) into circulation. Under physiologic conditions, plasma Hb binds to haptoglobin (Hp) and forms Hb-Hp dimers. The dimers bind to CD163 receptors on macrophages for further internalization and degradation. However, in SCD patients plasma Hp is depleted and free Hb is cleared primarily by proximal tubules of kidneys. Excess free Hb in plasma predisposes patients to renal damage. We hypothesized that administration of exogenous Hp reduces Hb-mediated renal damage. To test this hypothesis, human renal proximal tubular cells (HK-2) were exposed to HbA (50μM heme) for 24h. HbA increased the expression of heme oxygenase-1 (HO-1), an enzyme which degrades heme, reduces heme-mediated oxidative toxicity, and confers cytoprotection. Similarly, infusion of HbA (32μM heme/kg) induced HO-1 expression in kidneys of SCD mice. Immunohistochemistry confirmed the increased HO-1 expression in the proximal tubules of the kidney. Exogenous Hp attenuated the HbA-induced HO-1 expression in vitro and in SCD mice. Our results suggest that Hb-mediated oxidative toxicity may contribute to renal damage in SCD and that Hp treatment reduces heme/iron toxicity in the kidneys following hemolysis.

  9. Tyrosine kinase inhibitor BIBF1120 ameliorates inflammation, angiogenesis and fibrosis in CCl4-induced liver fibrogenesis mouse model (United States)

    Öztürk Akcora, Büsra; Storm, Gert; Prakash, Jai; Bansal, Ruchi


    Hepatic fibrosis, a progressive chronic disease mainly caused by hepatitis viral infections, alcohol abuse or metabolic syndrome leading to liver dysfunction and is the growing cause of mortality worldwide. Tyrosine kinase inhibitor BIBF1120 (Nintedanib) has been evaluated in clinical trials for idiopathic pulmonary fibrosis and advanced Hepatocellular carcinoma, but has not been explored for liver fibrosis yet. In this study, we aimed to investigate the therapeutic effects and mechanism of BIBF1120 in liver fibrogenesis. The effects of BIBF1120 were evaluated in TGFβ-activated mouse 3T3 fibroblasts, LX2 cells, primary human hepatic stellate cells (HSCs) and CCl4-induced liver fibrogenesis mouse model. Fibroblasts-conditioned medium studies were performed to assess the paracrine effects on macrophages and endothelial cells. In-vitro in TGFβ-activated fibroblasts, BIBF1120 significantly inhibited expression of major fibrotic parameters, wound-healing and contractility. In vivo in CCl4-induced acute liver injury model, post-disease BIBF1120 administration significantly attenuated collagen accumulation and HSC activation. Interestingly, BIBF1120 drastically inhibited intrahepatic inflammation and angiogenesis. To further elucidate the mechanism of action, 3T3-conditioned medium studies demonstrated increased 3T3-mediated macrophage chemotaxis and endothelial cells tube formation and activation, which was significantly decreased by BIBF1120. These results suggests that BIBF1120 can be a potential therapeutic approach for the treatment of liver fibrosis. PMID:28291245

  10. The Effect of Rebadioside A on Attenuation of Oxidative Stress in Kidney of Mice under Acetaminophen Toxicity

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    Seyed Ali Hashemi


    Full Text Available Background: Acetaminophen (APAP overdose causes renal and hepatic injury. It is also believed that oxidative stress has a pivotal role in APAP-induced renal injury. Therefore, protective effects of different antioxidants have been examined in APAP-induced renal and hepatic toxicity models. Stevia rebadiana is a plant with a high degree of natural antioxidant activity in its leaf extract. The aim of this study was to investigate the possible protective effects of rebadioside A; one of the main components of stevia extract, on APAP-induced oxidative stress in kidney of mice. Methods: Oxidative stress was induced in kidney of BALB/c mice by the intraperitoneal (i.p. administration of a single dose of 300 mg/kg APAP. Some of these mice also received rebadioside A (700 mg/kg (i.p. 30 minutes after APAP injection. Two and six hours after APAP injection, all mice were sacrificed and malondialdehyde (MDA, glutathione (GSH, free APAP, and glutathione conjugated of APAP (APAP-GSH were determined in the kidney tissue. Results: GSH depletion and MDA levels significantly (P<0.05 increased in mice treated with either APAP or APAP plus Rebadioside A, respectively in 2 and 6 hours intervals after APAP administration. Significantly (P<0.05 higher levels of free APAP and APAP-GSH levels detected in kidney of mice administrated with APAP plus rebadioside A compared to APAP treated ones. Conclusion: Rebadioside A may be a potential compound in alleviation of APAP-induced oxidative stress in kidney of mice after APAP overdoses.

  11. Induction of Tet3-dependent Epigenetic Remodeling by Low-dose Hydralazine Attenuates Progression of Chronic Kidney Disease

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    Björn Tampe


    Retrospective analysis of patients with hypertensive nephrosclerosis revealed that circulating methylated RASAL1 promoter DNA fragments in peripheral blood decrease with Dihydralazine treatment in patients with hypertensive nephrosclerosis, and provided evidence that low-dose Dihydralazine delays decline of excretory kidney function, whereas Dihydralazine at standard doses had no protective effect. We demonstrate that the protective effect of Dihydralazine is due to induction of endogenous Tet3/Tdg-mediated DNA-de-methylation activity reversing aberrant promoter CpG island methylation, while HIF1α induction at standard doses counterbalances its protective activity. We conclude that RASAL1 promoter methylation is a therapeutic target and a biomarker of renal fibrosis. Our study suggests that therapeutic use of low-dose Dihydralazine in patients with chronic kidney disease and fibrosis deserves further consideration.

  12. Kidney Dysplasia (United States)

    ... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

  13. The Role of Lipin-1 in the Regulation of Fibrogenesis and TGF-β Signaling in Hepatic Stellate Cells. (United States)

    Jang, Chang Ho; Kim, Kyu Min; Yang, Ji Hye; Cho, Sam Seok; Kim, Seung Jung; Shin, Sang Mi; Cho, Il Je; Ki, Sung Hwan


    The adipogenic transcriptional regulation was reported to inhibit transdifferentiation of hepatic stellate cells (HSCs), which constitute the main fibrogenic cell type in the liver. Lipin-1 exhibits a dual function: an enzyme that catalyzes the conversion of phosphatidate to diacylglycerol and a transcriptional regulator. However, the involvement of Lipin-1 in the regulation of transforming growth factor-β (TGF-β) signaling and fibrogenesis in HSCs is not fully understood. Here, we showed that Lipin-1 was downregulated in activated primary HSCs and TGF-β-treated LX-2 cells, immortalized human HSC cell lines. The downregulation of Lipin-1 by TGF-β was not dependent on altered mRNA stability but rather on protein stability. Treatment of LX-2 cells with the proteasome inhibitor led to the accumulation of Lipin-1. Moreover, we observed a significant increase in Lipin-1 polyubiquitination. Overexpression of Lipin-1 attenuated TGF-β-induced fibrogenic gene expression. In addition, Lipin-1 inhibited TGF-β-mediated activation of Sma and Mad-related family (SMAD), a major transcription factor that transduces intracellular signals from TGF-β. Resveratrol, a well-known natural polyphenolic antioxidant, is known to inhibit liver fibrosis, although its mechanism of action remains unknown. Our data showed that resveratrol significantly increased the levels of Lipin-1 protein and mRNA in HSCs. Further investigation revealed that resveratrol blocked the polyubiquitination of Lipin-1. Resveratrol inhibited TGF-β-induced fibrogenic gene expression. TGF-β-induced SMAD binding element-luciferase reporter activity was significantly diminished by resveratrol with a simultaneous decrease in SMAD3 phosphorylation. Consistently, knockdown of the Lipin-1 gene using siRNA abolished the inhibitory effect of resveratrol. We conclude that Lipin-1 can antagonize HSC activation through the inhibition of TGF-β/SMAD signaling and that resveratrol may affect Lipin-1 gene induction and

  14. Phenylbutyric acid protects against carbon tetrachloride-induced hepatic fibrogenesis in mice

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    Wang, Jian-Qing [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Second Affiliated Hospital, Anhui Medical University, Hefei 230601 (China); Chen, Xi [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Cheng [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Tao, Li [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Zhi-Hui; Liu, Xiao-Qian [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Xu, Yuan-Bao [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Wang, Hua [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Li, Jun, E-mail: [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Xu, De-Xiang, E-mail: [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China)


    A recent report showed that the unfolded protein response (UPR) signaling was activated in the pathogenesis of carbon tetrachloride (CCl{sub 4})-induced hepatic fibrosis. Phenylbutyric acid (PBA) is a well-known chemical chaperone that inhibits endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling. In the present study, we investigated the effects of PBA on CCl{sub 4}-induced hepatic fibrosis in mice. All mice were intraperitoneally (i.p.) injected with CCl{sub 4} (0.15 ml/kg BW, twice per week) for 8 weeks. In CCl{sub 4} + PBA group, mice were i.p. injected with PBA (150 mg/kg, twice per day) from the beginning of CCl{sub 4} injection to the end. As expected, PBA significantly attenuated CCl{sub 4}-induced hepatic ER stress and UPR activation. Although PBA alleviated, only to a less extent, hepatic necrosis, it obviously inhibited CCl{sub 4}-induced tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β). Moreover, PBA inhibited CCl{sub 4}-induced hepatic nuclear factor kappa B (NF-κB) p65 translocation and extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK) phosphorylation. Interestingly, CCl{sub 4}-induced α-smooth muscle actin (α-SMA), a marker for the initiation phase of HSC activation, was significantly attenuated in mice pretreated with PBA. Correspondingly, CCl{sub 4}-induced hepatic collagen (Col)1α1 and Col1α2, markers for the perpetuation phase of HSC activation, were inhibited in PBA-treated mice. Importantly, CCl{sub 4}-induced hepatic fibrosis, as determined using Sirius red staining, was obviously attenuated by PBA. In conclusion, PBA prevents CCl{sub 4}-induced hepatic fibrosis through inhibiting hepatic inflammatory response and HSC activation. Highlights: ► CCl{sub 4} induces hepatic ER stress, inflammation, HSC activation and hepatic fibrosis. ► PBA alleviates CCl{sub 4}-induced hepatic ER stress and UPR signaling activation. ► PBA inhibits CCl{sub 4}-induced

  15. Ectopic Kidney (United States)

    ... Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Ectopic Kidney What is an ectopic kidney? An ectopic kidney is a birth defect in ... has an ectopic kidney. 1 What are the kidneys and what do they do? The kidneys are ...

  16. Attenuation of PTEN increases p21 stability and cytosolic localization in kidney cancer cells: a potential mechanism of apoptosis resistance

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    Baksh Shairaz


    Full Text Available Abstract Background The PTEN (Phosphatase and Tensin homolog deleted on chromosome Ten tumor suppressor gene is frequently mutated or deleted in a wide variety of solid tumors, and these cancers are generally more aggressive and difficult to treat than those possessing wild type PTEN. While PTEN lies upstream of the phosphoinositide-3 kinase signaling pathway, the mechanisms that mediate its effects on tumor survival remain incompletely understood. Renal cell carcinoma (RCC is associated with frequent treatment failures (~90% in metastatic cases, and these tumors frequently contain PTEN abnormalities. Results Using the ACHN cell line containing wild type PTEN, we generated a stable PTEN knockdown RCC cell line using RNA interference. We then used this PTEN knockdown cell line to show that PTEN attenuation increases resistance to cisplatin-induced apoptosis, a finding associated with increased levels of the cyclin kinase inhibitor p21. Elevated levels of p21 result from stabilization of the protein, and they are dependent on the activities of phosphoinositide-3 kinase and Akt. More specifically, the accumulation of p21 occurs preferentially in the cytosolic compartment, which likely contributes to both cell cycle progression and resistance to apoptosis. Conclusion Since p21 regulates a decision point between repair and apoptosis after DNA damage, our data suggest that p21 plays a key role in mechanisms used by PTEN-deficient tumors to escape chemotherapy. This in turn raises the possibility to use p21 attenuators as chemotherapy sensitizers, an area under active continuing investigation in our laboratories.

  17. Endoglin in liver fibrogenesis: Bridging basic science and clinical practice

    Institute of Scientific and Technical Information of China (English)

    Steffen; K; Meurer; Muhammad; Alsamman; David; Scholten; Ralf; Weiskirchen


    Endoglin, also known as cluster of differentiation CD105, was originally identified 25 years ago as a novel marker of endothelial cells. Later it was shown that endoglin is also expressed in pro-fibrogenic cells including mesangial cells, cardiac and scleroderma fibroblasts, and hepatic stellate cells. It is an integral membranebound disulfide-linked 180 kDa homodimeric receptor that acts as a transforming growth factor-β(TGF-β) auxiliary co-receptor. In humans, several hundreds of mutations of the endoglin gene are known that give rise to an autosomal dominant bleeding disorder that is characterized by localized angiodysplasia and arteriovenous malformation. This disease is termed hereditary hemorrhagic telangiectasia type Ⅰ and induces various vascular lesions, mainly on the face, lips, hands and gastrointestinal mucosa. Two variants of endoglin(i.e., S- and L-endoglin) are formed by alternative splicing that distinguishes from each other in the length of their cytoplasmic tails. Moreover, a soluble form of endoglin, i.e.,sol-Eng, is shedded by the matrix metalloprotease-14 that cleaves within the extracellular juxtamembrane region. Endoglin interacts with the TGF-β signaling receptors and influences Smad-dependent and-independent effects. Recent work has demonstrated that endoglin is a crucial mediator during liver fibrogenesis that critically controls the activity of the different Smad branches. In the present review, we summarize the present knowledge of endoglin expression and function, its involvement in fibrogenic Smad signaling, current models to investigate endoglin function, and the diagnostic value of endoglin in liver disease.

  18. Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity. (United States)

    Matsui, Katsuomi; Kamijo-Ikemorif, Atsuko; Sugaya, Takeshi; Yasuda, Takashi; Kimura, Kenjiro


    Injection of aristolochic acid (AA) in mice causes AA-induced nephrotoxicity, in which oxidative stress contributes to development of tubulointerstitial damage (TID). Liver-type fatty acid binding protein (L-FABP) is expressed in human proximal tubules and has an endogenous antioxidative function. The renoprotection of renal L-FABP was examined in a model of AA-induced nephrotoxicity. Established human L-FABP (hL-FABP) transgenic (Tg) mice and wild-type (WT) mice were treated with AA for up to 5 days. Mice were sacrificed on days 1, 3, and 5 after the start of AA injection. Although mouse L-FABP was not expressed in proximal tubules of WT mice, hL-FABP was expressed in proximal tubules of Tg mice. The expression of renal hL-FABP was significantly increased in Tg mice administered AA (Tg-AA), compared with the control (saline-treated Tg mice). In WT-AA mice, there was high urinary excretion of N(ε)-(hexanoyl)-lysine, the production of heme oxygenase-1 and receptor for advanced glycation end products increased, and TID was provoked. In contrast, renal hL-FABP in Tg-AA mice suppressed production of N(ε)-(hexanoyl)lysine, heme oxygenase-1, and receptor for advanced glycation end products. Renal dysfunction was significantly milder in Tg-AA mice than in WT-AA mice. The degree of TID was significantly attenuated in Tg-AA mice, compared with WT-AA. In conclusion, renal hL-FABP reduced the oxidative stress in AA-induced nephrotoxicity and attenuated TID.

  19. Dopamine treatment attenuates acute kidney injury in a rat model of deep hypothermia and rewarming - The role of renal H2S-producing enzymes. (United States)

    Dugbartey, George J; Talaei, Fatemeh; Houwertjes, Martin C; Goris, Maaike; Epema, Anne H; Bouma, Hjalmar R; Henning, Robert H


    Hypothermia and rewarming produces organ injury through the production of reactive oxygen species. We previously found that dopamine prevents hypothermia and rewarming-induced apoptosis in cultured cells through increased expression of the H2S-producing enzyme cystathionine β-Synthase (CBS). Here, we investigate whether dopamine protects the kidney in deep body cooling and explore the role of H2S-producing enzymes in an in vivo rat model of deep hypothermia and rewarming. In anesthetized Wistar rats, body temperature was decreased to 15°C for 3h, followed by rewarming for 1h. Rats (n≥5 per group) were treated throughout the procedure with vehicle or dopamine infusion, and in the presence or absence of a non-specific inhibitor of H2S-producing enzymes, amino-oxyacetic acid (AOAA). Kidney damage and renal expression of three H2S-producing enzymes (CBS, CSE and 3-MST) was quantified and serum H2S level measured. Hypothermia and rewarming induced renal damage, evidenced by increased serum creatinine, renal reactive oxygen species production, KIM-1 expression and influx of immune cells, which was accompanied by substantially lowered renal expression of CBS, CSE, and 3-MST and lowered serum H2S levels. Infusion of dopamine fully attenuated renal damage and maintained expression of H2S-producing enzymes, while normalizing serum H2S. AOAA further decreased the expression of H2S-producing enzymes and serum H2S level, and aggravated renal damage. Hence, dopamine preserves renal integrity during deep hypothermia and rewarming likely by maintaining the expression of renal H2S-producing enzymes and serum H2S.

  20. Peptidyl arginine deiminase inhibitor effect on hepatic fibrogenesis in a CCl4 pre-clinical model of liver fibrosis

    DEFF Research Database (Denmark)

    Vassiliadis, E.; Veidal, Sanne Skovgård; Kristiansen, M. N.


    Having previously shown that levels of the citrullinated vimentin peptide VICM are raised in liver fibrosis in rats, we aimed to investigate whether inhibition of citrullination as measured by VICM levels could affect fibrogenesis. METHODS: Fibrogenesis was evaluated by quantitative histology and...

  1. Determination of representative renal depth for accurate attenuation corred in measurement of glomerular filtration rate in transplanted kidney

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    Oh, Soon Nam; Kim, Sung Hoon; Rha, Sung Eun; Chung, Yong An; Yoo, Ie Ryung; Sohn, Hyung Sun; Lee, Sung Young; Chung, Soo Kyo [The Catholic Univ. of Korea, Seoul (Korea, Republic of)


    To measure reliable glomerular filtration rate by using the representative values of transplanted renal depths, which are measured with ultrasonography. We included 54 patients (26 men, 28 women), with having both renal scintigraphy and ultrasonography after renal transplantation. We measured DFR with Gates' method using the renal depth measured by ultrasonography, and median and mean ones in each patient. We compared GFR derived from ultrasonography-measured renal depth with GFR derived from median and mean renal depths. The correlation coefficients were obtained among GFR derived from ultrasonography-measured renal depths, median and mean renal depth under linear regression analysis. We determined whether GFR derived from median or mean renal depth could substitute GFR derived from ultrasonography-measured renal depth with Bland-Altman method. We analyze the expected errors of the GFR using representative renal depth in terms of age, sex, weight, height, creatinine value, and body surface. The transplanted renal depths range from 3.20 cm to 5.96 cm. The mean value and standard deviation of renal depths measured by ultrasonography are 4.09{+-}0.65 cm in men, and 4.24{+-}0.78 cm in women. The median value of renal depths measured by ultrasonography is 4.36 cm in men and 4.14 cm in women. The GFR derived from median renal depth is more consistent with GFR derived from ultrasonography-measured renal depth than GFR derived from mean renal depth. Differences of GFR derived from median and ultrasonography-measured renal depth are not significantly different in the groups classified with creatinine value, age, sex, height, weight and body surface. When median value is adapted as a representative renal depth, we could obtain reliable GFR in transplanted kidney simply.

  2. Paraquat induces epithelial-mesenchymal transition-like cellular response resulting in fibrogenesis and the prevention of apoptosis in human pulmonary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Atsushi Yamada

    Full Text Available The aim of this study is to investigate the molecular mechanisms underlying delayed progressive pulmonary fibrosis, a characteristic of subacute paraquat (PQ poisoning. Epithelial-mesenchymal transition (EMT has been proposed as a cause of organ fibrosis, and transforming growth factor-β (TGF-β is suggested to be a powerful mediator of EMT. We thus examined the possibility that EMT is involved in pulmonary fibrosis during PQ poisoning using A549 human alveolar epithelial cells in vitro. The cells were treated with various concentrations of PQ (0-500 μM for 2-12 days. Short-term (2 days high-dose (>100 μM treatments with PQ induced cell death accompanied by the activation of caspase9 as well as a decrease in E-cadherin (an epithelial cell marker, suggesting apoptotic cell death with the features of anoikis (cell death due to the loss of cell-cell adhesion. In contrast, long-term (6-12 days low-dose (30 μM treatments with PQ resulted in a transformation into spindle-shaped mesenchymal-like cells with a decrease of E-cadherin as well as an increase of α-smooth muscle actin (α-SMA. The mesenchymal-like cells also secreted the extracellular matrix (ECM protein fibronectin into the culture medium. The administration of a TGF-β1 receptor antagonist, SB431542, almost completely attenuated the mesenchymal transformation as well as fibronectin secretion, suggesting a crucial role of TGF-β1 in EMT-like cellular response and subsequent fibrogenesis. It is noteworthy that despite the suppression of EMT-fibrogenesis, apoptotic death was observed in cells treated with PQ+SB431542. EMT-like cellular response and subsequent fibrogenesis were also observed in normal human bronchial epithelial (NHBE cells exposed to PQ in a TGF-β1-dependent manner. Taken together, our experimental model reflects well the etiology of PQ poisoning in human and shows the involvement of EMT-like cellular response in both fibrogenesis and resistance to cell death during

  3. Exposure of precision-cut rat liver slices to ethanol accelerates fibrogenesis

    NARCIS (Netherlands)

    Schaffert, Courtney S.; Duryee, Michael J.; Bennett, Robert G.; DeVeney, Amy L.; Tuma, Dean J.; Olinga, Peter; Easterling, Karen C.; Thiele, Geoffrey M.; Klassen, Lynell W.


    Schaffert CS, Duryee MJ, Bennett RG, DeVeney AL, Tuma DJ, Olinga P, Easterling KC, Thiele GM, Klassen LW. Exposure of precision-cut rat liver slices to ethanol accelerates fibrogenesis. Am J Physiol Gastrointest Liver Physiol 299: G661-G668, 2010. First published July 1, 2010; doi: 10.1152/ajpgi.002

  4. Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Van Beneden, Katrien, E-mail: [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Geers, Caroline [Department of Pathology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Pauwels, Marina [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Mannaerts, Inge [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Wissing, Karl M. [Department of Nephrology, Universitair Ziekenhuis Brussel, Brussels (Belgium); Van den Branden, Christiane [Department of Human Anatomy, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium); Grunsven, Leo A. van, E-mail: [Department of Cell Biology, Liver Cell Biology Lab, Vrije Universiteit Brussel, Brussels (Belgium)


    Histone deacetylase (HDAC) inhibitors are promising new compounds for the therapy of fibrotic diseases. In this study we compared the effect of two HDAC inhibitors, trichostatin A and valproic acid, in an experimental model of kidney fibrosis. In mice, doxorubicin (adriamycin) can cause nephropathy characterized by chronic proteinuria, glomerular damage and interstitial inflammation and fibrosis, as seen in human focal segmental glomerulosclerosis. Two treatment regimens were applied, treatment was either started prior to the doxorubicin insult or delayed until a significant degree of proteinuria and fibrosis was present. Pre-treatment of trichostatin A significantly hampered glomerulosclerosis and tubulointerstitial fibrosis, as did the pre-treatment with valproic acid. In contrast, the development of proteinuria was only completely inhibited in the pre-treated valproic acid group, and not in the pre-treated trichostatin A animals. In the postponed treatment with valproic acid, a complete resolution of established doxorubicin-induced proteinuria was achieved within three days, whereas trichostatin A could not correct proteinuria in such a treatment regimen. However, both postponed regimens have comparable efficacy in maintaining the kidney fibrosis to the level reached at the start of the treatments. Moreover, not only the process of fibrosis, but also renal inflammation was attenuated by both HDAC inhibitors. Our data confirm a role for HDACs in renal fibrogenesis and point towards a therapeutic potential for HDAC inhibitors. The effect on renal disease progression and manifestation can however be different for individual HDAC inhibitors. - Highlights: • Valproic acid is a potent antiproteinuric drug, whereas trichostatin A is not. • Trichostatin A and valproic acid reduce kidney fibrosis in doxorubicin nephropathy. • Both valproic acid and trichostatin A attenuate renal inflammation.

  5. CCN1 expression in interleukin-6 deficient mouse kidney in experimental model of heart failure. (United States)

    Bonda, Tomasz Andrzej; Taranta, Andrzej; Kaminski, Karol Adam; Dziemidowicz, Magdalena; Litvinovich, Sergey; Kozuch, Marcin; Bialuk, Izabela; Chyczewski, Lech; Winnicka, Maria Malgorzata


    Chronic heart failure often leads to worsening of the renal function. Mediators of this process include inflammatory and neuroendocrine factors. CCN1 (Cyr 61), a member of growth factor-inducible immediate early genes, which modulates inflammation and fibrogenesis, is excreted with urine in the early phase of acute renal injury and may be involved in the pathogenesis of the cardiorenal syndrome. The aim of the study was to evaluate CCN1 protein abundance and localization in the kidney of IL-6-deficient C57BL/6J (IL-6 KO) mice and respective wild-type (WT) animals in basal conditions and in animals with chronic heart failure twelve weeks after myocardial infarction. Age- and sex-matched mice from both strains subjected to sham operation served as controls. One group of WT animals subjected to myocardial infarction was treated with antagonist of AT1 receptor telmisartan over 12 weeks. Abundance and localization of CCN1 protein in kidney were assessed with Western blotting and immunohistochemistry, respectively. In all groups the strongest immunohistochemical reaction for CCN1 was observed in distal convoluted tubules and in smaller arteries, however, the total expression of CCN1 protein was lower in IL-6 KO mice in comparison to WT animals. The main difference in CCN1 distribution between the examined genotypes was lack of reaction in internal renal medulla and very weak reaction in proximal convoluted tubules in IL-6 KO mice. Experimental heart failure only slightly attenuated the expression of CCN1 protein in the kidney of WT mice and had no effect in IL-6 KO mice. Although, blockade of AT1 receptor did not alter CCN1 protein expression in kidneys of WT mice after myocardial infarction, it significantly changed its CCN1 distribution in the renal tubular system.

  6. Hypoxia,angiogenesis and liver fibrogenesis in the progression of chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Claudia; Paternostro; Ezio; David; Erica; Novo; Maurizio; Parola


    Angiogenesis is a dynamic,hypoxia-stimulated and growth factor-dependent process,and is currently referred to as the formation of new vessels from preexisting blood vessels.Experimental and clinical studies have unequivocally reported that hepatic angiogenesis,irrespective of aetiology,occurs in conditions of chronic liver diseases(CLDs) characterized by perpetuation of cell injury and death,inflammatory response and progressive fibrogenesis.Angiogenesis and related changes in liver vascular architecture,th...

  7. Your Kidneys (United States)

    ... Room? What Happens in the Operating Room? Your Kidneys KidsHealth > For Kids > Your Kidneys A A A ... and it will be lighter. What Else Do Kidneys Do? Kidneys are always busy. Besides filtering the ...

  8. Kidney Cysts (United States)

    ... fluid-filled sac. There are two types of kidney cysts. Polycystic kidney disease (PKD) runs in families. In PKD, the ... place of the normal tissue. They enlarge the kidneys and make them work poorly, leading to kidney ...

  9. Flax lignan concentrate attenuate hypertension and abnormal left ventricular contractility via modulation of endogenous biomarkers in two-kidney-one-clip (2K1C hypertensive rats

    Directory of Open Access Journals (Sweden)

    Sameer Hanmantrao Sawant

    Full Text Available ABSTRACT The present investigation was designed to study the effect of flax lignan concentrate obtained from Linum usitatissimum L., Linaceae, in two-kidney, one clip (2K1C hypertension model in Wistar rats. 2K1C Goldblatt model rats were divided randomly into six groups: sham, 2K1C control, captopril (30 mg/kg, flax lignan concentrate (200, 400 and 800 mg/kg. Flax lignan concentrate and captopril were administered daily for eight consecutive weeks. Sham-operated, and 2K1C control rats received the vehicle. Treatment with flax lignan concentrate (400 and 800 mg/kg significantly and dose-dependently restored the hemodynamic parameters systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and left ventricular functions. The flax lignan concentrate significantly restored the elevated hepatic, renal and cardiac marker enzymes in the serum. It also restored the organs weights (kidney and heart, serum electrolyte level and histological abnormalities. Furthermore, flax lignan concentrate significantly elevated the level of biochemical markers that is enzymatic antioxidants superoxide dismutase, glutathione and decreased malondialdehyde in the heart and kidney tissues. Meanwhile, we found that plasma nitric oxide and plasma nitric oxide synthase contents were significantly increased in the flax lignan concentrate-treated group, and plasma endothelin-1 and renal angiotensin-II levels were significantly lower than 2K1C hypertensive group. In conclusion, the antihypertensive and antioxidant effect of flax lignan concentrate were dose-dependent and at the highest dose (i.e. 800 mg/kg similar to those of captopril (30 mg/kg. It is suggested that flax lignan concentrate reduced blood pressure by reduction of renal angiotensin-II level, inhibition of plasma endothelin-1 production, induction of the nitric oxide, nitric oxide synthase and in vivo antioxidant defense system.

  10. Knockout of Na-glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus


    Vallon, Volker; Rose, Michael; Gerasimova, Maria; Satriano, Joseph; Platt, Kenneth A.; Koepsell, Hermann; Cunard, Robyn; Sharma, Kumar; Thomson, Scott C.; Rieg, Timo


    The Na-glucose cotransporter SGLT2 mediates high-capacity glucose uptake in the early proximal tubule and SGLT2 inhibitors are developed as new antidiabetic drugs. We used gene-targeted Sglt2 knockout (Sglt2−/−) mice to elucidate the contribution of SGLT2 to blood glucose control, glomerular hyperfiltration, kidney growth, and markers of renal growth and injury at 5 wk and 4.5 mo after induction of low-dose streptozotocin (STZ) diabetes. The absence of SGLT2 did not affect renal mRNA expressi...

  11. Kidney Disease (United States)

    ... version of this page please turn Javascript on. Kidney Disease What is Kidney Disease? What the Kidneys Do Click for more information You have two ... damaged, wastes can build up in the body. Kidney Function and Aging Kidney function may be reduced ...

  12. Kidney Diseases (United States)

    ... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...

  13. Kidney Infection (United States)

    ... X-ray called a voiding cystourethrogram. Antibiotics for kidney infections Antibiotics are the first line of treatment ... the infection is completely eliminated. Hospitalization for severe kidney infections For a severe kidney infection, your doctor ...

  14. Kidney School (United States)

    ... copies? Read our licensing agreement Living Successfully with Kidney Disease People with kidney disease can live long ... Listen Printing multiple copies? Read our licensing agreement Kidneys: How They Work, How They Fail, What You ...

  15. Kidney Problems (United States)

    ... our e-newsletter! Aging & Health A to Z Kidney Problems Basic Facts & Information The kidneys are two ... the production of red blood cells. What are Kidney Diseases? For about one-third of older people, ...

  16. Attenuation of lead-induced oxidative stress in rat brain, liver, kidney and blood of male Wistar rats by Moringa oleifera seed powder. (United States)

    Velaga, Manoj Kumar; Daughtry, Lucius K; Jones, Angelica C; Yallapragada, Prabhakara Rao; Rajanna, Sharada; Rajanna, Bettaiya


    Moringa oleifera is a tree belonging to Moringaceae family and its leaves and seeds are reported to have ameliorative effects against metal toxicity. In the present investigation, M. oleifera seed powder was tested against lead-induced oxidative stress and compared against meso-2, 3-dimercaptosuccinic acid (DMSA) treatment. Male Wistar rats (100-120 g) were divided into four groups: control (2000 ppm of sodium acetate for 2 weeks), exposed (2000 ppm of lead acetate for 2 weeks), Moringa treated (500 mg/kg for 7 days after lead exposure), and DMSA treated (90 mg/kg for 7 days after lead exposure). After exposure and treatment periods, rats were sacrificed and the brain was separated into cerebellum, hippocampus, frontal cortex, and brain stem; liver, kidney, and blood were also collected. The data indicated a significant (poleifera restored all the parameters back to control, tissue-specifically, and also showed improvement in restoration better than DMSA treatment, indicating reduction of the negative effects of lead-induced oxidative stress.

  17. Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

    DEFF Research Database (Denmark)

    Veidal, Sanne S; Vassiliadis, Efstathios; Barascuk, Natasha


    During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via their acti......During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via...... their activity in the proteolytic degradation of extracellular macromolecules such as collagens, resulting in the generation of specific cleavage fragments. These neo-epitopes may be used as markers of fibrosis....

  18. Solitary Kidney (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  19. Pharmacological blockage of fibro/adipogenic progenitor expansion and suppression of regenerative fibrogenesis is associated with impaired skeletal muscle regeneration

    Directory of Open Access Journals (Sweden)

    Daniela Fiore


    Full Text Available Acute skeletal muscle injury triggers an expansion of fibro/adipogenic progenitors (FAPs and a transient stage of fibrogenesis characterized by extracellular matrix deposition. While the perpetuation of such phase can lead to permanent tissue scarring, the consequences of its suppression remain to be studied. Using a model of acute muscle damage we were able to determine that pharmacological inhibition of FAP expansion by Nilotinib, a tyrosine kinase inhibitor with potent antifibrotic activity, exerts a detrimental effect on myogenesis during regeneration. We found that Nilotinib inhibits the damage-induced expansion of satellite cells in vivo, but it does not affect in vitro proliferation, suggesting a non cell-autonomous effect. Nilotinib impairs regenerative fibrogenesis by preventing the injury-triggered expansion and differentiation of resident CD45−:CD31−:α7integrin−:Sca1+ mesenchymal FAPs. Our data support the notion that the expansion of FAPs and transient fibrogenesis observed during regeneration play an important trophic role toward tissue-specific stem cells.

  20. Electroacupuncture attenuates liver and kidney oxidative stress in anesthetized rats Eletroacupuntura atenua o estresse oxidativo no fígado e no rim em ratos anestesiados

    Directory of Open Access Journals (Sweden)

    Agamenon Honório Silva


    Full Text Available PURPOSE: Investigate the effects of a single electroacupuncture (EA session at acupoints Zusanli (ST-36 and Zhongwan (CV-12 combined in regulating oxidative stress in liver and kidney in anesthetized rats. METHODS: Eighteen healthy rats randomly assigned to 3 groups (n=6 were anesthetized intraperitoneally with ketamine (90mg kg-1 body weight + xylazine (10mg/kg body weight: G-1: Control (anesthesia, G-2: anesthesia+EA10Hz and 10 mA, 10 Hz applied to right ST-36 and CV-12 acupoints for 30 minutes. G-3 was likewise treated, using a tenfold higher frequency (100 Hz. G6PDH activity, malondialdehyde (MDA and glutathione (GSH levels were assayed spectrophotometrically. RESULTS: Liver MDA and GSH concentrations increased significantly in rats submitted to EA 10Hz (pOBJETIVO: Investigar os efeitos de uma única sessão de eletroacupuntura (EA aplicada nos acupontos Zusanli (E-36 e Zhongwan (RM-12 simultaneamente, na regulação do estresse oxidativo no fígado e rins em ratos anestesiados. MÉTODOS: Dezoito ratos sadios, distribuídos aleatoriamente em três grupos (n = 6, foram anestesiados com cetamina (90mg/kg de peso + xilazina (10mg/kg de peso: G-1: Controle (anestesia, G-2: anestesia + EA10Hz e G-3: anestesia + EA100Hz. Os ratos do grupo G-2 foram submetidos à EA (ondas quadradas pulsadas, 10 mA, 10 Hz aplicada aos acupontos ST-36 direito e VC-12 por 30 minutos. Nos ratos do grupo G-3 utilizou-se uma freqüência dez vezes maior (100 Hz. A atividade da enzima G6PDH e as concentrações de malondialdeído (MDA e glutationa (GSH foram verificadas por espectrofotometria. RESULTADOS: As concentrações hepáticas de MDA e GSH aumentaram significativamente nos ratos submetidos à EA, utilizando 10Hz (p <0,01 e 100Hz (p <0,001, comparado com o controle. A atividade de G6GPH diminuiu significativamente no G-2 (p <0,01 e G-3 (p <0,001 no fígado e no rim em comparação ao grupo G-1 em ratos tratados com 100Hz. CONCLUSÃO: Uma única sessão de EA 10

  1. Hepatic stellate cell-expressed endosialin balances fibrogenesis and hepatocyte proliferation during liver damage (United States)

    Mogler, Carolin; Wieland, Matthias; König, Courtney; Hu, Junhao; Runge, Anja; Korn, Claudia; Besemfelder, Eva; Breitkopf-Heinlein, Katja; Komljenovic, Dorde; Dooley, Steven; Schirmacher, Peter; Longerich, Thomas; Augustin, Hellmut G


    Liver fibrosis is a reversible wound-healing response to injury reflecting the critical balance between liver repair and scar formation. Chronic damage leads to progressive substitution of liver parenchyma by scar tissue and ultimately results in liver cirrhosis. Stromal cells (hepatic stellate cells [HSC] and endothelial cells) have been proposed to control the balance between liver fibrosis and regeneration. Here, we show that endosialin, a C-type lectin, expressed in the liver exclusively by HSC and portal fibroblasts, is upregulated in liver fibrosis in mouse and man. Chronic chemically induced liver damage resulted in reduced fibrosis and enhanced hepatocyte proliferation in endosialin-deficient (ENKO) mice. Correspondingly, acute-liver-damage-induced hepatocyte proliferation (partial hepatectomy) was increased in ENKO mice. A candidate-based screen of known regulators of hepatocyte proliferation identified insulin-like growth factor 2 (IGF2) as selectively endosialin-dependent hepatocyte mitogen. Collectively, the study establishes a critical role of HSC in the reciprocal regulation of fibrogenesis vs. hepatocyte proliferation and identifies endosialin as a therapeutic target in non-neoplastic settings. PMID:25680861

  2. Eisenia fetida Protease-III-1 Functions in Both Fibrinolysis and Fibrogenesis

    Directory of Open Access Journals (Sweden)

    Jing Zhao


    Full Text Available The fibrinolytic function of earthworm protease-III-1 (EfP-III-1 has been studied in recent years. Here, we found that EfP-III-1 acted not only in fibrinogenolysis, but also in fibrogenesis. We have used EfP-III-1 to hydrolyze fibrinogen, and to activate plasminogen and prothrombin. Based on the N-terminal sequences of the hydrolytic fragments, EfP-III-1 was showed to specifically recognize the carboxylic sites of arginine and lysine. Analyses by fibrinogenolysis mapping and amino acid sequencing revealed that the isozyme could cleave the alpha, beta, and gamma chains of fibrinogen, showing a high α-fibrinogenase, moderate β-fibrinogenase, and low γ-fibrinogenase activities. Interestingly, EfP-III-1 activated plasminogen and released active plasmin, suggesting a tPA-like function. Furthermore, EfP-III-1 showed a factor Xa-like function on prothrombin, producing alpha-thrombin. The function in both activating prothrombin and catalyzing fibrinogenolysis suggests that EfP-III-1 may play a role in the balance between procoagulation and anticoagulation.

  3. Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium (United States)

    Barron, Melissa L; Rybchyn, Mark S; Ramesh, Sutharshani; Mason, Rebecca S; Fiona Bonar, S; Stalley, Paul; Khosla, Sundeep; Hudson, Bernie; Arthur, Christopher; Kim, Edward; Clifton-Bligh, Roderick J; Clifton-Bligh, Phillip B


    Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA (mRNA) for G-protein-coupled receptor 128 (GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient’s osteoblasts in culture. When normal osteoblasts were cultured with the patient’s serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function. PMID:28326223

  4. Injury - kidney and ureter (United States)

    Kidney damage; Toxic injury of the kidney; Kidney injury; Traumatic injury of the kidney; Fractured kidney; Inflammatory injury of the kidney; Bruised kidney; Ureteral injury; Pre-renal failure - injury, ...

  5. Kidney Failure (United States)

    Healthy kidneys clean your blood by removing excess fluid, minerals, and wastes. They also make hormones that keep your ... strong and your blood healthy. But if the kidneys are damaged, they don't work properly. Harmful ...

  6. Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria. (United States)

    Ortiz-Avila, Omar; Sámano-García, Carlos Alberto; Calderón-Cortés, Elizabeth; Pérez-Hernández, Ismael H; Mejía-Zepeda, Ricardo; Rodríguez-Orozco, Alain R; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian


    Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

  7. Molecular Mechanism Responsible for Fibronectin-controlled Alterations in Matrix Stiffness in Advanced Chronic Liver Fibrogenesis. (United States)

    Iwasaki, Ayumi; Sakai, Keiko; Moriya, Kei; Sasaki, Takako; Keene, Douglas R; Akhtar, Riaz; Miyazono, Takayoshi; Yasumura, Satoshi; Watanabe, Masatoshi; Morishita, Shin; Sakai, Takao


    Fibrosis is characterized by extracellular matrix (ECM) remodeling and stiffening. However, the functional contribution of tissue stiffening to noncancer pathogenesis remains largely unknown. Fibronectin (Fn) is an ECM glycoprotein substantially expressed during tissue repair. Here we show in advanced chronic liver fibrogenesis using a mouse model lacking Fn that, unexpectedly, Fn-null livers lead to more extensive liver cirrhosis, which is accompanied by increased liver matrix stiffness and deteriorated hepatic functions. Furthermore, Fn-null livers exhibit more myofibroblast phenotypes and accumulate highly disorganized/diffuse collagenous ECM networks composed of thinner and significantly increased number of collagen fibrils during advanced chronic liver damage. Mechanistically, mutant livers show elevated local TGF-β activity and lysyl oxidase expressions. A significant amount of active lysyl oxidase is released in Fn-null hepatic stellate cells in response to TGF-β1 through canonical and noncanonical Smad such as PI3 kinase-mediated pathways. TGF-β1-induced collagen fibril stiffness in Fn-null hepatic stellate cells is significantly higher compared with wild-type cells. Inhibition of lysyl oxidase significantly reduces collagen fibril stiffness, and treatment of Fn recovers collagen fibril stiffness to wild-type levels. Thus, our findings indicate an indispensable role for Fn in chronic liver fibrosis/cirrhosis in negatively regulating TGF-β bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions. Furthermore, this regulatory mechanism by Fn could be translated for a potential therapeutic target in a broader variety of chronic fibrotic diseases.

  8. HCV core protein promotes liver fibrogenesis via up-regulation of CTGF with TGF-beta1. (United States)

    Shin, Ju Yeop; Hur, Wonhee; Wang, Jin Sang; Jang, Jeong Won; Kim, Chang Wook; Bae, Si Hyun; Jang, Sung Key; Yang, Se-Hwan; Sung, Young Chul; Kwon, Oh-Joo; Yoon, Seung Kew


    Liver cirrhosis is one of the major complications of hepatitis C virus (HCV) infection, but the mechanisms underlying HCV-related fibrogenesis are still not clear. Although the roles of HCV core protein remain poorly understood, it is supposed to play an important role in the regulation of cellular growth and hepatocarcinogenesis. The aim of this study was to examine the role of HCV core protein on the hepatic fibrogenesis. We established an in vitro co-culture system with primary hepatic stellate cell (HSC) isolated from rats, and a stable HepG2-HCV core cell line which had been transfected with HCV core gene. The expressions of fibrosis-related molecules transforming growth factor beta1 (TGF-beta1), transforming growth factor beta receptor II (TGFbetaRII), alpha-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were analyzed via histological or molecular methods. In addition, the expression levels of matrix metaloprotinase-2 (MMP-2) and collagen type I (Col I) from the co-cultured media were measured by zymogram and ELISA, respectively. The expressions of alpha-SMA, TGF-beta1, Col I, TGFbetaRII and MMP-2 were significantly increased in the co-culture of stable HepG2-HCV core with HSC. Moreover, the significant increases of CTGF and TGF-beta1 in the HCV core-expressing cells were observed by either Northern or Western blot analysis. These results suggest that HCV core protein may contribute to the hepatic fibrogenesis via up-regulation of CTGF and TGF-beta1.

  9. Medullary Sponge Kidney (United States)

    ... Sponge Kidney? Complications of medullary sponge kidney include hematuria, or blood in the urine kidney stones urinary ... both kidneys. Complications of medullary sponge kidney include hematuria, or blood in the urine kidney stones urinary ...

  10. Kidney Cancer (United States)

    You have two kidneys. They are fist-sized organs on either side of your backbone above your waist. The tubes inside filter and ... blood, taking out waste products and making urine. Kidney cancer forms in the lining of tiny tubes ...

  11. Chronic Kidney Disease and Kidney Failure (United States)

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  12. Kidney (Renal) Failure (United States)

    ... How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain proper fluid ... marrow and strengthen the bones. The term kidney (renal) failure describes a situation in which the kidneys have ...

  13. Chronic Kidney Diseases (United States)

    ... Room? What Happens in the Operating Room? Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  14. Chronic kidney disease and fibrosis: the role of uremic retention solutes

    Directory of Open Access Journals (Sweden)

    Henricus A.M. Mutsaers


    Full Text Available Chronic kidney disease (CKD is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues. Fibrosis is characterized by excessive production and deposition of extracellular matrix proteins with a detrimental impact on organ function. Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney. Several of these uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate, have been suggested to be CKD-specific triggers for the development and perpetuation of fibrosis. The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney.

  15. Kidney Disease (Nephropathy) (United States)

    ... Text Size: A A A Listen En Español Kidney Disease (Nephropathy) Kidneys are remarkable organs. Inside them ... resulting in kidney disease. How Does Diabetes Cause Kidney Disease? When our bodies digest the protein we ...

  16. Polycystic kidney disease (United States)

    Cysts - kidneys; Kidney - polycystic; Autosomal dominant polycystic kidney disease; ADPKD ... Polycystic kidney disease (PKD) is passed down through families (inherited). The 2 inherited forms of PKD are autosomal dominant ...

  17. Kidney Disease Basics (United States)

    ... Links Take the first step Alternate Language URL Kidney Disease Basics Page Content Your kidneys filter extra ... blood pressure are the most common causes of kidney disease. ​These conditions can slowly damage the kidneys ...

  18. Micro-RNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis. (United States)

    Dattaroy, Diptadip; Pourhoseini, Sahar; Das, Suvarthi; Alhasson, Firas; Seth, Ratanesh Kumar; Nagarkatti, Mitzi; Michelotti, Gregory A; Diehl, Anna Mae; Chatterjee, Saurabh


    Hepatic fibrosis in nonalcoholic steatohepatitis (NASH) is the common pathophysiological process resulting from chronic liver inflammation and oxidative stress. Although significant research has been carried out on the role of leptin-induced NADPH oxidase in fibrogenesis, the molecular mechanisms that connect the leptin-NADPH oxidase axis in upregulation of transforming growth factor (TGF)-β signaling have been unclear. We aimed to investigate the role of leptin-mediated upregulation of NADPH oxidase and its subsequent induction of micro-RNA 21 (miR21) in fibrogenesis. Human NASH livers and a high-fat (60% kcal) diet-fed chronic mouse model, where hepatotoxin bromodichloromethane was used to induce NASH, were used for this study. To prove the role of the leptin-NADPH oxidase-miR21 axis, mice deficient in genes for leptin, p47phox, and miR21 were used. Results showed that wild-type mice and human livers with NASH had increased oxidative stress, increased p47phox expression, augmented NF-κB activation, and increased miR21 levels. These mice and human livers showed increased TGF-β, SMAD2/3-SMAD4 colocalizations in the nucleus, increased immunoreactivity against Col1α, and α-SMA with a concomitant decrease in protein levels of SMAD7. Mice that were deficient in leptin or p47phox had decreased activated NF-κB and miR21 levels, suggesting the role of leptin and NADPH oxidase in inducing NF-κB-mediated miR21 expression. Further miR21 knockout mice had decreased colocalization events of SMAD2/3-SMAD4 in the nucleus, increased SMAD7 levels, and decreased fibrogenesis. Taken together, the studies show the novel role of leptin-NADPH oxidase induction of miR21 as a key regulator of TGF-β signaling and fibrogenesis in experimental and human NASH.

  19. Novel Rho/MRTF/SRF Inhibitors Block Matrix-stiffness and TGF-β–Induced Fibrogenesis in Human Colonic Myofibroblasts (United States)

    Johnson, Laura A.; Rodansky, Eva S.; Haak, Andrew J.; Larsen, Scott D.; Neubig, Richard R.; Higgins, Peter D. R.


    Background Ras homolog gene family, member A (RhoA)/Rho-associated coiled-coil forming protein kinase signaling is a key pathway in multiple types of solid organ fibrosis, including intestinal fibrosis. However, the pleiotropic effects of RhoA/Rho-associated coiled-coil forming protein kinase signaling have frustrated targeted drug discovery efforts. Recent recognition of the role of Rho-regulated gene transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factor A (MRTF-A) suggest a novel locus for pharmacological intervention. Methods Because RhoA signaling is mediated by both physical and biochemical stimuli, we examined whether pharmacological inhibition of RhoA or the downstream transcription pathway of MRTF-A/SRF could block intestinal fibrogenesis in 2 in vitro models. Results In this study, we demonstrate that inhibition of RhoA signaling blocks both matrix-stiffness and transforming growth factor beta–induced fibrogenesis in human colonic myofibroblasts. Repression of alpha-smooth muscle actin and collagen expression was associated with the inhibition of MRTF-A nuclear localization. CCG-1423, a first-generation Rho/MRTF/SRF pathway inhibitor, repressed fibrogenesis in both models, yet has unacceptable cytotoxicity. Novel second-generation inhibitors (CCG-100602 and CCG-203971) repressed both matrix-stiffness and transforming growth factor beta–mediated fibrogenesis as determined by protein and gene expression in a dose-dependent manner. Conclusions Targeting the Rho/MRTF/SRF mechanism with second-generation Rho/MRTF/SRF inhibitors may represent a novel approach to antifibrotic therapeutics. PMID:24280883

  20. Kidney pain (image) (United States)

    A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the size of sand or ... A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the ...

  1. L-FABP: A novel biomarker of kidney disease. (United States)

    Xu, Yao; Xie, Yuanyuan; Shao, Xinghua; Ni, Zhaohui; Mou, Shan


    Human liver-type fatty acid-binding protein (hL-FABP), which is found in both the normal and the diseased human kidney, has been observed to bind free fatty acids. Recently, the predictive and prognostic value of L-FABP in kidney diseases has attracted considerable attention. Numerous studies have demonstrated that L-FABP is a promising biomarker of several kidney diseases, and it has also been shown to attenuate renal injury. We performed a literature review regarding the ability of L-FABP to identify patients at risk of developing kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD) and to protect the kidneys in the course of kidney disease.

  2. Fibrogenesis by mineral fibres: an in-vitro study of the roles of the macrophage and fibre length. (United States)

    Aalto, M; Heppleston, A G


    Evidence on the mechanism by which inhaled mineral fibres lead to pulmonary fibrosis has not been forthcoming. As with silica, a biphasic cell culture system was required to distinguish phagocytosis from collagen formation. Synthesis of total protein and collagen by rat fibroblasts was estimated by incorporation of labelled proline after treatment with the medium from rat peritoneal macrophages that had been cultured in the presence of different types of mineral fibre. The influence of fibre length was also examined. All the main varieties of asbestos reacted with macrophages to produce or release a fibrogenic factor. However, chrysotile and the longer amosite fibres evoked the response only after prolonging the period of incubation with macrophages, presumably by permitting more complete phagocytosis of curled or longer fibres. Short amosite fibres proved to be more active than longer ones and under certain conditions were as potent as quartz. Fibrous glass also possessed stimulatory properties and again a sample having a short length gave a stronger response than a long one. Collagen formation by asbestos thus appears to be mediated by a macrophage factor, so operating in a manner similar to that previously demonstrated for quartz. The conventional view that short fibres are comparatively insignificant in asbestos fibrogenesis cannot, on the present evidence, be sustained. Furthermore, it should not be assumed than man-made mineral fibres of respirable diameter are innocuous or that short ones can be ignored.

  3. Sonic hedgehog signaling in kidney fibrosis: a master communicator. (United States)

    Zhou, Dong; Tan, Roderick J; Liu, Youhua


    The hedgehog signaling cascade is an evolutionarily conserved pathway that regulates multiple aspects of embryonic development and plays a decisive role in tissue homeostasis. As the best studied member of three hedgehog ligands, sonic hedgehog (Shh) is known to be associated with kidney development and tissue repair after various insults. Recent studies uncover an intrinsic link between dysregulated Shh signaling and renal fibrogenesis. In various types of chronic kidney disease (CKD), Shh is upregulated specifically in renal tubular epithelium but targets interstitial fibroblasts, thereby mediating a dynamic epithelial- mesenchymal communication (EMC). Tubule-derived Shh acts as a growth factor for interstitial fibroblasts and controls a hierarchy of fibrosis-related genes, which lead to the excessive deposition of extracellular matrix in renal interstitium. In this review, we recapitulate the principle of Shh signaling, its activation and regulation in a variety of kidney diseases. We also discuss the potential mechanisms by which Shh promotes renal fibrosis and assess the efficacy of blocking this signaling in preclinical settings. Continuing these lines of investigations will provide novel opportunities for designing effective therapies to improve CKD prognosis in patients.

  4. (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione protects rats from carbon tetrachloride-induced liver injury and fibrogenesis

    Institute of Scientific and Technical Information of China (English)

    Zhi-Zhi Chen; Li-Juan Chen; Yu-Quan Wei; Zheng-Lin Wang; Chong-Yang Deng; Hao Zheng; Xian-Huo Wang; Liang Ma; Xia Ye; Ying-Hua Ma; Cai-Feng Xie


    AIM:To evaluate the hepatoprotective roles of (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (SKLB010) against carbon tetrachloride (CCl4)-induced acute and chronic liver injury and its underlying mechanisms of action.METHODS:In the first experiment,rats were weighed and randomly divided into 5 groups (five rats in each group) to assess the protective effect of SKLB010on acute liver injury.For induction of acute injury,rats were administered a single intraperitoneal injection of 2 mL/kg of 50% (v/v) CCl4 dissolved in olive oil (1∶1).Group 1 was untreated and served as the control group; group 2 received CCl4 for induction of liver injury and served as the model group.In groups 3,4 and 5,rats receiving CCl4 were also treated with SKLB010 at doses of 25,50 and 100 mg/kg,respectively.Blood samples were collected at 6,12 and 24 h after CCl4 intoxication to determine the serum activity of alanine amino transferase.Tumour necrosis factor-α (TNF-α),interleukin-1β (IL-1β) were determined using enzyme-linked immunosorbent assay.At 24 h after CCl4 injection,liver fibrogenesis was evaluated by hematoxylin-eosin (HE) staining and immunohistochemical analyses.Cytokine transcript levels of TNF-α,IL-1β and inducible nitric oxide synthase in the liver tissues of rats were measured using a reverse transcriptase reverse transcription-polymerase chain reaction technique.In the second experiment,rats were randomly divided into 2 groups (15 rats in each group),and liver injury in the CCl4-administered groups was induced by a single intraperitoneal injection of 2 mL/kg of 50% (v/v) CCl4 dissolved in olive oil (1∶1).The SKLB010-treated groups received oral 100 mg/kg SKLB010 before CCl4 administration.Five rats in each group were sacrificed at 2 h,6 h,12 h after CCl4 intoxication and small fortions of livers were rapidly frozen for extraction of total RNA,hepatic proteins and glutathione (GSH) assays.In the hepatic fibrosis model group,rats were randomly divided into 2

  5. Designing attenuators for total-body irradiation using virtual simulation. (United States)

    Corns, R; Evans, M; Olivares, M; Dyke, L; Podgorsak, E B; Freeman, C R


    In total-body photon irradiation, the lungs are the most commonly shielded organ. Lung compensators are often designed by using high-energy portal films. Other organs, such as the kidneys and liver, are poorly visualized in portal films due to their unit-density composition. A computed tomography-based technique to design kidney and liver attenuators involves outlining these organs in a virtual simulation. The position and the shape of the attenuator are then determined from a digitally-reconstructed radiograph. Appropriate attenuator thickness is determined from measured transmission curves. This article provides a summary of this technique for total-body photon irradiation in a 4-MV photon beam.

  6. Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats

    Institute of Scientific and Technical Information of China (English)

    Shuang-Suo Dang; Bao-Feng Wang; Yan-An Cheng; Ping Song; Zhen-Guo Liu; Zong-Fang Li


    AIM: To investigate the suppressive effect of saikosaponin-d (SSd) on hepatic fibrosis in rats induced by CCl4 injections in combination with alcohol and high fat, low protein feeding and its relationship with the expression of nuclear factor-κB (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukins-6 (IL-6).METHODS: Hepatic fibrosis models were induced by subcutaneous injection of CCl4 at a dosage of 3 mL/kg in rats. At the same time, rats in treatment groups were injected intraperitoneally with SSd at different doses (1.0,1.5 and 2.0 mg/kg) once daily for 6 wk in combination with CCl4, while the control group received olive oil instead of CCl4. At the end of the experiment, rats were anesthetized and killed (except for 8 rats which died during the experiment; 2 from the model group, 3 in high-dose group, 1 in medium-dose group and 2 in lowdose group). Hematoxylin and eosin (HE) staining and Van Gieson staining were used to examine the changes in liver pathology. The levels of alanine aminotransferase (ALT), triglyeride (TG), albumin (ALB), globulin (GLB),hyaluronic acid (HA) and laminin (LN) in serum and the content of hydroxyproline (HYP) in liver were measured by biochemical examinations and radioimmuneoassay,respectively. In addition, the expression of TNF-α and IL-6 in liver homogenate was evaluated by enzymelinked immunosorbent assay (ELISA) and the levels of NF-κBp65 and I-κBα in liver tissue were analyzed by Western blotting.RESULTS: Both histological examination and Van Gieson staining demonstrated that SSd could attenuate the area and extent of necrosis and reduce the scores of liver fibrosis. Similarly, the levels of ALT, TG, GLB, HA, and LN in serum, and the contents of HYP, TNF-α and IL-6 in liver were all significantly increased in model group in comparison with those in control group. Whereas,the treatment with SSd markedly reduced all the above parameters compared with the model group, especially in the medium group (ALT: 412 ± 94

  7. Identification of TGF-β receptor-1 as a key regulator of carbon nanotube-induced fibrogenesis. (United States)

    Mishra, Anurag; Stueckle, Todd A; Mercer, Robert R; Derk, Raymond; Rojanasakul, Yon; Castranova, Vincent; Wang, Liying


    Carbon nanotubes (CNTs) induce rapid interstitial lung fibrosis, but the underlying mechanisms are unclear. Previous studies indicated that the ability of CNTs to penetrate lung epithelium, enter interstitial tissue, and stimulate fibroblasts to produce collagen matrix is important to lung fibrosis. In this study, we investigated the activation of transforming growth factor-β receptor-1 [TGF-β R1; i.e., activin receptor-like kinase 5 (ALK5) receptor] and TGF-β/Smad signaling pathway in CNT-induced collagen production in human lung fibroblasts. Human lung fibroblasts and epithelial cells were exposed to low, physiologically relevant concentrations (0.02-0.6 μg/cm(2)) of single-walled CNTs (SWCNT) and multiwalled CNTs (MWCNT) in culture and analyzed for collagen, TGF-β1, TGF-β R1, and SMAD proteins by Western blotting and immunofluorescence. Chemical inhibition of ALK5 and short-hairpin (sh) RNA targeting of TGF-β R1 and Smad2 were used to probe the fibrogenic mechanism of CNTs. Both SWCNT and MWCNT induced an overexpression of TGF-β1, TGF-β R1 and Smad2/3 proteins in lung fibroblasts compared with vehicle or ultrafine carbon black-exposed controls. SWCNT- and MWCNT-induced collagen production was blocked by ALK5 inhibitor or shRNA knockdown of TGF-β R1 and Smad2. Our results indicate the critical role of TGF-β R1/Smad2/3 signaling in CNT-induced fibrogenesis by upregulating collagen production in lung fibroblasts. This novel finding may aid in the design of mechanism-based risk assessment and development of rapid screening tests for nanomaterial fibrogenicity.

  8. Acquired Cystic Kidney Disease (United States)

    ... Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD ... as polycystic kidney disease (PKD), another disease that causes the kidneys to ... chronic kidney disease (CKD)—a condition that develops over many years ...

  9. Acute Kidney Failure (United States)

    ... out of balance. Acute kidney failure — also called acute renal failure or acute kidney injury — develops rapidly over ... 2015. Palevsky PM. Definition of acute kidney injury (acute renal failure). Accessed April ...

  10. Diabetic Kidney Problems (United States)

    ... too high. Over time, this can damage your kidneys. Your kidneys clean your blood. If they are damaged, waste ... in your blood instead of leaving your body. Kidney damage from diabetes is called diabetic nephropathy. It ...

  11. Chronic Kidney Disease (United States)

    You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...

  12. Acute kidney failure (United States)

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  13. Suramin protects from cisplatin-induced acute kidney injury. (United States)

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


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

  14. Biologic Therapy (Immunotherapy) for Kidney Cancer (United States)

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  15. The LIM-only protein FHL2 attenuates lung inflammation during bleomycin-induced fibrosis.

    Directory of Open Access Journals (Sweden)

    Abdulaleem Alnajar

    Full Text Available Fibrogenesis is usually initiated when regenerative processes have failed and/or chronic inflammation occurs. It is characterised by the activation of tissue fibroblasts and dysregulated synthesis of extracellular matrix proteins. FHL2 (four-and-a-half LIM domain protein 2 is a scaffolding protein that interacts with numerous cellular proteins, regulating signalling cascades and gene transcription. It is involved in tissue remodelling and tumour progression. Recent data suggest that FHL2 might support fibrogenesis by maintaining the transcriptional expression of alpha smooth muscle actin and the excessive synthesis and assembly of matrix proteins in activated fibroblasts. Here, we present evidence that FHL2 does not promote bleomycin-induced lung fibrosis, but rather suppresses this process by attenuating lung inflammation. Loss of FHL2 results in increased expression of the pro-inflammatory matrix protein tenascin C and downregulation of the macrophage activating C-type lectin receptor DC-SIGN. Consequently, FHL2 knockout mice developed a severe and long-lasting lung pathology following bleomycin administration due to enhanced expression of tenascin C and impaired activation of inflammation-resolving macrophages.

  16. Morphological aspects of the myocarditis and myositis in Calomys callosus experimentally infected with Trypanosoma cruzi: fibrogenesis and spontaneous regression of fibrosis

    Directory of Open Access Journals (Sweden)

    Sonia G. Andrade


    Full Text Available Calomys callosus a wild rodent, is a natural host of Trypanosoma cruzi. Twelve C. callosus were infected with 10(5 trypomastigotes of the F strain (a myotropic strain of T. cruzi. Parasitemia decreased on the 21 st day becoming negative around the 40th day of infection. All animals survived but had positive parasitological tests, until the end of the experiment. The infected animals developed severe inflammation in the myocardium and skeletal muscle. This process was pronounced from the 26 th to the 30th day and gradually subsided from the 50 th day becoming absent or residual on the 64 th day after infection. Collagen was identified by the picro Sirius red method. Fibrogenesis developed early, but regression of fibrosis occurred between the 50th and 64th day. Ultrastructural study disclosed a predominance of macrophages and fibroblasts in the inflammatory infiltrates, with small numbers of lymphocytes. Macrophages had active phagocytosis and showed points of contact with altered muscle cells. Different degrees of matrix expansion were present, with granular and fibrilar deposits and collagen bundles. These alterations subsided by the 64th days. Macrophages seem to be the main immune effector cell in the C. callosus model of infection with T. cruzi. The mechanisms involved in the rapid fibrogenesis and its regression deserve further investigation.

  17. Peroxisome Proliferator-Activated Receptor Gamma Negatively Regulates the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells Toward Myofibroblasts in Liver Fibrogenesis

    Directory of Open Access Journals (Sweden)

    Shuangshuang Jia


    Full Text Available Background/Aims: Bone marrow-derived mesenchymal stem cells (BMSCs have been confirmed to have capacity to differentiate toward hepatic myofibroblasts, which contribute to fibrogenesis in chronic liver diseases. Peroxisome proliferator-activated receptor gamma (PPARγ, a ligand-activated transcription factor, has gained a great deal of recent attention as it is involved in fibrosis and cell differentiation. However, whether it regulates the differentiation of BMSCs toward myofibroblasts remains to be defined. Methods: Carbon tetrachloride or bile duct ligation was used to induce mouse liver fibrosis. Expressions of PPARγ, α-smooth muscle actin, collagen α1 (I and collagen α1 (III were detected by real-time RT-PCR and Western blot or immunofluorescence assay. Results: PPARγ expression was decreased in mouse fibrotic liver. In addition, PPARγ was declined during the differentiation of BMSCs toward myofibroblasts induced by transforming growth factor β1. Activation of PPARγ stimulated by natural or synthetic ligands suppressed the differentiation of BMSCs. Additionally, knock down of PPARγ by siRNA contributed to BMSC differentiation toward myofibroblasts. Furthermore, PPARγ activation by natural ligand significantly inhibited the differentiation of BMSCs toward myofibroblasts in liver fibrogenesis and alleviated liver fibrosis. Conclusions: PPARγ negatively regulates the differentiation of BMSCs toward myofibroblasts, which highlights a further mechanism implicated in the BMSC differentiation.

  18. [Acute kidney injury

    NARCIS (Netherlands)

    Hageman, D.; Kooman, J.P.; Lance, M.D.; Heurn, L.W. van; Snoeijs, M.G.


    - '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

  19. Simple Kidney Cysts (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  20. Amyloidosis and Kidney Disease (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  1. Kidney Infection (Pyelonephritis) (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  2. Polycystic Kidney Disease (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  3. Functional CT of the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Tsushima, Yoshito. E-mail:


    The iodinated contrast agents used for computed tomography (CT) are filtered at the glomerulus and not reabsorbed by the tubules and have pharmacokinetics comparable to inulin. They can thus measure physiological indices such as contrast clearance per unit volume, which is closely related to glomerular filtration rate per unit renal volume of kidney, after due allowance for the difference between blood and plasma clearance. In this review, we show how dynamic CT can be used to measure both regional and global blood clearance of contrast material. A single slice of kidney is scanned sequentially after bolus intravenous (i.v.) injection of contrast material. Next, time-attenuation curves are constructed and contrast clearance per unit volume is calculated using a Patlak graphical analysis. CT determination of renal volume is made and global contrast clearance can be then also calculated. In normal kidneys, clearance/volume averaged 0.49{+-}0.11 ml min{sup -1} ml{sup -1} (mean {+-}S.D.), and these values agreed with literature data obtained using other techniques. A negative correlation between patient's age and clearance/volume was seen. A strong correlation was observed between creatinine whole blood clearance and the global contrast clearance (the product of renal volume determined by CT and contrast clearance/volume). Dynamic CT can provide quantitative renal physiological information on a regional basis non-invasively.

  4. Matrix Producing Cells in Chronic Kidney Disease: Origin, Regulation, and Activation. (United States)

    Kramann, Rafael; Dirocco, Derek P; Maarouf, Omar H; Humphreys, Benjamin D


    Chronic injury to the kidney causes kidney fibrosis with irreversible loss of functional renal parenchyma and leads to the clinical syndromes of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Regardless of the type of initial injury, kidney disease progression follows the same pathophysiologic processes characterized by interstitial fibrosis, capillary rarefaction and tubular atrophy. Myofibroblasts play a pivotal role in fibrosis by driving excessive extracellular matrix (ECM) deposition. Targeting these cells in order to prevent the progression of CKD is a promising therapeutic strategy, however, the cellular source of these cells is still controversial. In recent years, a growing amount of evidence points to resident mesenchymal cells such as pericytes and perivascular fibroblasts, which form extensive networks around the renal vasculature, as major contributors to the pool of myofibroblasts in renal fibrogenesis. Identifying the cellular origin of myofibroblasts and the key regulatory pathways that drive myofibroblast proliferation and transdifferentiation as well as capillary rarefaction is the first step to developing novel anti-fibrotic therapeutics to slow or even reverse CKD progression and ultimately reduce the prevalence of ESRD. This review will summarize recent findings concerning the cellular source of myofibroblasts and highlight recent discoveries concerning the key regulatory signaling pathways that drive their expansion and progression in CKD.

  5. Microvascular pericytes in healthy and diseased kidneys

    Directory of Open Access Journals (Sweden)

    Pan SY


    Full Text Available Szu-Yu Pan,1,2 Yu-Ting Chang,3 Shuei-Liong Lin1,31Renal Division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan; 3Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanAbstract: Pericytes are interstitial mesenchymal cells found in many major organs. In the kidney, microvascular pericytes are defined anatomically as extensively branched, collagen-producing cells in close contact with endothelial cells. Although many molecular markers have been proposed, none of them can identify the pericytes with satisfactory specificity or sensitivity. The roles of microvascular pericytes in kidneys were poorly understood in the past. Recently, by using genetic lineage tracing to label collagen-producing cells or mesenchymal cells, the elusive characteristics of the pericytes have been illuminated. The purpose of this article is to review recent advances in the understanding of microvascular pericytes in the kidneys. In healthy kidney, the pericytes are found to take part in the maintenance of microvascular stability. Detachment of the pericytes from the microvasculature and loss of the close contact with endothelial cells have been observed during renal insult. Renal microvascular pericytes have been shown to be the major source of scar-forming myofibroblasts in fibrogenic kidney disease. Targeting the crosstalk between pericytes and neighboring endothelial cells or tubular epithelial cells may inhibit the pericyte-myofibroblast transition, prevent peritubular capillary rarefaction, and attenuate renal fibrosis. In addition, renal pericytes deserve attention for their potential to produce erythropoietin in healthy kidneys as pericytes stand in the front line, sensing the change of oxygenation and hemoglobin concentration. Further delineation of the mechanisms underlying the

  6. Precision-cut human kidney slices as a model to elucidate the process of renal fibrosis. (United States)

    Stribos, Elisabeth G D; Luangmonkong, Theerut; Leliveld, Anna M; de Jong, Igle J; van Son, Willem J; Hillebrands, Jan-Luuk; Seelen, Marc A; van Goor, Harry; Olinga, Peter; Mutsaers, Henricus A M


    Chronic kidney disease is a major health concern, and experimental models bridging the gap between animal studies and clinical research are currently lacking. Here, we evaluated precision-cut kidney slices (PCKSs) as a potential model for renal disease. PCKSs were prepared from human cortical tissue obtained from tumor nephrectomies and cultured up to 96 hours. Morphology, cell viability, and metabolic functionality (ie, uridine 5'-diphospho-glucuronosyltransferase and transporter activity) were determined to assess the integrity of PCKSs. Furthermore, inflammatory and fibrosis-related gene expressions were characterized. Finally, to validate the model, renal fibrogenesis was induced using transforming growth factor β1 (TGF-β1). Preparation of PCKSs induced an inflammatory tissue response, whereas long-term incubation (96 hours) induced fibrogenesis as shown by an increased expression of collagen type 1A1 (COL1A1) and fibronectin 1 (FN1). Importantly, PCKSs remained functional for more than 48 hours as evidenced by active glucuronidation and phenolsulfonphthalein uptake. In addition, cellular diversity appeared to be maintained, yet we observed a clear loss of nephrin messenger RNA levels suggesting that our model might not be suitable to study the role of podocytes in renal pathology. Moreover, TGF-β1 exposure augmented fibrosis, as illustrated by an increased expression of multiple fibrosis markers including COL1A1, FN1, and α-smooth muscle actin. In conclusion, PCKSs maintain their renal phenotype during culture and appear to be a promising model to investigate renal diseases, for example, renal fibrosis. Moreover, the human origin of PCKSs makes this model very suitable for translational research.

  7. Acute arterial occlusion - kidney (United States)

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidney can often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury or trauma to ...

  8. Nephrectomy (Kidney Removal) (United States)

    ... if your entire kidney needs to be removed. Robot-assisted laparoscopic surgery. In a variation of laparoscopic ... living kidney donor. Rochester, Minn.: Mayo Foundation for Medical Education and Research; 2014. AskMayoExpert. Partial nephrectomy. Rochester, ...

  9. Diet - chronic kidney disease (United States)

    ... page: // Diet - chronic kidney disease To use the sharing features on this page, ... make changes to your diet when you have chronic kidney disease. These changes may include limiting fluids, eating a ...

  10. Diabetes and Kidney Disease (United States)

    ... disease of diabetes, or diabetic nephropathy. How does diabetes cause kidney disease? High blood glucose , also called ... I keep my kidneys healthy if I have diabetes? The best way to slow or prevent diabetes- ...

  11. Kidney Stones (For Parents) (United States)

    ... of kidney stones if taken in large doses. Metabolic disorders. Having a metabolic disorder (a problem in the way the body breaks ... arthritis), other kidney diseases , conditions that affect the thyroid or parathyroid gland, and some urinary tract infections ( ...

  12. Kidney Replacement Therapy (United States)

    ... to fail. If the new kidney does develop diabetic nephropathy, it too will take many years to fail. ... 2013 Articles from Diabetes Forecast® magazine: cc-kidneys-nephropathy, In ... Diabetes » Close nonprofit software

  13. Kidneys and Urinary Tract (United States)

    ... amino acids, byproducts of bile from the liver, ammonia, and any substances that cannot be reabsorbed into ... Blood Dialysis Digestive System Kidney Transplant Kidney Stones Spleen and Lymphatic System Bones, Muscles, and Joints Contact ...

  14. Chronic Kidney Disease (CKD) (United States)

    ... CKD treated? Kidney-friendly diet for CKD What causes chronic kidney disease (CKD)? Anyone can get CKD. Some people are ... and high blood pressure are the most common causes of CKD. If you have diabetes or high blood pressure, ...

  15. Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

    Energy Technology Data Exchange (ETDEWEB)

    Gonçalves, J.O.; Tannuri, A.C.A.; Coelho, M.C.M.; Bendit, I.; Tannuri, U. [Laboratório de Pesquisa em Cirurgia Pediátrica (LIM-30), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)


    We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-β1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-β1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-β1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT‐PCR technique was more sensitive to expression changes than the semiquantitative method.

  16. Hydronephrosis of one kidney (United States)

    ... Acute hydronephrosis; Urinary obstruction; Unilateral hydronephrosis; Nephrolithiasis - hydronephrosis; Kidney stone - hydronephrosis; Renal calculi - hydronephrosis; Ureteral calculi - hydronephrosis; ...

  17. The senile kidney

    Directory of Open Access Journals (Sweden)

    Denisova Т.Р.


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

  18. Photonic Crystal Fiber Attenuator

    Institute of Scientific and Technical Information of China (English)

    Joo; Beom; Eom; Hokyung; Kim; Jinchae; Kim; Un-Chul; Paek; Byeong; Ha; Lee


    We propose a novel fiber attenuator based on photonic crystal fibers. The difference in the modal field diameters of a conventional single mode fiber and a photonic crystal fiber was used. A variable optical attenuator was also achieved by applying macro-bending on the PCF part of the proposed attenuator

  19. [CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Effect of vitamin D on kidney and cardiovascular system]. (United States)

    Fujii, Hideki


    Recently, many investigators have reported that treatment with vitamin D improves outcomes of patients with chronic kidney disease. Though the detailed mechanisms have remained unclear, it has been speculated that such a treatment may prevent progression of chronic kidney disease and cardiovascular disease. It has been reported that Vitamin D may attenuate renal injury and ameliorate renal function and proteinuria. In addition, several studies have shown that vitamin D may prevent progression of atherosclerosis, vascular calcification and left ventricular hypertrophy. The emerging experimental and clinical evidence has suggested that vitamin D may protect kidney and cardiovascular system.

  20. Tracer attenuation in groundwater (United States)

    Cvetkovic, Vladimir


    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  1. The balance of powers: Redox regulation of fibrogenic pathways in kidney injury. (United States)

    Okamura, Daryl M; Pennathur, Subramaniam


    Oxidative stress plays a central role in the pathogenesis of diverse chronic inflammatory disorders including diabetic complications, cardiovascular disease, aging, and chronic kidney disease (CKD). Patients with moderate to advanced CKD have markedly increased levels of oxidative stress and inflammation that likely contribute to the unacceptable high rates of morbidity and mortality in this patient population. Oxidative stress is defined as an imbalance of the generation of reactive oxygen species (ROS) in excess of the capacity of cells/tissues to detoxify or scavenge them. Such a state of oxidative stress may alter the structure/function of cellular macromolecules and tissues that eventually leads to organ dysfunction. The harmful effects of ROS have been largely attributed to its indiscriminate, stochastic effects on the oxidation of protein, lipids, or DNA but in many instances the oxidants target particular amino acid residues or lipid moieties. Oxidant mechanisms are intimately involved in cell signaling and are linked to several key redox-sensitive signaling pathways in fibrogenesis. Dysregulation of antioxidant mechanisms and overproduction of ROS not only promotes a fibrotic milieu but leads to mitochondrial dysfunction and further exacerbates kidney injury. Our studies support the hypothesis that unique reactive intermediates generated in localized microenvironments of vulnerable tissues such as the kidney activate fibrogenic pathways and promote end-organ damage. The ability to quantify these changes and assess response to therapies will be pivotal in understanding disease mechanisms and monitoring efficacy of therapy.

  2. Importance of Attenuation Correction (AC for Small Animal PET Imaging

    Directory of Open Access Journals (Sweden)

    Henrik H. El Ali


    Full Text Available The purpose of this study was to investigate whether a correction for annihilation photon attenuation in small objects such as mice is necessary. The attenuation recovery for specific organs and subcutaneous tumors was investigated. A comparison between different attenuation correction methods was performed. Methods: Ten NMRI nude mice with subcutaneous implantation of human breast cancer cells (MCF-7 were scanned consecutively in small animal PET and CT scanners (MicroPETTM Focus 120 and ImTek’s MicroCATTM II. CT-based AC, PET-based AC and uniform AC methods were compared. Results: The activity concentration in the same organ with and without AC revealed an overall attenuation recovery of 9–21% for MAP reconstructed images, i.e., SUV without AC could underestimate the true activity at this level. For subcutaneous tumors, the attenuation was 13 ± 4% (9–17%, for kidneys 20 ± 1% (19–21%, and for bladder 18 ± 3% (15–21%. The FBP reconstructed images showed almost the same attenuation levels as the MAP reconstructed images for all organs. Conclusions: The annihilation photons are suffering attenuation even in small subjects. Both PET-based and CT-based are adequate as AC methods. The amplitude of the AC recovery could be overestimated using the uniform map. Therefore, application of a global attenuation factor on PET data might not be accurate for attenuation correction.

  3. What Is Kidney Cancer (Renal Cell Carcinoma)? (United States)

    ... Treatment? Kidney Cancer About Kidney Cancer What Is Kidney Cancer? Kidney cancer is a cancer that starts ... and spread, see What Is Cancer? About the kidneys To understand more about kidney cancer, it helps ...

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

    Directory of Open Access Journals (Sweden)

    François Glowacki

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

  5. Cuba's kidney transplantation program. (United States)

    Mármol, Alexander; Pérez, Alexis; Pérez de Prado, Juan C; Fernández-Vega, Silvia; Gutiérrez, Francisco; Arce, Sergio


    The first kidney transplant in Cuba was performed on 24 February 1970, using a cadaveric donor. In 1979, living donor kidney transplantation began between first-degree relatives. A total of 2775 patients are enrolled in renal replacement therapy in 47 hospitals across the country, 1440 of whom are awaiting kidney transplantation. Organs for the kidney program are procured in 63 accredited hospitals equipped for multidisciplinary management of brain death. Accordingly, over 90% of transplanted kidneys are from cadaveric donors. Identification of potential recipients is carried out through a national, computerized program that affords all patients the same opportunity regardless of distance from a transplant center, and selection of the most suitable candidate is based primarily on HLA compatibility. KEYWORDS Chronic renal failure, kidney transplantation.

  6. Tissue engineering the kidney. (United States)

    Hammerman, Marc R


    The means by which kidney function can be replaced in humans include dialysis and renal allotransplantation. Dialytic therapies are lifesaving, but often poorly tolerated. Transplantation of human kidneys is limited by the availability of donor organs. During the past decades, a number of different approaches have been applied toward tissue engineering the kidney as a means to replace renal function. The goals of one or another of them included the recapitulation of renal filtration, reabsorptive and secretory functions, and replacement of endocrine/metabolic activities. This review will delineate the progress to date recorded for five approaches: (1) integration of new nephrons into the kidney; (2) growing new kidneys in situ; (3) use of stem cells; (4) generation of histocompatible tissues using nuclear transplantation; and (5) bioengineering of an artificial kidney. All five approaches utilize cellular therapy. The first four employ transplantation as well, and the fifth uses dialysis.

  7. Renoprotective mechanisms of morin in cisplatin-induced kidney injury. (United States)

    Wei, Zhengkai; He, Xuexiu; Kou, Jinhua; Wang, Jingjing; Chen, Libin; Yao, Minjun; Zhou, Ershun; Fu, Yunhe; Guo, Changming; Yang, Zhengtao


    In this study, we investigated the renoprotective effects of morin on cisplatin-induced kidney injury in mice. Serum creatinine and blood urea nitrogen (BUN) levels, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) activities were determined according to the corresponding kits. The mRNA levels of TNF-α and IL-1β in kidney tissues were measured by quantitative real-time PCR (qRT-PCR). The activities of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa B (NF-κB) p65, P38 mitogen-activated protein kinase (MAPK), Bax, p53 and cleaved caspase 3 were evaluated by western blotting. The results showed that the model of cisplatin-induced kidney injury was successfully replicated, and morin significantly attenuated histopathological changes and decreased the levels of TNF-α and IL-1β in the kidneys. In addition, morin attenuated the activation of CYP2E1, phospho-NF-κB p65, phospho-P38 MAPK, Bax, phospho-p53 and cleaved caspase 3 in CP-induced kidney injury. In conclusion, these results indicated that the renoprotective mechanisms of morin may be attributed to the suppression of oxidative stress, inflammation and apoptosis in CP-induced kidney injury.

  8. National Kidney Disease Education Program (United States)

    ... from our online catalog . Alternate Language URL National Kidney Disease Education Program (NKDEP) Page Content Improving the ... kidney disease. Minorities Are at Higher Risk for Kidney Disease. If you are African American, Hispanic, or ...

  9. Kidney and Urinary Tract

    Institute of Scientific and Technical Information of China (English)


    11.1.Kidney function2005391 Increased levels of advanced oxidationproducts are associated with atherosclerosis in chron-ic kidney disease.YANG Xiaobing(杨小兵),et al.Dept Nephrol,Nanfang Hops,1st Milit Med Univ,Guangzhou.Chin J Intern Med 2005;44(5):342-346.Objective:Accumulation of advanced oxidation protein

  10. Acute kidney injury during pregnancy. (United States)

    Van Hook, James W


    Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.

  11. Landing gear noise attenuation (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)


    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  12. Hemizygous deletion of CTGF/CCN2 does not suffice to prevent fibrosis of the severely injured kidney

    NARCIS (Netherlands)

    Falke, L.L.; Dendooven, A.; Leeuwis, J.W.; Nguyen, T.Q.; Geest, R.J. van; Giezen, D.M. van der; Broekhuizen, R.; Lyons, K.; Stoop, R.; Kemperman, H.; Schlingemann, R.; Joles, J.A.; Goldschmeding, R.


    Background: Connective Tissue Growth Factor (CTGF/CCN2) is an important mediator of kidney fibrosis. Previous observations indicated that attenuation of CCN2 expression sufficed to alleviate early kidney damage. However, little is known about the role of CCN2 in fibrosis of severely damaged and more

  13. Determination of kidney function with 99mTc-DTPA renography using a dual-head camera

    DEFF Research Database (Denmark)

    Madsen, Claus J; Møller, Michael L; Zerahn, Bo;


    Single-head gamma camera renography has been used for decades to estimate kidney function. An estimate of the glomerular filtration rate (GFR) can be obtained using Tc-diethylenetriaminepentaacetic acid (Tc-DTPA). However, because of differing attenuation, an error is introduced when the kidney...

  14. Quercetin attenuates the activation of hepatic stellate cells and liver fibrosis in mice through modulation of HMGB1-TLR2/4-NF-κB signaling pathways. (United States)

    Li, Xi; Jin, Qianwen; Yao, Qunyan; Xu, Beili; Li, Zheng; Tu, Chuantao


    This study aimed to investigate the effects of quercetin on liver fibrogenesis in mice and to elucidate the underlying molecular mechanisms. Mice were administered with carbon tetrachloride (CCl4) for eight weeks to induce liver fibrosis and concomitantly orally treated with quercetin (50mgkg(-1)day(-1)). Here, we demonstrated that quercetin dramatically ameliorated liver injury, inflammation, and hepatic fibrogenesis induced by CCl4. Quercetin also inhibited the activation of hepatic stellate cells (HSC) in vivo and in vitro, as evaluated by α-smooth muscle actin (α-SMA) expression, which is a specific marker of HSC activation. Moreover, reduced fibrosis was associated with decreased high-mobility group box 1 (HMGB1), toll like receptor (TLR) 2 and TLR4 genes, and protein expression. Quercetin also inhibited the cytoplasmic translocation of HMGB1 in hepatocytes of fibrotic livers. Further investigation demonstrated that quercetin treatment significantly attenuated CCl4-induced nuclear translocation of the nuclear factor-κB (NF-κB) p65 and inhibited degradation of IκBα (an inhibitor of NF-κB) expression in the liver compared with vehicle-treated fibrotic mice. Considered together, our data indicate that quercetin has hepatoprotective and anti-fibrotic effects in animal models of liver fibrosis, the mechanism of which may be involved in modulating the HMGB1-TLR2/4-NF-κB signaling pathways.

  15. Kidneys and How They Work (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  16. Pain Medicines and Kidney Damage (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  17. Kidney and Urinary Tract

    Institute of Scientific and Technical Information of China (English)


    2011229 Combined detection of markers in the early diagnosis of acute kidney injury following cardiac surgery. CHE Miaolin (车妙琳) ,et al. Renal Division,Renji Hosp,Med Sch,Shanghai Jiaotong Univ, Shanghai 200127.

  18. Kidneys in Rats

    Directory of Open Access Journals (Sweden)

    Ahmad Reza Bandegi


    Conclusion: These observations indicate that saffron and its active constituent crocin can prevent chronic stress–induced oxidative stress damage of the brain, liver and kidneys and suggest that these substances may be useful against oxidative stress.

  19. Chronic kidney disease (United States)

    ... 2010;362(1):56-65. PMID: 20054047 . Fogarty DG, Tall ... 5 Suppl 1):S1-S290. PMID: 15114537 . Kidney Disease: Improving ...

  20. Role of adiponectin in liver fibrogenesis: progress in basic and clinical research%脂联素在肝纤维化发生中的作用

    Institute of Scientific and Technical Information of China (English)

    王美娟; 马红


    脂联素(ADN)具有多种生物学作用.近年研究表明其可抑制肝纤维化的发展.一些动物实验显示ADN基因敲除(ADN-KO)鼠易发生纤维化,可能与ADN具有抗氧化应激及抗炎作用有关.肝星状细胞(HSC)在肝纤维化中起核心作用,ADN可抑制HSC增殖、迁移,促进其凋亡.临床研究报道ADN与慢性肝病的纤维化进展有关,为肝纤维化的无创性诊断提供新的方向.进一步分析ADN的抗肝纤维化机制有重要意义.%Adiponectin possesses many biological effects. Recent studies have found that adiponectin can inhibit the development of hepatic fibrosis. Some animal experiments demonstrate that adiponectin-knockout (ADN-KO)mice tend to develop severe hepatic fibrosis which may be associated with anti-oxidative stress and anti-inflammatory effects of adiponectin. Hepatic stellate cell (HSC) play a central role in liver fibrogenesis. Studies showed that adiponectin can inhibit proliferation, migration of HSC and promote its apoptosis. Clinical researches also reported that adiponectin was related to progression of hepatic fibrosis in chronic liver diseases, which is a new way for the non-invasive diagnosis of hepatic fibrosis. It is necessary to investigate the precise mechanism of adiponectin on hepatic fibrosis.

  1. Hepatitis C virus E2 protein induce reactive oxygen species (ROS)-related fibrogenesis in the HSC-T6 hepatic stellate cell line. (United States)

    Ming-Ju, Hsieh; Yih-Shou, Hsieh; Tzy-Yen, Chen; Hui-Ling, Chiou


    Chronic infection of hepatitis C virus (HCV) leads to hepatic fibrosis and subsequently cirrhosis, although the underlying mechanisms have not been established. Previous studies have indicated that the binding of HCV E2 protein and CD81 on the surface of hepatic stellate cells (HSCs) lead to the increased protein level and activity of matrix metallopeptidase (MMP) 2, indicating that E2 may involve in the HCV-induced fibrosis. This study was designed to investigate the involvement of HCV E2 protein in the hepatic fibrogenesis. Results showed that E2 protein may promote the expression levels of α-smooth muscle actin (α-SMA) and collagen α(I). Furthermore, several pro-fibrosis or pro-inflammatory cytokines, including transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), interleukin (IL)-6 and IL-1β, were significantly increased in E2 transfected-HSC cell lines, while the expression of MMP-2 are also considerably increased. Moreover, the significant increases of CTGF and TGF-β1 in a stable E2-expressing Huh7 cell line were also observed the same results. Further molecular studies indicated that the impact of E2 protein on collagen production related to higher production of ROS and activated Janus kinase (JAK)1, JAK2 and also enhance the activation of ERK1/2 and p38, while catalase and inhibitors specific for JAK, ERK1/2, and p38 abolish E2-enhanced expression of collagen α(I). Taken together, this study indicated that E2 protein involve in the pathogenesis of HCV-mediated fibrosis via an up-regulation of collagen α(I) and oxidative stress, which is JAK pathway related.

  2. Effects of low-power laser irradiation (LPLI) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing. (United States)

    Silveira, Paulo Cesar Lock; Silva, Luciano A; Freitas, Tiago P; Latini, Alexandra; Pinho, Ricardo A


    Gallium-arsenide (GaAs) and helium-neon (HeNe) lasers are the most commonly used low-energy lasers in physiotherapy for promoting wound healing and pain modulation. The aim of this study was investigate the effect of low-power laser irradiation (LPLI) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing. The animals were randomly divided into five groups (n=6): Controls (skin injured animals without local or systemic treatment), skin injury treated with HeNe 1 J/cm(2) (two seg); skin injury treated with HeNe 3 J/cm(2) (six seg); skin injury treated with GaAs 1 J/cm(2) (three seg); skin injury treated with GaAs 3 J/cm(2) (nine seg). A single circular wound measuring 8 mm in diameter was surgically created on the back of the animal. The rats were irradiated at 2, 12, 24, 48, 72, 96, and 120 h after skin injury. The parameters, namely hydroxyproline content, activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and lipid (TBARS) and protein oxidation (carbonyl groups) measurements were assessed. In addition, wound size regression was also analyzed. The results showed an improvement in the wound healing reflected by the reduction in wound size and increased collagen synthesis. Moreover, a significant reduction in TBARS levels, carbonyl content, and SOD and CAT activities were observed after laser irradiation, particularly with the treatments HeNe laser 1 and 3 J/cm(2) dose and GaAs 3 J/cm(2) dose. The data strongly indicate that LPLI therapy is efficient in accelerating the skin wound healing process after wounding, probably by reducing the inflammatory phase and inducing collagen synthesis.

  3. Signaling during Kidney Development

    Directory of Open Access Journals (Sweden)

    Mirja Krause


    Full Text Available The kidney plays an essential role during excretion of metabolic waste products, maintenance of key homeostasis components such as ion concentrations and hormone levels. It influences the blood pressure, composition and volume. The kidney tubule system is composed of two distinct cell populations: the nephrons forming the filtering units and the collecting duct system derived from the ureteric bud. Nephrons are composed of glomeruli that filter the blood to the Bowman’s capsule and tubular structures that reabsorb and concentrate primary urine. The collecting duct is a Wolffian duct-derived epithelial tube that concentrates and collects urine and transfers it via the renal pelvis into the bladder. The mammalian kidney function depends on the coordinated development of specific cell types within a precise architectural framework. Due to the availability of modern analysis techniques, the kidney has become a model organ defining the paradigm to study organogenesis. As kidney diseases are a problem worldwide, the understanding of mammalian kidney cells is of crucial importance to develop diagnostic tools and novel therapies. This review focuses on how the pattern of renal development is generated, how the inductive signals are regulated and what are their effects on proliferation, differentiation and morphogenesis.

  4. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury


    Yoon-Kyung Chang; Hyunsu Choi; Jin Young Jeong; Ki-Ryang Na; Kang Wook Lee; Beom Jin Lim; Dae Eun Choi


    Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated wi...

  5. Telmisartan attenuates chronic ciclosporin A nephrotoxicity in a pig model

    DEFF Research Database (Denmark)

    Cibulskyte, Donata; pedersen, michael; Hørlyck, Arne;


    BACKGROUND: We have previously demonstrated renal enlargement in pigs treated with ciclosporin A (CsA) 10 mg/kg/day orally for 6 months. The aim of the study was to investigate the effect of oral CsA (10 mg/kg/day) for 12 months on kidney structure and function and the potential renoprotective role...... and 54, we measured body weight, mean arterial blood pressure (MAP), serum creatinine, whole blood trough CsA, plasma Ang II, haemoglobin and liver function parameters. Magnetic resonance imaging was used to estimate kidney length, volume, relative glomerular filtration rate (rGFR) and renal blood flow...... (RBF). Kidney tissue biopsies were used for conventional histological examination. RESULTS: Plasma Ang II levels were significantly higher during telmisartan treatment. Interstitial fibrosis and glomerulosclerosis occurred in both groups, but were attenuated in the telmisartan-treated pigs (P = 0...

  6. Planetary Ices Attenuation Properties (United States)

    McCarthy, Christine; Castillo-Rogez, Julie C.

    In this chapter, we review the topic of energy dissipation in the context of icy satellites experiencing tidal forcing. We describe the physics of mechanical dissipation, also known as attenuation, in polycrystalline ice and discuss the history of laboratory methods used to measure and understand it. Because many factors - such as microstructure, composition and defect state - can influence rheological behavior, we review what is known about the mechanisms responsible for attenuation in ice and what can be inferred from the properties of rocks, metals and ceramics. Since attenuation measured in the laboratory must be carefully scaled to geologic time and to planetary conditions in order to provide realistic extrapolation, we discuss various mechanical models that have been used, with varying degrees of success, to describe attenuation as a function of forcing frequency and temperature. We review the literature in which these models have been used to describe dissipation in the moons of Jupiter and Saturn. Finally, we address gaps in our present knowledge of planetary ice attenuation and provide suggestions for future inquiry.

  7. Polycystic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Pedro Cena Rivero


    Full Text Available The Polycystic Kidney Disease (PKD is a genetic disease which is characterized by the gradual emergence of cystic lesions in the kidneys, which replace the renal parenchyma causing deterioration of its function to stage 5. The PKD is one of the causes of Chronic Kidney Disease on renal replacement therapy (RRT. The Polycystic Kidney Disease has two patterns of inheritance: autosomal dominant pattern and the autosomal recessive pattern. The dominant form is more common but less severe than autosomal recessive form. PKD is known that is caused by mutations in several loci of the human genome. The autosomal dominant form can be caused by mutations in two different genes (PKD1 and PKD2, unlike the autosomal recessive form only has a causal gene (PKHD1. At present the international scientific community efforts toward deeper understanding of the pathophysiology of this entity for the purpose of developing therapeutic alternatives that avoid the appearance of cysts or progression of those already in place. The aim is to systematize the available scientific knowledge about Polycystic Kidney Disease and provide a source of consultation update on clinical characteristics and therapeutic options for patients with PKD

  8. Necroinflammation in Kidney Disease. (United States)

    Mulay, Shrikant R; Linkermann, Andreas; Anders, Hans-Joachim


    The bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury-related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Accumulating data now suggest that renal cell necrosis is a genetically determined and regulated process involving specific outside-in signaling pathways. These findings support a unifying theory in which kidney injury and inflammation are reciprocally enhanced in an autoamplification loop, referred to here as necroinflammation. This integrated concept is of potential clinical importance because it offers numerous innovative molecular targets for limiting kidney injury by blocking cell death, inflammation, or both. Here, the contribution of necroinflammation to AKI is discussed in thrombotic microangiopathies, necrotizing and crescentic GN, acute tubular necrosis, and infective pyelonephritis or sepsis. Potential new avenues are further discussed for abrogating necroinflammation-related kidney injury, and questions and strategies are listed for further exploration in this evolving field.

  9. Ear length and kidney function decline after kidney donation. (United States)

    Katavetin, Pisut; Watanatorn, Salin; Townamchai, Natavudh; Avihingsanon, Yingyos; Praditpornsilpa, Kearkiat


    The preservation of kidney function after kidney donation depends on the kidney reserve - the potential of the remaining kidney to boost their function after loss of the other kidney. In Traditional Chinese Medicine, size and shape of the external ears are examined to evaluate the person's kidney health. We hypothesized that ear size might be a practical yet overlooked marker of kidney reserve. Fifty kidney transplantation donors were participated in this study. The length and width of both ears of all participants were measured during one of the post-donation visits. Pre-donation serum creatinine and post-donation serum creatinine as well as other relevant parameters (age, sex, weight, height, etc.) of the participants were extracted from medical records. The estimated GFR was calculated from serum creatinine, age and sex using the CKD-EPI equation. Ear length negatively associated with %GFR decline after kidney donation. For every 1 cm increase in ear length, it was associated with 5.7% less GFR decline after kidney donation (95% Confidence Interval 0.2 to 11.3, P = 0.04). Ear width, as well as age, sex, body weight, height, body mass index, and pre-donation eGFR did not significantly associate with the GFR decline. Our findings support the notion of Traditional Chinese Medicine that ear morphology may be associated with kidney health and suggest that ear length might be a useful predictor of kidney function decline after kidney donation.

  10. The angiotensin type 2 receptor and the kidney

    DEFF Research Database (Denmark)

    Peluso, Antonio A B; Santos, Robson A S; Unger, Thomas


    by internalisation of these transporters, thus reducing reabsorption and increasing natriuresis/diuresis. Regarding renal pathology, several studies demonstrated an attenuation of renal injury caused by diabetes or by obesity with or without high-salt diet through anti-inflammatory, antifibrotic, and antioxidative...... with selective agonists is a promising therapeutic strategy for inducing diuresis/natriuresis (also additive to established diuretics) and for the treatment of diabetic nephropathy or kidney disease of other pathogenesis....

  11. Frequency Dependent Attenuation Revisited

    CERN Document Server

    Richard, Kowar; Xavier, Bonnefond


    The work is inspired by thermo-and photoacoustic imaging, where recent efforts are devoted to take into account attenuation and varying wave speed parameters. In this paper we study causal equations describing propagation of attenuated pressure waves. We review standard models like frequency power laws and and the thermo-viscous equation. The lack of causality of standard models in the parameter range relevant for photoacoustic imaging requires to derive novel equations. The main ingredients for deriving causal equations are the Kramers-Kronig relation and the mathematical concept of linear system theory. The theoretical results of this work are underpined by numerical experiments.

  12. [Pregnancy and kidney diseases]. (United States)

    Siekierka-Harreis, M; Rump, L C


    The prevalence of chronic kidney disease in women of childbearing age reaches approximately 0.2%. Under physiological conditions pregnancy results in important hemodynamic changes on the maternal organism. In the case of chronic kidney disease these adaptations often are only partial. Physiological changes of immune response during pregnancy may contribute to the progress of renal disease. Regardless of the underlying kidney disease, one can assume that the better the glomerular filtration rate and blood pressure are the more favorable the course of pregnancy will be with the chance for a healthy child and stable renal function. To achieve this goal, a close interaction is required between gynecologist, nephrologist, and other specialists in a center with appropriate experience.


    Directory of Open Access Journals (Sweden)

    Komarabattina Rattaia


    Full Text Available INTRODUCTION: T he subject of kidney anomalies has created much interest to the scientists in late 1950 and 1960 with the aim of prevention and curing. E tiological factors includes variou s genetic environmental factors , teratogens such as physical, chemical, nutritional, causing mutations in the genes. Hypoplastic kidney indicates small kidney that have less normal number of calices and nephrons. MATERIAL AND METHODS: T he present study has been under taken on 76 kidneys from cadavers and 60 from sonograms and 40 from fetal kidneys. Kidneys identified and photographs are taken in situ wherever necessary OBSERVATION : 10 hypo plastic kidneys were observed. SUMM A RY AND CONCLUSION: The cause for this is many birth defects, it may be unilateral or bilateral, in unilateral the oth er kidney shows greater compensatory group

  14. Effects of long-term low-dose oxygen supplementation on the epithelial function, collagen metabolism and interstitial fibrogenesis in the guinea pig lung

    Directory of Open Access Journals (Sweden)

    Ishizaka Akitoshi


    Full Text Available Abstract Background The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis. Methods Guinea pigs (n = 159 were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum of albumin (ALB were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue. Results The clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group. Conclusion These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low

  15. Kidney stones - self-care (United States)

    ... self-care; Nephrolithiasis and self-care; Stones and kidney - self-care; Calcium stones and self-care; Oxalate ... provider or the hospital because you have a kidney stone. You will need to take self-care ...

  16. Screening for Chronic Kidney Disease (United States)

    Understanding Task Force Recommendations Screening for Chronic Kidney Disease The U.S. Preventive Services Task Force (Task Force) has issued a final recommendation on Screening for Chronic Kidney Disease (CKD) . This recommendation ...

  17. Aging changes in the kidneys (United States)

    ... this page: // Aging changes in the kidneys and bladder To use ... in the reproductive system can affect bladder control. AGING CHANGES AND THEIR EFFECTS ON THE KIDNEYS AND ...

  18. Renal (Kidney) Manifestations in TSC (United States)

    ... International TSC Research Conference Text Size Get Involved RENAL (KIDNEY) MANIFESTATIONS IN TSC Download a PDF of ... sclerosis complex (TSC) will develop some form of renal (kidney) disease during their lifetime. There are three ...

  19. Everolimus in kidney transplantation

    Directory of Open Access Journals (Sweden)

    Cooper JE


    Full Text Available James E Cooper¹, Uwe Christians², Alexander C Wiseman¹¹Division of Renal Diseases and Hypertension, Transplant Center, ²iC42 Integrated Solutions in Systems Biology for Clinical Research and Development, University of Colorado Denver, Aurora, CO, USAAbstract: Everolimus is a novel target of rapamycin (mTOR-I analog that has recently been approved in combination with cyclosporine A and steroids for use in the prevention of organ rejection in kidney transplant recipients. Compared with rapamycin, everolimus is characterized by a shorter half-life and improved bioavailability. Prior to US Food and Drug Administration approval, a number of Phase II and III clinical trials were undertaken to evaluate the effectiveness of everolimus in combination with calcineurin inhibitors for preventing acute rejection and promoting allograft survival in kidney transplant recipients. In this report, we review the pharmacokinetic properties of everolimus, the clinical efficacy studies that led to its approval for use in kidney transplantation, as well as reported data on patient safety and tolerability associated with its use.Keywords: mTOR inhibitors, kidney transplantation, everolimus


    Institute of Scientific and Technical Information of China (English)


    13.1 Kidney function2004258 Safety and efficacy of very low protein di-et in the treatment of patients withsevere chronic renal insufficiency. LIU Yan (刘岩), et al. Dept Nephrol Guangzhou Red Cross Hosp, Guangzhou 510220. Chin J Nephrol 2004;20(1):18-22.Objective: To investigate the effects of long-term


    Institute of Scientific and Technical Information of China (English)


    10.1 Kidney function2004116 Measurement of urinary neutral endopeptid-ase and its significance in diagnosing renal tubular injury. ZHANG Zhi (张智), et al. Div Nephrol, Ruijin Hosp, Shanghai 2nd Med Univ, Shanghai 200025. Chin J Nephrol 2003; 19(6) :392-396.


    Institute of Scientific and Technical Information of China (English)


    11.1 Kidney function2004416 The role of adhesion molecules and dendritic cells in hepatic/renal ischemia-reperfusion injury and the effect of antiadhesive treatment in rats.ZHOU Tong(周同), et al. Dept Nephrol, Ruijing Hosp Shanghai 2nd Med Univ, Shanghai 200025. Chin J Emerg Med 2004; 13(5):315 -318.

  3. Connexins and the kidney

    DEFF Research Database (Denmark)

    Hanner, Fiona; Sørensen, Charlotte Mehlin; Holstein-Rathlou, Niels-Henrik


    Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules...

  4. Chronic Kidney Disease (United States)

    ... of the feet and ankles Causes & Risk FactorsWhat causes CKD?The most common causes of CKD are high blood pressure, diabetes and heart disease. ... caused by CKD.How else is CKD treated?Chronic kidney disease can cause other problems. Talk with your doctor about how ...


    Institute of Scientific and Technical Information of China (English)


    11.1 Kidney function2003454 Effects of protein kinase C on type 1 inosi-tol 1,4, 5-triphosphate receptor expression in smooth muscle cells of rat glomerular afferent arterioles.WANG Jingyan(王静艳), et al. Dept Infect DLs, 2nd Affili Hosp, China Med Univ, Shenyang 110004. China World J Digestol 2003; (11)6:705-707.

  6. Fibrogenesis in progressive renal disease

    NARCIS (Netherlands)

    Baelde, H.


    Molecular biology offers new opportunities for experimental and clinical medicine. Promising clinical applications for patient care include identification of mRNA expression patterns (gene profiling) in diseased organs in correlation with diagnosis, prognosis, and responsiveness to different treatme

  7. Chronic Kidney Disease and Medicines (United States)

    ... from our online catalog. Alternate Language URL Español Chronic Kidney Disease and Medicines: What You Need to Know Page ... What you need to know Because you have chronic kidney disease, you should take steps to protect your kidneys. ...

  8. Urological Complications in Kidney Transplantation

    NARCIS (Netherlands)

    I.K.B. Slagt (Inez)


    markdownabstract__Abstract__ The kidney is an essential organ that plays an crucial role in acid-base balance, sodium and potassium balance, calcium metabolism, regulation of blood pressure, red blood cell synthesis and excretion of metabolites. Kidney diseases may result in kidney failure with the

  9. Establishing a national knowledge translation and generation network in kidney disease: the CAnadian KidNey KNowledge TraNslation and GEneration NeTwork. (United States)

    Manns, Braden; Barrett, Brendan; Evans, Michael; Garg, Amit; Hemmelgarn, Brenda; Kappel, Joanne; Klarenbach, Scott; Madore, Francois; Parfrey, Patrick; Samuel, Susan; Soroka, Steven; Suri, Rita; Tonelli, Marcello; Wald, Ron; Walsh, Michael; Zappitelli, Michael


    Patients with chronic kidney disease (CKD) do not always receive care consistent with guidelines, in part due to complexities in CKD management, lack of randomized trial data to inform care, and a failure to disseminate best practice. At a 2007 conference of key Canadian stakeholders in kidney disease, attendees noted that the impact of Canadian Society of Nephrology (CSN) guidelines was attenuated given limited formal linkages between the CSN Clinical Practice Guidelines Group, kidney researchers, decision makers and knowledge users, and that further knowledge was required to guide care in patients with kidney disease. The idea for the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) developed from this meeting. CANN-NET is a pan-Canadian network established in partnership with CSN, the Kidney Foundation of Canada and other professional societies to improve the care and outcomes of patients with and at risk for kidney disease. The initial priority areas for knowledge translation include improving optimal timing of dialysis initiation, and increasing the appropriate use of home dialysis. Given the urgent need for new knowledge, CANN-NET has also brought together a national group of experienced Canadian researchers to address knowledge gaps by encouraging and supporting multicentre randomized trials in priority areas, including management of cardiovascular disease in patients with kidney failure.

  10. Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study.

    Directory of Open Access Journals (Sweden)

    Christiane Drechsler

    Full Text Available BACKGROUND: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD. METHODS: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19 using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. RESULTS: Study participants were at baseline on average 47±13 years old and 65% were male. Mean±standard deviation of homoarginine concentrations were 2.5±1.1 µmol/L and concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.90±1.02 µmol/L (GFR>90 ml/min, 2.64±1.06 µmol/L (GFR 60-90 ml/min, 2.52±1.24 µmol/L (GFR 30-60 ml/min and 2.05±0.78 µmol/L (GFR<30 ml/min, respectively (p = 0.002. The age- and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (1.1 µmol/L of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005. This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01, and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06. CONCLUSIONS: Homoarginine concentrations are directly correlated with kidney function and are significantly

  11. Kidney and Urinary Tract

    Institute of Scientific and Technical Information of China (English)


    12.1 Kidney function2007244 Short-and long-term outcome of the kidney after acute ischemia-reperfusion injury. JIANG suhua(蒋素华), et al. Dept Nephrol, Zhongshan Hosp, Fudan Univ, Shanghai 200032. Chin J Nephrol 2007;23(4):246-250. Objective To investigate short-and long-term outcome of the kidney after acute ischemia-reperfusion (IR) injury. Methods Rat model of renal IR was established by clamping both pedicles for 40 min followed by reperfusion. Blood sample and kidneys were collected at indicated times. Serum creatinine levels, mortality and histological change were observed throughout the study. Transmission electron microscopy (TEM) was used to observe tubular ultra-structure. Apoptosis was confirmed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay. The extent of tubulointerstitial fibrosis was evaluated by Masson trichome staining. The expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) was determined by Western blot and immunohistochemical analysis. Results Extensive proximal tubular necrosis, functional impairment and high mortality (32%, 8/25) were found in the early phase after renal IR injury, accompanied by a small number of apoptotic cells. Patchy tubulointerstitial fibrosis was obvious at 5th and 10th week postischemia in correlation with renal hypertrophy and increased urinary output. Moreover, the expression of a-SMA and TGF-β1 increased significantly at first, 5th and 10th week in the kidneys of IR group compared to sham-operated group. The expression mentioned above was localized mainly in the injured tubulointerstitium, consistent with the distribution of renal fibrosis. Conclusion Severe renal IR injury may lead to acute tubular necrosis, functional disorder and high mortality in short term. The initial structural injury in the kidney is irreversible and tubulointerstitial fibrosis is the final outcome. Increased myofibrolasts (s-SMA positive) and

  12. Kidney injury and heme oxygenase-1

    Directory of Open Access Journals (Sweden)

    Hai-xing MAI


    Full Text Available     Heme oxygenase-1 (HO-1 is one of the main pathways to degrade heme in mammals, and the main degradation products are free iron (Fe2+, carbon monoxide (CO, and bilirubin. Heme plays an important role in promoting cell survival, circulation of intracellular substrates, and immune regulation. Previous studies suggest that HO-1 pathway is an important internal factor in determining the susceptibility and severity of acute kidney injury (AKI. The induction of HO-1 expression can attenuate the severity of renal ischemia-reperfusion injury (IRI, and the inhibition of HO-1 expression will aggravate IRI. The present article summarizes the latest advances in research abroad and at home on protective mechanism by which HO-1 prevents AKI to further deepen our understanding of the role of HO-1 in the treatment of AKI.   

  13. The kidney research predicament. (United States)

    Bryan, Lisa; Ibrahim, Tod; Zent, Roy; Fischer, Michael J


    Research funding from public and private sources has reached an all-time low. Economic conditions, sequestration, and a trend of low award success rates have created an imbalance between the supply of highly qualified research investigators and the availability of critically necessary research dollars. This grim environment continues to hinder the success of established investigators and deter potential investigators from joining the research workforce. Without action and support of innovative science, the future of the US health care system is in jeopardy, and its leadership role in medical research will decrease. This work discusses the effects of the decline in research funding, the plight of kidney research, and the impact of the American Society of Nephrology Grants Program on scientists. The ASN also calls on the entire nephrology community to rejuvenate the research environment, improve the lives of millions of people with kidney disease, and ultimately, find a cure.

  14. Kidney Transplantation in Iran

    Directory of Open Access Journals (Sweden)

    Behzad Einollahi


    Full Text Available Kidney transplantation in patients with end stage renal diseaseis preferred to dialysis because transplantation provides a betterquality of life and improved survival. However, the gapbetween the supply and demand for a renal allograft is wideningand the waiting time is increasing. Iranian protocol, a controlledtransplant program supported by the government forliving unrelated donors, was initiated for solving the problemof organ shortage. Although this system might experiencechallenges, clearly it has advantages over other organ procurementsystems primarily that thousands in need do not diewhile waiting for a compatible donor.In the present review I discuss the history of renal transplantationin Iran, "Iranian model" protocol, the situation ofIran’s kidney transplantation from either living or deceaseddonors compared with the Middle East countries, and our experiencesof unrelated renal transplantation.

  15. Ultrasonic attenuation in pearlitic steel. (United States)

    Du, Hualong; Turner, Joseph A


    Expressions for the attenuation coefficients of longitudinal and transverse ultrasonic waves are developed for steel with pearlitic microstructure. This type of lamellar duplex microstructure influences attenuation because of the lamellar spacing. In addition, longitudinal attenuation measurements were conducted using an unfocused transducer with 10 MHz central frequency on the cross section of a quenched railroad wheel sample. The dependence of longitudinal attenuation on the pearlite microstructure is observed from the changes of longitudinal attenuation from the quenched tread surface to deeper locations. The results show that the attenuation value is lowest and relatively constant within the quench depth, then increases linearly. The experimental results demonstrate a reasonable agreement with results from the theoretical model. Ultrasonic attenuation provides an important non-destructive method to evaluate duplex microstructure within grains which can be implemented for quality control in conjunction with other manufacturing processes.

  16. Kidney Cell Electrophoresis (United States)

    Todd, P.


    Materials and procedures for microgravity electrophoresis of living human embryonic kidney cells were evaluated, ground support in the form of analytical cell electrophoresis and flow cytometry was provided and cells returned from space flight were analyzed. Preflight culture media, electrophoresis buffer, fraction collection media, temperature profiles, and urokinase assay procedures were tested prior to flight. Electrophoretic mobility distributions of aliquots of the cell population to be fractionated in flight were obtained. The protocol established and utilized is given.

  17. Kidney Transplantation in Iran



    Kidney transplantation in patients with end stage renal diseaseis preferred to dialysis because transplantation provides a betterquality of life and improved survival. However, the gapbetween the supply and demand for a renal allograft is wideningand the waiting time is increasing. Iranian protocol, a controlledtransplant program supported by the government forliving unrelated donors, was initiated for solving the problemof organ shortage. Although this system might experiencechallenges, clea...

  18. [Acute Kidney Injury]. (United States)

    Brix, Silke; Stahl, Rolf


    Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.

  19. Kidney stones during pregnancy. (United States)

    Semins, Michelle J; Matlaga, Brian R


    Kidney stones affect 10% of people at some point in their lives and, for some unfortunate women, this happens during pregnancy. Pregnancy is a complex state and both physiological and mechanical changes alter risk factors for kidney stone formation. When a pregnant woman develops acute nephrolithiasis, the situation is more complicated than in nonpregnant women. Imaging limitations and treatment restrictions mean that special diagnostic and management algorithms are needed upon presentation. Ultrasonography remains the gold-standard first-line diagnostic imaging modality for kidney stones during pregnancy but several second-line alternatives exist. Acute renal colic during pregnancy is associated with risks to both mother and fetus. As such, these patients need to be handled with special attention. First-line management is generally conservative (trial of passage and pain management) and is associated with a high rate of stone passage. Presentation of obstructive nephrolithiasis with associated infection represents a unique and serious clinical situation requiring immediate drainage. If infection is not present and conservative management fails, ureteroscopy can be offered if clinically appropriate, but, in some circumstances, temporary drainage with ureteral stent or nephrostomy tube might be indicated. Shockwave lithotripsy and percutaneous nephrolithotomy are contraindicated during pregnancy.

  20. Pregnancy and kidney transplantation. (United States)

    Josephson, Michelle A; McKay, Dianne B


    Despite decades of experience with child bearing in women with kidney transplants, these pregnancies remain high risk with an increased prevalence of hypertension and pre-eclampsia. Infertility, common in women with end-stage renal disease, is rapidly restored after transplant although pregnancy rates appear lower in transplant recipients than the general public. Many unanswered questions exist, some old questions such as what is the optimal timing of pregnancy after transplant, whether breast feeding is safe, the long-term impact if any on the offspring, and whether pregnancy negatively affects the kidney graft; and some new questions such as whether to modify immunosuppression in a patient taking a mycophenolic acid-containing drug, whether kidney donation has a deleterious impact on future pregnancies, whether to use erythropoietin-stimulating agents, and the role of BK virus. Counseling about contraception and pregnancy after transplant should be initiated during the pretransplant evaluation process. It is important because of the rapid restoration of fertility that occurs after transplant as well as the many risks and unanswered questions that remain.

  1. Connexins and the kidney. (United States)

    Hanner, Fiona; Sorensen, Charlotte Mehlin; Holstein-Rathlou, Niels-Henrik; Peti-Peterdi, János


    Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules, there is morphological evidence for the presence of gap junction plaques only in the proximal tubules. In the distal nephron, Cx30, Cx30.3, and Cx37 are expressed, but it is not known whether they form gap junctions connecting neighboring cells or whether they primarily act as hemichannels. As in other systems, the major function of Cxs in the kidney appears to be intercellular communication, although they may also form hemichannels that allow cellular secretion of large signaling molecules. Renal Cxs facilitate vascular conduction, juxtaglomerular apparatus calcium signaling, and tubular purinergic signaling. Accordingly, current evidence points to roles for these Cxs in several important regulatory mechanisms in the kidney, including the renin angiotensin system, tubuloglomerular feedback, and salt and water reabsorption. At the systemic level, renal Cxs may help regulate blood pressure and may be involved in hypertension and diabetes.

  2. Four miniature kidneys: supernumerary kidney and multiple organ system anomalies. (United States)

    Afrouzian, Marjan; Sonstein, Joseph; Dadfarnia, Tahereh; Sreshta, J Nicholas; Hawkins, Hal K


    More than 350 years after Martius's first reported case in 1656, supernumerary kidney (SNK) continues to fascinate the world of medicine, generating new ideas in the domain of embryogenesis. Association of a normal kidney with a second or third ipsilateral smaller kidney is an extremely rare anomaly with only a total of 81 cases reported until today. We are reporting a case of SNK, clinically diagnosed as right hydronephrosis, associated with an ipsilateral ectopic ureter, a contralateral partially duplicated ureter, and a multiseptate gallbladder. Pathologic examination of the nephrectomy revealed 4 miniature kidneys, joining a dilated ureter through 4 separate conduits. Our patient is the first reported case of SNK with absent ipsilateral normal kidney, presence of more than 3 kidneys on 1 side, and associated anomaly in the gallbladder. This case represents a unique combination of rarities, suggesting insights in the domain of molecular embryology.

  3. Nonlinear 3-D simulation of high-intensity focused ultrasound therapy in the kidney

    CERN Document Server

    Suomi, Visa; Treeby, Bradley; Cleveland, Robin


    Kidney cancer is a severe disease which can be treated non-invasively using high-intensity focused ultrasound (HIFU) therapy. However, tissue in front of the transducer and the deep location of kidney can cause significant losses to the efficiency of the treatment. The effect of attenuation, refraction and reflection due to different tissue types on HIFU therapy of the kidney was studied using a nonlinear ultrasound simulation model. The geometry of the tissue was derived from a computed tomography (CT) dataset of a patient which had been segmented for water, bone, soft tissue, fat and kidney. The combined effect of inhomogeneous attenuation and sound-speed was found to result in an 11.0 dB drop in spatial peak-temporal average (SPTA) intensity in the kidney compared to pure water. The simulation without refraction effects showed a 6.3 dB decrease indicating that both attenuation and refraction contribute to the loss in focal intensity. The losses due to reflections at soft tissue interfaces were less than 0....

  4. Trasplante renal Kidney transplant

    Directory of Open Access Journals (Sweden)

    P. Martín


    Full Text Available El trasplante renal es la terapia de elección para la mayoría de las causas de insuficiencia renal crónica terminal porque mejora la calidad de vida y la supervivencia frente a la diálisis. El trasplante renal de donante vivo es una excelente alternativa para el paciente joven en situación de prediálisis porque ofrece mejores resultados. El tratamiento inmunosupresor debe ser individualizado buscando la sinergia inmunosupresora y el mejor perfil de seguridad, y debe adaptarse a las diferentes etapas del trasplante renal. En el seguimiento del trasplante renal hay que tener muy en cuenta los factores de riesgo cardiovascular y los tumores puesto que la muerte del paciente con injerto funcionante es la segunda causa de pérdida del injerto tras el primer año del trasplante. La función alterada del injerto es un factor de mortalidad cardiovascular independiente que requerirá seguimiento y control de todas sus complicaciones para retrasar la entrada en diálisis.The kidney transplant is the therapy of choice for the majority of the causes of chronic terminal kidney insufficiency, because it improves the quality of life and survival in comparison with dialysis. A kidney transplant from a live donor is an excellent alternative for the young patient in a state of pre-dialysis because it offers the best results. Immunosuppressive treatment must be individualised, seeking immunosuppressive synergy and the best safety profile, and must be adapted to the different stages of the kidney transplant. In the follow-up to the kidney transplant, cardiovascular risk factors and tumours must be especially taken into account, given that the death of the patient with a working graft is the second cause of loss of the graft following the first year of the transplant. The altered function of the graft is a factor of independent cardiovascular mortality that will require follow-up and the control of all its complications to postpone the entrance in dialysis.

  5. Metformin in patients with chronic kidney disease: strengths and weaknesses. (United States)

    Rocha, Ana; Almeida, Marta; Santos, Josefina; Carvalho, André


    A wide array of benefits has been attributed to metformin. These include attenuation of abnormal glucose metabolism (diabetes treatment and prevention), weight neutrality or weight loss, improvement in the pathophysiologic components of metabolic syndrome (insulin resistance, subclinical inflammation, and endothelial dysfunction), lipid-lowering properties, cardiovascular protection, and antineoplastic potential. Metformin itself is not a nephrotoxic drug. Initially appointed as the safest hypoglycemic agent in chronic kidney disease, its use has been limited in these patients because of the perceived risk of lactic acidosis. A fear perpetuated by numerous case reports in which it is implicated. Current guidelines stipulate that it must be used with caution in estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute. Identified risk factors for metformin-associated lactic acidosis include acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock. Treatment may include supportive care and dialysis techniques. On the other hand, it is likely that the use of metformin would be beneficial in many with chronic kidney disease according to the advantages associated with attenuation of metabolic syndrome and cardiovascular protection. The reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment raises the question of limitation of its use in these patients.

  6. ABO-incompatible kidney transplantation

    DEFF Research Database (Denmark)

    Schousboe, Karoline; Titlestad, Kjell; Baudier, Francois;


    INTRODUCTION: Kidney transplantation is the optimal treatment for many patients with end-stage renal disease (ESRD). Due to shortage of donor kidneys in Denmark, there is a need to expand the possibilities for donation. At the Odense University Hospital (OUH), we have introduced ABO......-incompatible kidney transplantation. We used antigenspecific immunoadsorptions to remove blood group antibodies and anti-CD20 antibody (rituximab) to inhibit the antibody production. The aim of introducing the ABO-incompatible kidney transplantation at the OUH was to increase the rate of living donor kidney...... transplantation without increasing rejection or mortality rates. MATERIAL AND METHODS: Retrospective evaluation. Eleven patients received ABO-incompatible kidney transplantation. The patients were followed for 3-26 months. RESULTS: One patient had an antibody-mediated rejection, one patient suffered T...

  7. Living Kidney Donors and ESRD


    Ross, Lainie Friedman


    There are over 325 living kidney donors who have developed end-stage renal disease (ESRD) and have been listed on the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) deceased donor kidney wait list. The OPTN/UNOS database records where these kidney donors are listed and, if they donated after April 1994, where that donation occurred. These two locations are often not the same. In this commentary, I examine whether a national living donor registry s...

  8. CD74 in kidney disease

    Directory of Open Access Journals (Sweden)

    Lara eValiño-Rivas


    Full Text Available CD74 (invariant MHC class II regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF and D-dopachrome tautomerase (D-DT/MIF-2. CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3 levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeutics.

  9. [Autosomal recessive polycystic kidney]. (United States)

    Todorov, V; Penkova, S; Lalev, I


    A case of a 22 years old woman with autosomal-recessive form of kidney polycystosis is presented. The diagnosis was made in early childhood. A combination of renal anomaly and hepatic fibrosis with manifestations of portal hypertension was present. No deviations from the other internal organs were found. At the age of 12 she entered into the stage of chronic renal failure. The last five years she is on dialysis treatment. She had survived several acute bleedings from esophageal varices. The authors are of the opinion that the case is of interest since patients with autosomal-recessive renal polycystosis very rarely reach majority.

  10. Boron and the kidney. (United States)

    Pahl, Madeleine V; Culver, B Dwight; Vaziri, Nosratola D


    Boron, the fifth element in the periodic table, is ubiquitous in nature. It is present in food and in surface and ocean waters, and is frequently used in industrial, cosmetic, and medical settings. Exposure to boron and related compounds has been recently implicated as a potential cause of chronic kidney disease in Southeast Asia. This observation prompted the present review of the published data on the effects of acute and chronic exposure to boron on renal function and structure in human beings and in experimental animals.

  11. [Human physiology: kidney]. (United States)

    Natochin, Iu V


    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  12. The Vulcan kidney. (United States)

    Waud, D R


    One can often gain new insights into a topic when approaching it from a new angle. The paradigm example involves the insights into histology that can be gained from studying pathology. For example, a rare cell type in the pituitary suddenly becomes very easy to recognize once a whole field of them can be seen in a tumour. Similarly, one can gain insights by looking at species other than our own. In this article, Doug Waud, using the kidney in Vulcans, takes this latter theme one step further to provide useful insights into renal physiology and pharmacology.

  13. Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerates cutaneous wound healing.

    Directory of Open Access Journals (Sweden)

    Katsunari Makino

    Full Text Available Endothelin (ET-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF-α and connective tissue growth factor (CTGF were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

  14. Antagonist of leukotriene B4 receptor 1 attenuates cisplatin induced acute kidney injury in mice and its associated mechanism%白三烯B4受体1拮抗剂对顺铂致小鼠急性肾损伤的保护作用及机制研究

    Institute of Scientific and Technical Information of China (English)

    邓博; 林玉丽; 马帅; 何睿; 丁峰


    目的 观察白三烯B4受体1(leukotriene B4 receptor 1,BLT1)拮抗剂U75302对顺铂导致的小鼠急性肾损伤(Acute Kidney Injury,AKI)的保护作用,并探讨可能的抗炎机制.方法8周龄健康雄性C57BL/6小鼠随机分组为:正常对照组、U75302对照组、顺铂处理组、顺铂+U75302处理组,每组6只.其中顺铂处理组及顺铂+U75302处理组于第0天给予顺铂20 mg/kg,U75302对照组及顺铂+U75302处理组于第0、2天两次给予U75302 5μg/只.顺铂给药后3d处死小鼠,检测各组小鼠血清BUN、Scr水平,PAS糖原染色法观察肾脏病理改变,流式细胞术检测肾脏中浸润的炎症细胞数量,比色法检测肾组织匀浆MPO活性,抽提各组小鼠肾组织总RNA,实时荧光定量PCR检测肾组织炎症因子TNF-α、IL-1β及趋化因子CXCL1、CXCL2基因表达水平.结果 顺铂给药后3d,顺铂处理组小鼠血清BUN、Scr水平高于正常对照组(均P< 0.01);并出现明显的肾脏病理损伤;肾脏中浸润的炎症细胞包括中性粒细胞、巨噬细胞、CD4+T淋巴细胞、CD8+T淋巴细胞,数量明显增多(均P<0.01);肾组织匀浆中MPO活性明显上升(P<0.01);肾组织炎症因子TNF-α、IL-1β,趋化因子CXCL1、CXCL2基因表达明显上调(均P< 0.01).与顺铂处理组相比,顺铂+U75302处理组血清BUN改变减少[(17.75±1.80) mmol/L比(42.6±6.66) mmol/L,P<0.05],肾脏病理损伤减轻,肾脏中浸润的中性粒细胞、巨噬细胞数目减少[(146±13)×103/g比(296±66)×103/g,P<0.05]、[(245±13)×103/g比(420±78)×103/g,P<0.05],肾组织匀浆中MPO活性上升不明显[(1.756±0.283) U/g比(3.308±0.577) U/g,P<0.05],肾组织炎症因子TNF-α、IL-1β,趋化因子CXCL1、CXCL2基因表达增加程度降低.结论 BLT1拮抗剂U75302对顺铂导致的小鼠AKI具有保护作用,其保护机制与减少肾脏炎症细胞浸润,抑制肾脏炎症反应有关.%Objective To investigate the effect of pretreatment with U75302,antagonist of

  15. Kidneys and Urinary Tract (For Parents) (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... the kidneys gives the kidneys their dark red color. While the blood is in the kidneys, water ...

  16. Kidney Disease: Early Detection and Treatment (United States)

    ... Bar Home Current Issue Past Issues Special Section Kidney Disease: Early Detection and Treatment Past Issues / Winter ... called a "urine albumin-to-creatinine ratio." Treating Kidney Disease Kidney disease is usually a progressive disease, ...

  17. Kidney Stones in Children and Teens (United States)

    ... Issues Listen Español Text Size Email Print Share Kidney Stones in Children and Teens Page Content Article ... teen girls having the highest incidence. Types of Kidney Stones There are many different types of kidney ...

  18. Acute kidney injury: changing lexicography, definitions, and epidemiology. (United States)

    Himmelfarb, J; Ikizler, T A


    In recent years, there have been numerous advances in understanding the molecular determinants of functional kidney injury after ischemic and/or toxic exposure. However, translation of successful novel therapies designed to attenuate kidney functional injury from animal models to the clinical sphere has had modest results. This lack of translatability is at least in part due to lack of sufficient standardization in definitions and classification of cases of acute kidney injury (AKI), an incomplete understanding of the natural history of human AKI, and a limited understanding of how kidney injury interacts with other organ system failure in the context of systemic metabolic abnormalities. A concerted effort is now being made by nephrologists and intensivists to arrive at standardized terminology and classification of AKI. There have also been dramatic advances in our understanding of the epidemiology and natural history of AKI, particularly in the hospital and intensive care unit setting. Promising strategies are now being developed which may ultimately lead to improved outcomes for patients at risk for or who have developed AKI, which should be readily testable in the coming decade.

  19. Engineering attenuated virulence of a Theileria annulata-infected macrophage.

    Directory of Open Access Journals (Sweden)

    Nadia Echebli

    Full Text Available Live attenuated vaccines are used to combat tropical theileriosis in North Africa, the Middle East, India, and China. The attenuation process is empirical and occurs only after many months, sometimes years, of in vitro culture of virulent clinical isolates. During this extensive culturing, attenuated lines lose their vaccine potential. To circumvent this we engineered the rapid ablation of the host cell transcription factor c-Jun, and within only 3 weeks the line engineered for loss of c-Jun activation displayed in vitro correlates of attenuation such as loss of adhesion, reduced MMP9 gelatinase activity, and diminished capacity to traverse Matrigel. Specific ablation of a single infected host cell virulence trait (c-Jun induced a complete failure of Theileria annulata-transformed macrophages to disseminate, whereas virulent macrophages disseminated to the kidneys, spleen, and lungs of Rag2/γC mice. Thus, in this heterologous mouse model loss of c-Jun expression led to ablation of dissemination of T. annulata-infected and transformed macrophages. The generation of Theileria-infected macrophages genetically engineered for ablation of a specific host cell virulence trait now makes possible experimental vaccination of calves to address how loss of macrophage dissemination impacts the disease pathology of tropical theileriosis.

  20. Pyrrolidine dithiocarbamate reduces the progression of total kidney volume and cyst enlargement in experimental polycystic kidney disease. (United States)

    Ta, Michelle H T; Rao, Padmashree; Korgaonkar, Mayuresh; Foster, Sheryl F; Peduto, Anthony; Harris, David C H; Rangan, Gopala K


    Heterocyclic dithiocarbamates have anti-inflammatory and anti-proliferative effects in rodent models of chronic kidney disease. In this study, we tested the hypothesis that pyrrolidine dithiocarbamate (PDTC) reduces the progression of polycystic kidney disease (PKD). Male Lewis polycystic kidney (LPK) rats (an ortholog of Nek8/NPHP9) received intraperitoneal injections of either saline vehicle or PDTC (40 mg/kg once or twice daily) from postnatal weeks 4 until 11. By serial magnetic resonance imaging at weeks 5 and 10, the relative within-rat increase in total kidney volume and cyst volume were 1.3-fold (P = 0.01) and 1.4-fold (P < 0.01) greater, respectively, in LPK + Vehicle compared to the LPK + PDTC(40 mg/kg twice daily) group. At week 11 in LPK rats, PDTC attenuated the increase in kidney weight to body weight ratio by 25% (P < 0.01) and proteinuria by 66% (P < 0.05 vs. LPK + Vehicle) but did not improve renal dysfunction. By quantitative whole-slide image analysis, PDTC did not alter interstitial CD68+ cell accumulation, interstitial fibrosis, or renal cell proliferation in LPK rats at week 11. The phosphorylated form of the nuclear factor (NF)-κB subunit, p105, was increased in cystic epithelial cells of LPK rats, but was not altered by PDTC. Moreover, PDTC did not significantly alter nuclear expression of the p50 subunit or NF-κB (p65)-DNA binding. Kidney enlargement in LPK rats was resistant to chronic treatment with a proteasome inhibitor, bortezomib. In conclusion, PDTC reduced renal cystic enlargement and proteinuria but lacked anti-inflammatory effects in LPK rats.

  1. ABO-Incompatible Kidney Transplantation (United States)

    Morath, Christian; Zeier, Martin; Döhler, Bernd; Opelz, Gerhard; Süsal, Caner


    ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation, but is poorly understood. There is still concern, however, that infectious complications such as viral disease, Pneumocystis jirovecii pneumonia, and severe urinary tract infections are increased after ABOi transplantations. Recent data from the Collaborative Transplant Study show that during the first year after kidney transplantation, one additional patient death from an infectious complication occurs in 100 ABOi kidney transplant recipients. Herein, we review the recent evidence on ABOi kidney transplantation with a focus on desensitization strategies and respective outcomes. PMID:28321223

  2. Anemia in Chronic Kidney Disease (United States)

    ... High Blood Pressure Heart Disease Mineral & Bone Disorder Anemia in Chronic Kidney Disease What is anemia? Anemia is a condition in which the body ... function as well as they should. How is anemia related to chronic kidney disease? Anemia commonly occurs ...

  3. Cancer rates after kidney transplantation

    DEFF Research Database (Denmark)

    Sodemann, Ulrik; Bistrup, Claus; Marckmann, Peter


    Previous studies demonstrated a 3-5-fold increased cancer risk in kidney allograft recipients compared with the general population. Our aim was to estimate cancer frequencies among kidney allograft recipients who were transplanted in 1997-2000 and who were immunosuppressed according to a more...

  4. Dual kidney transplantation: case report. (United States)

    Vidas, Zeljko; Kocman, Branislav; Knotek, Mladen; Skegro, Dinko


    Chronic shortage of kidney transplants worldwide has led to the use of organs from so called marginal or borderline donors, now termed "expanded-criteria donors". There has been an emerging practice of dual kidney transplantation (DKT) to compensate for sub optimal nephron mass of such kidneys. We performed DKT in "Merkur" University Hospital in August 2005. The donor was a 72-year old female with a history of long-term hypertension, aneurysm of the posterior cerebral artery, cerebrovascular insult (CVI), and with normal creatinine values and kidney function at the time of explantation. Initial biopsy of donor kidneys revealed acute tubular damage, with connective changes in 22% and 11% of glomeruli in the left and the right kidney, respectively. The recipient was a 60-year old male diagnosed with the IgA nephropathy on the last biopsy in 1999, and on dialysis since November 2003. Postoperative course was uneventful without any surgical complications. A triple immunosuppressive protocol was used. On follow-up ultrasonography 4 years posttransplantation both kidneys appeared of normal size and parenchymal pattern and with no signs of dilatation of the canal system, and color Doppler examination demonstrated normal flow in both kidneys. In conclusion, the use of DKT ie. donors by the expanded-criteria will continue to increase, and further studies of the results will, with no doubt, support this method.

  5. Antioxidant protection of statins in acute kidney injury induced by sepsis

    Directory of Open Access Journals (Sweden)

    Franciele do Nascimento Santos


    Full Text Available Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control; SHAM+Statin (0.5 mg/kg simvastatin, orally; Sepsis (cecal puncture ligation – CPL; Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

  6. Intestinal microbiota-kidney cross talk in acute kidney injury and chronic kidney disease. (United States)

    Noel, Sanjeev; Martina-Lingua, Maria N; Bandapalle, Samatha; Pluznick, Jennifer; Hamad, Abdel Rahim A; Peterson, Daniel A; Rabb, Hamid


    The pathophysiology of acute kidney injury (AKI) involves multiple and overlapping immunological, biochemical, and hemodynamic mechanisms that modulate the effects of both the initial insult and the subsequent repair. Limited but recent experimental data have revealed that the intestinal microbiota significantly affects outcomes in AKI. Additional evidence shows significant changes in the intestinal microbiota in chronic kidney disease patients and in experimental AKI. In this minireview, we discuss the current status of the effect of intestinal microbiota on kidney diseases, the immunomodulatory effects of intestinal microbiota, and the potential mechanisms by which microbiota can modify kidney diseases and vice versa. We also propose future studies to clarify the role of intestinal microbiota in kidney diseases and to explore how the modification of gut microbiota may be a potential therapeutic tool.

  7. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease. (United States)

    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi


    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.

  8. Deep Tissue Microscopic Imaging of the Kidney with a Gradient-Index Lens System. (United States)

    Li, Xin; Yu, Weiming


    Intravital microscopy using two-photon excitation is proven to be a valuable tool for studying the kidney and associated disease processes. However, routine performance of intravital kidney imaging is limited by the fact that fluorescence signal is attenuated by the tissue and at certain tissue depth lost its strength completely. For most of the animal tissues, this finite imaging depth is limited to a few hundred microns. Currently it is not possible to non-invasively image the kidney beyond the superficial tissue layers of the cortex. This has imposed significant limitations on the animal models one can use for imaging since structure such the glomerulus is typically located below the superficial layer of the cortex that can not be imaged using a conventional fluorescence microscope. Here we report the use of a needle-like lens system based on gradient-index (GRIN) microlenses capable of transferring high quality fluorescence images of the tissue through a regular microscope objective for deep tissue imaging of the kidney. By combining this GRIN lens system with a Zeiss LSM 510 NLO microscope, we are able to extend the imaging depth for kidney tissues far beyond the few hundred microns limit. This GRIN lens imaging system provides an alternative microendoscopic imaging tool that will enhance current intravital kidney imaging techniques for studying structural and functional properties of local tissues at locations below the superficial layers of the kidney.

  9. [MicroRNAs and kidneys]. (United States)

    Stříteská, Jana; Nekvindová, Jana; Cerný, Vladimír; Palička, Vladimír


    MicroRNAs are short non-coding ribonucleic acid molecules that regulate gene expression at the post-transcriptional level thus affecting important physiological as well as pathophysiological processes in the organism, for example cell differentiation, proliferation, apoptosis, and metabolism. They are involved in pathogenesis of many diseases including cancer. Many microRNAs are tissue or organ-specific which implies their possible potential as biomarkers or maybe even therapeutical agents as documented by microRNA research interest rising exponentially during last years. Among all, microRNAs are important also for physiological function of the kidney and they are involved in various renal disorders. Today research is focused mainly on renal and urinary tract carcinogenesis, acute kidney injury, chronic renal diseases (polycystic kidney disease) or renal complications of systemic diseases such as diabetic or hypertension nephropathy and autoimmune kidney injury including acute allograft rejection after kidney transplantation. The review summarizes current information about microRNA effect on kidney development and function and also on the most common kidney diseases.

  10. Horseshoe kidney: a case report

    Directory of Open Access Journals (Sweden)

    Naveena S


    Full Text Available The horseshoe kidney was originally regarded as a rare anatomical curiosity, but with the aid of retrograde pyelogram, intravenous urogram and renal arteriograms in this present age of diagnosis, the incidence of horseshoe kidney is estimated at 1 in 200-400 individuals or 1 in 700 autopsies and usually remains asymptomatic. The present report is concerned with a case of horseshoe kidney, which was observed during routine cadaveric dissection, for student education in anatomy dissection hall of Osmania medical college, in a male cadaver. The kidneys formed a U-shaped structure as a result of fusion at the inferior poles of the original kidneys by a parenchymatous isthmus. As a whole, the structure presented a typical horseshoe shape. The location of the kidney was lower than that of the normal kidney. The renal arterial system was almost normal except for a surplus artery into the isthmus that directly originated from the aorta, at the origin of inferior mesenteric artery. Venous drainage of both the kidneys and the isthmus was through two veins which opened independently into the inferior vena cava. The hila on both sides opened towards the ventral direction, and the ureters descended in front of the isthmus and entered the bladder normally. This report is being made because it affords material for a review of embryological and gross anatomy findings in a case of horseshoe kidney, which could help in a thorough urologic evaluation in diagnosed cases prior to any surgical intervention. [Int J Res Med Sci 2013; 1(3.000: 304-307

  11. Galacto-oligosaccharides attenuate renal injury with microbiota modification. (United States)

    Furuse, Satoshi U; Ohse, Takamoto; Jo-Watanabe, Airi; Shigehisa, Akira; Kawakami, Koji; Matsuki, Takahiro; Chonan, Osamu; Nangaku, Masaomi


    Tubulointerstitial injury is central to the progression of end-stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto-oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham-operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS-treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury.

  12. The blind kidney: disorders affecting kidneys and eyes. (United States)

    Russell-Eggitt, Isabelle; Bockenhauer, Detlef


    There are many disorders that can affect both the kidneys and the eyes. Awareness of the ocular manifestations of kidney disorders is important as it can guide the diagnosis and facilitate the choice of a specific treatment. Conversely, ophthalmologists need to be aware of potential renal manifestations in disorders presenting initially with visual failure. We review disorders affecting both of these organ systems, based upon cases from our clinical practice to highlight the importance of interdisciplinary collaboration.

  13. Genetic loci influencing kidney function and chronic kidney disease

    NARCIS (Netherlands)

    Chambers, John C.; Zhang, Weihua; Lord, Graham M.; van der Harst, Pim; Lawlor, Debbie A.; Sehmi, Joban S.; Gale, Daniel P.; Wass, Mark N.; Ahmadi, Kourosh R.; Bakker, Stephan J. L.; Beckmann, Jacqui; Bilo, Henk J. G.; Bochud, Murielle; Brown, Morris J.; Caulfield, Mark J.; Connell, John M. C.; Cook, H. Terence; Cotlarciuc, Ioana; Smith, George Davey; de Silva, Ranil; Deng, Guohong; Devuyst, Olivier; Dikkeschei, Lambert D.; Dimkovic, Nada; Dockrell, Mark; Dominiczak, Anna; Ebrahim, Shah; Eggermann, Thomas; Farrall, Martin; Ferrucci, Luigi; Floege, Jurgen; Forouhi, Nita G.; Gansevoort, Ron T.; Han, Xijin; Hedblad, Bo; van der Heide, Jaap J. Homan; Hepkema, Bouke G.; Hernandez-Fuentes, Maria; Hypponen, Elina; Johnson, Toby; de Jong, Paul E.; Kleefstra, Nanne; Lagou, Vasiliki; Lapsley, Marta; Li, Yun; Loos, Ruth J. F.; Luan, Jian'an; Luttropp, Karin; Marechal, Celine; Melander, Olle; Munroe, Patricia B.; Nordfors, Louise; Parsa, Afshin; Peltonen, Leena; Penninx, Brenda W.; Perucha, Esperanza; Pouta, Anneli; Prokopenko, Inga; Roderick, Paul J.; Ruokonen, Aimo; Samani, Nilesh J.; Sanna, Serena; Schalling, Martin; Schlessinger, David; Schlieper, Georg; Seelen, Marc A. J.; Shuldiner, Alan R.; Sjogren, Marketa; Smit, Johannes H.; Snieder, Harold; Soranzo, Nicole; Spector, Timothy D.; Stenvinkel, Peter; Sternberg, Michael J. E.; Swaminathan, Ramasamyiyer; Tanaka, Toshiko; Ubink-Veltmaat, Lielith J.; Uda, Manuela; Vollenweider, Peter; Wallace, Chris; Waterworth, Dawn; Zerres, Klaus; Waeber, Gerard; Wareham, Nicholas J.; Maxwell, Patrick H.; McCarthy, Mark I.; Jarvelin, Marjo-Riitta; Mooser, Vincent; Abecasis, Goncalo R.; Lightstone, Liz; Scott, James; Navis, Gerjan; Elliott, Paul; Kooner, Jaspal S.


    Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney

  14. Haptoglobin Phenotype Predicts a Low Heart Rate Variability in Patients with Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Svensson, My; Strandhave, Charlotte; Krarup, H.B.;

    F-PO1096 Haptoglobin Phenotype Predicts a Low Heart Rate Variability in Patients with Chronic Kidney Disease My Svensson,1 Charlotte Strandhave,1 Henrik My Svensson,1 Charlotte Strandhave,1 HenrikKrarup,2 Jeppe H. Christensen.1 1Department of Nephrology, Aalborg Hospital, Aalborg, Denmark; 2...... to a phenotype-dependent antioxidant capacity where Hp 2-2 exhibits a low antioxidant ability, increasing the risk of cardiovascular disease. An attenuated heart rate variability (HRV) may be an important predictor of mortality in patients with chronic kidney disease (CKD). In the present study, we examined...

  15. Diet for Kidney Stone Prevention (United States)

    ... from foods Uric Acid Stones Limit animal protein Reduce sodium Talk with a health care professional about how ... MSG sodium alginate sodium nitrate or nitrite To reduce sodium to help prevent kidney stones, avoid processed and ...

  16. [Ascites and acute kidney injury]. (United States)

    Piano, Salvatore; Tonon, Marta; Angeli, Paolo


    Ascites is the most common complication of cirrhosis. Ascites develops as a consequence of an abnormal splanchnic vasodilation with reduction of effecting circulating volume and activation of endogenous vasoconstrictors system causing salt and water retention. Patients with ascites have a high risk to develop further complications of cirrhosis such as hyponatremia, spontaneous bacterial peritonitis and acute kidney injury resulting in a poor survival. In recent years, new studies helped a better understanding of the pathophysiology of ascites and acute kidney injury in cirrhosis. Furthermore, new diagnostic criteria have been proposed for acute kidney injury and hepatorenal syndrome and a new algorithm for their management has been recommended with the aim of an early diagnosis and treatment. Herein we will review the current knowledge on the pathophysiology, diagnosis and treatment of ascites and acute kidney injury in patients with cirrhosis and we will identify the unmet needs that should be clarified in the next years.

  17. Semiactive control for vibration attenuation

    Energy Technology Data Exchange (ETDEWEB)

    Leitmann, G. [Univ. of California, Berkeley, CA (United States). Coll. of Engineering


    With the advent of materials, such as electrorheological fluids, whose material properties can be altered rapidly by means of external stimuli, employing such materials as actuators for the controlled attenuation of undesirable vibrations is now possible. Such control schemes are dubbed semiactive in that they attenuate vibrations whether applied actively or passively. The author investigates various such control schemes, allowing for both separate and joint control of the stiffness and damping characteristics of the material.

  18. Hepatitis C and Kidney Disease

    Directory of Open Access Journals (Sweden)

    Ashik Hayat


    Full Text Available Multiple extrahepatic manifestations have been associated with chronic hepatitis C, the most important among them being cryoglobulinemia, glomerulonephritis, porphyria cutanea tarda, lichen planus, seronegative arthritis, and lymphoproliferative disorders as in the sudies of Bonkovsky and Mehta (2001 and El-Serag et al. (2002. We will discuss in this paper chronic hepatitis C- related kidney disease and course and management of patients with chronic hepatitis C in special circumstances like hemodialysis and kidney transplantation.

  19. Finerenone : third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease

    NARCIS (Netherlands)

    Liu, Licette C. Y.; Schutte, Elise; Gansevoort, Ron T.; van der Meer, Peter; Voors, Adriaan A.


    Introduction: The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone reduce the risk of hospitalizations and mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF), and attenuate progression of diabetic kidney disease. However, their use is limi

  20. Caffeic acid phenethyl ester attenuates liver fibrosis via inhibition of TGF-β1/Smad3 pathway and induction of autophagy pathway. (United States)

    Yang, Ning; Dang, Shuangsuo; Shi, Juanjuan; Wu, Fengping; Li, Mei; Zhang, Xin; Li, Yaping; Jia, Xiaoli; Zhai, Song


    Caffeic acid phenethyl ester (CAPE) has been reported to possess the hepatoprotective effect. This study was to investigate the mechanism underlying CAPE against liver fibrosis in a liver fibrosis model induced by toxic carbon tetrachloride (CCl4) in male Sprague-Dawley rats and in vitro in CAPE (5 μM, 10 μM, 15 μM) treated hepatic stellate cells (HSC-T6). We found that CAPE treatment remarkably attenuated CCl4-induced liver fibrosis by blocking the activation of HSCs as determined by the expression alternation of transforming growth factor (TGF)-β1, phosphorylated Smad3 (p-Smad3), collage I, α-smooth muscle actin (α-SMA), matrix metalloproteinases (MMPs) 2, tissue inhibitor of matrix metalloproteinases (TIMPs) 1. The hepatoprotective effects of CAPE were also associated with upregulation of autophasomes in HSCs as determined by transmission electron microscopy (TEM) detection. The in vitro study further confrimed that CAPE attenuated liver fibrogenesis via inducing authophagic markers including LC3, ATG5, Beclin 1 expressions, while inhibiting AKT/mTOR signaling in HSC-T6 cells. Thus, the protective effects of CAPE against liver fibrosis might due to the inhibition of TGF-β1/Smad3 signaling and induction of authophagy in HSCs.

  1. Peroxisome proliferator-activated receptor-γ agonist pioglitazone attenuates cisplatin-induced acute kidney injury through inhibiting inflammation in mice%PPAR-γ激动剂吡格列酮通过抑制炎症反应减轻顺铂诱导的小鼠急性肾损伤

    Institute of Scientific and Technical Information of China (English)

    张炯; 徐钢; 李俊华; 肖芳; 兰小勤; 裴广畅; 李月强; 刘蔚; 高红宇; 韩敏


    目的 研究过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)-γ激动剂吡格列酮对顺铂(cisplatin,CDDP)诱导的小鼠急性肾损伤(acute kidney injury,AKI)的可能保护作用及其机制.方法 腹腔注射顺铂制备小鼠AKI模型.18只小鼠随机分为正常对照组(CT组),AKI模型组(C组)和吡格列酮治疗组(C+P组).C组和C+P组按25 mg/kg给予顺铂处理.C+P组在顺铂注射前3 d,连续三天给予吡格列酮灌胃.CT组给予生理盐水作为对照.顺铂或盐水处理72 h后处死小鼠,收集血清和肾脏标本.测定血清肌酐和尿素氮,PAS染色后显微镜下观察肾脏形态学变化,同时通过Western blot检测炎症指标诱生型一氧化氮合酶(inducible nitric oxide synthase,iNOS).结果 与CT组相比,CDDP诱导C组血清肌酐及尿素氮明显升高,病理检查可见肾小管上皮细胞肿胀坏死、蛋白管型形成及炎症细胞浸润明显增加,同时炎症指标iNOS表达上调.与C组相比,C+P组血清肌酐、尿素氮明显下降,肾小管上皮细胞肿胀坏死减轻,炎症细胞浸润减少,iNOS表达下调.结论 PPAR-γ激动剂吡格列酮可通过抑制iNOS削弱炎症反应从而减轻顺铂诱导的小鼠急性肾损伤.

  2. Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury. (United States)

    Heilman, R L; Smith, M L; Kurian, S M; Huskey, J; Batra, R K; Chakkera, H A; Katariya, N N; Khamash, H; Moss, A; Salomon, D R; Reddy, K S


    Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p-value kidneys from deceased donors with AKI is safe and has excellent outcomes.

  3. [Kidney donors and kidney transplantation in the elderly]. (United States)

    Giessing, M; Conrad, S; Schönberger, B; Huland, H; Budde, K; Neumayer, H-H; Loening, S A


    The likelihood of terminal renal insufficiency escalates with age, increasing the risk of dying as a patient requiring dialysis. In 1999, Eurotransplant initiated the Eurotransplant Senior Programm (ESP), in which the kidneys of old donors (>64 years) are allocated to recipients 64 years and older. Allocation does not take HLA-matching into account and is performed regionally only according to blood-group-compatibility to keep the storage time short. As a consequence of the short ischemic time, and thus reduced non-immunological damage to the anyways susceptible old kidney, graft-function and graft-survival in the ESP are very good. The results of the initial 5 years of this program show that it successfully utilizes more kidneys from old donors and that more old recipients are being transplanted, with a satisfactory graft-function. Increased donor- and/or recipient age require a thorough evaluation to exclude malignant and other diseases. Furthermore, short term controls on the waiting list and following kidney transplantation are prerequisites for successful transplantation in the aged recipient. If this is guaranteed, kidney transplantation in the old recipient-even with old donor organs-is a good alternative to the morbidity of a prolonged dialysis. Nevertheless, the role of HLA-matching should be reconsidered to reduce rejections.

  4. An examination on the correction of attenuation for calculating the renal RI accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Onoue, Koichi; Tachibana, Keizo; Maeda, Yoshihiro; Yanoo, Sanae; Morishita, Etsuko; Kawanaka, Masahiro; Kashiwagi, Toru; Fukuchi, Minoru [Hyogo Coll. of Medicine, Nishinomiya (Japan). Hospital


    An examination was made on the attenuation coefficients for calculation of true renal accumulation rate together with the precision of measurement of depth in the kidney. Kidney phantom for attenuation coefficients was a 20 x 20 cm cube where water was filled and radioactivity source of {sup 99m}Tc was placed at various depths. Radioactivity was measured by four kinds of scinti-camera with the collimator LEGP and LEHR. The phantom for radioactivity accumulation in the kidney was a 10 x 5 x 1, 3 or 5 cm box where {sup 99m}Tc solution of the standard 30 MBq was filled, and subjected to radioactivity measurement from various angles. Phantom radioactivity was found corrected by the effective attenuation coefficient, 0.131 cm, within the range of 98-114% of the standard counts. The precision of measurement of the depth was examined in sideways scintigrams obtained in clinical practice and was found to have the deviation of 1.1 cm as the mean of maximum ones and the variation coefficient of 7.1%. Measured depth was found to be well correlated with estimated ones by the method of Tonnesen or Ito which had the maximum deviation of 5.4 or 3.5 cm, respectively. (K.H.)

  5. Photoacoustic Imaging Taking into Account Attenuation

    CERN Document Server

    Kowar, Richard


    First, we review existing attenuation models and discuss their causality properties, which we believe to be essential for algorithms for inversion with attenuated data. Then, we survey causality properties of common attenuation models. We also derive integro-differential equations which the attenuated waves are satisfying. In addition we discuss the ill--conditionness of the inverse problem for calculating the unattenuated wave from the attenuated one.

  6. Attenuation in Superconducting Circular Waveguides

    Directory of Open Access Journals (Sweden)

    K. H. Yeap


    Full Text Available We present an analysis on wave propagation in superconducting circular waveguides. In order to account for the presence of quasiparticles in the intragap states of a superconductor, we employ the characteristic equation derived from the extended Mattis-Bardeen theory to compute the values of the complex conductivity. To calculate the attenuation in a circular waveguide, the tangential fields at the boundary of the wall are first matched with the electrical properties (which includes the complex conductivity of the wall material. The matching of fields with the electrical properties results in a set of transcendental equations which is able to accurately describe the propagation constant of the fields. Our results show that although the attenuation in the superconducting waveguide above cutoff (but below the gap frequency is finite, it is considerably lower than that in a normal waveguide. Above the gap frequency, however, the attenuation in the superconducting waveguide increases sharply. The attenuation eventually surpasses that in a normal waveguide. As frequency increases above the gap frequency, Cooper pairs break into quasiparticles. Hence, we attribute the sharp rise in attenuation to the increase in random collision of the quasiparticles with the lattice structure.

  7. Current Bioengineering Methods for Whole Kidney Regeneration

    Directory of Open Access Journals (Sweden)

    Shuichiro Yamanaka


    Full Text Available Kidney regeneration is likely to provide an inexhaustible source of tissues and organs for immunosuppression-free transplantation. It is currently garnering considerable attention and might replace kidney dialysis as the ultimate therapeutic strategy for renal failure. However, anatomical complications make kidney regeneration difficult. Here, we review recent advances in the field of kidney regeneration, including (i the directed differentiation of induced pluripotent stem cells/embryonic stem cells into kidney cells; (ii blastocyst decomplementation; (iii use of a decellularized cadaveric scaffold; (iv embryonic organ transplantation; and (v use of a nephrogenic niche for growing xenoembryos for de novo kidney regeneration from stem cells. All these approaches represent potentially promising therapeutic strategies for the treatment of patients with chronic kidney disease. Although many obstacles to kidney regeneration remain, we hope that innovative strategies and reliable research will ultimately allow the restoration of renal function in patients with end-stage kidney disease.

  8. Regenerating a kidney in a lymph node. (United States)

    Francipane, Maria Giovanna; Lagasse, Eric


    The ultimate treatment for end-stage renal disease (ESRD) is orthotopic transplantation. However, the demand for kidney transplantation far exceeds the number of available donor organs. While more than 100,000 Americans need a kidney, only 17,000 people receive a kidney transplant each year (National Kidney Foundation's estimations). In recent years, several regenerative medicine/tissue engineering approaches have been exploited to alleviate the kidney shortage crisis. Although these approaches have yielded promising results in experimental animal models, the kidney is a complex organ and translation into the clinical realm has been challenging to date. In this review, we will discuss cell therapy-based approaches for kidney regeneration and whole-kidney tissue engineering strategies, including our innovative approach to regenerate a functional kidney using the lymph node as an in vivo bioreactor.

  9. [Secondary cystic changes in the kidneys in chronic kidney failure]. (United States)

    Todorov, V; Lalev, I; Monov, A; Penkova, S


    In patients with chronic renal failure the presence and frequency of acquired cystic changes in the kidneys (acquired cystic renal disease) were studied. 46 patients, 21 to 62 years of age and duration of hemodialysis treatment from 2 up to 126 months, were examined. The patients with polycystic kidneys were excluded. Cysts were found in 67.4% of the patients. They were classified into five groups. Between the duration of the hemodialysis treatment (the chronic renal failure respectively) and the development of the cystic renal disease correlation was found. The correlation between the length of the kidneys and the cystic changes is statistically significant. There is no correlation with the sex, age, basic disease, hematologic indices, diuresis and arterial pressure of the patients. In 50% of the patients examined splenomegaly was found the cause of which is not known.

  10. Fatty Liver and Chronic Kidney Disease: Novel Mechanistic Insights and Therapeutic Opportunities. (United States)

    Musso, Giovanni; Cassader, Maurizio; Cohney, Solomon; De Michieli, Franco; Pinach, Silvia; Saba, Francesca; Gambino, Roberto


    Chronic kidney disease (CKD) is a risk factor for end-stage renal disease (ESRD) and cardiovascular disease (CVD). ESRD or CVD develop in a substantial proportion of patients with CKD receiving standard-of-care therapy, and mortality in CKD remains unchanged. These data suggest that key pathogenetic mechanisms underlying CKD progression go unaffected by current treatments. Growing evidence suggests that nonalcoholic fatty liver disease (NAFLD) and CKD share common pathogenetic mechanisms and potential therapeutic targets. Common nutritional conditions predisposing to both NAFLD and CKD include excessive fructose intake and vitamin D deficiency. Modulation of nuclear transcription factors regulating key pathways of lipid metabolism, inflammation, and fibrosis, including peroxisome proliferator-activated receptors and farnesoid X receptor, is advancing to stage III clinical development. The relevance of epigenetic regulation in the pathogenesis of NAFLD and CKD is also emerging, and modulation of microRNA21 is a promising therapeutic target. Although single antioxidant supplementation has yielded variable results, modulation of key effectors of redox regulation and molecular sensors of intracellular energy, nutrient, or oxygen status show promising preclinical results. Other emerging therapeutic approaches target key mediators of inflammation, such as chemokines; fibrogenesis, such as galectin-3; or gut dysfunction through gut microbiota manipulation and incretin-based therapies. Furthermore, NAFLD per se affects CKD through lipoprotein metabolism and hepatokine secretion, and conversely, targeting the renal tubule by sodium-glucose cotransporter 2 inhibitors can improve both CKD and NAFLD. Implications for the treatment of NAFLD and CKD are discussed in light of this new therapeutic armamentarium.

  11. Molecular Imaging of the Kidneys (United States)

    Szabo, Zsolt; Alachkar, Nada; Xia, Jinsong; Mathews, William B.; Rabb, Hamid


    Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms in order to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive and accurate diagnosis. The most recent imaging technology, PET, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H215O, 82RbCl, and [64Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype AT1R using in vivo PET imaging. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc-99m MAG3 as well as some novel radiopharmaceuticals such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands have been utilized for molecular renal imaging. Additionally, other radioligands that interact with the organic cation transporters or peptide transporters have developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule- 1 (KIM-1) that is highly expressed in kidney injury and renal cancer but not in normal kidneys. While pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on upregulated molecules in response to tissue stress resulted from obstruction will be of great implication. Monocyte chemoattractant protein -1 (MCP-1) is a well-suited molecule in this case. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [18F]FDG, other radioligands such as [11C]acetate and anti-[18F]FACBC have emerged. Radioimmuno-imaging with [124I]G250 could lead to radioimmunotherapy for renal cancer

  12. Isorhamnetin attenuates liver fibrosis by inhibiting TGF-β/Smad signaling and relieving oxidative stress. (United States)

    Yang, Ji Hye; Kim, Sang Chan; Kim, Kyu Min; Jang, Chang Ho; Cho, Sam Seok; Kim, Seung Jung; Ku, Sae Kwang; Cho, Il Je; Ki, Sung Hwan


    Hepatic fibrosis is considered integral to the progression of chronic liver diseases, leading to the development of cirrhosis and hepatocellular carcinoma. Activation of hepatic stellate cells (HSCs) is the dominant event in hepatic fibrogenesis. We investigated the ability of isorhamnetin, the 3'-O-methylated metabolite of quercetin, to protect against hepatic fibrosis in vitro and in vivo. Isorhamnetin inhibited transforming growth factor (TGF)-β1-induced expression of α-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and collagen in primary murine HSCs and LX-2 cells. The TGF-β1- or Smad-induced luciferase reporter activity of Smad binding elements was significantly decreased by isorhamnetin with a concomitant decrease in Smad2/3 phosphorylation. Isorhamnetin increased the nuclear translocation of Nrf2 in HSCs and increased antioxidant response element reporter gene activity. Furthermore, isorhamnetin blocked TGF-β1-induced reactive oxygen species production. The specific role of Nrf2 in isorhamnetin-mediated suppression of PAI-1 and phosphorylated Smad3 was verified using a siRNA against Nrf2. To examine the anti-fibrotic effect of isorhamnetin in vivo, liver fibrosis was induced by CCl4 in mice. Isorhamnetin significantly prevented CCl4-induced increases in serum alanine transaminase and aspartate transaminase levels, and caused histopathological changes characterized by decreases in hepatic degeneration, inflammatory cell infiltration, and collagen accumulation. Moreover, isorhamnetin markedly decreased the expression of phosphorylated Smad3, TGF-β1, α-SMA, and PAI-1. Isorhamnetin attenuated the CCl4-induced increase in the number of 4-hydroxynonenal and nitrotyrosine-positive cells, and prevented glutathione depletion. We propose that isorhamnetin inhibits the TGF-β/Smad signaling pathway and relieves oxidative stress, thus inhibiting HSC activation and preventing liver fibrosis.

  13. Serum thymic factor, FTS, attenuates cisplatin nephrotoxicity by suppressing cisplatin-induced ERK activation. (United States)

    Kohda, Yuka; Kawai, Yoshiko; Iwamoto, Noriaki; Matsunaga, Yoshiko; Aiga, Hiromi; Awaya, Akira; Gemba, Munekazu


    Serum thymic factor (FTS), a thymic peptide hormone, has been reported to attenuate the bleomycin-induced pulmonary injury and also experimental pancreatitis and diabetes. In the present study, we investigated the effect of FTS on cis-diamminedichloroplatinum II (cisplatin)-induced nephrotoxicity. We have already demonstrated that cephaloridine, a nephrotoxic antibiotic, leads to extracellular signal-regulated protein kinase (ERK) activation in the rat kidney, which probably contributes to cephaloridine-induced renal dysfunction. The aim of this study was to examine the effect of cisplatin on ERK activation in the rat kidney and also the effect of FTS on cisplatin-induced nephrotoxicity in rats. In vitro treatment of LLC-PK1 cells with FTS significantly ameliorated cisplatin-induced cell injury. Treatment of rats with intravenous cisplatin for 3 days markedly induced renal dysfunction and increased platinum contents in the kidney cortex. An increase in pERK was detected in the nuclear fraction prepared from the rat kidney cortex from days 1 to 3 after injection of cisplatin. FTS suppressed cisplatin-induced renal dysfunction and ERK activation in the kidney. FTS did not influence any Pt contents in the kidney after cisplatin administration. FTS has been shown to enhance the in vivo expression of heat shock protein (HSP) 70 in the kidney cortex. The beneficial role of FTS against cisplatin nephrotoxicity may be mediated in part by HSP70, as suggested by its up-regulation in the kidney cortex treated with FTS alone. Our results suggest that FTS participates in protection from cisplatin-induced nephrotoxicity by suppressing ERK activation caused by cisplatin.

  14. X-Ray Attenuation Cell

    Energy Technology Data Exchange (ETDEWEB)

    Ryutov, D.; Toor, A.


    To minimize the pulse-to-pulse variation, the LCLS FEL must operate at saturation, i.e. 10 orders of magnitude brighter spectral brilliance than 3rd-generation light sources. At this intensity, ultra-high vacuums and windowless transport are required. Many of the experiments, however, will need to be conducted at a much lower intensity thereby requiring a reliable means to reduce the x-ray intensity by many orders of magnitude without increasing the pulse-to-pulse variation. In this report we consider a possible solution for controlled attenuation of the LCLS x-ray radiation. We suggest using for this purpose a windowless gas-filled cell with the differential pumping. Although this scheme is easily realizable in principle, it has to be demonstrated that the attenuator can be made short enough to be practical and that the gas loads delivered to the vacuum line of sight (LOS) are acceptable. We are not going to present a final, optimized design. Instead, we will provide a preliminary analysis showing that the whole concept is robust and is worth further study. The spatial structure of the LCLS x-ray pulse at the location of the attenuator is shown in Fig. 1. The central high-intensity component, due to the FEL, has a FWHM of {approx}100 {micro}m. A second component, due to the undulator's broad band spontaneous radiation is seen as a much lower intensity ''halo'' with a FWHM of 1 mm. We discuss two versions of the attenuation cell. The first is directed towards a controlled attenuation of the FEL up to the 4 orders of magnitude in the intensity, with the spontaneous radiation halo being eliminated by collimators. In the second version, the spontaneous radiation is not sacrificed but the FEL component (as well as the first harmonic of the spontaneous radiation) gets attenuated by a more modest factor up to 100. We will make all the estimates assuming that the gas used in the attenuator is Xenon and that the energy of the FEL is 8.25 keV. At

  15. Primary Leiomyosarcoma of the Kidney

    Directory of Open Access Journals (Sweden)

    Kusuma Venkatesh


    Full Text Available Primary leiomyosarcoma of the kidney is a rare tumor with an aggressive behaviour. A 55-year-old woman presented with a left sided abdominal mass in our outpatient department. Radiologic investigations revealed the mass to be renal in origin with colonic adhesions for which radical nephrectomy and hemicolectomy were done. The tumor completely appeared to replace the left kidney and had a whorled character focally on cut section. Microscopically, spindle cells having malignant features with cigar shaped nuclei were seen. The smooth muscle origin of the cells was confirmed by immunohistochemical positivity for smooth muscle actin. Sarcomatoid variant of the renal cell carcinoma was ruled out as the tumor was negative for cytokeratin. Tumors with spindle cell morphology in the kidney should not always be taken for a sarcomatoid variant of renal cell carcinoma and should be investigated thoroughly.

  16. An attempt to reconstruct the lithotriptor shock wave pulse in kidney: possible temperature effects. (United States)

    Filipczyński, L; Etienne, J; Piechocki, M


    Based on measurements carried out in water in two lithotriptor systems, the authors have made an attempt to reconstruct numerically amplitudes and shapes of shock wave pulses penetrating into kidney which differ from those in water. The difference between these pulses and those observed in water was analyzed and was also demonstrated experimentally. The amplitude and the steepness of the reconstructed pulse front were shown to be much lower than in water depending on the distance of the kidney stone from the patient's body surface. For a distance equal to 4 cm, the shock wave pulse amplitude of 40 MPa in water was estimated to decrease in the kidney by a factor of about two and the steepness of the positive shock pulse front to decrease several times. The analysis was carried out by considering the possible changes of absorption and attenuation in tissues which increase in an unknown way with the wave amplitude. It was shown that the temperature elevation caused by the increase of nonlinear high amplitude absorption is limited due to a corresponding increase in attenuation of the shock wave penetrating soft tissues. The temperature elevation was estimated on the basis of this work to be at most 1.8 times that one estimated in the case of two considered lithotripsy systems when assuming small amplitude absorption and attenuation coefficients.


    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia


    Full Text Available Aim: evaluation of the incidence and the pattern of vessel complications, efficacy of the prophylactic anticoagulation therapy after kidney transplantation. Materials and methods. From March 2007 till January 2013 421 patients: 230 men (54,6% and 191 women (45,4%; mean age 43,07 ± 11,62 undergone 429 kidney transplantations in the department of pancreas and kidney transplantation of the Scientific-Research Institute of Emergency Care named after N.V. Sklifosovsky. In order to evaluate the condition and the function of the kidney transplant ultrasound investigation (daily andacquisition(weekly wereused. In cases of kidney dysfunction and assumption of vessel complications we used computerized tomography. Besides, we used daily analysis of biochemical and clinical parameters of blood and urine. Results. The most common vessel complication was the thrombosis of the microvasculature of the kidney transplant due to acute humoral and combined rejection resistant to antirejection therapy (n = 9; 2,1%; in 4 cases there was a breakage of the transplant due to the acute rejection and the urgent transplantatectomy in an effort to save the patient; thrombosis of the transplantat artery occurred in 1 case (0,23%; we observed 2 cases (0,46% of the artery stenosis and 2 cases (0,46% of venous thrombosis. Conclusion. Summary frequency of vessel complications in our clinic, including thrombosis due to rejection, was 3,49%. It fully corresponds with data obtained from the global medical community. The incidence of great vessel thrombosis was less than 1% which indicates the adequate prophylactic anticoagulation therapy. For the benefit of early diacrisis of complications Doppler sonography is needed. In case of assumption of vessel complications urgent acquisition, computerized tomography and/ or angiography are to be held. 

  18. Attenuation in silica-based optical fibers

    DEFF Research Database (Denmark)

    Wandel, Marie Emilie


    In this thesis on attenuation in silica based optical fibers results within three main topics are reported. Spectral attenuation measurements on transmission fibers are performed in the wide wavelength range 290 nm – 1700 nm. The measured spectral attenuation is analyzed with special emphasis...... on absorption peaks in order to investigate the cause of an unusual high attenuation in a series of transmission fibers. Strong indications point to Ni2+ in octahedral coordination as being the cause of the high attenuation. The attenuation of fibers having a high core refractive index is analyzed and the cause...... of the high attenuation measured in such fibers is described as being due to scattering of light on fluctuations of the core diameter. A novel semi-empirical model for predicting the attenuation of high index fibers is presented. The model is shown to be able to predict the attenuation of high index fibers...

  19. [Mechanism of and Therapy for Kidney Fibrosis]. (United States)

    Kuma, Akihiro; Tamura, Masahito; Otsuji, Yutaka


    Fibrosis occurs in systemic tissues other than the brain and finally induces dysfunction of the fibrotic organ. Kidney fibrosis is related to scarring after acute kidney injury and the progression of chronic kidney disease. Kidney function decreases with the progression of kidney fibrosis. As fibrotic tissue cannot return to its original status, advanced kidney fibrosis requires the administration of dialysis or kidney transplantation. Thus, elucidation the mechanism of kidney fibrosis is an important research theme. The proliferation and activation of (myo) fibroblasts and the excessive production of an extracellular matrix are common mechanisms in fibrosis in many organs, but it seems that kidney fibrosis has specific pathways. Tubular epithelial, mesangial cells, and erythropoietin producing cells, which exist only in the kidney, participate in forming kidney fibrosis. This review highlights an understanding of the cells and their underlying mechanisms, which are specific to kidney fibrosis process: transforming growth factor-β (TGF-β), epithelial-mesenchymal transition, wingless/int-1 (WNT) signaling, renal anemia, and uremia. Finally, we describe potential therapies that focus on the mechanisms of kidney fibrosis: anti-TGF-β antibody and mammalian target of rapamycin (mTOR).

  20. Utility evaluation on application of geometric mean depending on depth of kidney in split renal function test using 99mTc-MAG{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Byeul; Ahn, Sung Min [Dept. of Radiological Science, Gachon University, Incheon (Korea, Republic of); Lee, Wang Hui [Dept. of Nuclear Medicine, Gil-Hospital, Incheon (Korea, Republic of)


    99mTc-MAG{sub 3} Renal scan is a method that acquires dynamic renal scan image by using 99mTc-MAG{sub 3} and dynamically visualizes process of radioactive agent being absorbed to kidney and excreted continuously. Once the test starts, ratio in both kidneys in 1-2.5 minutes was measured to obtain split renal function and split renal function can be expressed in ratio based on overall renal function. This study is based on compares split renal function obtained from data acquired from posterior detector, which is a conventional renal function test method, with split renal function acquired from the geometric mean of values obtained from anterior and posterior detectors, and studies utility of attenuation compensation depending on difference in geometric mean kidney depth. From July, 2015 to February 2016, 33 patients who undertook 99mTc-MAG{sub 3} Renal scan(13 male, 20 female, average age of 44.66 with range of 5-70, average height of 160.40 cm, average weight of 55.40 kg) were selected as subjects. Depth of kidney was shown to be 65.82 mm at average for left and 71.62 mm at average for right. In supine position, 30 out of 33 patients showed higher ratio of deep-situated kidney and lower ratio of shallow-situated kidney. Such result is deemed to be due to correction by attenuation between deep-situated kidney and detector and in case where there is difference between the depth of both kidneys such as, lesions in or around kidney, spine malformation, and ectopic kidney, ratio of deep-situated kidney must be compensated for more accurate calculation of split renal function, when compared to the conventional test method (posterior detector counting)

  1. Mathematical modeling of kidney transport. (United States)

    Layton, Anita T


    In addition to metabolic waste and toxin excretion, the kidney also plays an indispensable role in regulating the balance of water, electrolytes, nitrogen, and acid-base. In this review, we describe representative mathematical models that have been developed to better understand kidney physiology and pathophysiology, including the regulation of glomerular filtration, the regulation of renal blood flow by means of the tubuloglomerular feedback mechanisms and of the myogenic mechanism, the urine concentrating mechanism, epithelial transport, and regulation of renal oxygen transport. We discuss the extent to which these modeling efforts have expanded our understanding of renal function in both health and disease.

  2. Myeloperoxidase in Chronic Kidney Disease


    Madhusudhana Rao, A.; Anand, Usha; Anand, C. V.


    Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD...

  3. Platelet-derived growth factor-D modulates extracellular matrix homeostasis and remodeling through TIMP-1 induction and attenuation of MMP-2 and MMP-9 gelatinase activities

    Energy Technology Data Exchange (ETDEWEB)

    Borkham-Kamphorst, Erawan, E-mail:; Alexi, Pascal; Tihaa, Lidia; Haas, Ute; Weiskirchen, Ralf, E-mail:


    Platelet-derived growth factor-D (PDGF-D) is a more recent recognized growth factor involved in the regulation of several cellular processes, including cell proliferation, transformation, invasion, and angiogenesis by binding to and activating its cognate receptor PDGFR-β. After bile duct ligation or in the carbon tetrachloride-induced hepatic fibrosis model{sub ,} PDGF-D showed upregulation comparable to PDGF-B. Moreover, adenoviral PDGF-D gene transfer induced hepatic stellate cell proliferation and liver fibrosis. We here investigated the molecular mechanism of PDGF-D involvement in liver fibrogenesis. Therefore, the GRX mouse cell line was stimulated with PDGF-D and evaluated for fibrotic markers and PDGF-D signaling pathways in comparison to the other PDGF isoforms. We found that PDGF-D failed to enhance Col I and α-smooth muscle actin (α-SMA) production but has capacity to upregulate expression of the tissue inhibitor of metalloprotease 1 (TIMP-1) resulting in attenuation of MMP-2 and MMP-9 gelatinase activity as indicated by gelatinase zymography. This phenomenon was restored through application of a PDGF-D neutralizing antibody. Unexpectedly, PDGF-D incubation decreased both PDGFR-α and -β in mRNA and protein levels, and PDGF-D phosphorylated typrosines specific for PDGFR-α and -β. We conclude that PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP system and that PDGF-D signaling is mediated through both PDGF-α and -β receptors. - Highlights: • PDGF-D signals through PDGF receptor type α and β. • PDGF-D modulates extracellular matrix homeostasis and remodeling. • Like PDGF-B, PDGF-D triggers phosphorylation of PLC-γ, Akt/PKB, JNK, ERK1/2, and p38. • PDGF-D induces TIMP-1 expression through ERK and p38 MAPK. • PDGF-D attenuates MMP-2 and MMP-9 gelatinase activities.

  4. Why kidneys fail in autosomal dominant polycystic kidney disease. (United States)

    Grantham, Jared J; Mulamalla, Sumanth; Swenson-Fields, Katherine I


    The weight of evidence gathered from studies in humans with hereditary polycystic kidney disease (PKD)1 and PKD2 disorders, as well as from experimental animal models, indicates that cysts are primarily responsible for the decline in glomerular filtration rate that occurs fairly late in the course of the disease. The processes underlying this decline include anatomic disruption of glomerular filtration and urinary concentration mechanisms on a massive scale, coupled with compression and obstruction by cysts of adjacent nephrons in the cortex, medulla and papilla. Cysts prevent the drainage of urine from upstream tributaries, which leads to tubule atrophy and loss of functioning kidney parenchyma by mechanisms similar to those found in ureteral obstruction. Cyst-derived chemokines, cytokines and growth factors result in a progression to fibrosis that is comparable with the development of other progressive end-stage renal diseases. Treatment of renal cystic disorders early enough to prevent or reduce cyst formation or slow cyst growth, before the secondary changes become widespread, is a reasonable strategy to prolong the useful function of kidneys in patients with autosomal dominant polycystic kidney disease.

  5. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.


    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc bias...

  6. Compact plasmonic variable optical attenuator

    DEFF Research Database (Denmark)

    Leosson, Kristjan; Rosenzveig, Tiberiu; Hermannsson, Pétur Gordon


    We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators operating in the 1525-1625 nm wavelength range. The devices have a footprint as low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and full modulation bandwidth of 1 kHz. The polarization...

  7. Control Blood Pressure, Protect Your Kidneys (United States)

    ... Bar Home Current Issue Past Issues Health Lines Control Blood Pressure, Protect Your Kidneys Past Issues / Fall ... Not Alone / Keep Weight Off / Facts About Fat / Control Blood Pressure, Protect Your Kidneys Fall 2008 Issue: ...

  8. Low Phosphorus Diet: Best for Kidney Disease? (United States)

    ... diet: Best for kidney disease? Why is a low-phosphorus diet useful in managing kidney disease? What ... choose foods that are lower in phosphorus. Choose low-phosphorus foods The best way to limit phosphorus ...

  9. When Your Child Needs a Kidney Transplant (United States)

    ... live as they did before developing kidney failure. Different Types of Kidney Transplants There are two kinds of ... So it's vital for parents to communicate the importance of taking all medicines as directed. Be there for your child to ...

  10. 真皮与脂肪组织来源成纤维细胞致纤维化能力的比较研究%Fibrogenesis between dermal and adipose tissue-derived fibroblasts

    Institute of Scientific and Technical Information of China (English)

    原博; 王西樵; 青春; 陆树良


    Objective To investigate the fibrogenesis of dermal and adipose tissue-derived fibroblasts, and explore the mechanism. Methods Fibroblasts derived from dermal tissues and subcutaneous adipose tissues in the same pig were isolated and cultured. Inverted microscope and transmission electron microscope were used to observe the cell morphology and ultrastructure, and Real-Time PCR was employed to detect the relative expression of procollagen type I Mrna, procollagen type III Mrna, a-smooth muscle actin (α-SMA) Mrna, transforming growth factor β1(TGF-β1) Mrna and insulin-like growth factor-1 (IGF-1) Mrna in cells. Results Compared with adipose tissue-derived fibroblasts, the cell body of dermal tissue-derived fibroblasts was larger, with expanded rough endoplasmic reticulum. The relative expression of precollagen type I Mrna and α-SMA Mrna in dermal tissue-derived fibroblasts was significantly higher than that in adipose tissue-derived fibroblasts (P 0. 05). Conclusion There are differences in cell morphology and function concerning with fibrogenesis between dermal tissue-derived fibroblasts and adipose tissue-derived fibroblasts. The starting points of wound healing process after dermal and adipose tissue impairment are different between dermal tissue-derived fibroblasts and adipose tissue-derived fibroblasts.%目的 初步探讨真皮与脂肪组织来源的成纤维细胞的致纤维化能力及其作用机制.方法 自同一杜洛克雌性猪真皮和皮下脂肪组织中分别分离和培养成纤维细胞,利用倒置显微镜和透射电子显微镜观察细胞形态和超微结构,采用Real-Time PCR技术检测细胞Ⅰ型和Ⅲ型前胶原、α平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)和类胰岛素样生长因子1(IGF-1)mRNA的相对表达量.结果 与脂肪来源的成纤维细胞比较,真皮组织来源的成纤维细胞胞体较大,粗面内质网扩张明显.Real-Time PCR检测结果显示:真皮组织来源的成纤维细胞

  11. Stormwater Attenuation by Green Roofs (United States)

    Sims, A.; O'Carroll, D. M.; Robinson, C. E.; Smart, C. C.


    Innovative municipal stormwater management technologies are urgently required in urban centers. Inadequate stormwater management can lead to excessive flooding, channel erosion, decreased stream baseflows, and degraded water quality. A major source of urban stormwater is unused roof space. Green roofs can be used as a stormwater management tool to reduce roof generated stormwater and generally improve the quality of runoff. With recent legislation in some North American cities, including Toronto, requiring the installation of green roofs on large buildings, research on the effectiveness of green roofs for stormwater management is important. This study aims to assess the hydrologic response of an extensive sedum green roof in London, Ontario, with emphasis on the response to large precipitation events that stress municipal stormwater infrastructure. A green roof rapidly reaches field capacity during large storm events and can show significantly different behavior before and after field capacity. At field capacity a green roof has no capillary storage left for retention of stormwater, but may still be an effective tool to attenuate peak runoff rates by transport through the green roof substrate. The attenuation of green roofs after field capacity is linked to gravity storage, where gravity storage is the water that is temporarily stored and can drain freely over time after field capacity has been established. Stormwater attenuation of a modular experimental green roof is determined from water balance calculations at 1-minute intervals. Data is used to evaluate green roof attenuation and the impact of field capacity on peak flow rates and gravity storage. In addition, a numerical model is used to simulate event based stormwater attenuation. This model is based off of the Richards equation and supporting theory of multiphase flow through porous media.

  12. Attitude toward living kidney donation

    NARCIS (Netherlands)

    Martínez-Alarcón, L.; Ramis, G.; Gómez-Laguna, J.; Quereda, J.J.; Herrero-Medrano, J.M.; Mrowiec, A.; Mendonça, L.; López-Navas, A.; Ríos, A.


    Introduction Due to the current deficit of organs for transplantation, living kidney related donations (LKRD) should be promoted. Veterinarians often hold decision-making positions in the public health care system, and therefore can influence public opinion about organ donation. The objective was

  13. Prorenin receptor in kidney development. (United States)

    Yosypiv, Ihor V


    Prorenin receptor (PRR), a receptor for renin and prorenin and an accessory subunit of the vacuolar proton pump H(+)-ATPase, is expressed in the developing kidney. Global loss of PRR is lethal in mice, and PRR mutations are associated with a high blood pressure, left ventricular hypertrophy and X-linked mental retardation in humans. With the advent of modern gene targeting techniques, including conditional knockout approaches, several recent studies have demonstrated critical roles for the PRR in several lineages of the developing kidney. PRR signaling has been shown to be essential for branching morphogenesis of the ureteric bud (UB), nephron progenitor survival and nephrogenesis. PRR regulates these developmental events through interactions with other transcription and growth factors. Several targeted PRR knockout animal models have structural defects mimicking congenital anomalies of the kidney and urinary tract observed in humans. The aim of this review, is to highlight new insights into the cellular and molecular mechanisms by which PRR may regulate UB branching, terminal differentiation and function of UB-derived collecting ducts, nephron progenitor maintenance, progression of nephrogenesis and normal structural kidney development and function.

  14. Sepsis and Acute Kidney Injury. (United States)

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail


    Acute kindney injury (AKI) 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. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  15. Collective Phenomena in Kidney Autoregulation

    DEFF Research Database (Denmark)

    Mosekilde, Erik; Sosnovtseva, Olga; Holstein-Rathlou, N.-H.


    By controling the excretion of water and salts, the kidneys play all important role ill regulating the blood pressure and maintaining a proper environment for the cells of the body. This control depends to a large extent oil mechanisms that are associated with the individual functional unit...


    Directory of Open Access Journals (Sweden)

    V. B. Berdichevskiy


    Full Text Available By analyzing data from the literature and the results of own clinical the authors suggest the presence of its own physiological rhythmogenesis motility of the urinary system to ensure its functional viability after denervation in the process of donor kidney recоvery and its transplantation to the recipient. 

  17. Pharm GKB: Kidney Failure, Acute [PharmGKB

    Lifescience Database Archive (English)

    Full Text Available iew Alternate Names: Synonym ARF - Acute renal failure; Acute Kidney Failure; Acute Kidney Failures; Acute K...idney Insufficiencies; Acute Kidney Insufficiency; Acute Renal Failure; Acute Renal Failures; Acute... Renal Insufficiencies; Acute Renal Insufficiency; Acute renal failure syndrome, NOS; Failure, Acute... Kidney; Failure, Acute Renal; Failures, Acute Kidney; Failures, Acute Renal; Insufficiencies, Acute... Kidney; Insufficiencies, Acute Renal; Insufficiency, Acute Kidney; Insufficiency, Acute

  18. Matricaria chamomilla attenuates cisplatin nephrotoxicity. (United States)

    Salama, Ragaa H M


    Matricaria chamomilla is extensively consumed as a tea or tonic. Despite its widespread use as a home remedy, relatively few trials evaluated its benefits in nephro protection. Hence, this study evaluates the protective role of M. chamomilla in cisplatin nephrotoxicity rat model. The study was conducted on 32 rats divided into four groups. The first group (G1) was injected with saline intra-peritoneally (IP); G2 was injected with 5 mg/kg cisplatin on day 0 of the experiment and repeated four times, with five days free interval. G3 and G4 were injected daily with M. chamomilla (50 mg/kg) IP, starting five days before the experiment (-5 day); in addition, G4 was injected with cisplatin. On day 16, animals were scarified and serum and/or kidney tissue was used to determine: (a) kidney function tests (serum urea, creatinine, gamma glutamyl transferase (GGT), NAG, β-gal), (b) oxidative stress indices (NO, LPO), (c) antioxidant activities (SOD, GSH, total thiols), (d) apoptotic indices (Cathepsin D, DNA fragmentation) and (e) mineral (calcium). M. chamomilla significantly increased the body weight, normalized the kidney functions, improved the apoptotic markers, reduced the oxidative stress markers and corrected the hypo-calcemia that resulted from cisplatin nephrotoxicity. M. chamomilla is a promising nephro-protective compound reducing cisplatin nephrotoxicity most probably by its antioxidant activities and inhibition of gamma glutamyl transferase activity.

  19. Matricaria chamomilla attenuates cisplatin nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Ragaa H.M. Salama


    Full Text Available Matricaria chamomilla is extensively consumed as a tea or tonic. Despite its widespread use as a home remedy, relatively few trials evaluated its benefits in nephro protection. Hence, this study evaluates the protective role of M. chamomilla in cisplatin nephrotoxicity rat model. The study was conducted on 32 rats divided into four groups. The first group (G1 was injected with saline intra-peritoneally (IP; G2 was injected with 5 mg/kg cisplatin on day 0 of the experiment and repeated four times, with five days free interval. G3 and G4 were injected daily with M. chamomilla (50 mg/kg IP, starting five days before the experiment (-5 day; in addition, G4 was injected with cisplatin. On day 16, animals were scarified and serum and/or kidney tissue was used to determine: (a kidney function tests (serum urea, creatinine, gamma glutamyl transferase (GGT, NAG, β-gal, (b oxidative stress indices (NO, LPO, (c antioxidant activities (SOD, GSH, total thiols, (d apoptotic indices (Cathepsin D, DNA fragmentation and (e mineral (calcium. M. chamomilla significantly increased the body weight, normalized the kidney functions, improved the apoptotic markers, reduced the oxidative stress markers and corrected the hypo-calcemia that resulted from cisplatin nephrotoxicity. M. chamomilla is a promising nephro-protective compound reducing cisplatin nephrotoxicity most probably by its antioxidant activities and inhibition of gamma glutamyl transferase activity.

  20. Kidney Tumors | Office of Cancer Genomics (United States)

    Pediatric kidney tumors fall into four primary categories: Wilms tumors (~85% of all cases), clear cell sarcomas of the kidney (~5%), congenital mesoblastic nephromas (~4%), and rhabdoid tumors of the kidney (~3%). The TARGET initiative is investigating three of these tumor types.

  1. Kidney regeneration and repair after transplantation

    NARCIS (Netherlands)

    M. Franquesa (Marcella); M. Flaquer (Maria); J.M. Cruzado; J. Grinyo (Josep)


    textabstractPURPOSE OF REVIEW: To briefly show which are the mechanisms and cell types involved in kidney regeneration and describe some of the therapies currently under study in regenerative medicine for kidney transplantation. RECENT FINDINGS: The kidney contains cell progenitors that under specif

  2. Transplantation of horseshoe kidney en bloc. (United States)

    Nahas, W C; Hakim, N S; Mazzucchi, E; Antonopoulos, L M; Eltayar, A R; Labruzzo, C; Chocair, P R; Arap, S


    Horseshoe kidney is probably the most common renal fusion anomaly. With the continuous donor shortage, transplant surgeons tend to accept donors previously considered unsuitable. We present a successful case of en bloc horseshoe kidney transplant in a single recipient. The literature is reviewed. The use of horseshoe kidneys in transplantation is recommended in selected cases.

  3. Overview of Kidney Diseases in Children (United States)

    ... Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD ... or may go away completely once the underlying cause has been treated. Chronic kidney disease (CKD) does not go away with treatment and ...

  4. Clinical implications of the solitary functioning kidney

    NARCIS (Netherlands)

    Westland, R.; Schreuder, M.F.; Goudoever, J.B. van; Sanna-Cherchi, S.; Wijk, J.A. van


    Congenital anomalies of the kidney and urinary tract are the major cause of ESRD in childhood. Children with a solitary functioning kidney form an important subgroup of congenital anomalies of the kidney and urinary tract patients, and a significant fraction of these children is at risk for progress

  5. HIV and chronic kidney disease. (United States)

    Naicker, Saraladevi; Rahmanian, Sadaf; Kopp, Jeffrey B


    Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 - 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is the second most common diagnosis obtained from biopsies of patients with HIV-CKD. CKD is mediated by factors related to the virus, host genetic predisposition and environmental factors. The host response to HIV infection may influence disease phenotype through activation of cytokine pathways. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated the overall improvement in kidney function when initiating ART for HIV CKD. Progression to end stage kidney disease has been reported to be more likely when high grade proteinuria, severely reduced eGFR, hepatitis B and/C co-infection, diabetes mellitus, extensive glomerulosclerosis, and chronic interstitial fibrosis are present. Improved renal survival is associated with use of renin angiotensin system blockers and viral suppression. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. Certain drug classes, such as the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are metabolized by the liver and do not require dose adjustment. HIV-infected patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV

  6. Antioxidant treatment attenuates lactate production in diabetic nephropathy

    DEFF Research Database (Denmark)

    Laustsen, Christoffer; Nielsen, Per Mose; Stokholm Nørlinger, Thomas


    The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying......-of-the-art hyperpolarized magnetic resonance (MR) imaging. Ten-week-old female Wistar rats were randomly divided into three groups: healthy controls, untreated diabetic (streptozotocin treatment to induce insulinopenic diabetes), and diabetic, receiving chronic antioxidant treatment with TEMPOL (4-hydroxy-2......-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels...

  7. Galacto‐oligosaccharides attenuate renal injury with microbiota modification (United States)

    Furuse, Satoshi U.; Ohse, Takamoto; Jo‐Watanabe, Airi; Shigehisa, Akira; Kawakami, Koji; Matsuki, Takahiro; Chonan, Osamu; Nangaku, Masaomi


    Abstracts Tubulointerstitial injury is central to the progression of end‐stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto‐oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham‐operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS‐treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury. PMID:24994892

  8. Ferrite attenuator modulation improves antenna performance (United States)

    Hooks, J. C.; Larson, S. G.; Shorkley, F. H.; Williams, B. T.


    Ferrite attenuator inserted into appropriate waveguide reduces the gain of the antenna element which is causing interference. Modulating the ferrite attenuator to change the antenna gain at the receive frequency permits ground tracking until the antenna is no longer needed.

  9. Metformin Protects Against Cisplatin-Induced Tubular Cell Apoptosis and Acute Kidney Injury via AMPKα-regulated Autophagy Induction. (United States)

    Li, Jianzhong; Gui, Yuan; Ren, Jiafa; Liu, Xin; Feng, Ye; Zeng, Zhifeng; He, Weichun; Yang, Junwei; Dai, Chunsun


    Metformin, one of the most common prescriptions for patients with type 2 diabetes, is reported to protect the kidney from gentamicin-induced nephrotoxicity. However, the role and mechanisms for metformin in preventing cisplatin-induced nephrotoxicity remains largely unknown. In this study, a single intraperitoneal injection of cisplatin was employed to induce acute kidney injury (AKI) in CD1 mice. The mice exhibited severe kidney dysfunction and histological damage at day 2 after cisplatin injection. Pretreatment of metformin could markedly attenuate cisplatin-induced acute kidney injury, tubular cell apoptosis and inflammatory cell accumulation in the kidneys. Additionally, pretreatment of metformin could enhance both AMPKα phosphorylation and autophagy induction in the kidneys after cisplatin injection. In cultured NRK-52E cells, a rat kidney tubular cell line, metformin could stimulate AMPKα phosphorylation, induce autophagy and inhibit cisplatin-induced cell apoptosis. Blockade of either AMPKα activation or autophagy induction could largely abolish the protective effect of metformin in cisplatin-induced cell death. Together, this study demonstrated that metformin may protect against cisplatin-induced tubular cell apoptosis and AKI through stimulating AMPKα activation and autophagy induction in the tubular cells.

  10. Utilization of kidneys with similar kidney donor risk index values from standard versus expanded criteria donors. (United States)

    Woodside, K J; Merion, R M; Leichtman, A B; de los Santos, R; Arrington, C J; Rao, P S; Sung, R S


    With the shortage of standard criteria donor (SCD) kidneys, efficient expanded criteria donor (ECD) kidney utilization has become more vital. We investigated the effects of the ECD label on kidney recovery, utilization and outcomes. Using data from the Scientific Registry of Transplant Recipients from November 2002 to May 2010, we determined recovery and transplant rates, and modeled discard risk, for kidneys within a range of kidney donor risk index (KDRI) 1.4-2.1 that included both SCD and ECD kidneys. To further compare similar quality kidneys, these kidneys were again divided into three KDRI intervals. Overall, ECD kidneys had higher recovery rates, but lower transplant rates. However, within each KDRI interval, SCD and ECD kidneys were transplanted at similar rates. Overall, there was increased risk for discard for biopsied kidneys. SCD kidneys in the lower two KDRI intervals had the highest risk of discard if biopsied. Pumped kidneys had a lower risk of discard, which was modulated by KDRI for SCD kidneys but not ECD kidneys. Although overall ECD graft survival was worse than SCD, there were no differences within individual KDRI intervals. Thus, ECD designation adversely affects neither utilization nor outcomes beyond that predicted by KDRI.


    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O


    In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

  12. Salicylic Acid Attenuates Gentamicin-Induced Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Pavle Randjelovic


    Full Text Available Gentamicin (GM is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

  13. Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats. (United States)

    Randjelovic, Pavle; Veljkovic, Slavimir; Stojiljkovic, Nenad; Jankovic-Velickovic, Ljubinka; Sokolovic, Dusan; Stoiljkovic, Milan; Ilic, Ivan


    Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.

  14. Chlorine signal attenuation in concrete. (United States)

    Naqvi, A A; Maslehuddin, M; ur-Rehman, Khateeb; Al-Amoudi, O S B


    The intensity of prompt gamma-ray was measured at various depths from chlorine-contaminated silica fume (SF) concrete slab concrete specimens using portable neutron generator-based prompt gamma-ray setup. The intensity of 6.11MeV chloride gamma-rays was measured from the chloride contaminated slab at distance of 15.25, 20.25, 25.25, 30.25 and 35.25cm from neutron target in a SF cement concrete slab specimens. Due to attenuation of thermal neutron flux and emitted gamma-ray intensity in SF cement concrete at various depths, the measured intensity of chlorine gamma-rays decreases non-linearly with increasing depth in concrete. A good agreement was noted between the experimental results and the results of Monte Carlo simulation. This study has provided useful experimental data for evaluating the chloride contamination in the SF concrete utilizing gamma-ray attenuation method.

  15. Development of a porcine renal extracellular matrix scaffold as a platform for kidney regeneration. (United States)

    Choi, Seock Hwan; Chun, So Young; Chae, Seon Yeong; Kim, Jin Rae; Oh, Se Heang; Chung, Sung Kwang; Lee, Jin Ho; Song, Phil Hyun; Choi, Gyu-Seog; Kim, Tae-Hwan; Kwon, Tae Gyun


    Acellular scaffolds, possessing an intact three-dimensional extracellular matrix (ECM) architecture and biochemical components, are promising for regeneration of complex organs, such as the kidney. We have successfully developed a porcine renal acellular scaffold and analyzed its physical/biochemical characteristics, biocompatibility, and kidney reconstructive potential. Segmented porcine kidney cortexes were treated with either 1% (v/v) Triton X-100 (Triton) or sodium dodecyl sulfate (SDS). Scanning electron microscopy showed both treatments preserved native tissue architecture, including porosity and composition. Swelling behavior was higher in the Triton-treated compared with the SDS-treated scaffold. Maximum compressive strength was lower in the Triton-treated compared with the SDS-treated scaffold. Attenuated total reflective-infrared spectroscopy showed the presence of amide II (-NH) in both scaffolds. Furthermore, richer ECM protein and growth factor contents were observed in the Triton-treated compared with SDS-treated scaffold. Primary human kidney cell adherence, viability, and proliferation were enhanced on the Triton-treated scaffold compared with SDS-treated scaffold. Following murine in vivo implantation, tumorigenecity was absent for both scaffolds after 8 weeks and in the Triton-treated scaffold only, glomeruli-like structure formation and neovascularity were observed. We identified 1% Triton X-100 as a more suitable decellularizing agent for porcine renal ECM scaffolds prior to kidney regeneration.

  16. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function. (United States)

    Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P


    Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

  17. Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Teng; Tian, Wulin; Liu, Fangning; Xie, Guanghong, E-mail:


    Highlights: • β-Hydroxybutyrate inhibits paraquat-induced toxicity in rat kidney. • β-Hydroxybutyrate inhibits lipid peroxidation and caspase-mediated apoptosis. • β-Hydroxybutyrate increases the activities of SOD and CAT. • The study describes a novel finding for the renoprotective ability of β-hydroxybutyrate. - Abstract: In this study, we demonstrated the protective effects of β-hydroxybutyrate (β-HB) against paraquat (PQ)-induced kidney injury and elucidated the underlying molecular mechanisms. By histological examination and renal dysfunction specific markers (serum BUN and creatinine) assay, β-HB could protect the PQ-induced kidney injury in rat. PQ-induced kidney injury is associated with oxidative stress, which was measured by increased lipid peroxidation (MDA) and decreased intracellular anti-oxidative abilities (SOD, CAT and GSH). β-HB pretreatment significantly attenuated that. Caspase-mediated apoptosis pathway contributed importantly to PQ toxicity, as revealed by the activation of caspase-9/-3, cleavage of PARP, and regulation of Bcl-2 and Bax, which were also effectively blocked by β-HB. Moreover, treatment of PQ strongly decreased the nuclear Nrf2 levels. However, pre-treatment with β-HB effectively suppressed this action of PQ. This may imply the important role of β-HB on Nrf2 pathway. Taken together, this study provides a novel finding that β-HB has a renoprotective ability against paraquat-induced kidney injury.

  18. Adult stem-like cells in kidney

    Institute of Scientific and Technical Information of China (English)

    Keiichi Hishikawa; Osamu Takase; Masahiro Yoshikawa; Taro Tsujimura; Masaomi Nangaku; Tsuyoshi Takato


    Human pluripotent cells are promising for treatmentfor kidney diseases, but the protocols for derivationof kidney cell types are still controversial. Kidneytissue regeneration is well confirmed in several lowervertebrates such as fish, and the repair of nephronsafter tubular damages is commonly observed after renalinjury. Even in adult mammal kidney, renal progenitorcell or system is reportedly presents suggesting thatadult stem-like cells in kidney can be practical clinicaltargets for kidney diseases. However, it is still unclearif kidney stem cells or stem-like cells exist or not. Ingeneral, stemness is defined by several factors suchas self-renewal capacity, multi-lineage potency andcharacteristic gene expression profiles. The definiteuse of stemness may be obstacle to understand kidneyregeneration, and here we describe the recent broadfindings of kidney regeneration and the cells thatcontribute regeneration.

  19. Mechanisms of geometrical seismic attenuation

    Directory of Open Access Journals (Sweden)

    Igor B. Morozov


    Full Text Available In several recent reports, we have explained the frequency dependence of the apparent seismic quality-factor (Q observed in many studies according to the effects of geometrical attenuation, which was defined as the zero-frequency limit of the temporal attenuation coefficient. In particular, geometrical attenuation was found to be positive for most waves traveling within the lithosphere. Here, we present three theoretical models that illustrate the origin of this geometrical attenuation, and we investigate the causes of its preferential positive values. In addition, we discuss the physical basis and limitations of both the conventional and new attenuation models. For waves in media with slowly varying properties, geometrical attenuation is caused by variations in the wavefront curvature, which can be both positive (for defocusing and negative (for focusing. In media with velocity/density contrasts, incoherent reflectivity leads to geometrical-attenuation coefficients which are proportional to the mean squared reflectivity and are always positive. For «coherent» reflectivity, the geometrical attenuation is approximately zero, and the attenuation process can be described according to the concept of «scattering Q». However, the true meaning of this parameter is in describing the mean reflectivity within the medium, and not that of the traditional resonator quality factor known in mechanics. The general conclusion from these models is that non-zero and often positive levels of geometrical attenuation are common in realistic, heterogeneous media, both observationally and theoretically. When transformed into the conventional Q-factor form, this positive geometrical attenuation leads to Q values that quickly increase with frequency. These predictions show that the positive frequency-dependent Q observed in many datasets might represent artifacts of the transformations of the attenuation coefficients into Q.

  1. Pregnancy and chronic kidney disease. (United States)

    Davison, John M; Lindheimer, Marshall D


    This article reviews the association of chronic renal disease and pregnancy. Included are discussions of guidelines for counseling pregnant women with underlying chronic renal disease who are considering conceiving as well as management of those already pregnant. Specifically highlighted are recent studies that question the validity of using estimated glomerular filtration rate and other formulae and questions of whether we should strive to replace the classic counseling approaches based primarily on serum creatinine levels with guidelines based on chronic kidney disease classification. The article concludes with a review as well as a critique of recent research on the prevalence of preeclampsia in women with underlying chronic renal disease, as well as if women with preeclampsia and underlying kidney disease have accelerated courses toward end-stage renal disease.

  2. Dietary phosphorus and kidney disease. (United States)

    Uribarri, Jaime


    High serum phosphate is linked to poor health outcome and mortality in chronic kidney disease (CKD) patients before or after the initiation of dialysis. Therefore, maintenance of normal serum phosphate levels is a major concern in the clinical care of this population with dietary phosphorus restriction and/or use of oral phosphate binders considered to be the best corrective care. This review discusses (1) evidence for an association between serum phosphate levels and bone and cardiovascular disease (CVD) in CKD patients as well as progression of kidney disease itself; (2) the relationship between serum phosphate and dietary phosphorus intake; and (3) implications from these data for future research. Increasing our understanding of the relationship between altered phosphorus metabolism and disease in CKD patients may clarify the potential role of excess dietary phosphorus as a risk factor for disease in the general population.

  3. [ACE inhibitors and the kidney]. (United States)

    Hörl, W H


    Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

  4. Kidney involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    P. Lazzarini


    Full Text Available Rheumatoid Arthritis (RA is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively, followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy. Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment, followed by minimal change glomerulopathy (3-14% and p-ANCA positive necrotizing crescentic

  5. Epigenetic memory in kidney diseases. (United States)

    Mimura, Imari


    Epigenetic mechanisms have been the focus of intensive research. De Marinis et al. demonstrated that high glucose levels exert stimulatory effects on activation histone marks, leading to the upregulation of thioredoxin-interacting protein (TXNIP) gene expression, which is proinflammatory. They also showed that the effect was reversed by the inhibition of histone acetyltransferase, suggesting a new therapeutic approach for improving diabetic kidney disease. Epigenetic changes are memorized as epigenetic memory that could exacerbate diabetic complications.

  6. Lithium-Associated Kidney Microcysts


    Jennifer Tuazon; David Casalino; Ehteshamuddin Syed; Daniel Batlle


    Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from tubulointerstitial nephropathy. Biopsy findings in patients with lithium-induced chronic tubulointerstitial nephropathy include tubular atrophy and interstitial fibrosis interspersed with tubular cysts and dilatations. Recent studies have shown that cysts are seen in 33––62.5% of the patients undergoing lithium therapy. MR imaging is highly ca...

  7. Renal tubular epithelial-mesenchymal transition in kidney fibrosis%肾小管上皮间充质转化与肾脏纤维化

    Institute of Scientific and Technical Information of China (English)

    王来亮; 罗群


    Epithelial-mesenchymal transition ( EMT) , a process by which differentiated epithelial cells under-go a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury.However, the degree to which renal tubular epithelial EMT contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent.Renal tubular EMT is an adap-tive response of epithelial cells to a hostile or changing microenvironment and is regulated by many factors.Several intrace-llular signal transduction pathways such as transforming growth factor-β( TGF-β)/Smad and Wnt/β-catenin signaling are essential in controlling the process of renal tubular epithelial EMT which are potential targets of antifibrotic therapy present-ly.This review highlights the current understanding of renal tubular epithelial EMT and its underlying mechanisms to stimu-late further discussion on its role in the pathogenesis of renal interstitial fibrosis.

  8. NAFLD and Chronic Kidney Disease. (United States)

    Marcuccilli, Morgan; Chonchol, Michel


    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries and it is now considered a risk factor for cardiovascular disease. Evidence linking NAFLD to the development and progression of chronic kidney disease (CKD) is emerging as a popular area of scientific interest. The rise in simultaneous liver-kidney transplantation as well as the significant cost associated with the presence of chronic kidney disease in the NAFLD population make this entity a worthwhile target for screening and therapeutic intervention. While several cross-sectional and case control studies have been published to substantiate these theories, very little data exists on the underlying cause of NAFLD and CKD. In this review, we will discuss the most recent publications on the diagnosis of NAFLD as well new evidence regarding the pathophysiology of NAFLD and CKD as an inflammatory disorder. These mechanisms include the role of obesity, the renin-angiotensin system, and dysregulation of fructose metabolism and lipogenesis in the development of both disorders. Further investigation of these pathways may lead to novel therapies that aim to target the NAFLD and CKD. However, more prospective studies that include information on both renal and liver histology will be necessary in order to understand the relationship between these diseases.

  9. Chronic Kidney Disease and Endothelium

    Directory of Open Access Journals (Sweden)

    Damir Rebić


    Full Text Available The endothelial cell layer is responsible for molecular traffic between the blood and surrounding tissue, and endothelial integrity plays a pivotal role in many aspects of vascular function. Cardiovascular disease (CVD is the main cause of death in patients with chronic kidney disease (CKD and its incidence and severity increase in direct proportion with kidney function decline. Non-traditional risk factors for CVDs, including endothelial dysfunction (ED, are highly prevalent in this population and play an important role in cardiovascular (CV events. ED is the first step in the development of atherosclerosis and its severity has prognostic value for CV events. Several risk markers have been associated with ED. Reduced bioavailability of nitric oxide plays a central role, linking kidney disease to ED, atherosclerosis, and CV events. Inflammation, loss of residual renal function, and insulin resistance are closely related to ED in CKD. ED may be followed by structural damage and remodelling that can precipitate both bleeding and thrombotic events. The endothelium plays a main role in vascular tone and metabolic pathways. ED is the first, yet potentially reversible step in the development of atherosclerosis and its severity has prognostic value for CV events.

  10. Role of kidney Doppler ultrasonography in the diagnosis and management of anuric kidney failure. (United States)

    Zand, Ladan; King, Bernard F; Qian, Qi


    Kidney perfusion can be acutely compromised by many factors including reduced systemic blood pressure and elevated intra-abdominal pressure. We present a case of near complete absence of kidney perfusion in a 57-year-old man with heart failure and new onset ascites. The renal perfusion defect was directly detected by Doppler ultrasonography. Immediate decompression with large-volume paracentesis restored the kidney perfusion and kidney function. This case illustrates that renal ultrasonography with Doppler flow analysis in appropriate settings can serve as an important adjunct in the diagnosis and treatment of acute oligoanuric kidney failure. Timely reversal of the perfusion defect can rescue kidney function.

  11. Metallothionein in rabbit kidneys preserved for transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Elinder, C.G.; Lundgren, G.; Nordberg, M.; Palm, B.; Piscator, M.


    Thirteen rabbits were given cadmium injections to achieve cadmium concentrations in kidney cortex ranging from 0.05 to 1 mmole Cd/kg wet weight. Another four animals served as controls. One kidney from each animal was frozen directly to -70/sup 0/C whereas the other kidney was kept for 24 hr at +4/sup 0/C in a preservative (Sachs' solution) to simulate conditions for preservation of human donor kidneys before transplantation. Protein binding of cadmium, zinc and copper in kidney homogenates and the concentration of metallothionein (MT) were measured in the kidney that was frozen directly and in the kidney that had been preserved. No gross differences in either the protein binding of cadmium, zinc and copper or in the MT content were seen between the directly frozen and preserved kidney from the same animal. This indicates that MT is not rapidly broken down in rabbit kidneys which have been preserved similarly to human donor kidneys for 24 hr in a standard preservative solution prior to a transplantation. 27 references, 3 figures, 1 table.

  12. Metallothionein in rabbit kidneys preserved for transplantation. (United States)

    Elinder, C G; Lundgren, G; Nordberg, M; Palm, B; Piscator, M


    Thirteen rabbits were given repeated cadmium injections to achieve cadmium concentrations in kidney cortex ranging from 0.05 to 1 mmole Cd/kg wet weight. Another four animals served as controls. One kidney from each animal was frozen directly to -70 degrees C whereas the other kidney was kept for 24 hr at +4 degrees C in a preservative (Sachs' solution) to simulate conditions for preservation of human donor kidneys before transplantation. Protein binding of cadmium, zinc and copper in kidney homogenates and the concentration of metallothionein (MT) were measured in the kidney that was frozen directly and in the kidney that had been preserved. No gross differences in either the protein binding of cadmium, zinc and copper or in the MT content were seen between the directly frozen and preserved kidneys from the same animal. This indicates that MT is not rapidly broken down in rabbit kidneys which have been preserved similarly to human donor kidneys for 24 hr in a standard preservative solution prior to a transplantation.

  13. Special nutrition challenges: current approach to acute kidney injury. (United States)

    McCarthy, Mary S; Phipps, Shauna C


    Acute kidney injury (AKI), previously known as acute renal failure, is defined as a sudden decline in glomerular filtration rate with accumulation of metabolic waste products, toxins, and drugs, as well as alteration in the intrinsic functions of the kidney. Reports of mortality are as high as 80%, with numerous contributing causes including infection, cardiorespiratory complications, and cardiovascular disease. Concurrent with the high prevalence of critical illness in this population is the protein energy wasting (PEW), seen in up to 42% of patients upon intensive care unit admission. The pathophysiologic derangements of critical illness, the low energy and protein stores, and uremic complications require early nutrition intervention to attenuate the inflammatory response and oxidative stress, improve endothelial function, stabilize blood sugar, and preserve lean body mass. This article addresses the unique challenges of nutrition support for the patient with AKI in the setting of critical illness and renal replacement therapy. Evidence-based recommendations are provided to meet the macronutrient and micronutrient requirements of this heterogeneous and complex patient population.

  14. Amygdalin inhibits renal fibrosis in chronic kidney disease. (United States)

    Guo, Junqi; Wu, Weizheng; Sheng, Mingxiong; Yang, Shunliang; Tan, Jianming


    Renal interstitial fibrosis is a common outcome of chronic renal diseases. Amygdalin is one of a number of nitrilosides, the natural cyanide‑containing substances abundant in the seeds of plants of the prunasin family that are used to treat cancer and relieve pain. However, whether amygdalin inhibits the progression of renal fibrosis or not remains unknown. The present study aimed to assess the therapeutic potential of amygdalin by investigating its effect and potential mechanism on the activation of renal interstitial fibroblast cells and renal fibrosis in rat unilateral ureteral obstruction (UUO). Treatment of the cultured renal interstitial fibroblasts with amygdalin inhibited their proliferation and the production of transforming growth factor (TGF)‑β1. In the rat model of obstructive nephropathy, following ureteral obstruction, the administration of amygdalin immediately eliminated the extracellular matrix accumulation and alleviated the renal injury on the 21st day. Collectively, amygdalin attenuated kidney fibroblast (KFB) activation and rat renal interstitial fibrosis. These results indicate that amygdalin is a potent antifibrotic agent that may have therapeutic potential for patients with fibrotic kidney diseases.

  15. Olmesartan Attenuates Tacrolimus-Induced Biochemical and Ultrastructural Changes in Rat Kidney Tissue


    Al-Harbi, Naif O.; Faisal Imam; Al-Harbi, Mohammed M.; Muzaffar Iqbal; Ahmed Nadeem; Sayed-Ahmed, Mohammed M.; Alabidy, Ali D.; Almukhallafi, Ali F.


    Tacrolimus, a calcineurin inhibitor, is clinically used as an immunosuppressive agent in organ transplantation, but its use is limited due to its marked nephrotoxicity. The present study investigated the effect of olmesartan (angiotensin receptor blocker) on tacrolimus-induced nephrotoxicity in rats. A total of 24 rats were divided into four groups, which included control, tacrolimus, tacrolimus + olmesartan, and olmesartan groups. Tacrolimus-induced nephrotoxicity was assessed biochemically ...

  16. Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney (United States)

    Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Zong, Zhi-Hong; Du, Zhen-Xian; Li, De-Tian; Wang, Hua-Qin; Liu, Bo; Miao, Jia-Ning; Bian, Xiao-Hui


    BAG3 regulates a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, and epithelial-mesenchymal transition (EMT). However, the role of BAG3 in renal tubular EMT and renal interstitial fibrosis remains elusive. This study aimed to examine the dynamic expression of BAG3 during renal fibrosis, and to investigate the efficacy of Cordyceps sinensis (C. sinensis) on renal fibrosis. A rat model of unilateral ureteral obstruction (UUO) was established, and the expression of BAG3 and α-SMA, and the efficacy of C. sinensis on renal fibrosis induced by UUO were examined. The results showed that UUO led to collagen accumulation, which was significantly suppressed by C. sinensis. UUO increased the expression of BAG3 and α-SMA, a mesenchymal marker, while UUO induced BAG3 and α-SMA expression was significantly inhibited by C. sinensis. In addition, immunohistochemical staining demonstrated that BAG3 immunoreactivity was restricted to tubular epithelium. In conclusion, BAG3 is a potential target for the prevention and/or treatment of renal fibrosis, and C. Sinensis is a promising agent for renal fibrosis. PMID:26175854

  17. Attenuated renal response to moxonidine and rilmenidine in one kidney-one clip hypertensive rats. (United States)

    Li, P.; Penner, S. B.; Smyth, D. D.


    1. I1 non-adrenoceptor, imidazoline receptor agonists, such as moxonidine, increase urine flow rate and sodium excretion following infusion into the renal artery. The functions of these agonists in genetic and acquired models of hypertension have not been determined. 2. We therefore studied the renal effects of two known non-adrenoceptor, imidazoline receptor agonists, rilmenidine and moxonidine, in 1K-1C hypertensive and 1K-sham normotensive rats. Rilmenidine (0, 3, 10, 30 nmol kg-1 min-1) or moxonidine (0, 1, 3, 10 nmol kg-1 min-1) was infused directly into the renal artery (30 gauge needle) of 1K-sham normotensive and 1K-1C hypertensive rats. 3. In 1K-sham normotensive rats, rilmenidine and moxonidine produced dose related increases in urine flow rate, sodium excretion and osmolar clearance. Both rilmenidine and moxonidine failed to increase urine flow rate, sodium excretion and osmolar clearance in 1K-1C hypertensive rats to the same extent as in 1K-sham animals. At comparable doses, rilmenidine had no effect, while moxonidine (3 and 10 nmol kg-1 min-1) did result in a small increase in urine volume and osmolar clearance which was less than that observed in the 1K sham control animals. 4. These studies indicate that the renal effects of non-adrenoceptor, imidazoline receptor stimulation are diminished in 1K-1C hypertensive rats compared with 1K-sham normotensive rats. Whether this decrease in activity of the natriuretic non-adrenoceptor, imidazoline receptors contributes to the increase in blood pressure in the 1K-1C acquired model of hypertension remains to be determined. PMID:8032642

  18. Attenuated renal response to moxonidine and rilmenidine in one kidney-one clip hypertensive rats.


    Li, P; Penner, S. B.; Smyth, D. D.


    1. I1 non-adrenoceptor, imidazoline receptor agonists, such as moxonidine, increase urine flow rate and sodium excretion following infusion into the renal artery. The functions of these agonists in genetic and acquired models of hypertension have not been determined. 2. We therefore studied the renal effects of two known non-adrenoceptor, imidazoline receptor agonists, rilmenidine and moxonidine, in 1K-1C hypertensive and 1K-sham normotensive rats. Rilmenidine (0, 3, 10, 30 nmol kg-1 min-1) o...

  19. Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications. (United States)

    Bover, Jordi; Ureña-Torres, Pablo; Górriz, José Luis; Lloret, María Jesús; da Silva, Iara; Ruiz-García, César; Chang, Pamela; Rodríguez, Mariano; Ballarín, José

    Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.

  20. Imaging Rayleigh wave attenuation with USArray (United States)

    Bao, Xueyang; Dalton, Colleen A.; Jin, Ge; Gaherty, James B.; Shen, Yang


    The EarthScope USArray provides an opportunity to obtain detailed images of the continental upper mantle at an unprecedented scale. The majority of mantle models derived from USArray data to date contain spatial variations in seismic-wave speed; however, in many cases these data sets do not by themselves allow a non-unique interpretation. Joint interpretation of seismic attenuation and velocity models can improve upon the interpretations based only on velocity and provide important constraints on the temperature, composition, melt content, and volatile content of the mantle. The surface wave amplitudes that constrain upper-mantle attenuation are sensitive to factors in addition to attenuation, including the earthquake source excitation, focusing and defocusing by elastic structure, and local site amplification. Because of the difficulty of isolating attenuation from these other factors, little is known about the attenuation structure of the North American upper mantle. In this study, Rayleigh wave traveltime and amplitude in the period range 25-100 s are measured using an interstation cross-correlation technique, which takes advantage of waveform similarity at nearby stations. Several estimates of Rayleigh wave attenuation and site amplification are generated at each period, using different approaches to separate the effects of attenuation and local site amplification on amplitude. It is assumed that focusing and defocusing effects can be described by the Laplacian of the traveltime field. All approaches identify the same large-scale patterns in attenuation, including areas where the attenuation values are likely contaminated by unmodelled focusing and defocusing effects. Regionally averaged attenuation maps are constructed after removal of the contaminated attenuation values, and the variations in intrinsic shear attenuation that are suggested by these Rayleigh wave attenuation maps are explored.

  1. Dynamic Renal Scintigraphy in Diagnosis of Upper Urinary Tract Obstruction in Transplanted Kidney

    Institute of Scientific and Technical Information of China (English)


    Nuclide renal dynamic imaging was performed on 88 (110 times) transplanted kidney. Two kinds of renal scintigraphic characteristics were identified in recipients with supravesical obstruction of the graft. First, the regular type was characterized by radioactivity defect area in kidney parenchyma during early uptake period followed by ureteropelvic retention. Second, the tubular type was typified by cortical retention and attenuation in collecting system during the whole test period with a special sign of “hollow kidney”. Non-obstructive dilated calyces showed similar signs as the regular type. Acute rejection reaction and tubule necrosis demonstrated obstructive time-activity curves. However, the radioactivity retention appeared in cortex. It was suggested that dilated calyces and obstructive renogram might not be reliable evidence for upper urinary tract obstruction. The signs of radioactivity attenuation in kidney parenchyma during early uptake period followed by ureteropelvic retention may be more valuable for the evaluation. As for tubular obstruction, specified “hollow kidney” was the characteristic sign which is helpful for the diagnosis.

  2. The kidney and hypertension: causes and treatment. (United States)

    Sica, Domenic A


    Chronic kidney disease is both a cause and a consequence of hypertension. Extracellular volume expansion is an important, if not the most important, contributing factor to hypertension seen in chronic kidney disease. Beyond volume expansion, chronic kidney disease-related hypertension is without truly defining characteristics. Consequently, the sequencing of antihypertensive medications for the patient with chronic kidney disease and hypertension becomes arbitrary. Prescription practice in such patients should be mindful of the need for multiple drug classes with at least one of them being a diuretic. Blood pressure goals in the patient with chronic kidney disease and hypertension are set at lower levels than those for patients with essential hypertension alone. It remains to be determined to what level blood pressure should be lowered in the patient with chronic kidney disease, however.

  3. Tailor-Made Live Kidney Donation


    Klop, Karel


    markdownabstract__Abstract__ This thesis describes several aspects of live kidney donation, such as surgical techniques, cost-effectivity, cosmetics en quality of life. Kidney transplantation offer several benefits when compared to dialysis. These benefits include better recipient and graft survival, better access to transplantation and pre-emptive transplantation. Eligibility criteria for live kidney donation have been extended in the last decade, leading to an increase in live donors and an...

  4. Anemia in children with chronic kidney disease


    Koshy, Susan M.; Geary, Denis F.


    Anemia is a common feature of chronic kidney disease, but the management of anemia in children is complex. Erythropoietin and supplemental iron are used to maintain hemoglobin levels. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) clinical practice guidelines for the management of anemia specifically in children were recently published. Pediatric nephrologists are encouraged to use current clinical practice guidelines and best evidence in conjunction wit...

  5. Cyclooxygenase (COX) Inhibitors and the Newborn Kidney


    Wei Qi; Smith, Francine G.; Megan L. Lewis; Wade, Andrew W


    This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role...

  6. Culture Systems for Regenerative Kidney Therapy (United States)


    regenerative medicine field, two key advances have demonstrated the feasibility of a cell -based therapy approach for renal replacement: i) Functional...kidney tissue from embryonic stem cells . This will allow us to generate patient- specific models of polycystic kidney disease, which affects many...the propagation of nephron progenitor cells derived either from embryonic mouse kidneys or human embryonic stem cells . We have used a combinatorial

  7. Wait too long to talk about kidney disease and you could be waiting for a kidney. (United States)

    ... Home Current Issue Past Issues Public Service Announcement Kidney Disease Past Issues / Summer 2006 Table of Contents ... Javascript on. Wait too long to talk about kidney disease and you could be waiting for a ...

  8. Carissa carandas Linn. fruit extract ameliorates gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Jayesh B. Dhodi; Deepavali R. Thanekar; Snehal N. Mestry; Archana R. Juvekar


    Objective: To elucidate the mechanism of action of methanolic extract of Carissa carandas fruits (MCCF) in attenuation of diabetic nephropathy using gentamicin induced nephrotoxicity model.Methods:Extract was daily administered to Sprague Dawley rats at doses of 100, 200 and 400 mg/kg for 8 days along with intramuscular injection of gentamicin (80 mg/kg). After completion of the study, serum was analyzed for blood urea nitrogen, albumin and creatinine; urine (24 h) was analyzed for albumin and creatinine. Kidney was evaluated for its biochemical and morphological changes. Results: Extract at doses of 200 and 400 mg/kg significantly normalized the nephrotoxic biomarkers in serum and urine and increased the kidney antioxidant activities which were altered due to gentamicin toxicity. The histological findings reveal that MCCF was capable of protecting the kidney against gentamicin toxicity. Conclusions: Extract ameliorated oxidative stress generated by gentamicin administration, which is one of the mechanisms for its preventive action against diabetic nephropathy.

  9. Evaluation of the gender difference in the protective effects of ischemic postconditioning on ischemia-reperfusion-induced acute kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Atefeh Mahmoudi


    Full Text Available Background: Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR injury. Recently, postconditioning (POC, induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney.Methods: In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation.Results: Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0.05. Also, POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA level and increased superoxide dismutase (SOD activity (P<0.05. In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Conclusion: Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.


    Energy Technology Data Exchange (ETDEWEB)

    Joel Walls; M.T. Taner; Naum Derzhi; Gary Mavko; Jack Dvorkin


    We have developed and tested technology for a new type of direct hydrocarbon detection. The method uses inelastic rock properties to greatly enhance the sensitivity of surface seismic methods to the presence of oil and gas saturation. These methods include use of energy absorption, dispersion, and attenuation (Q) along with traditional seismic attributes like velocity, impedance, and AVO. Our approach is to combine three elements: (1) a synthesis of the latest rock physics understanding of how rock inelasticity is related to rock type, pore fluid types, and pore microstructure, (2) synthetic seismic modeling that will help identify the relative contributions of scattering and intrinsic inelasticity to apparent Q attributes, and (3) robust algorithms that extract relative wave attenuation attributes from seismic data. This project provides: (1) Additional petrophysical insight from acquired data; (2) Increased understanding of rock and fluid properties; (3) New techniques to measure reservoir properties that are not currently available; and (4) Provide tools to more accurately describe the reservoir and predict oil location and volumes. These methodologies will improve the industry's ability to predict and quantify oil and gas saturation distribution, and to apply this information through geologic models to enhance reservoir simulation. We have applied for two separate patents relating to work that was completed as part of this project.

  11. Magnetoelectric Composite Based Microwave Attenuator (United States)

    Tatarenko, A. S.; Srinivasan, G.


    Ferrite-ferroelectric composites are magnetoelectric (ME) due to their response to elastic and electromagnetic force fields. The ME composites are characterized by tensor permittivity, permeability and ME susceptibility. The unique combination of magnetic, electrical, and ME interactions, therefore, opens up the possibility of electric field tunable ferromagnetic resonance (FMR) based devices [1]. Here we discuss an ME attenuator operating at 9.3 GHz based on FMR in a layered sample consisting of lead magnesium niobate-lead titanate bonded to yttrium iron garnet (YIG) film on a gadolinium gallium garnet substrate. Electrical tuning is realized with the application of a control voltage due to ME effect; the shift is 0-15 Oe as E is increased from 0 to 3 kV/cm. If the attenuator is operated at FMR, the corresponding insertion loss will range from 25 dB to 2 dB. 1. S. Shastry and G. Srinivasan, M.I. Bichurin, V.M. Petrov, A.S. Tatarenko. Phys. Rev. B, 70 064416 (2004). - supported by grants the grants from the National Science Foundation (DMR-0302254), from Russian Ministry of Education (Å02-3.4-278) and from Universities of Russia Foundation (UNR 01.01.026).

  12. Involvement of hydrogen sulfide and homocysteine transsulfuration pathway in the progression of kidney fibrosis after ureteral obstruction. (United States)

    Jung, Kyong-Jin; Jang, Hee-Seong; Kim, Jee In; Han, Sang Jun; Park, Jeen-Woo; Park, Kwon Moo


    Hydrogen sulfide (H2S) produced by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in the transsulfuration pathway of homocysteine plays a number of pathophysiological roles. Hyperhomocysteinemia is involved in kidney fibrosis. However, the role of H2S in kidney fibrosis remains to be defined. Here, we investigated the role of H2S and its acting mechanism in unilateral ureteral obstruction (UO)-induced kidney fibrosis in mice. UO decreased expressions of CBS and CSE in the kidney with decrease of H2S concentration. Treatment with sodium hydrogen sulfide (NaHS, a H2S producer) during UO reduced UO-induced oxidative stress with preservations of catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD) expression, and glutathione level. In addition, NaHS mitigated decreases of CBS and CSE expressions, and H2S concentration in the kidney. NaHS treatment attenuated UO-induced increases in levels of TGF-β1, activated Smad3, and activated NF-κB. This study provided the first evidence of involvement of the transsulfuration pathway and H2S in UO-induced kidney fibrosis, suggesting that H2S and its transsulfuration pathway may be a potential target for development of therapeutics for fibrosis-related diseases.

  13. An experimental study on the effect of capsaicin on hepatic stellate cells and liver fibrogenesis%辣椒素调节肝星状细胞活性延缓肝纤维化的实验研究

    Institute of Scientific and Technical Information of China (English)

    俞富祥; 吴志伟; 朱千东; 符竣惠; 张启瑜


    目的 探讨辣椒素对大鼠肝星状细胞(hepatic stellate cells,HSCs)活性的影响及其对活体肝纤维化的治疗作用.方法 DCFH-DA法检测辣椒素对HSCs中活性氧的影响;用酶标法检测辣椒素对HSCs增殖的影响;Western blot检测HSCs α-肌动蛋白(α-SMA)的表达;RT-PCR检测辣椒素对HSCs纤维化相关基因表达的影响;流式细胞仪检测辣椒素对HSCs凋亡的影响;Western blot法检测bcl-2、bax、细胞色素酶c(cytochrome,cyt-c)等蛋白的表达;建立鼠肝纤维化模型,经腹腔输注辣椒素,检测肝组织病理切片,肝纤维化指标.结果 辣椒素抑制HSCs中活性氧的产生,抑制HSCs的活化(F=57.392,P<0.05)与增殖(F=13.267,P<0.05),促进HSCs的凋亡(F=235.571,P<0.05),促进凋亡相关蛋白Bax、cyt-c、caspase-3的表达(分别F=29.334,38.274,138.329,均P<0.05).改变HSCs纤维化相关基因TGF-β1、TIMP-1的表达(分别F=376.534,253.751,均P<0.05),活体实验显示辣椒素可降低肝羟脯氨酸含量及血清Ⅲ型胶原和透明质酸水平(分别F=153.397,27.149,38.392,均P<0.05).结论 辣椒素抑制HSCs增殖活化并诱导其凋亡.辣椒素对肝纤维化具有一定的抑制作用.%Objective To investigate the effect of capsaicin on hepatic stellate cells (HSCs) and liver fibrogenesis.Methods HSCs were cultured.The reactive oxygen in HSCs under capsaicin at different concentrations was tested by DCFH-DA kit.The proliferation of HSCs was detected by CCK-8 test kit.Smoothmuscle α-actin (α-SMA) expression of HSCs was evaluated by Western blot.The fibrosisrelated genes were tested by RT-PCR.The apoptosis of HSCs was measured by flow cytometer.Bcl-2,bax and cyt-c was detected by Western blot.A murine model of liver fibrogenes was established.Capsaicin of different concentration was injected intraperitoneally.Liver pathology was observed using HE staining.Hydroxyproline content of liver and levels of collagen Ⅲ and hyaluronic acid in serum were

  14. Contrast-associated Acute Kidney Injury. (United States)

    Weisbord, Steven D; Palevsky, Paul M


    Contrast-associated acute kidney injury (CAAKI) is a common iatrogenic condition. The principal risk factors for CAAKI are underlying renal impairment; diabetes in the setting of kidney disease; and intravascular volume depletion, effective or absolute. CAAKI is associated with serious adverse short-term and long-term outcomes, including mortality and more rapidly progressive chronic kidney disease, although the causal nature of these associations remains unproved. Patients with chronic kidney disease and other risk factors for CAAKI who present with acute coronary syndrome should undergo indicated angiographic procedures.

  15. Optical Coherence Tomography in Kidney Transplantation (United States)

    Andrews, Peter M.; Wierwille, Jeremiah; Chen, Yu

    End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients' lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or "ATN") induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation.

  16. Fetal polycystic kidney disease: Pathological overview

    Directory of Open Access Journals (Sweden)

    Sunita B Patil


    Full Text Available Polycystic kidney disease is a rare developmental anomaly inherited as autosomal dominant or autosomal recessive. It is characterized by cystic dilatation of the collecting ducts frequently associated with hepatic involvement and progression to renal failure. It is included in the differential diagnosis of cystic diseases of the kidney. We report a case of polycystic kidney disease, in 22 weeks fetus incidentally detected on routine antenatal ultrasonography and confirmed by fetal autopsy. This report elucidates the importance of early diagnosis and intervention in cystic kidney diseases.

  17. Nutritional Management of Kidney Stones (Nephrolithiasis) (United States)

    Segal, Adam M.; Seifter, Julian L.; Dwyer, Johanna T.


    The incidence of kidney stones is common in the United States and treatments for them are very costly. This review article provides information about epidemiology, mechanism, diagnosis, and pathophysiology of kidney stone formation, and methods for the evaluation of stone risks for new and follow-up patients. Adequate evaluation and management can prevent recurrence of stones. Kidney stone prevention should be individualized in both its medical and dietary management, keeping in mind the specific risks involved for each type of stones. Recognition of these risk factors and development of long-term management strategies for dealing with them are the most effective ways to prevent recurrence of kidney stones. PMID:26251832

  18. Statins in chronic kidney disease and kidney transplantation. (United States)

    Kassimatis, Theodoros I; Goldsmith, David J A


    HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular (CV) outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their pleiotropic effects statins have been shown to reduce inflammation, alleviate oxidative stress, modify the immunologic responses, improve endothelial function and suppress platelet aggregation. Patients with chronic kidney disease (CKD) exhibit an enormous increase in CVD rates even from early CKD stages. As considerable differences exist in dyslipidemia characteristics and the pathogenesis of CVD in CKD, statins' CV benefits in CKD patients (including those with a kidney graft) should not be considered unequivocal. Indeed, accumulating clinical evidence suggests that statins exert diverse effects on dialysis and non-dialysis CKD patients. Therefore, it seems that statins improve CV outcomes in non-dialysis patients whereas exert little (if any) benefit in the dialysis population. It has also been proposed that dyslipidemia might play a causative role or even accelerate renal injury. Moreover, ample experimental evidence suggests that statins ameliorate renal damage. However, a high quality randomized controlled trial (RCT) and metaanalyses do not support a beneficial role of statins in renal outcomes in terms of proteinuria reduction or retardation of glomerular filtration rate (GFR) decline.

  19. Acute kidney injury in children

    Directory of Open Access Journals (Sweden)

    Peco-Antić Amira


    Full Text Available Acute kidney injury (AKI is a clinical condition considered to be the consequence of a sudden decrease (>25% or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, kidney injury molecule-1 (KIM-1, interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP. Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients.

  20. Transforming growth factor-beta1 reduces megalin- and cubilin-mediated endocytosis of albumin in proximal-tubule-derived opossum kidney cells. (United States)

    Gekle, Michael; Knaus, Petra; Nielsen, Rikke; Mildenberger, Sigrid; Freudinger, Ruth; Wohlfarth, Verena; Sauvant, Christoph; Christensen, Erik I


    Transforming growth factor (TGF)-beta1 is a member of a superfamily of multifunctional cytokines involved in several pathological processes of the kidney, including fibrogenesis, apoptosis and epithelial-mesenchymal transition. These events lead to tubulointerstitial fibrosis and glomerulosclerosis. Less is known about TGF-beta1-induced alterations of cell function. An important function of proximal tubular cells is reabsorption of filtered proteins, including albumin, via megalin-cubilin-dependent receptor-mediated endocytosis. In this study we used a well established cell culture model (proximal-tubule-derived opossum kidney (OK) cells) in order to test the hypothesis that TGF-beta1 reduces megalin-cubilin-mediated endocytosis. Previously we have shown that albumin endocytosis in OK cells is mediated by megalin/cubulin. TGF-beta1 led to a time- and dose-dependent downregulation of megalin-cubilin-mediated endocytosis without affecting two other transport systems tested. Binding, internalization and intracellular trafficking of the ligand albumin were affected. Decreased binding resulted from reduced cubilin and megalin expression in the 200 000 g membrane fraction. The underlying mechanism of TGF-beta1 action does not involve mitogen-activated protein kinases, protein kinase C or A, or reactive oxygen species. In contrast, TGF-beta1-induced downregulation of megalin-cubilin-mediated endocytosis was sensitive to inhibition of translation and transcription and was preceded by Smad2 and 3 phosphorylation. Dominant negative Smad2/3 constructs prevented the effect of TGF-beta1. In conclusion our data indicate that enhanced levels of TGF-beta1 occurring in various nephropathies can lead to downregulation of megalin-cubilin-dependent endocytosis. Probably, TGF-beta1 leads to Smad2- and Smad3-dependent expression of negative regulators of receptor-mediated endocytosis.

  1. Attenuation map reconstruction from TOF PET data

    CERN Document Server

    Yang, Qingsong; Wang, Ge


    To reconstruct a radioactive tracer distribution with positron emission tomography (PET), the background attenuation correction is needed to eliminate image artifacts. Recent research shows that time-of-flight (TOF) PET data determine the attenuation sinogram up to a constant, and its gradient can be computed using an analytic algorithm. In this paper, we study a direct estimation of the sinogram only from TOF PET data. First, the gradient of the attenuation sinogram is estimated using the aforementioned algorithm. Then, a relationship is established to link the differential attenuation sinogram and the underlying attenuation background. Finally, an iterative algorithm is designed to determine the attenuation sinogram accurately and stably. A 2D numerical simulation study is conducted to verify the correctness of our proposed approach.

  2. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats. (United States)

    Yildirim, Zeki; Sogut, Sadik; Odaci, Ersan; Iraz, Mustafa; Ozyurt, Huseyin; Kotuk, Mahir; Akyol, Omer


    The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.

  3. [Isolated giant hydatid in kidney]. (United States)

    Ozgör, Faruk; Erbin, Akif; Berberoğlu, Ahmet Yalçın; Binbay, Murat; Sarılar, Omer; Müslümanoğlu, Ahmet Yaser


    Cyst hydatid of the kidney is parasitic condition caused by Echinococcus granulosus and identified in many countries, especially associated with sheep farming. Echinococcal larvae enter the bloodstream using the digestive system and invade any organs in the human body. The urinary system is the third most common area affected by parasitic infection after liver and lungs, but isolated renal involvement is a very rare situation, even in endemic areas. İn our case, we aimed to report a 57-year-old female patient with an 18-centimeter isolated renal cyst hydatid treated by retroperitoneal nephrectomy. The diagnosis was based on imaging findings and confirmed by histopathologically.

  4. [Hypertensive crisis in kidney patients]. (United States)

    Scrivano, Jacopo; Giuliani, Anna; Pettorini, Laura; Punzo, Giorgio; Mene', Paolo; Pirozzi, Nicola


    The classification and management of hypertensive crisis have been recently reviewed in the context of both European and American guidelines. The key points for proper blood pressure control in severe arterial hypertension are: 1 - Distinction between urgent intervention and emergencies 2 - Choice of the best drug(s) 3 - Choice of the correct route of administration. In patients with renal disease, beside the common causes of hypertension/ hypertensive crises, kidney-specific causes should be taken into account such as renal parenchymal hypertension, renovascular hypertension, sclerodermic crises, and preeclampsia.

  5. Abnormal nocturnal heart rate variability response among chronic kidney disease and dialysis patients during wakefulness and sleep


    Roumelioti, Maria-Eleni; Ranpuria, Reena; Hall, Martica; Hotchkiss, John R.; Chan, Chris T.; Mark L Unruh; Argyropoulos, Christos


    Background. Dialysis patients and patients with chronic kidney disease (CKD) experience a substantial risk for abnormal autonomic function and abnormal heart rate variability (HRV). It remains unknown whether HRV changes across sleep stages in patients with different severity of CKD or dialysis dependency. We hypothesized that high-frequency (HF) HRV (vagal tone) will be attenuated from wakefulness to non-rapid eye movement (NREM) and then to rapid eye movement (REM) sleep in dialysis patient...

  6. Rolipram Attenuates Bile Duct Ligation–Induced Liver Injury in Rats: A Potential Pathogenic Role of PDE4 (United States)

    Barve, Shirish; Breitkopf-Heinlein, Katja; Li, Yan; Zhang, JingWen; Avila, Diana V.; Dooley, Steven; McClain, Craig J.


    Anti-inflammatory and antifibrotic effects of the broad spectrum phosphodiesterase (PDE) inhibitor pentoxifylline have suggested an important role for cyclic nucleotides in the pathogenesis of hepatic fibrosis; however, studies examining the role of specific PDEs are lacking. Endotoxemia and Toll-like receptor 4 (TLR4)-mediated inflammatory and profibrotic signaling play a major role in the development of hepatic fibrosis. Because cAMP-specific PDE4 critically regulates lipopolysaccharide (LPS)-TLR4–induced inflammatory cytokine expression, its pathogenic role in bile duct ligation-induced hepatic injury and fibrogenesis in Sprague-Dawley rats was examined. Initiation of cholestatic liver injury and fibrosis was accompanied by a significant induction of PDE4A, B, and D expression and activity. Treatment with the PDE4-specific inhibitor rolipram significantly decreased liver PDE4 activity, hepatic inflammatory and profibrotic cytokine expression, injury, and fibrosis. At the cellular level, in relevance to endotoxemia and inflammatory cytokine production, PDE4B was observed to play a major regulatory role in the LPS-inducible tumor necrosis factor (TNF) production by isolated Kupffer cells. Moreover, PDE4 expression was also involved in the in vitro activation and transdifferentiation of isolated hepatic stellate cells (HSCs). Particularly, PDE4A, B, and D upregulation preceded induction of the HSC activation marker α-smooth muscle actin (α-SMA). In vitro treatment of HSCs with rolipram effectively attenuated α-SMA, collagen expression, and accompanying morphologic changes. Overall, these data strongly suggest that upregulation of PDE4 expression during cholestatic liver injury plays a potential pathogenic role in the development of inflammation, injury, and fibrosis. PMID:23887098

  7. The relationship between chemical-induced kidney weight increases and kidney histopathology in rats. (United States)

    Craig, Evisabel A; Yan, Zhongyu; Zhao, Q Jay


    The kidney is a major site of chemical excretion, which results in its propensity to exhibit chemically-induced toxicological effects at a higher rate than most other organs. Although the kidneys are often weighed in animal toxicity studies, the manner in which these kidney weight measurements are interpreted and the value of this information in predicting renal damage remains controversial. In this study we sought to determine whether a relationship exists between chemically-induced kidney weight changes and renal histopathological alterations. We also examined the relative utility of absolute and relative (kidney-to-body weight ratio) kidney weight in the prediction of renal toxicity. For this, data extracted from oral chemical exposure studies in rats performed by the National Toxicology Program were qualitatively and quantitatively evaluated. Our analysis showed a statistically significant correlation between absolute, but not relative, kidney weight and renal histopathology in chemically-treated rats. This positive correlation between absolute kidney weight and histopathology was observed even with compounds that statistically decreased terminal body weight. Also, changes in absolute kidney weight, which occurred at subchronic exposures, were able to predict the presence or absence of kidney histopathology at both subchronic and chronic exposures. Furthermore, most increases in absolute kidney weight reaching statistical significance (irrespective of the magnitude of change) were found to be relevant for the prediction of histopathological changes. Hence, our findings demonstrate that the evaluation of absolute kidney weight is a useful method for identifying potential renal toxicants.

  8. Optimal ultrasonic array focusing in attenuative media. (United States)

    Ganguli, A; Gao, R X; Liang, K; Jundt, J


    This paper presents a parametric study on the efficiency of ultrasound focusing in an attenuative medium, using phased arrays. Specifically, an analytical model of ultrasound wave focusing in a homogeneous, isotropic and attenuative fluid with point sources is presented. Calculations based on the model have shown that in an attenuative medium, an optimum frequency exists for the best focusing performance for a particular size of aperture and focal distance. The effect of different f numbers on the focusing performance in the attenuative medium is further investigated. The information obtained from the analytical model provides insights into the design and installation of a phased transducer array for energy efficient wave focusing.

  9. Four decades of kidney transplantation in Cuba. (United States)

    Alfonzo, Jorge P


    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

  10. Polydatin Protecting Kidneys against Hemorrhagic Shock-Induced Mitochondrial Dysfunction via SIRT1 Activation and p53 Deacetylation

    Directory of Open Access Journals (Sweden)

    Zhenhua Zeng


    Full Text Available Objectives. To ascertain if mitochondrial dysfunction (MD of kidney cells is present in severe hemorrhagic shock and to investigate whether polydatin (PD can attenuate MD and its protective mechanisms. Research Design and Methods. Renal tubular epithelial cells (RTECs from rat kidneys experiencing HS and a cell line (HK-2 under hypoxia/reoxygenation (H/R treatment were used. Morphology and function of mitochondria in isolated RTECs or cultured HK-2 cells were evaluated, accompanied by mitochondrial apoptosis pathway-related proteins. Result. Severe MD was found in rat kidneys, especially in RTECs, as evidenced by swollen mitochondria and poorly defined cristae, decreased mitochondrial membrane potential (ΔΨm, and reduced ATP content. PD treatment attenuated MD partially and inhibited expression of proapoptotic proteins. PD treatment increased SIRT1 activity and decreased acetylated-p53 levels. Beneficial effect of PD was abolished partially when the SIRT1 inhibitor Ex527 was added. Similar phenomena were shown in the H/R cell model; when pifithrin-α (p53 inhibitor was added to the PD/Ex527 group, considerable therapeutic effects were regained compared with the PD group apart from increased SIRT1 activity. Conclusions. MD is present in severe HS, and PD can attenuate MD of RTECs via the SIRT1-p53 pathway. PD might be a promising therapeutic drug for acute renal injury.

  11. Wideband, 50 dB Attenuation Range Liquid Crystal Based Variable Optical Attenuator

    Institute of Scientific and Technical Information of China (English)

    J.J.; Pan; Henry; He; Eric; Zhang


    A compact variable optical attenuator, covering C and L bands with over 50 dB attenuation range, is realized using a single liquid crystal cell with a tilted fused silica coating compensating the cell's small residual birefringence.

  12. ET-1 deletion from endothelial cells protects the kidney during the extension phase of ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Arfian, Nur [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Vignon-Zellweger, Nicolas; Nakayama, Kazuhiko; Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)


    Highlights: Black-Right-Pointing-Pointer Ischemia/reperfusion injury (IRI) induced increased endothelin-1 (ET-1) expression. Black-Right-Pointing-Pointer IRI was accompanied by tubular injury and remodeling of renal arteries. Black-Right-Pointing-Pointer IRI increased oxidative stress and inflammation. Black-Right-Pointing-Pointer Genetic suppression of ET-1 in endothelial cells attenuates IRI in the kidney. Black-Right-Pointing-Pointer The mechanisms include the inhibition of oxidative stress and inflammation. -- Abstract: Background: The prognosis of patients after acute kidney injury (AKI) is poor and treatment is limited. AKI is mainly caused by renal ischemia/reperfusion injury (IRI). During the extension phase of IRI, endothelial damage may participate in ischemia and inflammation. Endothelin-1 (ET-1) which is mostly secreted by endothelial cells is an important actor of IRI, particularly through its strong vasoconstrictive properties. We aimed to analyze the specific role of ET-1 from the endothelial cells in AKI. Methods: We used mice lacking ET-1 in the vascular endothelial cells (VEETKO). We induced IRI in VEETKO mice and wild type controls by clamping both kidneys for 30 min. Sham operated mice were used as controls. Mice were sacrificed one day after IRI in order to investigate the extension phase of IRI. Kidney function was assessed based on serum creatinine concentration. Levels of expression of ET-1, its receptor ET{sub A}, protein kinase C, eNOS, E-Cadherin and inflammation markers were evaluated by real time PCR or western blot. Tubular injury was scored on periodic acid Schiff stained kidney preparations. Lumen and wall area of small intrarenal arteries were measured on kidney slices stained for alpha smooth muscle cell actin. Oxidative stress, macrophage infiltration and cell proliferation was evaluated on slices stained for 8-hydroxy-2 Prime -deoxyguanosine, F4/80 and PCNA, respectively. Results: IRI induced kidney failure and increased ET-1 and

  13. Sleep disorders in kidney disease. (United States)

    De Santo, R M; Perna, A; Di Iorio, B R; Cirillo, M


    Sleep disorders are common in patients with end stage renal disease receiving hemodialysis or peritoneal dialysis. However also a well functioning renal graft does not cure the poor sleep pattern which now emerges as a problem even in early chronic kidney disease (CKD). When patients are made aware for the first time of a disease such as CKD, which may brink to dialysis or at the best to a renal transplant patients begin to experience a disordered sleep. Sleeping disorders include insomnia (I), sleep apnoea (SAS), restless legs syndrome (RLS), periodic limb movement disorder (PLMD), excessive daily sleeping (EDS), sleepwalking, nightmares, and narcolepsy. Disordered sleep did not meet the clinical and scientific interest it deserves, in addition and we do not have a well defined solution for sleeping complaints. However, awareness that a poor sleep is associated with poor quality of life and carries an increase in mortality risk has recently stimulated interest in the field. There are many putative causes for a disordered sleep in chronic kidney disease and in end-stage renal disease. For a unifying hypothesis demographic factors, lifestyles, disease related factors, psychological factors, treatment related factors, and social factor must be taken into consideration.

  14. Encrusted pyelitis of native kidneys. (United States)

    Hertig, A; Duvic, C; Chretien, Y; Jungers, P; Grünfeld, J P; Rieu, P


    This study reports the first four cases of encrusted pyelitis involving native kidneys. The clinical features, management, and outcome of these patients were analyzed. Predisposing factors were underlying urologic disease and/or urologic manipulations, debilitating diseases, hospitalization, and prolonged antibiotic therapies. Presenting symptoms were renal failure in three patients with ureteroileal urinary diversion and manifestations of cystitis in one patient. Computed tomography scan of the urinary tract was critical for diagnosis. Presence of struvite was demonstrated by crystalluria and infrared spectrophotometry analysis of the encrusted material. Corynebacterium urealyticum urinary infection was identified in one case. Surgery (one patient) and palliative ureteral diversion (one patient), respectively, led to death and end-stage renal failure. Successful dissolution of encrusted pyelitis was obtained in two patients treated with intravenous vancomycin and local acidification of the renal collecting system. Clinical observation shows that encrusted pyelitis is a threatening disorder that destroys the native kidneys and may lead to end-stage renal failure. Successful treatment of the disease by chemolysis and antibiotics depends on correct and early diagnosis. Diagnosis required recognition of the predisposing factors, computed tomography imaging of the urinary tract, crystalluria, and identification of urea-splitting bacteria with prolonged culture on selective medium.

  15. Lithium-Associated Kidney Microcysts

    Directory of Open Access Journals (Sweden)

    Jennifer Tuazon


    Full Text Available Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from tubulointerstitial nephropathy. Biopsy findings in patients with lithium-induced chronic tubulointerstitial nephropathy include tubular atrophy and interstitial fibrosis interspersed with tubular cysts and dilatations. Recent studies have shown that cysts are seen in 33––62.5% of the patients undergoing lithium therapy. MR imaging is highly capable of defining renal morphological features and has been demonstrated to be superior to US and CT scan for the visualization of small renal cysts. The microcysts are found in both cortex and medulla, particularly in the regions with extensive atrophy and fibrosis, and can be multiple and bilateral. They tend to be sparse and do not normally exceed 1–2 mm in diameter. The renal microcysts in the image here reported are subtle, but consistent with lithium-induced chronic nephropathy. An MRI of the kidneys provides noninvasive evidence that strengthens the diagnosis of lithium-induced nephropathy.

  16. Lithium-associated kidney microcysts. (United States)

    Tuazon, Jennifer; Casalino, David; Syed, Ehteshamuddin; Batlle, Daniel


    Long-term lithium therapy is associated with impairment in concentrating ability and, occasionally, progression to advanced chronic kidney disease from tubulointerstitial nephropathy. Biopsy findings in patients with lithium-induced chronic tubulointerstitial nephropathy include tubular atrophy and interstitial fibrosis interspersed with tubular cysts and dilatations. Recent studies have shown that cysts are seen in 33-62.5% of the patients undergoing lithium therapy. MR imaging is highly capable of defining renal morphological features and has been demonstrated to be superior to US and CT scan for the visualization of small renal cysts. The microcysts are found in both cortex and medulla, particularly in the regions with extensive atrophy and fibrosis, and can be multiple and bilateral. They tend to be sparse and do not normally exceed 1-2 mm in diameter. The renal microcysts in the image here reported are subtle, but consistent with lithium-induced chronic nephropathy. An MRI of the kidneys provides noninvasive evidence that strengthens the diagnosis of lithium-induced nephropathy.

  17. Kidney transplantation after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Li-Yang Wu; Hang Liu; Wei Liu; Han Li; Xiao-Dong Zhang


    Kidney transplantation after liver transplanta-tion (KALT) offers longer survival and a better quality of life to liver transplantation recipients who develop chronic renal failure. This article aimed to discuss the efifcacy and safety of KALT compared with other treatments. The medical records of 5 patients who had undergone KALT were retrospectively studied, together with a literature review of studies. Three of them developed chronic renal failure after liver transplanta-tion because of calcineurin inhibitor (CNI)-induced neph-rotoxicity, while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No mortality was observed in the 5 patients. Three KALT cases showed good prognoses, maintaining a normal serum creatinine level during entire follow-up period. Chronic rejection occurred in the other two patients, and a kidney graft was removed from one of them. Our data suggested that KALT is a good alternative to dialysis for liver transplantation recipients. The cases also indicate that KALT can be performed with good long-term survival.

  18. Myeloperoxidase in chronic kidney disease. (United States)

    Madhusudhana Rao, A; Anand, Usha; Anand, C V


    Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II-V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = -0.85, P < 0.001) and creatinine (r = -0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.

  19. Double knockout of Bax and Bak from kidney proximal tubules reduces unilateral urethral obstruction associated apoptosis and renal interstitial fibrosis (United States)

    Mei, Shuqin; Li, Lin; Wei, Qingqing; Hao, Jielu; Su, Yunchao; Mei, Changlin; Dong, Zheng


    Interstitial fibrosis, a common pathological feature of chronic kidney diseases, is often associated with apoptosis in renal tissues. To determine the associated apoptotic pathway and its role in renal interstitial fibrosis, we established a mouse model in which Bax and Bak, two critical genes in the intrinsic pathway of apoptosis, were deleted specifically from kidney proximal tubules and used this model to examine renal apoptosis and interstitial fibrosis following unilateral urethral obstruction (UUO). It was shown that double knockout of Bax and Bak from proximal tubules attenuated renal tubular cell apoptosis and suppressed renal interstitial fibrosis in UUO. The results indicate that the intrinsic pathway of apoptosis contributes significantly to the tubular apoptosis and renal interstitial fibrosis in kidney diseases. PMID:28317867

  20. Ultrasonic attenuation in cuprate superconductors

    Indian Academy of Sciences (India)

    T Gupta; D M Gaitonde


    We calculate the longitudinal ultrasonic attenuation rate (UAR) in clean d-wave superconductors in the Meissner and the mixed phases. In the Meissner phase we calculate the contribution of previously ignored processes involving the excitation of a pair of quasi-holes or quasi-particles. There is a contribution ∝ in the regime B ≪ F ≪ 0 and a contribution ∝ 1/ in the regime F ≪ B ≪ 0. We find that these contributions to the UAR are large and cannot be ignored. In the mixed phase, using a semi-classical description, we calculate the electronic quasi-particle contribution to the UAR which at very low , has a independent term proportional to $\\sqrt{H}$.


    Directory of Open Access Journals (Sweden)

    Eduardo Fonseca-Pedrero


    Full Text Available Psychotic syndrome includes several devastating mental disorders characterized by a rupture of higher mental functions. The signs and symptoms of psychosis begin in adolescence or early adulthood and usually begin gradually and progress over time. Attenuated psychosis syndrome is a new DSM-5 diagnostic proposal which deals with identifying people at high-risk mental state (ARMS/UHR which may be a predictor of conversion to psychosis. The potential benefit would be that if psychotic disorder is treated more effectively in its early stages, it could produce a lasting beneficial effect that probably could not be achieved with later intervention. This syndrome has generated intense discussion in specialized scientific and professional forums, crisscrossing arguments in favor and against its inclusion. HRMS is preferentially evaluated in the adolescent or young adult population. HRMS evolution is associated with a higher rate of transition toward nonaffective psychosis, although it can evolve toward other mental disorders, remain stable or remit over time. Empirical evidence shows that early intervention seems to have a certain beneficial effect, although for now the results are still insufficient and contradictory. The lack of specificity of symptoms in predicting psychosis, presence of certain limitations (e.g., stigmatization, results found in early interventions and lack of empirical evidence, have led to include the attenuated psychosis syndrome in the DSM-5 Appendix III. The main benefits and limitations of including this supposed category, possible lessons learned from this type of study and future lines of action are discussed in the light of these findings.

  2. 42 CFR 410.48 - Kidney disease education services. (United States)


    ... Kidney disease education services. (a) Definitions. As used in this section: Kidney disease patient... treatments replace the kidney, which includes, but not limited to, the following topics: (i) Hemodialysis... hemodialysis and peritoneal dialysis. (iv) Transplantation. (4) Opportunities for beneficiaries to...

  3. Chronic Kidney Disease: What Does It Mean for Me? (United States)

    ... online catalog. Alternate Language URL Españ​ol Chronic Kidney Disease (CKD) Basics Page Content Chronic Kidney Disease: ... My Lifestyle CKD: Tracking My Test Results Chronic Kidney Disease: The Basics You've been told that ...

  4. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Directory of Open Access Journals (Sweden)

    Yifei Zhong

    Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  5. Novel retinoic acid receptor alpha agonists for treatment of kidney disease. (United States)

    Zhong, Yifei; Wu, Yingwei; Liu, Ruijie; Li, Zhengzhe; Chen, Yibang; Evans, Todd; Chuang, Peter; Das, Bhaskar; He, John Cijiang


    Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  6. MAL/VIP17, a new player in the regulation of NKCC2 in the kidney. (United States)

    Carmosino, Monica; Rizzo, Federica; Procino, Giuseppe; Basco, Davide; Valenti, Giovanna; Forbush, Biff; Schaeren-Wiemers, Nicole; Caplan, Michael J; Svelto, Maria


    The renal-specific Na+-K+-2Cl- cotransporter (NKCC2) is the major salt transport pathway of the apical membrane of the mammalian thick ascending limb of Henle's loop. Here, we analyze the role of the tetraspan protein myelin and lymphocytes-associated protein (MAL)/VIP17 in the regulation of NKCC2. We demonstrated that 1) NKCC2 and MAL/VIP17 colocalize and coimmunoprecipitate in Lilly Laboratories cell porcine kidney cells (LLC-PK1) as well as in rat kidney medullae, 2) a 150-amino acid stretch of NKCC2 C-terminal tail is involved in the interaction with MAL/VIP17, 3) MAL/VIP17 increases the cell surface retention of NKCC2 by attenuating its internalization, and 4) this coincides with an increase in cotransporter phosphorylation. Interestingly, overexpression of MAL/VIP17 in the kidney of transgenic mice results in cysts formation in distal nephron structures consistent with the hypothesis that MAL/VIP17 plays an important role in apical sorting or in maintaining the stability of the apical membrane. The NKCC2 expressed in these mice was highly glycosylated and phosphorylated, suggesting that MAL/VIP17 also is involved in the stabilization of NKCC2 at the apical membrane in vivo. Thus, the involvement of MAL/VIP17 in the activation and surface expression of NKCC2 could play an important role in the regulated absorption of Na+ and Cl- in the kidney.

  7. Zinc-α2-Glycoprotein Exerts Antifibrotic Effects in Kidney and Heart. (United States)

    Sörensen-Zender, Inga; Bhayana, Sagar; Susnik, Nathan; Rolli, Veronique; Batkai, Sandor; Baisantry, Arpita; Bahram, Siamak; Sen, Payel; Teng, Beina; Lindner, Robert; Schiffer, Mario; Thum, Thomas; Melk, Anette; Haller, Hermann; Schmitt, Roland


    Zinc-α2-glycoprotein (AZGP1) is a secreted protein synthesized by epithelial cells and adipocytes that has roles in lipid metabolism, cell cycling, and cancer progression. Our previous findings in AKI indicated a new role for AZGP1 in the regulation of fibrosis, which is a unifying feature of CKD. Using two models of chronic kidney injury, we now show that mice with genetic AZGP1 deletion develop significantly more kidney fibrosis. This destructive phenotype was rescued by injection of recombinant AZGP1. Exposure of AZGP1-deficient mice to cardiac stress by thoracic aortic constriction revealed that antifibrotic effects were not restricted to the kidney but were cardioprotective. In vitro, recombinant AZGP1 inhibited kidney epithelial dedifferentiation and antagonized fibroblast activation by negatively regulating TGF-β signaling. Patient sera with high levels of AZGP1 similarly attenuated TGF-β signaling in fibroblasts. Taken together, these findings indicate a novel role for AZGP1 as a negative regulator of fibrosis progression, suggesting that recombinant AZGP1 may have translational effect for treating fibrotic disease.

  8. Ameliorated Effects of Green Tea Extract on Lead Induced Kidney Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Nadia Ait Hamadouche


    Full Text Available In the present study, the protective effect of an aqueous extract of green tea (GTE against renal oxidative damage induced by lead was undertaken. Adult males rats were divided into 4 groups: Control group receives distilled water as sole drinking source. GTE group received green tea extract (6.6% w/v.Pb group received Pb at dose of 0.4 % w/v in distilled water. Pb + GTE group received mixture of Pb and GTE as sole drinking source. Renal oxidative damage was observed in Pb-treated rats as evidenced via augmentation in kidney lipid peroxidation (LPO as well as depletion in kidney antioxidant enzymes; catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GPx. Histopathological analysis revealed degeneration in the endothelium of glomerular tuft and the epithelium of lining tubules. In conclusion, GTE appeared to be beneficial to rats, to a great extent by attenuating and restoring the damage sustained by lead exposure.

  9. Attenuation characteristics of a light attenuator combined by polarizers with different extinction ratios

    Institute of Scientific and Technical Information of China (English)

    Huang Chong; Deng Peng; Zhao Shuang; Chen Hai-Qing


    This paper deals with a systematical analysis and an algorithm of attenuation characteristics of a light attenuator combined by n pieces of polarizers(n-LACP)whose extinction ratios are different from each other.The attenuation ratio expression of a two-LACP is deduced. We find that the monotonic attenuation interval depends on the first polarizer and that the attenuation range depends on the second one.For the three-LACP,a method for obtaining a monotonic attenuation interval is proposed.Moreover,the attenuation ratio expression is demonstrated.Analysis and experiment show that when the initial status of the three-LACP is at the maximum output,if the second or third polarizer rotates alone,the minimum attenuation ratios can reach K2-1and K3-1,respectively,and if the first polarizer rotates,a minimum attenuation ratio of K2-1K3-1can be obtained(K1,K2 and K3 represent the extinction ratios of the three polarizers in turn).Furthermore,the attenuation ratio expression of n-LACP and the relevant attenuation characteristics are proposed.The minimum attenuation ratio of an n-LACP is(K2K3...Kn)-1.

  10. Tailor-Made Live Kidney Donation

    NARCIS (Netherlands)

    K.W.J. Klop (Karel)


    markdownabstract__Abstract__ This thesis describes several aspects of live kidney donation, such as surgical techniques, cost-effectivity, cosmetics en quality of life. Kidney transplantation offer several benefits when compared to dialysis. These benefits include better recipient and graft surviva

  11. Innate immune functions in kidney transplantation

    NARCIS (Netherlands)

    Berger, Stefan Philip


    The innate immune system plays an important role in solid organ transplantation. This thesis focuses on the role of the lectin pathway of complement activation in kidney and simultaneous pancreas-kidney transplantation (SPKT) and describes the role of properdin in tubular complement activation and c

  12. Gene based therapies for kidney regeneration

    NARCIS (Netherlands)

    Janssen, Manoe J; Arcolino, Fanny O; Schoor, Perry; Kok, Robbert Jan; Mastrobattista, Enrico


    In this review we provide an overview of the expanding molecular toolbox that is available for gene based therapies and how these therapies can be used for a large variety of kidney diseases. Gene based therapies range from restoring gene function in genetic kidney diseases to steering complex molec

  13. Renal acidification defects in medullary sponge kidney

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F


    Thirteen patients with medullary sponge kidney underwent a short ammonium chloride loading test to investigate their renal acidification capacity. All but 1 presented with a history of recurrent renal calculi and showed bilateral widespread renal medullary calcification on X-ray examination. Nine...... of renal calculi in medullary sponge kidney, have considerable therapeutic implications....

  14. P2 receptors in the kidney. (United States)

    Bailey, M A; Hillman, K A; Unwin, R J


    Our understanding of the actions of extracellular ATP in controlling kidney function via stimulation of P2 receptors is still at an early stage. Recently, several groups, including our own, have begun to address this subject: in this brief review, we discuss some of these effects and speculate on likely function of extracellular nucleotides in the kidney.

  15. High Blood Pressure and Kidney Disease (United States)

    ... Disease Mineral & Bone Disorder View All Content High Blood Pressure & Kidney Disease What is high blood pressure? Blood pressure is the force of blood ... million filtering units called nephrons. How does high blood pressure affect the kidneys? High blood pressure can ...

  16. Diabetes Mellitus in the Transplanted Kidney

    Directory of Open Access Journals (Sweden)

    Vasil ePeev


    Full Text Available Diabetes mellitus (DM is the most common cause of chronic kidney disease (CKD and end stage renal disease (ESRD. New onset diabetes mellitus after transplant (NODAT has been described in approximately 30 percent of non-diabetic kidney transplant recipients many years post transplantation. DM in patients with kidney transplantation constitutes a major comorbidity, and has significant impact on the patients and allografts’ outcome. In addition to the major comorbidity and mortality that result from cardiovascular and other DM complications, long standing DM after kidney transplant has significant pathological injury to the allograft, which results in lowering the allografts and the patients’ survivals. In spite of the cumulative body of data on diabetic nephropathy (DN in the native kidney, there has been very limited data on the DN in the transplanted kidney. In this review, we will shed the light on the risk factors that lead to the development of NODAT. We will also describe the impact of DM on the transplanted kidney, and the outcome of kidney transplant recipients with NODAT. Additionally, we will present the most acceptable data on management of NODAT.

  17. Allopurinol and kidney function: An update. (United States)

    Stamp, Lisa K; Chapman, Peter T; Palmer, Suetonia C


    Allopurinol is the most commonly used urate lowering therapy in the management of gout. Despite the fact that it has been available for over 40 years there is ongoing debate about optimal allopurinol dosing in gout patients with chronic kidney disease. Given that gout is common in patients with renal impairment, clinicians need to be aware of the relationships between serum urate and kidney function as well as the effects of allopurinol on kidney function and vice versa. The use of allopurinol in patients on dialysis is an understudied area. Dialysis reduces plasma oxypurinol concentrations, therefore the dose and time of administration in relationship to dialysis need to be carefully considered. Recently, it has been suggested that there may be a role for allopurinol in patients with chronic kidney disease without gout. Observational studies have reported an association between serum urate and chronic kidney disease and end stage renal failure. The effect of urate lowering therapy with allopurinol on progression of kidney disease has been examined in small studies with varying results. Larger clinical trials are currently underway. This review will examine the relationships between allopurinol and kidney function in adults with and without renal disease and address allopurinol dosing in gout patients with impaired kidney function.

  18. Radiation damage in rat kidney microvasculature. (United States)

    Nelson, A C; Shah-Yukich, A; Babayan, R


    Scanning electron microscopy (SEM) combined with a specialized polymer injection casting technique permits the analysis of radiation induced damage in rat kidney glomeruli. A lead shielding device is constructed to enable the irradiation of the living rat left kidney, while the remainder of the animal is shielded from the dose, the right kidney serves as a control. The source of radiation is 137Cs which produces 0.66 MeV gamma-rays to achieve a kidney dose of 100 rad and 5000 rad in these experiments. Radiation damage to kidney glomeruli is assessed at intervals of 0, 1, 3 and 7 days post-irradiation at the two dose levels. It is found that radiation damage to kidney glomeruli is expressed morphologically at 7 days post-irradiation at the 100 rad dose level, while glomerular damage is apparent as early as 3 days post-irradiation at the 5000 rad dose level. Moreover, by 7 days post-irradiation with a 5000 rad dose, the kidney glomerulus thoroughly degenerates to a leaky fused mass of vessels. From a morphological viewpoint, kidney glomeruli are significantly more sensitive to radiation than surrounding vasculature. The methods developed here for assessment of radiation damage are highly repeatable and could serve as a standard technique in radiobiology.

  19. Kidney Transplantation in the Diabetic Patient

    Directory of Open Access Journals (Sweden)

    María José Pérez-Sáez


    Full Text Available Diabetes mellitus is one of the most important causes of chronic kidney disease (CKD. In patients with advanced diabetic kidney disease, kidney transplantation (KT with or without a pancreas transplant is the treatment of choice. We aimed to review current data regarding kidney and pancreas transplant options in patients with both type 1 and 2 diabetes and the outcomes of different treatment modalities. In general, pancreas transplantation is associated with long-term survival advantages despite an increased short-term morbidity and mortality risk. This applies to simultaneous pancreas kidney transplantation or pancreas after KT compared to KT alone (either living donor or deceased. Other factors as living donor availability, comorbidities, and expected waiting time have to be considered whens electing one transplant modality, rather than a clear benefit in survival of one strategy vs. others. In selected type 2 diabetic patients, data support cautious utilization of simultaneous pancreas kidney transplantation when a living kidney donor is not an option. Pancreas and kidney transplantation seems to be the treatment of choice for most type 1 diabetic and selected type 2 diabetic patients.

  20. Screening techniques for detecting chronic kidney disease

    NARCIS (Netherlands)

    de Jong, PE; Gansevoort, RT


    Purpose of review As patients with impaired kidney function are at increased risk not only for progressive renal function loss, but also for cardiovascular disease, it is of importance to have accurate techniques to screen patients for the presence of an impaired kidney function. Recent findings Glo

  1. Sex differences in ischemia/reperfusion-induced acute kidney injury are dependent on the renal sympathetic nervous system. (United States)

    Tanaka, Ryosuke; Tsutsui, Hidenobu; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo


    Resistance to ischemic acute kidney injury has been shown to be higher in female rats than in male rats. We found that renal venous norepinephrine overflow after reperfusion played important roles in the development of ischemic acute kidney injury. In the present study, we investigated whether sex differences in the pathogenesis of ischemic acute kidney injury were derived from the renal sympathetic nervous system using male and female Sprague-Dawley rats. Ischemia/reperfusion-induced acute kidney injury was achieved by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was impaired after reperfusion in both male and female rats; however, renal dysfunction and histological damage were more severe in male rats than in female rats. Renal venous plasma norepinephrine levels after reperfusion were markedly elevated in male rats, but were not in female rats. These sex differences were eliminated by ovariectomy or treatment with tamoxifen, an estrogen receptor antagonist, in female rats. Furthermore, an intravenous injection of hexamethonium (25mg/kg), a ganglionic blocker, 5 min before ischemia suppressed the elevation in renal venous plasma norepinephrine levels after reperfusion, and attenuated renal dysfunction and histological damage in male rats, and ovariectomized and tamoxifen-treated female rats, but not in intact females. Thus, the present findings confirmed sex differences in the pathogenesis of ischemic acute kidney injury, and showed that the attenuation of ischemia/reperfusion-induced acute kidney injury observed in intact female rats may be dependent on depressing the renal sympathetic nervous system with endogenous estrogen.

  2. Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes. (United States)

    Grutzmacher, Cathy; Park, SunYoung; Zhao, Yun; Morrison, Margaret E; Sheibani, Nader; Sorenson, Christine M


    Diabetic nephropathy is the most common cause of end-stage renal disease and is a major risk factor for cardiovascular disease. In the United States, microvascular complications during diabetic nephropathy contribute to high morbidity and mortality rates. However, the cell-autonomous impact of diabetes on kidney endothelial cell function requires further investigation. Male Akita/+ [autosomal dominant mutation in the insulin II gene (Ins2)] mice reproducibly develop diabetes by 4 wk of age. Here, we examined the impact a short duration of diabetes had on kidney endothelial cell function. Kidney endothelial cells were prepared from nondiabetic and diabetic mice (4 wk of diabetes) to delineate the early changes in endothelial cell function. Kidney endothelial cells from Akita/+ mice following 4 wk of diabetes demonstrated aberrant expression of extracellular matrix proteins including decreased osteopontin and increased fibronectin expression which correlated with increased α5-integrin expression. These changes were associated with the attenuation of migration and capillary morphogenesis. Kidney endothelial cells from Akita/+ mice had decreased VEGF levels but increased levels of endothelial nitric oxide synthase(eNOS) and NO, suggesting uncoupling of VEGF-mediated NO production. Knocking down eNOS expression in Akita/+ kidney endothelial cells increased VEGF expression, endothelial cell migration, and capillary morphogenesis. Furthermore, attenuation of sprouting angiogenesis of aortas from Akita/+ mice with 8 wk of diabetes was restored in the presence of the antioxidant N-acetylcysteine. These studies demonstrate that aberrant endothelial cell function with a short duration of diabetes may set the stage for vascular dysfunction and rarefaction at later stages of diabetes.

  3. Transplantation of Kidneys From Donors With Acute Kidney Injury: Friend or Foe? (United States)

    Boffa, C; van de Leemkolk, F; Curnow, E; Homan van der Heide, J; Gilbert, J; Sharples, E; Ploeg, R J


    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 large UK cohort. A retrospective analysis of the UK Transplant Registry evaluated deceased donors between 2003 and 2013. Donors were classified as no AKI, or AKI stage 1-3 according to Acute Kidney Injury Network (AKIN) criteria. Relationship of AKI with delayed graft function/primary nonfunction (DGF/PNF), estimated glomerular filtration rate (eGFR), and graft-survival at 90 days and 1 year was analyzed. There were 11 219 kidneys (1869 [17%] with AKI) included. Graft failure at 1 year is greater for donors with AKI than for those without (graft survival 89% vs. 91%, p = 0.02; odds ratio (OR) 1.20 [95% confidence interval (CI): 1.03-1.41]). DGF rates increase with donor AKI stage (p kidneys (9% vs. 4%, p = 0.04) Analysis of association between AKI and recipient eGFR suggests a risk of inferior eGFR with AKI versus no AKI (p kidneys from donors with AKI. We conclude that AKI stage 1 or 2 kidneys should be used; however, caution is advised for AKI stage 3 donors.

  4. Kidneys at higher risk of discard: expanding the role of dual kidney transplantation. (United States)

    Tanriover, B; Mohan, S; Cohen, D J; Radhakrishnan, J; Nickolas, T L; Stone, P W; Tsapepas, D S; Crew, R J; Dube, G K; Sandoval, P R; Samstein, B; Dogan, E; Gaston, R S; Tanriover, J N; Ratner, L E; Hardy, M A


    Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI)>85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (90%). Kidneys with KDPI>90% were associated with increased odds of discard (OR=1.99, 95% CI 1.74-2.29) compared to ones with KDPI90% were associated with lower overall allograft failure (HR=0.74, 95% CI 0.62-0.89) and better patient survival (HR=0.79, 95% CI 0.64-0.98) compared to single ECD kidneys with KDPI>90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile.

  5. Cyclic Nucleotide Signalling in Kidney Fibrosis

    Directory of Open Access Journals (Sweden)

    Elisabeth Schinner


    Full Text Available Kidney fibrosis is an important factor for the progression of kidney diseases, e.g., diabetes mellitus induced kidney failure, glomerulosclerosis and nephritis resulting in chronic kidney disease or end-stage renal disease. Cyclic adenosine monophosphate (cAMP and cyclic guanosine monophosphate (cGMP were implicated to suppress several of the above mentioned renal diseases. In this review article, identified effects and mechanisms of cGMP and cAMP regarding renal fibrosis are summarized. These mechanisms include several signalling pathways of nitric oxide/ANP/guanylyl cyclases/cGMP-dependent protein kinase and cAMP/Epac/adenylyl cyclases/cAMP-dependent protein kinase. Furthermore, diverse possible drugs activating these pathways are discussed. From these diverse mechanisms it is expected that new pharmacological treatments will evolve for the therapy or even prevention of kidney failure.

  6. Cyclooxygenase (COX Inhibitors and the Newborn Kidney

    Directory of Open Access Journals (Sweden)

    Wei Qi


    Full Text Available This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2 plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function.

  7. [Lithiasis and ectopic pelvic kidney. Therapeutic aspects]. (United States)

    Aboutaieb, R; Rabii, R; el Moussaoui, A; Joual, A; Sarf, I; el Mrini, M; Benjelloun, S


    Kidney in ectopic position is dysplasic, and associated to other malformations. The advent of a lithiasis in these conditions rises questions about therapeutic options. We report on five observations of pelvic ectopic kidney with urinary lithiasis. Patients were aged from 16 to 42 years. Kidney was non functional in two cases, or with normal appearance sized 10 to 12 cm. We performed total nephrectomy in two cases, pyelolithotomy in the other cases. Surgical approach was subperitoneal via iliac route. A dismembered pyeloplasty was associated in one case. All patients did well. Radiologic control at 6 and 12 months showed no recurrence in a well functioning kidney. Surgical lithotomy is advocated as a treatment in urinary lithiasis affecting ectopic kidney. It is an easy procedure which permits correction of other associated malformations.

  8. Planar cell polarity of the kidney. (United States)

    Schnell, Ulrike; Carroll, Thomas J


    Planar cell polarity (PCP) or tissue polarity refers to the polarization of tissues perpendicular to the apical-basal axis. Most epithelia, including the vertebrate kidney, show signs of planar polarity. In the kidney, defects in planar polarity are attributed to several disease states including multiple forms of cystic kidney disease. Indeed, planar cell polarity has been shown to be essential for several cellular processes that appear to be necessary for establishing and maintaining tubule diameter. However, uncovering the genetic mechanisms underlying PCP in the kidney has been complicated as the roles of many of the main players are not conserved in flies and vice versa. Here, we review a number of cellular and molecular processes that can affect PCP of the kidney with a particular emphasis on the mechanisms that do not appear to be conserved in flies or that are not part of canonical determinants.

  9. De Novo Kidney Regeneration with Stem Cells

    Directory of Open Access Journals (Sweden)

    Shinya Yokote


    Full Text Available Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD, traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration.


    Institute of Scientific and Technical Information of China (English)

    BI Weiping; MU Xiaowu; SUN Yuqiang


    In present paper, the disturbance attenuation problem of uncertain nonlinear cascaded systems is studied. Based on the adding one power integrator technique and recursive design, a feedback controller that solves the disturbance attenuation problem is constructed for uncertain nonlinear cascaded systems with internal stability.

  11. Light attenuation on Chlorella vulgaris cells (United States)

    Krol, Tadeusz; Lotocka, Maria


    The laboratory measurements of spectrum of light attenuation on phytoplankton particles i.e. monoculture of unicellural green algae Chlorella vulgaris are presented. The measurements were carried out for alive culture and the cultures subjected to chemical (NaOH) or physical (ultrasounds) modification. The distinct changes in the light attenuation spectrum were a result of modification of the internal cell structures.

  12. Attenuation coefficients for water quality trading. (United States)

    Keller, Arturo A; Chen, Xiaoli; Fox, Jessica; Fulda, Matt; Dorsey, Rebecca; Seapy, Briana; Glenday, Julia; Bray, Erin


    Water quality trading has been proposed as a cost-effective approach for reducing nutrient loads through credit generation from agricultural or point source reductions sold to buyers facing costly options. We present a systematic approach to determine attenuation coefficients and their uncertainty. Using a process-based model, we determine attenuation with safety margins at many watersheds for total nitrogen (TN) and total phosphorus (TP) loads as they transport from point of load reduction to the credit buyer. TN and TP in-stream attenuation generally increases with decreasing mean river flow; smaller rivers in the modeled region of the Ohio River Basin had TN attenuation factors per km, including safety margins, of 0.19-1.6%, medium rivers of 0.14-1.2%, large rivers of 0.13-1.1%, and very large rivers of 0.04-0.42%. Attenuation in ditches transporting nutrients from farms to receiving rivers is 0.4%/km for TN, while for TP attenuation in ditches can be up to 2%/km. A 95 percentile safety margin of 30-40% for TN and 6-10% for TP, applied to the attenuation per km factors, was determined from the in-stream sensitivity of load reductions to watershed model parameters. For perspective, over 50 km a 1% per km factor would result in 50% attenuation = 2:1 trading ratio.

  13. Relative length of human kidney as more precise measuring of normal kidney

    Directory of Open Access Journals (Sweden)

    Ilić Goran


    Full Text Available Introduction. Malformations in kidney development and kidney diseases are accompanied with changes in their size. For kidney evaluation in clinical practice, the kidney length is the most widely used measurement, since it provides the most precise results and it is easy to perform. Recently, the measurement of relative renal length has become more preferable as it takes into account the body height. The aim of this study was to measure both the absolute and relative length of normal cadaveric kidneys according to the body height, sex and age. Material and methods. In this study, we examined 95 adult cadaveric kidneys, without renal and vascular impairment, their age ranging from 23-87 years. To determine the period of the most abundant changes in kidney length, we separated them into a 10-year range. The relative renal length was calculated using the kidney length anybody height ratio (kidney/body ratio. Results. The absolute and relative length of left kidney in males was longer than the right one, with a statistically significant correlation. In females, the left kidney length was also longer than the right one, however, without a statistical significance. In contrast to the absolute length, the relative length of both kidneys did not show a significant difference between sexes, and did not manifest a significant decrease with age. There was a significant correlation between the kidney length and the subject’s height. Conclusion. The relative renal length represents kidney size better than the absolute renal length because it eliminates sex and height differences until the age of 59 year. From the seventh decade of life, there is a significant decrease in both the absolute and relative renal length.

  14. Flavocoxid attenuates gentamicin-induced nephrotoxicity in rats. (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Suddek, Ghada M; Salem, Hatem A


    Gentamicin is a widely used antibiotic against serious and life-threatening infections; however, its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine whether flavocoxid has a protective effect against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of flavocoxid on gentamicin induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was determined. Twenty-four male Wistar albino rats were randomly divided into three groups, namely control, gentamicin (100 mg/kg, i.p.) and gentamicin plus flavocoxid (20 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood, urine samples and kidneys were collected for further analysis. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated renal somatic index (RSI), serum creatinine, blood urea nitrogen, serum lactate dehydrogenase, and protein in urine with a concomitant reduction in serum albumin and normalized creatinine clearance value as compared with the controls. Moreover, a significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione and superoxide dismutase activities was detected upon gentamicin administration together with increasing the sensitivity of isolated urinary bladder rings to ACh. Exposure to gentamicin induced necrosis of renal tubular epithelial cells. Flavocoxid protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by gentamicin treatment. In addition, flavocoxid significantly reduced the responses of isolated bladder rings to ACh. The results from our study indicate that flavocoxid supplement attenuates gentamicin-induced renal injury via the amelioration of

  15. Impact of AT2-receptor stimulation on vascular biology, kidney function, and blood pressure

    DEFF Research Database (Denmark)

    Danyel, L.A.; Schmerler, P.; Paulis, L.;


    angiotensin II) and with relevance for blood pressure (BP) regulation or hypertensive end-organ damage. These data will include studies on vasodilation/vasoconstriction in isolated resistance arteries ex vivo, studies on kidney function, studies on vascular remodeling, and studies that measured the net effect...... to attenuate hypertension-induced vascular remodeling and reduce arterial stiffening, which in more chronic settings and together with the natriuretic effect may result in modest lowering of BP. We conclude from these preclinical data that AT2R agonists are not suitable for antihypertensive monotherapy...

  16. Both msa genes in Renibacterium salmoninarum are needed for full virulence in bacterial kidney disease (United States)

    Coady, A.M.; Murray, A.L.; Elliott, D.G.; Rhodes, L.D.


    Renibacterium salmoninarum, a gram-positive diplococcobacillus that causes bacterial kidney disease among salmon and trout, has two chromosomal loci encoding the major soluble antigen (msa) gene. Because the MSA protein is widely suspected to be an important virulence factor, we used insertion-duplication mutagenesis to generate disruptions of either the msa1 or msa2 gene. Surprisingly, expression of MSA protein in broth cultures appeared unaffected. However, the virulence of either mutant in juvenile Chinook salmon (Oncorhynchus tshawytscha) by intraperitoneal challenge was severely attenuated, suggesting that disruption of the msa1 or msa2 gene affected in vivo expression. Copyright ?? 2006, American Society for Microbiology. All Rights Reserved.

  17. Ultrasound fields in an attenuating medium

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Gandhi,, D; O'Brien,, W.D., Jr.


    Ultrasound fields propagating in tissue will undergo changes in shape not only due to diffraction, but also due to the frequency dependent attenuation. Linear fields can be fairly well predicted for a non-attenuating medium like water by using the Tupholme-Stepanishen method for calculating...... the spatial impulse response, whereas the field cannot readily be found for an attenuating medium. In this paper we present a simulation program capable of calculating the field in a homogeneous attenuating medium. The program splits the aperture into rectangles and uses a far-field approximation for each...... of the rectangles and sums all contributions to arrive at the spatial impulse response for the aperture and field point. This approach makes it possible to model all transducer apertures, and the program can readily calculate the emitted, pulse-echo and continuous wave field. Attenuation is included by splitting...

  18. Kidney injuries related to ipilimumab. (United States)

    Izzedine, Hassane; Gueutin, Victor; Gharbi, Chems; Mateus, Christine; Robert, Caroline; Routier, Emilie; Thomas, Marina; Baumelou, Alain; Rouvier, Philippe


    Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) have been investigated in metastatic melanoma and other cancers and have shown promising results. Inhibition of CTLA-4 characteristically induces well-known side effects called "immune-related adverse events" (irAEs). IrAEs mainly include colitis, dermatitis, hepatitis, endocrinopathies; uveitis, iridocyclitis, neuropathies, and inflammatory myopathy have occasionally been reported. Kidney involvement is rare. We report 2 cases of acute granulomatous interstitial nephritis and present, based on literature review, renal disorders related to Ipilimumab therapy. Autoimmune symptoms have to be carefully checked for patients treated with CTLA-4 inhibitors. In order to reduce the risk of sequelae, early recognition of irAEs and treatment initiation are crucial.

  19. Metformin in chronic kidney disease

    DEFF Research Database (Denmark)

    Heaf, James


    reduction, including weight loss, which are beneficial to patients. The risk of death and cardiovascular disease is reduced by about a third in non-CKD patients. Since metformin intoxication undoubtedly causes LA, and metformin is renally excreted, inappropriate dosage of metformin will increase the risk......Metformin has traditionally been regarded as contraindicated in chronic kidney disease (CKD), though guidelines in recent years have been relaxed to permit therapy if the glomerular filtration rate (GFR) is > 30 mL/min. The main problem is the perceived risk of lactic acidosis (LA). Epidemiological...... of LA. It is suggested that introduction of metformin therapy to more advanced stages of CKD may bring therapeutic benefits that outweigh the possible risks....

  20. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice. (United States)

    Gallo, Linda A; Ward, Micheal S; Fotheringham, Amelia K; Zhuang, Aowen; Borg, Danielle J; Flemming, Nicole B; Harvie, Ben M; Kinneally, Toni L; Yeh, Shang-Ming; McCarthy, Domenica A; Koepsell, Hermann; Vallon, Volker; Pollock, Carol; Panchapakesan, Usha; Forbes, Josephine M


    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

  1. Renal Cell Protection of Erythropoietin beyond Correcting The Anemia in Chronic Kidney Disease Patients. (United States)

    Nasri, Hamid


    -erythropoietic tissue/ organ protective efficacy of erythropoietin has become evident, especially in the kidneys (5-12). Various investigations have shown the kidney protective property of erythropoietin in acute kidney injury. In a study to evaluate the ameliorative effects of erythropoietin on renal tubular cells, we studied 40 male rats. We found that erythropoietin was able to prevent the increase in serum creatinine and blood urea nitrogen. Furthermore, co-administration of gentamicin and erythropoietin effectively reduced kidney tissue damage compared to the control group. However, the protective properties of erythropoietin were also evident in our study. When the drug was applied after gentamicin- induced tubular damage we were able to show that the drug was still effective after tissue injury onset. This indicates that erythropoietin may have curative effects in addition to its preventive properties (13). Thus, erythropoietin is a promising kidney protective agent to prevent, ameliorate or attenuate tubular damage induced by gentamicin or other nephrotoxic agents that act in a similar manner to this drug (14-17). Recent studies have elucidated the cellular mechanism involved in kidney erythropoietin production and the consequent events that lead to kidney fibrosis, showing that they are closely related to each other (18-20). In contrast to previous findings, fibroblasts originating from damaged renal tubular epithelial cells do not have an important role in kidney fibrosis, but renal erythropoietin- producing cells, stemming from neural crests, have been shown to trans-differentiate into myofibroblasts after long-term exposure to inflammatory situations related to kidney fibrosis. In fact, almost all myofibroblasts expressing α-smooth muscle actin originate from renal erythropoietin-producing cells, which are naturally peritubular interstitial fibroblastic cells expressing neural cell marker genes but not α-smooth muscle actin. Macrophages and myofibroblasts are responsible

  2. Kidney disease in pregnancy: (Women's Health Series). (United States)

    Gyamlani, Geeta; Geraci, Stephen A


    Kidney disease and pregnancy may exist in two general settings: acute kidney injury that develops during pregnancy, and chronic kidney disease that predates conception. In the first trimester of pregnancy, acute kidney injury is most often the result of hyperemesis gravidarum, ectopic pregnancy, or miscarriage. In the second and third trimesters, the common causes of acute kidney injury are severe preeclampsia, hemolysis-elevated liver enzymes-low platelets syndrome, acute fatty liver of pregnancy, and thrombotic microangiopathies, which may pose diagnostic challenges to the clinician. Cortical necrosis and obstructive uropathy are other conditions that may lead to acute kidney injury in these trimesters. Early recognition of these disorders is essential to timely treatment that can improve both maternal and fetal outcomes. In women with preexisting kidney disease, pregnancy-related outcomes depend upon the degree of renal impairment, the amount of proteinuria, and the severity of hypertension. Neonatal and maternal outcomes in pregnancies among renal transplant patients are generally good if the mother has normal baseline allograft function. Common renally active drugs and immunosuppressant medications must be prescribed, with special considerations in pregnant patients.

  3. Multicystic Dysplastic Kidney: Four-Year Evaluation

    Directory of Open Access Journals (Sweden)

    Berna AYTAÇ


    Full Text Available Objective: Multicystic dysplastic kidney is a relatively common developmental abnormality in infants and children. Additional abnormalities like vesicoureteral reflux, ureteropelvic junction obstruction, and ureterovesical junction obstruction may accompany multicystic dysplastic kidney. In this article, we reviewed the pathogenesis, diagnosis, associated urinary tract anomalies and results of management of multicystic dysplastic kidney in the light of the literature.Material and Method: We retrospectively assessed 20 children with unilateral multicystic dysplastic kidney between January 2005 and December 2009. Mean duration of follow-up was 35 ± 8.7 months. All children with multicystic dysplastic kidney underwent nephrectomy. Patient characteristics, the pathology findings, associated urinary tract anomalies and results of management were reviewed.Results: Abdominal ultrasound, voiding cystourethrography and renal scintigraphy revealed vesicoureteral reflux in 3 (15% children, ureteropelvic junction obstruction in 3 (15% children, and a duplex system in the contralateral kidney in 1 (5% child. Blood pressure values, serum urea, creatinine and urinalysis were within normal range in all children during follow-up.Conclusion: A conservative approach to children with multicystic dysplastic kidney has been advocated, but surgical removal is also another management modality on the basis of risk of hypertension, mass effect, potential for malignant change, and cost of repeated ultrasound examination.

  4. Attenuation of diacylglycerol second messengers

    Energy Technology Data Exchange (ETDEWEB)

    Bishop, W.R.; Ganong, B.R.; Bell, R.M.


    Diacylglycerol(DAG) derived from phosphatidylinositol activates protein kinase C in agonist-stimulated cells. At least two pathways may contribute to the attenuation of the DAG signal: (1) phosphorylation to phosphatidic acid(PA) by DAG kinase(DGK), and (2) deacylation by DAG and monoacylglycerol lipases. A number of DAG analogs were tested as substrates and inhibitors of partially purified pig brain DGK. Two analogs were potent inhibitors in vitro, 1-monooleoylglycerol(MOG,K/sub I/ = 91 and diotanoylethyleneglycol (diC/sub 8/EG, K/sub I/ = 58 These compounds were tested in human platelets. DiC/sub 8/EG inhibited (70 - 100%) (/sup 32/P/sub i/) incorporation into PA in thrombin-stimulated platelets. Under these conditions the DAG signal was somewhat long-lived but was still metabolized, presumably by the lipase pathway. MOG treatment elevated DAG levels up to 4-fold in unstimulated platelets. The DAG formed was in a pool where it did not activate protein kinase C. Thrombin-stimulation of MOG-treated platelets resulted in DAG levels 10-fold higher than control platelets. This appears to be due to the inability of these platelets to metabolize agonist-linked DAG via the lipase pathway. The development of specific inhibitors of DAG kinase and DAG lipase, in conjunction with mass quantification of DAG levels as used here, will provide further insights into the regulation of DAG second messengers.

  5. Live attenuated intranasal influenza vaccine. (United States)

    Esposito, Susanna; Montinaro, Valentina; Groppali, Elena; Tenconi, Rossana; Semino, Margherita; Principi, Nicola


    Annual vaccination is the most effective means of preventing and controlling influenza epidemics, and the traditional trivalent inactivated vaccine (TIV) is by far the most widely used. Unfortunately, it has a number of limitations, the most important of which is its poor immunogenicity in younger children and the elderly, the populations at greatest risk of severe influenza. Live attenuated influenza vaccine (LAIV) has characteristics that can overcome some of these limitations. It does not have to be injected because it is administered intranasally. It is very effective in children and adolescents, among whom it prevents significantly more cases of influenza than the traditional TIV. However, its efficacy in adults has not been adequately documented, which is why it has not been licensed for use by adults by the European health authorities. LAIV is safe and well tolerated by children aged > 2 y and adults, but some concerns arisen regarding its safety in younger children and subjects with previous asthma or with recurrent wheezing. Further studies are needed to solve these problems and to evaluate the possible role of LAIV in the annual vaccination of the general population.

  6. Antiphospholipid Syndrome and Kidney Involvement: New Insights

    Directory of Open Access Journals (Sweden)

    José A. Martínez-Flores


    Full Text Available Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thromboses and pregnancy morbidity associated with antiphospholipid antibodies: lupus anticoagulant, IgG or IgM anticardiolipin or anti-beta 2-glycoprotein I. The kidney is one of the major target organs in antiphospholipid syndrome (APS. However, beyond the known involvement of the kidney in primary and associated APS, we may be observing a new form of APS within the context of renal failure. This review describes the classical kidney manifestations of APS and provides new considerations to be taken into account.

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

    Directory of Open Access Journals (Sweden)

    Wenpeng Cui


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

  8. Withania coagulans fruit extract reduces oxidative stress and inflammation in kidneys of streptozotocin-induced diabetic rats. (United States)

    Ojha, Shreesh; Alkaabi, Juma; Amir, Naheed; Sheikh, Azimullah; Agil, Ahmad; Fahim, Mohamed Abdelmonem; Adem, Abdu


    The present study was carried out to investigate the changes in oxidative and inflammatory status in streptozotocin-induced diabetic rat's kidneys and serum following treatment with Withania coagulans, a popular herb of ethnomedicinal significance. The key markers of oxidative stress and inflammation such as inflammatory cytokines (IL-1β, IL-6, and TNF-α) and immunoregulatory cytokines (IL-4 and IFN-γ) were increased in kidneys along with significant hyperglycemia. However, treatment of four-month diabetic rats with Withania coagulans (10 mg/kg) for 3 weeks significantly attenuated hyperglycemia and reduced the levels of proinflammatory cytokines in kidneys. In addition, Withania coagulans treatment restored the glutathione levels and inhibited lipid peroxidation along with marked reduction in kidney hypertrophy. The present study demonstrates that Withania coagulans corrects hyperglycemia and maintained antioxidant status and reduced the proinflammatory markers in kidneys, which may subsequently reduce the development and progression of renal injury in diabetes. The results of the present study are encouraging for its potential use to delay the onset and progression of diabetic renal complications. However, the translation of therapeutic efficacy in humans requires further studies.

  9. Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Jing Zhang


    Full Text Available Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN. Endoplasmic reticulum (ER stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p. twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress–associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN.

  10. Graphene-based Electronically Tuneable Microstrip Attenuator

    Directory of Open Access Journals (Sweden)

    L. Pierantoni


    Full Text Available This paper presents the design of a graphene- based electronically tuneable microstrip attenuator operating at a frequency of 5 GHz. The use of graphene as a variable resistor is discussed and the modelling of its electromagnetic properties at microwave frequencies is fully addressed. The design of the graphene-based attenuator is described. The structure integrates a patch of graphene, whose characteristics can range from being a fairly good conductor to a highly lossy material, depending on the applied voltage. By applying the proper voltage through two high-impedance bias lines, the surface resistivity of graphene can be modified, thereby changing the insertion loss of the microstrip attenuator.

  11. Acute Kidney Injury: Tubular Markers and Risk for Chronic Kidney Disease and End-Stage Kidney Failure. (United States)

    Tan, Hon Liang; Yap, John Q; Qian, Qi


    Acute kidney injury (AKI) is a common clinical syndrome directly related to patient short-term and long-term morbidity and mortality. Over the last decade, the occurrence rate of AKI has been increasing, and there has also been a growing epidemic of chronic kidney diseases (CKD) and end-stage kidney disease (ESRD) linked to severe and repeated episodes of AKIs. The detection and management of AKI are currently far from satisfactory. A large proportion of AKI patients, especially those with preexisting CKD, are at an increased risk of non-resolving AKI and progressing to CKD and ESRD. Proposed pathological processes that contribute to the transition of AKI to CKD and ESRD include severity and frequency of kidney injury, alterations of tubular cell phenotype with cells predominantly in the G2/M phase, interstitial fibrosis and microvascular rarification related to loss of endothelial-pericyte interactions and pericyte dedifferentiation. Innate immune responses, especially dendritic cell responses related to inadequate adenosine receptor (2a)-mediated signals, autophagic insufficiency and renin-angiotensin system activation have also been implicated in the progression of AKI and transitions from AKI to CKD and ESRD. Although promising advances have been made in understanding the pathophysiology of AKI and AKI consequences, much more work needs to be done in developing biomarkers for detecting early kidney injury, prognosticating kidney disease progression and developing strategies to effectively treat AKI and to minimize AKI progression to CKD and ESRD.

  12. P2Y2 receptor deficiency aggravates chronic kidney disease progression

    Directory of Open Access Journals (Sweden)

    Sebastian Alexander Potthoff


    Full Text Available Purinergic signaling is involved in a variety of physiological states. P2 receptors are mainly activated by adenosine triphosphate (ATP. Activation of specific P2Y receptor subtypes might influence progression of kidney disease. To investigate the in vivo effect of a particular P2 receptor subtype on chronic kidney disease progression, subtotal nephrectomy was performed on wild type (WT and P2Y2 receptor knockout (KO mice.During the observational period of 56 ± 2 days, survival of KO mice was inferior compared to WT mice after SNX. Subtotal nephrectomy reduced creatinine clearance in both groups of mice, but the decrease was significantly more pronounced in KO compared to WT mice (53.9±7.7 vs. 84.3±8.7µl/min at day 56. The KO mice also sustained a greater increase in systolic blood pressure after SNX compared to WT mice (177±2 vs. 156±7 mmHg and a 2.5-fold increase in albuminuria compared to WT. In addition, WT kidneys showed a significant increase in remnant kidney mass 56 days after SNX, but significant attenuation of hypertrophy in KO mice was observed. In line with the observed hypertrophy in WT SNX mice, a significant dose-dependent increase in DNA synthesis, a marker of proliferation, was present in cultured WT glomerular epithelial cells upon ATP stimulation. Markers for tissue damage (TGF-β1, PAI-1 and proinflammatory target genes (MCP1 were significantly upregulated in KO mice after SNX compared to WT SNX mice. In summary, deletion of the P2Y2 receptor leads to greater renal injury after SNX compared to WT mice. Higher systolic blood pressure and inability of compensatory hypertrophy in KO mice are likely causes for the accelerated progression of chronic kidney disease.

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

    Energy Technology Data Exchange (ETDEWEB)

    Barregard, Lars, E-mail: [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)


    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.

  14. 9 CFR 310.19 - Inspection of kidneys. (United States)


    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Inspection of kidneys. 310.19 Section... INSPECTION AND CERTIFICATION POST-MORTEM INSPECTION § 310.19 Inspection of kidneys. An employee of the establishment shall open the kidney capsule and expose the kidneys of all livestock at the time of slaughter...

  15. What I Need to Know about Living with Kidney Failure (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  16. Periodontal Disease and Decreased Kidney Function in Japanese Elderly

    NARCIS (Netherlands)

    Iwasaki, Masanori; Taylor, George W.; Nesse, Willem; Vissink, Arjan; Yoshihara, Akihiro; Miyazaki, Hideo


    Background: Early detection of decreased kidney function can help prevent the progression of kidney disease to kidney failure and cardiovascular events. Potentially significant associations between kidney function and periodontal disease have been reported in cross-sectional studies. However, no lon

  17. Sulforaphane Attenuates Gentamicin-Induced Nephrotoxicity: Role of Mitochondrial Protection (United States)

    Huerta-Yepez, Sara; Medina-Campos, Omar Noel; Zatarain-Barrón, Zyanya Lucía; Hernández-Pando, Rogelio; Torres, Ismael; Tapia, Edilia; Pedraza-Chaverri, José


    Sulforaphane (SFN), an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM) is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl-β-D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity) and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress. PMID:23662110

  18. Sulforaphane Attenuates Gentamicin-Induced Nephrotoxicity: Role of Mitochondrial Protection

    Directory of Open Access Journals (Sweden)

    Mario Negrette-Guzmán


    Full Text Available Sulforaphane (SFN, an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl-β-D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress.

  19. Treatment Methods for Kidney Failure in Children (United States)

    ... after the transplant before they get any additional vaccines. Children who take immunosuppressive medications should not receive vaccines ... Children with kidney failure should receive the standard vaccinations recommended for all children, as well as vaccinations to prevent influenza and ...

  20. [Chronic kidney diseases, metformin and lactic acidosis]. (United States)

    Borbély, Zoltán


    Chronic kidney disease and diabetes mellitus represent a worldwide public health problem. The incidence of these diseases is gradually growing into epidemic proportions. In many cases they occur simultaneously, what leads to increased morbidity and mortality among the affected patients. The majority of the patients treated for diabetes mellitus are unaware of the presence of renal insufficiency. Vascular hypertrophy and diabetic kidney disease in patients with type 2 diabetes are the most common causes of kidney failure in countries with advanced healthcare systems. Metformin is a basic drug used for the treatment of type 2 diabetes mellitus. It is excreted in an unchanged form by the kidneys. When administered to patients with renal insufficiency, sepsis, dehydration or after the parenteral administration of iodinated contrast agents, metformin can cause lactic acidosis, which is also associated with an increased mortality rate.


    Directory of Open Access Journals (Sweden)

    M. L. Arefjev


    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. 

  2. Genetics Home Reference: polycystic kidney disease (United States)

    ... ED. Pathophysiology of childhood polycystic kidney diseases: new insights into disease-specific therapy. Pediatr Res. 2014 Jan; ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links Copyright ...

  3. Percutaneous Nephrolithotomy and Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Sairam, Krish; Scoffone, Cesare M; Alken, Peter;


    by glomerular filtration rate, including chronic kidney disease stages 0/I/II-greater than 60, stage III-30 to 59 and stages IV/V-less than 30 ml/minute/1.73 m(2). Patient characteristics, operative characteristics, outcomes and morbidity were assessed. RESULTS: Estimated glomerular filtration rate data were...... available on 5,644 patients, including 4,436 with chronic kidney disease stages 0/I/II, 994 with stage III and 214 with stages IV/V. A clinically significant minority of patients with nephrolithiasis presented with severe chronic kidney disease. A greater number of patients with stages IV/V previously...... underwent percutaneous nephrolithotomy, ureteroscopy or nephrostomy and had positive urine cultures than less severely affected patients, consistent with the higher incidence of staghorn stones in these patients. Patients with chronic kidney disease stages IV/V had statistically significantly worse...

  4. Plasma adiponectin before and after kidney transplantation

    DEFF Research Database (Denmark)

    Idorn, Thomas; Hornum, Mads; Bjerre, Mette;


    The role of plasma adiponectin (ADPN) in patients with impaired kidney function and following kidney transplantation (Tx) is debated. We aimed to: (i) determine whether pretransplant ADPN level is an independent risk factor for deterioration of glucose tolerance including development of new......-onset diabetes mellitus after Tx, (ii) describe which parameters that influence the ADPN concentration before and after Tx. Fifty-seven nondiabetic kidney allograft recipients and 40 nondiabetic uraemic patients were included. The Tx group was examined at baseline and 3 and 12 months after Tx. The uraemic...... analysis, whereas an ordinal logistic regression analysis revealed no predictive characteristic of ADPN for aggravation of the glucose tolerance after Tx. In conclusion, kidney transplantation is accompanied by a significant reduction in ADPN concentration. Several factors determine the ADPN concentration...

  5. Podocyte biology and pathogenesis of kidney disease. (United States)

    Reiser, Jochen; Sever, Sanja


    Proteinuric chronic kidney disease (CKD), once a rare affliction believed to be mainly caused by genetic mutations, has become a global pandemic that severely diminishes the quality of life for millions. Despite the changing face of CKD, treatment options and resources remain woefully antiquated and have failed to arrest or reverse the effects of kidney-related diseases. Histological and genetic data strongly implicate one promising target: the podocyte. Podocytes are terminally differentiated cells of the kidney glomerulus that are essential for the integrity of the kidney filter. Their function is primarily based on their intricate structure, which includes foot processes. Loss of these actin-driven membrane extensions is tightly connected to the presence of protein in the urine, podocyte loss, development of CKD, and ultimately renal failure.

  6. Spectroscopic Monitoring of Kidney Tissue Ischemic Injury

    Energy Technology Data Exchange (ETDEWEB)

    Demos, S G; Fitzgerald, J T; Michalopoulou, A P; Troppmann, C


    Noninvasive evaluation of tissue viability of donor kidneys used for transplantation is an issue that current technology is not able to address. In this work, we explore optical spectroscopy for its potential to assess the degree of ischemic damage in kidney tissue. We hypothesized that ischemic damage to kidney tissue will give rise to changes in its optical properties which in turn may be used to asses the degree of tissue injury. The experimental results demonstrate that the autofluorescence intensity of the injured kidney is decreasing as a function of time exposed to ischemic injury. Changes were also observed in the NIR light scattering intensities most probably arising from changes due to injury and death of the tissue.

  7. Treatment Methods for Kidney Failure: Hemodialysis (United States)

    ... hemodialysis treatments by avoiding high-potassium foods, including bananas, oranges, potatoes, and tomatoes. Read more in the NKDEP fact sheet Potassium: Tips for People with Chronic Kidney Disease . ...

  8. Drugs Approved for Kidney (Renal Cell) Cancer (United States)

    ... 2015 2014 2013 2012 Media Resources Media Contacts Multicultural Media ... This page lists cancer drugs approved by the Food and Drug Administration (FDA) for kidney (renal cell) cancer. The list ...

  9. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder. (United States)

    Seifert, Michael E; Hruska, Keith A


    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  10. Allograft loss from acute Page kidney secondary to trauma after kidney transplantation (United States)

    Takahashi, Kazuhiro; Prashar, Rohini; Putchakayala, Krishna G; Kane, William J; Denny, Jason E; Kim, Dean Y; Malinzak, Lauren E


    We report a rare case of allograft loss from acute Page kidney secondary to trauma that occurred 12 years after kidney transplantation. A 67-year-old Caucasian male with a past surgical history of kidney transplant presented to the emergency department at a local hospital with left lower abdominal tenderness. He recalled that his cat, which weighs 15 lbs, jumped on his abdomen 7 d prior. On physical examination, a small tender mass was noticed at the incisional site of the kidney transplant. He was producing a normal amount of urine without hematuria. His serum creatinine level was slightly elevated from his baseline. Computer tomography revealed a large subscapular hematoma around the transplant kidney. The patient was observed to have renal trauma grade II at the hospital over a period of three days, and he was finally transferred to a transplant center after his urine output significantly decreased. Doppler ultrasound demonstrated an extensive peri-allograft hypoechoic area and abnormal waveforms with absent arterial diastolic flow and a patent renal vein. Despite surgical decompression, the allograft failed to respond appropriately due to the delay in surgical intervention. This is the third reported case of allograft loss from acute Page kidney following kidney transplantation. This case reinforces that kidney care differs if the kidney is solitary or a transplant. Early recognition and aggressive treatments are mandatory, especially in a case with Doppler signs that are suggestive of compression. PMID:28280700

  11. Measurement of renal function in patients with chronic kidney disease. (United States)

    Sandilands, Euan A; Dhaun, Neeraj; Dear, James W; Webb, David J


    Chronic kidney disease affects millions of people worldwide and is associated with an increased morbidity and mortality as a result of kidney failure and cardiovascular disease. Accurate assessment of kidney function is important in the clinical setting as a screening tool and for monitoring disease progression and guiding prognosis. In clinical research, the development of new methods to measure kidney function accurately is important in the search for new therapeutic targets and the discovery of novel biomarkers to aid early identification of kidney injury. This review considers different methods for measuring kidney function and their contribution to the improvement of detection, monitoring and treatment of chronic kidney disease.

  12. Bilateral s-shaped kidneys: A rare congenital malformation

    Directory of Open Access Journals (Sweden)

    Nikhil Ranjan


    Full Text Available A bilateral S-shaped kidney is a rare anomaly in which both the kidneys are in their normal position, in contrast to the commonly reported S-shaped fusion anomaly, in which the contralateral kidney crosses the midline to fuse with opposite kidney leaving the ipsilateral renal fossa empty. Here we present the diagnosis and management of a case of bilateral S-shaped renal anomaly with associated left pelviureteric junction obstruction and nonfunctioning kidney and right renal stones. Left kidney was managed by open nephrectomy and right kidney by PNL.

  13. The kidneys in the Bible: what happened? (United States)

    Eknoyan, Garabed


    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

  14. Antiphospholipid Syndrome and the Kidney. (United States)

    Sciascia, Savino; Baldovino, Simone; Schreiber, Karen; Solfietti, Laura; Roccatello, Dario


    The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial and/or venous thrombosis, pregnancy morbidity, and the persistent presence of circulating antiphospholipid antibodies (aPL). APS has been described as primary APS when it occurs in the absence of any features of other autoimmune disease, and as secondary in the presence of other autoimmune diseases, mainly systemic lupus erythematosus (SLE). There is a well-known link between SLE and APS; 40% of SLE patients have aPL, and, in turn, some, but only a minority of patients with APS, eventually will develop features of SLE. Because SLE and APS can target the kidneys independently or at the same time, discriminating between inflammatory or thrombotic lesions is crucial in planning therapy. We provide an overview of the renal manifestations associated with the presence of aPL in patients with SLE, and discuss the impact of aPL in selected scenarios such as lupus nephritis, end-stage renal disease, and pregnancy.

  15. Premalignant Lesions in the Kidney

    Directory of Open Access Journals (Sweden)

    Ziva Kirkali


    Full Text Available Renal cell carcinoma (RCC is the most malignant urologic disease. Different lesions, such as dysplasia in the tubules adjacent to RCC, atypical hyperplasia in the cyst epithelium of von Hippel-Lindau syndrome, and adenoma have been described for a number of years as possible premalignant changes or precursor lesions of RCC. In two recent papers, kidneys adjacent to RCC or removed from other causes were analyzed, and dysplastic lesions were identified and defined in detail. Currently renal intraepithelial neoplasia (RIN is the proposed term for classification. The criteria for a lesion to be defined as premalignant are (1 morphological similarity; (2 spatial association; (3 development of microinvasive carcinoma; (4 higher frequency, severity, and extent then invasive carcinoma; (5 progression to invasive cancer; and (6 similar genetic alterations. RIN resembles the neoplastic cells of RCC. There is spatial association. Progression to invasive carcinoma is described in experimental cancer models, and in some human renal tumors. Similar molecular alterations are found in some putative premalignant changes. The treatment for RCC is radical or partial nephrectomy. Preneoplastic lesions may remain in the renal remnant in patients treated by partial nephrectomy and may be the source of local recurrences. RIN seems to be a biologic precursor of some RCCs and warrants further investigation. Interpretation and reporting of these lesions would reveal important resources for the biological nature and clinical significance. The management of RIN diagnosed in a renal biopsy and partial nephrectomy needs to be answered.

  16. Probiotics and chronic kidney disease. (United States)

    Koppe, Laetitia; Mafra, Denise; Fouque, Denis


    Probiotics are the focus of a thorough investigation as a natural biotreatment due to their various health-promoting effects and inherent ability to fight specific diseases including chronic kidney disease (CKD). Indeed, intestinal microbiota has recently emerged as an important player in the progression and complications of CKD. Because many of the multifactorial physiological functions of probiotics are highly strain specific, preselection of appropriate probiotic strains based on their expression of functional biomarkers is critical. The interest in developing new research initiatives on probiotics in CKD have increased over the last decade with the goal of fully exploring their therapeutic potentials. The efficacy of probiotics to decrease uremic toxin production and to improve renal function has been investigated in in vitro models and in various animal and human CKD studies. However to date, the quality of intervention trials investigating this novel CKD therapy is still lacking. This review outlines potential mechanisms of action and efficacy of probiotics as a new CKD management tool, with a particular emphasis on uremic toxin production and inflammation.

  17. Cake kidney drained by single ureter

    Directory of Open Access Journals (Sweden)

    Adriano A. Calado


    Full Text Available Cake kidney is a rare congenital anomaly of the urogenital tract, with a few more than 20 cases described in the literature. It can be diagnosed at any age range. Normally, drainage is achieved by 2 ureters, and there are only 5 reports in the literature of cake kidney drained by a single ureter. The authors describe one more case of this rare malformation of the urinary tract.

  18. Kidney involvement in a wegener granulomatosis case

    Directory of Open Access Journals (Sweden)

    Gioacchino Li Cavoli


    Full Text Available Wegener Granulomatosis is a systemic Anti-Neutrophil Cytoplasmic Autoantibody- associated Vasculitis, affecting small-to-medium vessels. Clinical presentation with simultaneous involvement of kidney and upper and lower respiratory tract is unusual. We report an instructive case of WG, analyzing clinical course, laboratory, and radiological features, kidney, lung, and larynx histological pictures. Besides renal biopsy, nephrology team performed larynx and lung biopsies because of unusual clinical presentation, computed tomography chest examination, and relevant malignancy risk regarding following immunosuppressant therapy.

  19. Erythropoietin (EPO) in acute kidney injury


    Moore, Elizabeth; Bellomo, Rinaldo


    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, ...

  20. [Pregnancy-related acute kidney injury]. (United States)

    Filipowicz, Ewa; Staszków, Monika

    Acute kidney injury (AKI) in obstetrics may be caused by the same disorders that are observed in the general population or may be specific for a pregnancy such as: preeclampsia, HELLP syndrome or acute fatty liver of pregnancy. The renal changes may be only temporary, and resolve within a few weeks postpartum, or may become irreversible leading to a progression of chronic kidney disease (CKD). In the article the most important pregnancy related syndromes associated with AKI have been shortly reviewed.

  1. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

    Directory of Open Access Journals (Sweden)

    Raimundo M. G. del Moral


    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  2. Precision Model for Microwave Rotary Vane Attenuator

    DEFF Research Database (Denmark)

    Guldbrandsen, Tom


    A model for a rotary vane attenuator is developed to describe the attenuator reflection and transmission coefficients in detail. All the parameters of the model can be measured in situ, i.e., without diassembling any part. The tranmission errors caused by internal reflections are calculated from ...... measurements of the much larger reflection parameters, hence commonly used nonprecision instruments can be used to determine the transmission errors with sufficient accuracy for the highest precision obtainable in standard laboratories....

  3. Wave attenuation charcteristics of tethered float system

    Digital Repository Service at National Institute of Oceanography (India)

    Vethamony, P.

    and transmitted wave powers, transmission coefficients are computed. The results show that transmission coefficient does not vary with changes in wave height or water depth. When depth of submergence of float increases, wave attenuation decreases, showing... that the system performs well when it is just submerged. As float velocity decreases with increase in float size, transmission coefficient increases with increase in float size. The influence of wave period on wave attenuation is remarkable compared to other...


    DEFF Research Database (Denmark)

    Brunskog, Jonas; Lhomond, Alice; Ohlrich, Mogens


    In this paper the attenuation and flanking transmissions of impact noise in lightweight building structures is studied using a modal approach. The structural field is mainly analysed, putting the main attention to the parts being important in the modelling. The amount of attenuation produced...... by the periodically reinforcing beams used in lightweight building structures is analysed. The consequence of these factors in modelling flanking transmission is also discussed....

  5. Coordination of kidney organogenesis by Wnt signaling. (United States)

    Halt, Kimmo; Vainio, Seppo


    Several Wnt proteins are expressed in the embryonic kidney during various stages of development. Gene knockout models and ex vivo studies have provided strong evidence that Wnt-mediated signals are essential in renal ontogeny. Perhaps the most critical factors, Wnt9b and Wnt4, function during the early phase when the cap mesenchyme is induced to undergo morphogenesis into a nephron. Wnt11 controls early ureteric bud branching and contributes to the final kidney size. In addition to its inductive role, later on Wnt9b plays a significant role in the convergent extension of the tubular epithelial cells, while Wnt4 signaling controls smooth muscle cell fates in the medulla. Wnt7b has a specific function together with its likely antagonist Dkk1 in controlling the morphogenesis of the renal medulla. The signal-transduction mechanisms of the Wnts in kidney ontogeny have not been resolved, but studies characterizing the downstream signaling pathways are emerging. Aberrant Wnt signaling may lead to kidney diseases ranging from fatal kidney agenesis to more benign phenotypes. Wnt-mediated signaling regulates several critical aspects of kidney development from the early inductive stages to later steps of tubular epithelial maturation.

  6. The Global Role of Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Guillermo Garcia Garcia


    Full Text Available World Kidney Day on March 8 th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness. Anything that is both cheaper and better, but is not actually the dominant therapy, must have other drawbacks that prevent replacement of all dialysis treatment by transplantation. The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which, in some countries place transplantation, appropriately, at a lower priority than public health fundamentals such as clean water, sanitation and vaccination. Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients, but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical, surgical and nursing workforces with the required expertise. These problems have solutions which involve the full range of societal, professional, governmental and political environments. World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.

  7. The Global Role of Kidney Transplantation

    Institute of Scientific and Technical Information of China (English)

    Guillermo Garcia Garcia; Paul Harden; Jeremy Chapman


    World Kidney Day on March 8th 2012 provides a chance to reflect on the success of kidney transplantation as a therapy for end stage kidney disease that surpasses dialysis treatments both for the quality and quantity of life that it provides and for its cost effectiveness.Anything that is both cheaper and better,but is not actually the dominant therapy,must have other drawbacks that prevent replacement of all dialysis treatment by transplantation.The barriers to universal transplantation as the therapy for end stage kidney disease include the economic limitations which,in some countries place transplantation,appropriately,at a lower priority than public health fundamentals such as clean water,sanitation and vaccination.Even in high income countries the technical challenges of surgery and the consequences of immunosuppression restrict the number of suitable recipients,but the major finite restrictions on kidney transplantation rates are the shortage of donated organs and the limited medical,surgical and nursing workforces with the required expertise.These problems have solutions which involve the full range of societal,professional,governmental and political environments.World Kidney Day is a call to deliver transplantation therapy to the one million people a year who have a right to benefit.

  8. New biomarkers of acute kidney injury

    Directory of Open Access Journals (Sweden)

    Ruya Ozelsancak


    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

  9. Black markets, transplant kidneys and interpersonal coercion (United States)

    Taylor, J S


    One of the most common arguments against legalising markets in human kidneys is that this would result in the widespread misuse that is present in the black market becoming more prevalent. In particular, it is argued that if such markets were to be legalised, this would lead to an increase in the number of people being coerced into selling their kidneys. Moreover, such coercion would occur even if markets in kidneys were regulated, for those subject to such coercion would not be able to avail themselves of the legal protections that regulation would afford them. Despite the initial plausibility of this argument, there are three reasons to reject it. Firstly, the advantages of legalising markets in human kidneys would probably outweigh its possible disadvantages. Secondly, if it is believed that no such coercion can ever be tolerated, markets in only those human kidneys that fail to do away with coercion should be condemned. Finally, if coercion is genuinely opposed, then legalising kidney markets should be supported rather than opposed, for more people would be coerced (ie, into not selling) were such markets to be prohibited. PMID:17145908

  10. Experiences obtaining insurance after live kidney donation. (United States)

    Boyarsky, B J; Massie, A B; Alejo, J L; Van Arendonk, K J; Wildonger, S; Garonzik-Wang, J M; Montgomery, R A; Deshpande, N A; Muzaale, A D; Segev, D L


    The impact of kidney donation on the ability to change or initiate health or life insurance following donation is unknown. To quantify this risk, we surveyed 1046 individuals who donated a kidney at our center between 1970 and 2011. Participants were asked whether they changed or initiated health or life insurance after donation, and if they had any difficulty doing so. Among 395 donors who changed or initiated health insurance after donation, 27 (7%) reported difficulty; among those who reported difficulty, 15 were denied altogether, 12 were charged a higher premium and 8 were told they had a preexisting condition because they were kidney donors. Among 186 donors who changed or initiated life insurance after donation, 46 (25%) reported difficulty; among those who reported difficulty, 23 were denied altogether, 27 were charged a higher premium and 17 were told they had a preexisting condition because they were kidney donors. In this single-center study, a high proportion of kidney donors reported difficulty changing or initiating insurance, particularly life insurance. These practices by insurers create unnecessary burden and stress for those choosing to donate and could negatively impact the likelihood of live kidney donation among those considering donation.

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

    LENUS (Irish Health Repository)

    D'Arcy, Frank T


    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.

  12. Light attenuation in estuarine mangrove lakes (United States)

    Frankovich, Thomas A.; Rudnick, David T.; Fourqurean, James W.


    Submerged aquatic vegetation (SAV) cover has declined in brackish lakes in the southern Everglades characterized by low water transparencies, emphasizing the need to evaluate the suitability of the aquatic medium for SAV growth and to identify the light attenuating components that contribute most to light attenuation. Underwater attenuation of downwards irradiance of photosynthetically active radiation (PAR) was determined over a three year period at 42 sites in shallow (lakes in two sub-estuaries in the coastal Everglades, Florida USA. Turbidity, chromophoric dissolved organic matter (CDOM), and phytoplankton chlorophyll a (chl a) were measured concurrently and their respective contributions to the light attenuation rate were estimated. Light transmission to the benthos relative to literature estimates of minimum requirements for SAV growth indicated that the underwater light environment was often unsuitable for SAV. Light attenuation rates (n = 417) corrected for solar elevation angles ranged from 0.16 m-1 to 9.83 m-1 with a mean of 1.73 m-1. High concentrations of CDOM with high specific light absorption contributed the most to light attenuation followed by turbidity and chl a. CDOM alone sufficiently reduces light transmission beyond the estimated limits for SAV growth, making it difficult for ecosystem managers to increase SAV abundance by management activities. Light limitation of SAV in these areas may be a persistent feature because of their proximity to CDOM source materials from the surrounding mangrove swamp. Increasing freshwater flow into these areas may dilute CDOM concentrations and improve the salinity and light climate for SAV communities.

  13. Acute kidney injury and bilateral symmetrical enlargement of the kidneys as first presentation of B-cell lymphoblastic lymphoma. (United States)

    Shi, Su-fang; Zhou, Fu-de; Zou, Wan-zhong; Wang, Hai-yan


    Lymphoblastic lymphoma is an uncommon subtype of lymphoid neoplasm in adults. Acute kidney injury at initial presentation due to lymphoblastic lymphoma infiltration of the kidneys has rarely been described. We report a 19-year-old woman who presented with acute kidney injury due to massive lymphomatous infiltration of the kidneys. The diagnosis of B-cell lymphoblastic lymphoma was established by immunohistochemical study of the biopsied kidney. The patient had an excellent response to the VDCLP protocol (vincristine, daunomycin, cyclophosphamide, asparaginase, and dexamethasone) with sustained remission. We recommend that lymphomatous infiltration be considered in patients presenting with unexplained acute kidney injury and enlarged kidneys.

  14. Chronic kidney disease, severe arterial and arteriolar sclerosis and kidney neoplasia: on the spectrum of kidney involvement in MELAS syndrome

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    Piccoli Giorgina


    Full Text Available Abstract Background MELAS syndrome (MIM ID#540000, an acronym for Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with protean manifestations and occasional kidney involvement. Interest in the latter is rising due to the identification of cases with predominant kidney involvement and to the hypothesis of a link between mitochondrial DNA and kidney neoplasia. Case presentation We report the case of a 41-year-old male with full blown MELAS syndrome, with lactic acidosis and neurological impairment, affected by the "classic" 3243A > G mutation of mitochondrial DNA, with kidney cancer. After unilateral nephrectomy, he rapidly developed severe kidney functional impairment, with nephrotic proteinuria. Analysis of the kidney tissue at a distance from the two tumor lesions, sampled at the time of nephrectomy was performed in the context of normal blood pressure, recent onset of diabetes and before the appearance of proteinuria. The morphological examination revealed a widespread interstitial fibrosis with dense inflammatory infiltrate and tubular atrophy, mostly with thyroidization pattern. Vascular lesions were prominent: large vessels displayed marked intimal fibrosis and arterioles had hyaline deposits typical of hyaline arteriolosclerosis. These severe vascular lesions explained the different glomerular alterations including ischemic and obsolescent glomeruli, as is commonly observed in the so-called "benign" arteriolonephrosclerosis. Some rare glomeruli showed focal segmental glomerulosclerosis; as the patient subsequently developed nephrotic syndrome, these lesions suggest that silent ischemic changes may result in the development of focal segmental glomerulosclerosis secondary to nephron loss. Conclusions Nephron loss may trigger glomerular sclerosis, at least in some cases of MELAS-related nephropathy. Thus the incidence of kidney disease in the "survivors" of MELAS

  15. Inhibition of IκB Kinase Attenuates the Organ Injury and Dysfunction Associated with Hemorrhagic Shock. (United States)

    Sordi, Regina; Chiazza, Fausto; Johnson, Florence L; Patel, Nimesh S A; Brohi, Karim; Collino, Massimo; Thiemermann, Christoph


    Nuclear factor-kappa B (NF-κB) activation is widely implicated in multiple organ failure (MOF); however, a direct inhibitor of IκB kinase (IKK), which plays a pivotal role in the activation of NF-κB, has not been investigated in shock. Thus, the aim of the present work was to investigate the effects of an IKK inhibitor on the MOF associated with hemorrhagic shock (HS). Therefore, rats were subjected to HS and were resuscitated with the shed blood. Rats were treated with the inhibitor of IKK or vehicle at resuscitation. Four hours later, blood and organs were assessed for organ injury and signaling events involved in the activation of NF-κB. Additionally, survival following serum deprivation was assessed in HK-2 cells treated with the inhibitor of IKK. HS resulted in renal dysfunction, lung, liver and muscular injury, and increases in serum inflammatory cytokines. Kidney and liver tissue from HS rats revealed increases in phosphorylation of IKKαβ and IκBα, nuclear translocation of NF-κB and expression of inducible isoform of nitric oxide synthase (iNOS). IKK16 treatment upon resuscitation attenuated NF-κB activation and activated the Akt survival pathway, leading to a significant attenuation of all of the above parameters. Furthermore, IKK16 exhibited cytoprotective effects in human kidney cells. In conclusion, the inhibitor of IKK complex attenuated the MOF associated with HS. This effect may be due to the inhibition of the NF-κB pathway and activation of the survival kinase Akt. Thus, the inhibition of the IKK complex might be an effective strategy for the prevention of MOF associated with HS.

  16. Chronic bilateral renal denervation attenuates renal injury in a transgenic rat model of diabetic nephropathy. (United States)

    Yao, Yimin; Fomison-Nurse, Ingrid C; Harrison, Joanne C; Walker, Robert J; Davis, Gerard; Sammut, Ivan A


    Bilateral renal denervation (BRD) has been shown to reduce hypertension and improve renal function in both human and experimental studies. We hypothesized that chronic intervention with BRD may also attenuate renal injury and fibrosis in diabetic nephropathy. This hypothesis was examined in a female streptozotocin-induced diabetic (mRen-2)27 rat (TGR) shown to capture the cardinal features of human diabetic nephropathy. Following diabetic induction, BRD/sham surgeries were conducted repeatedly (at the week 3, 6, and 9 following induction) in both diabetic and normoglycemic animals. Renal denervation resulted in a progressive decrease in systolic blood pressure from first denervation to termination (at 12 wk post-diabetic induction) in both normoglycemic and diabetic rats. Renal norepinephrine content was significantly raised following diabetic induction and ablated in denervated normoglycemic and diabetic groups. A significant increase in glomerular basement membrane thickening and mesangial expansion was seen in the diabetic kidneys; this morphological appearance was markedly reduced by BRD. Immunohistochemistry and protein densitometric analysis of diabetic innervated kidneys confirmed the presence of significantly increased levels of collagens I and IV, α-smooth muscle actin, the ANG II type 1 receptor, and transforming growth factor-β. Renal denervation significantly reduced protein expression of these fibrotic markers. Furthermore, BRD attenuated albuminuria and prevented the loss of glomerular podocin expression in these diabetic animals. In conclusion, BRD decreases systolic blood pressure and reduces the development of renal fibrosis, glomerulosclerosis, and albuminuria in this model of diabetic nephropathy. The evidence presented strongly suggests that renal denervation may serve as a therapeutic intervention to attenuate the progression of renal injury in diabetic nephropathy.

  17. Dissection of the adult zebrafish kidney. (United States)

    Gerlach, Gary F; Schrader, Lauran N; Wingert, Rebecca A


    Researchers working in the burgeoning field of adult stem cell biology seek to understand the signals that regulate the behavior and function of stem cells during normal homeostasis and disease states. The understanding of adult stem cells has broad reaching implications for the future of regenerative medicine. For example, better knowledge about adult stem cell biology can facilitate the design of therapeutic strategies in which organs are triggered to heal themselves or even the creation of methods for growing organs in vitro that can be transplanted into humans. The zebrafish has become a powerful animal model for the study of vertebrate cell biology. There has been extensive documentation and analysis of embryonic development in the zebrafish. Only recently have scientists sought to document adult anatomy and surgical dissection techniques, as there has been a progressive movement within the zebrafish community to broaden the applications of this research organism to adult studies. For example, there are expanding interests in using zebrafish to investigate the biology of adult stem cell populations and make sophisticated adult models of diseases such as cancer. Historically, isolation of the zebrafish adult kidney has been instrumental for studying hematopoiesis, as the kidney is the anatomical location of blood cell production in fish. The kidney is composed of nephron functional units found in arborized arrangements, surrounded by hematopoietic tissue that is dispersed throughout the intervening spaces. The hematopoietic component consists of hematopoietic stem cells (HSCs) and their progeny that inhabit the kidney until they terminally differentiate. In addition, it is now appreciated that a group of renal stem/progenitor cells (RPCs) also inhabit the zebrafish kidney organ and enable both kidney regeneration and growth, as observed in other fish species. In light of this new discovery, the zebrafish kidney is one organ that houses the location of two

  18. Kidneys in chronic liver diseases

    Institute of Scientific and Technical Information of China (English)

    Marek Hartleb; Krzysztof Gutkowski


    Acute kidney injury (AKI),defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL,occurs in about 20% of patients hospitalized for decompensating liver cirrhosis.Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state,reduced effective blood volume and stimulation of vasoconstrictor hormones.The most common causes of AKI in cirrhosis are pre-renal azotemia,hepatorenal syndrome and acute tubular necrosis.Differential diagnosis is based on analysis of circumstances of AKI development,natriuresis,urine osmolality,response to withdrawal of diuretics and volume repletion,and rarely on renal biopsy.Chronic glomeruIonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients.AKI is one of the last events in the natural history of chronic liver disease,therefore,such patients should have an expedited referral for liver transplantation.Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension,and may be prematurely triggered by bacterial infections,nonbacterial systemic inflammatory reactions,excessive diuresis,gastrointestinal hemorrhage,diarrhea or nephrotoxic agents.Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy.The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion,which is effective in about 50% of patients.The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt,renal vasoprotection or systems of artificial liver support.

  19. Failure of Posaconazole Therapy in a Renal Transplant Patient with Invasive Aspergillosis Due to Aspergillus fumigatus with Attenuated Susceptibility to Posaconazole ▿


    Kuipers, Saskia; Brüggemann, Roger J. M.; Ruud G.L. de Sévaux; Heesakkers, John P. F. A.; Melchers, Willem J. G.; Mouton, Johan W.; Verweij, Paul E.


    We report the case of a kidney transplant recipient with invasive aspergillosis due to Aspergillus fumigatus resistant to voriconazole and intermediately susceptible to posaconazole who failed posaconazole therapy. Plasma posaconazole concentrations indicated an unfavorable ratio of the area under the concentration-time curve over the MIC. Posaconazole should be used with caution for invasive aspergillosis caused by strains with attenuated posaconazole susceptibility, as drug exposure may be ...

  20. Influence of the kidney histology at the time of donation on long term kidney function in living kidney donors. (United States)

    Goecke, H; Ortiz, A M; Troncoso, P; Martinez, L; Jara, A; Valdes, G; Rosenberg, H


    Living donation is the best choice for kidney transplantation, obtaining long-lasting good results for the recipient. Some concern still remains regarding the donor's long-term health. Kidney biopsy was routinely performed in our donor population at the time of donation many years ago. We found the existence of morphological kidney disease in those samples, in spite of normal clinical evaluations before donation. We attempted to correlate those abnormalities with long-term clinical outcomes. Donors were at least 10 years after surgery. A medical interview, including the SF-36 Health Survey, laboratory evaluation, and ambulatory blood pressure monitoring was performed on 27 donors meeting the inclusion criteria. Two donors had died after donation from unrelated causes with no known nephropathy. Histological analysis showed abnormalities in 16 of 29 donors. We found an increased prevalence of hypertension compared to the general population. Interestingly, there was no proteinuria in the donor population, and none developed clinical nephropathy. All subjects felt emotionally rewarded with donation, stating that their lives had no limitations. Our results suggest that kidney biopsy is neither necessary nor useful prior to donation because, although many donors had morphological kidney disease, none developed clinical nephropathy in the long term.

  1. Suppression of NLRP3 Inflammasome Activation Ameliorates Chronic Kidney Disease-Induced Cardiac Fibrosis and Diastolic Dysfunction (United States)

    Bugyei-Twum, Antoinette; Abadeh, Armin; Thai, Kerri; Zhang, Yanling; Mitchell, Melissa; Kabir, Golam; Connelly, Kim A.


    Cardiac fibrosis is a common finding in patients with chronic kidney disease. Here, we investigate the cardio-renal effects of theracurmin, a novel formulation of the polyphenolic compound curcumin, in a rat model of chronic kidney disease. Briefly, Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery. At 3 weeks post surgery, SNx animals were further randomized to received theracurmin via once daily oral gavage or vehicle for 5 consecutive weeks. At 8 weeks post surgery, cardiac function was assessed via echocardiography and pressure volume loop analysis, followed by LV and renal tissue collection for analysis. SNx animals developed key hallmarks of renal injury including hypertension, proteinuria, elevated blood urea nitrogen, and glomerulosclerosis. Renal injury in SNx animals was also associated with significant diastolic dysfunction, macrophage infiltration, and cardiac NLRP3 inflammasome activation. Treatment of SNx animals with theracurmin improved structural and functional manifestations of cardiac injury associated with renal failure and also attenuated cardiac NLRP3 inflammasome activation and mature IL-1β release. Taken together, our findings suggest a significant role for the NLRP3 inflammasome in renal injury-induced cardiac dysfunction and presents inflammasome attenuation as a unique strategy to prevent adverse cardiac remodeling in the setting of chronic kidney disease. PMID:28000751

  2. Thioredoxin-Interacting Protein Mediates NLRP3 Inflammasome Activation Involved in the Susceptibility to Ischemic Acute Kidney Injury in Diabetes

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    Ye Da Xiao


    Full Text Available Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI. However, the underlying mechanisms remain unclear. Herein, we examined the impact of diabetes mellitus on thioredoxin-interacting protein (TXNIP expression and whether mediated NLRP3 activation was associated with renal ischemia/reperfusion- (I/R- induced AKI. In an in vivo model, streptozotocin-induced diabetic rats showed higher susceptibility to I/R injury with increased TXNIP expression, which was significantly attenuated by resveratrol (RES treatment (10 mg/kg intraperitoneal daily injection for 7 consecutive days prior to I/R induction. RES treatment significantly inhibited TXNIP binding to NLRP3 in diabetic rats subjected to renal I/R injury. Furthermore, RES treatment significantly reduced cleaved caspase-1 expression and production of IL-1β and IL-18. In an in vitro study using cultured human kidney proximal tubular cell (HK-2 cells in high glucose condition (HG, 30 mM subjected to hypoxia/reoxygenation (H/R, HG combined H/R (HH/R stimulated TXNIP expression which was accompanied by increased NLRP3 expression, ROS generation, caspase-1 activity and IL-1β levels, and aggravated HK-2 cells apoptosis. All these changes were significantly attenuated by TXNIP RNAi and RES treatment. In conclusion, our results demonstrate that TXNIP-mediated NLRP3 activation through oxidative stress is a key signaling mechanism in the susceptibility to AKI in diabetic models.

  3. Further Report on Carcinogenesis or Tumorigenicity of MDCK Canine Kidney Cell(CKC) Lines and Analysis of Their Chromosome Karyotypes

    Institute of Scientific and Technical Information of China (English)

    ZHANG De-li; FANG Fu-de; XIA Geng-tian; HE Xu-yu; GAO Bu-xian; BAI Xiao-hong; LI Liu-jin; HUANG Gao-sheng; LIU Shang-gao; YEN Lung-fei


    Using Hela cell cultures as positive control and primary canine kidney cell (CKC) or feline kidney cell (FKC) cultures purified in vitro on passage 3 as negative control, the tumorigenicity of Madin-Darby canine kidney (MDCK) cells was tested in >273 nude mice, and colony formation in soft agarose and haemagglutination under different concentration of plant lectins of these cells were carried out at the same time. Subsequently, very low tumorigenicity strains of MDCK line were successfully selected; these were evaluated for the production of canine or feline combination viral vaccines, free of infectious agents, and of known cytogenetic and tumorigenic. It is thus evident that MDCK cell of M, JB, JC, WB or H strain can be approved as substrate for the preparation of attenuated viral vaccines, but MDCK cell of YA, YB and KA strains can not be approved as substrate for the preparation of attenuated viral vaccines. The heritable character of these cell sub-lines is comparatively stable, and shows little significant difference between passages.

  4. Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

    NARCIS (Netherlands)

    Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.


    The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of vasopre

  5. Outcomes of shipped live donor kidney transplants compared with traditional living donor kidney transplants. (United States)

    Treat, Eric G; Miller, Eric T; Kwan, Lorna; Connor, Sarah E; Maliski, Sally L; Hicks, Elisabeth M; Williams, Kristen C; Whitted, Lauren A; Gritsch, Hans A; McGuire, Suzanne M; Mone, Thomas D; Veale, Jeffrey L


    The disparity between kidney transplant candidates and donors necessitates innovations to increase organ availability. Transporting kidneys allows for living donors and recipients to undergo surgery with a familiar transplant team, city, friends, and family. The effect of shipping kidneys and prolonged cold ischemia time (CIT) with living donor transplantation outcomes is not clearly known. This retrospective matched (age, gender, race, and year of procedure) cohort study compared allograft outcomes for shipped live donor kidney transplants and nonshipped living donor kidney transplants. Fifty-seven shipped live donor kidneys were transplanted from 31 institutions in 26 cities. The mean shipping distance was 1634 miles (range 123-2811) with mean CIT of 12.1 ± 2.8 h. The incidence of delayed graft function in the shipped cohort was 1.8% (1/57) compared to 0% (0/57) in the nonshipped cohort. The 1-year allograft survival was 98% in both cohorts. There were no significant differences between the mean serum creatinine values or the rates of serum creatinine decline in the immediate postoperative period even after adjusted for gender and differences in recipient and donor BMI. Despite prolonged CITs, outcomes for shipped live donor kidney transplants were similar when compared to matched nonshipped living donor kidney transplants.

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

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Carol F., E-mail: [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)


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

  7. Diagnostic value of kidney length and volume in sonography for determining kidney scar among infants with urinary infection

    Directory of Open Access Journals (Sweden)

    Mahmoud Jalili


    Full Text Available Background: Diagnosis of kidney scar could prevent vesico urethral reflax and its complications such as hypertension and renal failure. This study was conducted to determine average kidney length and volume in infants by sonography to accurate diagnosis of scars.Methods: This study was conducted on infants with the history of UTI who referred to Imam Reza Hospital, Kermanshah Iran, for DMSA scan. They underwent kidney sonography before DMSA scan. Difference in kidney length and volume were calculated and data was recorded and were analyzed using statistical tests.Results: Right kidney length was less than left in 60% of right kidney scars this rate was 77.8% in nonscar patients (P=0.657. Left kidney length was less than right in 50% of left kidney scar and that was 22% in nonscar patients (P=0.241. Kidney volume was smaller than other side in 55.6% of right kidney scar and 62.5% of left kidney scar. Higher length detected in 100% and 47% of right and left kidney inflammation respectively. Higher volume detected in 40% and 76.5% of right and left kidney inflammation.Conclusion: In comparison with other studies suggesting kidney length as a valuble predictor for diagnosis of scar we did not find any relationship between scar and kidney length or volume.

  8. Maximum likelihood estimation of the attenuated ultrasound pulse

    DEFF Research Database (Denmark)

    Rasmussen, Klaus Bolding


    The attenuated ultrasound pulse is divided into two parts: a stationary basic pulse and a nonstationary attenuation pulse. A standard ARMA model is used for the basic pulse, and a nonstandard ARMA model is derived for the attenuation pulse. The maximum likelihood estimator of the attenuated...

  9. Awareness of kidney disorders in Nigeria. (United States)

    Alebiosu, Christopher O


    This paper assesses the level of awareness of the generality of the populace towards kidney disease, in the Ogun State University Teaching Hospital and its environment. Questionnaires were administered to the administrative staff (excluding medical/nursing workers)) of he Ogun State University teaching hospital, bank workers, market women and artisans in its environment. Responses were analyzed by standard statistical methods. Out of 455 questionnaires administered, there were 415 (91.2%) respondents. Eighty-eight (21.2%) were non-academic staff of the hospital, 123 (29.6 %) were market women, 106 (25.5%) were artisans and 98 (23.6%) were bank workers. Their ages ranged form 15 years to 54 years (mean 34.2+/- 9.7 years), with a sex ratio, (M/F) of 1:1 (192 males and 223 females). Majority of the interviewees, 273 (65.8%) do not know the function of the kidneys. The use of local herbs, indiscriminate use of drug, skin lightening cream, jaundice and scarifications are also believed to be associated with kidney diseases in 300 (72.3%), 270 (5.1%), 140 (33.7%) 263(63.4%) and 98 (23.6%) of respondents respectively. Sixty-eight respondents (16.4%) do not know the common complains associated with kidney diseases. One hundred and eighty-seven (45.1%) believed that kidney diseases are associated with urinary complaints while 99(23.9%) , 56 (13.5%) and 3(0.7%) believed that the common complaints associated with kidney diseases are swelling of the body, body weakness and swelling of the face respectively. This study demonstrated that there is a low awareness of the populace regarding the prevalence, causes and prevention of kidney diseases in the environment. There is need for introducing measures that will improve the awareness of the populace, aim at preventive measures such as pre-employment urinalysis screening and health education.

  10. Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease Proven by Transient Elastography

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    Ivana Mikolasevic


    Full Text Available Background/Aim: Preliminary data suggest an association between chronic kidney disease (CKD and non-alcoholic fatty liver disease (NAFLD. The aim of this study was to further investigate the association between NAFLD and decreased kidney function. Methods: A total of 62 patients with CKD were enrolled in the study. Liver stiffness was used to detect liver fibrosis and CAP (controlled attenuation parameter was used to detect and quantify liver steatosis (Fibroscan®. NAFLD was defined by CAP values ≥238 dB.m-1. Results: CKD stage III was present in 29 patients (46.8% and CKD stage IV in 33 patients (53.2%. Out of 62 CKD patients 53 (85.5% had NAFLD and of these 14/53 patients (26.4% had also liver stiffness >7 kPa. The severity of liver steatosis was positively correlated with serum creatinine (r=0.399;pConclusion: The results suggest a high prevalence of NAFLD in CKD patients. The severity of liver steatosis is negatively correlated with kidney function. The study documents the value of ultrasonographic elastography as an effective non-invasive screening method for the diagnosis of NAFLD.

  11. The biochemical effect of probiotic and /or mesenchymal stem cells on LPS-induced kidney disorder

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    Ayman Mohamed Badawi


    Full Text Available  The current study  aimed to evaluate the beneficial effect of kefir  probiotic  and /or Mesenchymal stem cells (MSCs on acute kidney injury (AKI induced by lipopolysaccharide (LPS challenge, and to investigate could kefir potentiate the therapeutic action of MSCs. Sixty female albino rats were used in this study and  divided into 6 groups (10 rats each: control group; LPS-challenged group; LPS+ MSCs group; LPS + kefir group; kefir +LPS +kefir (prophylactic group and kefir + LPS + MSCs + kefir (prophylactic-MSCs group. Samples were collected at two point's time. Renal function, serum IL-10, TNF-α, renal MDA, GSH contents, SOD and PON-I were assayed. The mRNA expression of NF-κB, iNOS and caspase-3 were monitored in kidney tissue. Our results revealed that LPS significantly increased renal function tests, TNF-α in association with dramatic decrease of creatinine clearance and serum IL-10 levels. Oxidative stress was proved in LPS group by increasing MDA level, reduction in GSH content, SOD and PON-1 activities in kidney. The mRNA expression of NF-κB, iNOS and caspase-3 were significantly up-regulated in AKI. Administration of kefir or MSCs alone significantly attenuated LPS-induced AKI. The pre and co-treatment of kefir with MSCs potentiate their therapeutic action. Conclusion: A combination of kefir probiotic and MSCs may be of interest for clinical use. 

  12. Abrogation of plasminogen activator inhibitor-1-vitronectin interaction ameliorates acute kidney injury in murine endotoxemia.

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    Kamlesh K Gupta

    Full Text Available Sepsis-induced acute kidney injury (AKI contributes to the high mortality and morbidity in patients. Although the pathogenesis of AKI during sepsis is poorly understood, it is well accepted that plasminogen activator inhibitor-1 (PAI-1 and vitronectin (Vn are involved in AKI. However, the functional cooperation between PAI-1 and Vn in septic AKI has not been completely elucidated. To address this issue, mice were utilized lacking either PAI-1 (PAI-1-/- or expressing a PAI-1-mutant (PAI-1R101A/Q123K in which the interaction between PAI-1 and Vn is abrogated, while other functions of PAI-1 are retained. It was found that both PAI-1-/- and PAI-1R101A/Q123K mice are associated with decreased renal dysfunction, apoptosis, inflammation, and ERK activation as compared to wild-type (WT mice after LPS challenge. Also, PAI-1-/- mice showed attenuated fibrin deposition in the kidneys. Furthermore, a lack of PAI-1 or PAI-1-Vn interaction was found to be associated with an increase in activated Protein C (aPC in plasma. These results demonstrate that PAI-1, through its interaction with Vn, exerts multiple deleterious mechanisms to induce AKI. Therefore, targeting of the PAI-1-Vn interaction in kidney represents an appealing therapeutic strategy for the treatment of septic AKI by not only altering the fibrinolytic capacity but also regulating PC activity.

  13. A simultaneous liver-kidney transplant recipient with IgA nephropathy limited to native kidneys and BK virus nephropathy limited to the transplant kidney. (United States)

    Ujire, Manasa P; Curry, Michael P; Stillman, Isaac E; Hanto, Douglas W; Mandelbrot, Didier A


    Immunoglobulin A (IgA) deposition in the native kidneys of patients with liver disease is well described. Secondary IgA nephropathy usually is thought to be benign, but hematuria, proteinuria, and loss of kidney function have been reported in this context. BK virus nephropathy is an important cause of kidney transplant loss; however, BK virus nephropathy is rare in the native kidneys of patients who underwent transplantation of other organs. We report the case of a patient with alcohol-related end-stage liver disease and chronic kidney disease with hematuria who underwent simultaneous liver-kidney transplantation. His kidney function decreased over the course of several weeks posttransplantation. Biopsy of the transplant kidney showed BK virus nephropathy, but no IgA deposits. In contrast, biopsy of the native kidneys showed IgA deposits, but no BK virus nephropathy. To our knowledge, this is the first reported case of a simultaneous liver-kidney transplantation wherein both the native and transplant kidneys were biopsied posttransplantation and showed exclusively different pathologies. These findings confirm the predilection of BK virus nephropathy for transplant rather than native kidneys.

  14. The Lipid lowering and Onset of Renal Disease (LORD Trial: A randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease

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    Geraghty Dominic P


    Full Text Available Abstract Background There is evidence that dyslipidemia is associated with chronic kidney disease (CKD. Experimental studies have established that lipids are damaging to the kidney and animal intervention studies show statins attenuate this damage. Small clinical trials, meta-analyses, observational studies and post-hoc analyses of cardiovascular intervention studies all support the concept that statins can reduce kidney damage in humans. Based on this background, a double blind randomized placebo controlled trial was designed to assess the effectiveness of atorvastatin 10 mg on slowing the progression of kidney disease in a population of patients with CKD. Method/Design The Lipid lowering and Onset of Renal Disease (LORD trial is a three-year, single center, multi-site, double blind, randomized, placebo controlled trial. The primary outcome measure is kidney function measured by eGFR calculated by both Modification of Diet in Renal Disease (MDRD and Cockcroft and Gault equations. Secondary outcome measures include kidney function measured by 24-hour urine creatinine clearance and also 24-hour urinary protein excretion, markers of oxidative stress, inflammation and drug safety and tolerability. Discussion The results of this study will help determine the effectiveness and safety of atorvastatin and establish its effects on oxidative stress and inflammation in patients with CKD. Trial Registration ANZCTRN012605000693628

  15. Pomegranate seed extract attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in rats. (United States)

    Cayır, Kerim; Karadeniz, Ali; Simşek, Nejdet; Yıldırım, Serap; Karakuş, Emre; Kara, Adem; Akkoyun, Hürrem Turan; Sengül, Emin


    Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.

  16. Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy. (United States)

    Hou, Yanjuan; Li, Shuangcheng; Wu, Ming; Wei, Jinying; Ren, Yunzhuo; Du, Chunyang; Wu, Haijiang; Han, Caili; Duan, Huijun; Shi, Yonghong


    Oxidative stress is implicated in the pathogenesis of diabetic kidney injury. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge reactive oxygen species (ROS). Here, we investigated the effect and molecular mechanism of mitochondria-targeted antioxidant peptide SS-31 on injuries in diabetic kidneys and mouse mesangial cells (MMCs) exposed to high-glucose (HG) ambience. CD-1 mice underwent uninephrectomy and streptozotocin treatment prior to receiving daily intraperitoneal injection of SS-31 for 8 wk. The diabetic mice treated with SS-31 had alleviated proteinuria, urinary 8-hydroxy-2-deoxyguanosine level, glomerular hypertrophy, and accumulation of renal fibronectin and collagen IV. SS-31 attenuated renal cell apoptosis and expression of Bax and reversed the expression of Bcl-2 in diabetic mice kidneys. Furthermore, SS-31 inhibited expression of transforming-growth factor (TGF)-β1, Nox4, and thioredoxin-interacting protein (TXNIP), as well as activation of p38 MAPK and CREB and NADPH oxidase activity in diabetic kidneys. In vitro experiments using MMCs revealed that SS-31 inhibited HG-mediated ROS generation, apoptosis, expression of cleaved caspase-3, Bax/Bcl-2 ratio, and cytochrome c (cyt c) release from mitochondria. SS-31 normalized mitochondrial potential (ΔΨm) and ATP alterations, and inhibited the expression of TGF-β1, Nox4, and TXNIP, as well as activation of p38 MAPK and CREB and NADPH oxidase activity in MMCs under HG conditions. SS-31 treatment also could reverse the reduction of thioredoxin (TRX) biologic activity and upregulate expression of thioredoxin 2 (TRX2) in MMCs under HG conditions. In conclusion, this study demonstrates a protective effect of SS-31 against HG-induced renal injury via an antioxidant mechanism in diabetic nephropathy.

  17. Urinary sodium excretion and kidney failure in nondiabetic chronic kidney disease. (United States)

    Fan, Li; Tighiouart, Hocine; Levey, Andrew S; Beck, Gerald J; Sarnak, Mark J


    Current guidelines recommend under 2 g/day sodium intake in chronic kidney disease, but there are a few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-h urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-h urinary sodium excretion was 3.46 g/day. Kidney failure developed in 617 participants, and the composite outcome was reached in 723. In the primary analyses, there was no association between 24-h urine sodium and kidney failure (HR 0.99 (95% CI 0.91-1.08)) nor on the composite outcome (HR 1.01 (95% CI 0.93-1.09)), each per 1 g/day higher urine sodium. In exploratory analyses, there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a two-slope model, when urine sodium was under 3 g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1 g/day and with lower risk of kidney failure in those with baseline proteinuria of ⩾ 1 g/day. There was no association between urine sodium and kidney failure when urine sodium was ⩾ 3 g/day. Results were consistent using first baseline and time-dependent urinary sodium excretion. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored.

  18. Comparison of non-attenuation corrected and attenuation corrected myocardial perfusion SPE

    Directory of Open Access Journals (Sweden)

    Hasan Raza


    Conclusion: This study demonstrates that CT based attenuation corrected Tc-99mm sestamibi SPECT myocardial perfusion imaging significantly improved the specificity of the RCA territory compared with non-attenuation corrected Tc-99mm sestamibi SPECT myocardial perfusion imaging in both genders irrespective of BMI.

  19. Attenuation tomography in West Bohemia/Vogtland (United States)

    Mousavi, Sima; Haberland, Christian; Bauer, Klaus; Hejrani, Babak; Korn, Michael


    We present a three-dimensional (3-D) P-wave attenuation (Qp) model for the geodynamically active swarm earthquake area of West Bohemia/Vogtland in the Czech/German border region. Path-averaged attenuation t* is calculated from amplitude spectra of time windows around the P-wave arrivals of local earthquakes. Average t/t* value or Qp for stations close to Nový Kostel are very low (focal zone (increases up to 500 within 80 km distance). The SIMUL2000 tomography scheme is used to invert the t* for P-wave attenuation perturbation. Analysis of resolution shows that our model is well-resolved in the vicinity of earthquake swarm hypocenters. The prominent features of the model are located around Nový Kostel focal zone and its northern vicinity. Beneath Nový Kostel a vertically stretched (down to depth of 11 km) and a highly attenuating body is observed. We believe that this is due to fracturing and high density of cracks inside the weak earthquake swarm zone in conjunction with presence of free gas/fluid. Further north of Nový Kostel two highly attenuating bodies are imaged which could represent fluid channels toward the surface. The eastern anomaly shows a good correlation with the fluid accumulation area which was suggested in 9HR seismic profile.

  20. Circulating CXCL16 in Diabetic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Usama Elewa


    Full Text Available Background/Aims: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. Methods: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. Results: Plasma CXCL16 levels were 4.0±0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33±1.03 vs 3.88±0.86 ng/ml; p=0.013. In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. Conclusion: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels.

  1. Matrix Metalloproteinases-7 and Kidney Fibrosis (United States)

    Ke, Ben; Fan, Chuqiao; Yang, Liping; Fang, Xiangdong


    Matrix metalloproteinase-7 (MMP-7) is a secreted zinc- and calcium-dependent endopeptidase that degrades a broad range of extracellular matrix substrates and additional substrates. MMP-7 playsa crucial role in a diverse array of cellular processes and appears to be a key regulator of fibrosis in several diseases, including pulmonary fibrosis, liver fibrosis, and cystic fibrosis. In particular, the relationship between MMP-7 and kidney fibrosis has attracted significant attention in recent years. Growing evidence indicates that MMP-7 plays an important role in the pathogenesis of kidney fibrosis. Here, we summarize the recent progress in the understanding of the role of MMP-7 in kidney fibrosis. In particular, we discuss how MMP-7 contributes to kidney fibrotic lesions via the following three pathways: epithelial-mesenchymal transition (EMT), transforming growth factor-beta (TGF-β) signaling, and extracellular matrix (ECM) deposition. Further dissection of the crosstalk among and regulation of these pathways will help clinicians and researchers develop effective therapeutic approaches for treating chronic kidney disease.

  2. Measuring glomerular number from kidney MRI images (United States)

    Thiagarajan, Jayaraman J.; Natesan Ramamurthy, Karthikeyan; Kanberoglu, Berkay; Frakes, David; Bennett, Kevin; Spanias, Andreas


    Measuring the glomerular number in the entire, intact kidney using non-destructive techniques is of immense importance in studying several renal and systemic diseases. Commonly used approaches either require destruction of the entire kidney or perform extrapolation from measurements obtained from a few isolated sections. A recent magnetic resonance imaging (MRI) method, based on the injection of a contrast agent (cationic ferritin), has been used to effectively identify glomerular regions in the kidney. In this work, we propose a robust, accurate, and low-complexity method for estimating the number of glomeruli from such kidney MRI images. The proposed technique has a training phase and a low-complexity testing phase. In the training phase, organ segmentation is performed on a few expert-marked training images, and glomerular and non-glomerular image patches are extracted. Using non-local sparse coding to compute similarity and dissimilarity graphs between the patches, the subspace in which the glomerular regions can be discriminated from the rest are estimated. For novel test images, the image patches extracted after pre-processing are embedded using the discriminative subspace projections. The testing phase is of low computational complexity since it involves only matrix multiplications, clustering, and simple morphological operations. Preliminary results with MRI data obtained from five kidneys of rats show that the proposed non-invasive, low-complexity approach performs comparably to conventional approaches such as acid maceration and stereology.

  3. Gene based therapies for kidney regeneration. (United States)

    Janssen, Manoe J; Arcolino, Fanny O; Schoor, Perry; Kok, Robbert Jan; Mastrobattista, Enrico


    In this review we provide an overview of the expanding molecular toolbox that is available for gene based therapies and how these therapies can be used for a large variety of kidney diseases. Gene based therapies range from restoring gene function in genetic kidney diseases to steering complex molecular pathways in chronic kidney disorders, and can provide a treatment or cure for diseases that otherwise may not be targeted. This approach involves the delivery of recombinant DNA sequences harboring therapeutic genes to improve cell function and thereby promote kidney regeneration. Depending on the therapy, the recombinant DNA will express a gene that directly plays a role in the function of the cell (gene addition), that regulates the expression of an endogenous gene (gene regulation), or that even changes the DNA sequence of endogenous genes (gene editing). Some interventions involve permanent changes in the genome whereas others are only temporary and leave no trace. Efficient and safe delivery are important steps for all gene based therapies and also depend on the mode of action of the therapeutic gene. Here we provide examples on how the different methods can be used to treat various diseases, which technologies are now emerging (such as gene repair through CRISPR/Cas9) and what the opportunities, perspectives, potential and the limitations of these therapies are for the treatment of kidney diseases.

  4. CDKD: a clinical database of kidney diseases

    Directory of Open Access Journals (Sweden)

    Singh Sanjay


    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.

  5. Nuclear medicine in pediatric kidney diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lauer, O.; Langhammer, H.; Reidel, G.; Pabst, H.W.; Heidenreich, P.; Fendel, H.; Helmig, F.J.; Belohradsky, B.


    Renal dynamic scintigraphy and quantitative determination of the total, the divided and - if necessary - the regional clearance (principle of OBERHAUSEN) using I-123-OIH (ortho-iodo-hippurate) were performed simultaneously in 156 children suffering from various renal or urological diseases. Results were compared to X-ray investigations and in the case of nephrectomy to histological findings. The clinical diagnoses and questions before and the therapeutic consequences after clearance studies were analyzed in order to deduce the most important indications for quantitative dynamic scintigraphy in pediatric kidney disease. In patients with unequal renal size the relationship between kidney length-ratio, as shown by urography, and the corresponding ratio of individual clearances, indicated that the radiographical estimate of kidney size is not a reliable index for split renal function. In many cases the dynamic scintigraphy combined with renal clearance determination contributed clinically important additional information to the predominantly morphological aspects of radiology. It proved as a valuable help in decision making with regard to surgical problems, especially in cases of unilaterally small kidneys, obstructive uropathy, duplication of the urinary tract and radiographically undetectable kidneys. In nonsurgical renal diseases the radionuclide study served as a long term follow up of renal function thereby reducing repeat urograms.

  6. Payment for donor kidneys: pros and cons. (United States)

    Friedman, E A; Friedman, A L


    Continuous growth of the end stage renal disease population treated by dialysis, outpaces deceased donor kidneys available, lengthens the waiting time for a deceased donor transplant. As estimated by the United States Department of Health & Human Services: '17 people die each day waiting for transplants that can't take place because of the shortage of donated organs.' Strategies to expand the donor pool--public relations campaigns and Drivers' license designation--have been mainly unsuccessful. Although illegal in most nations, and viewed as unethical by professional medical organizations, the voluntary sale of purchased donor kidneys now accounts for thousands of black market transplants. The case for legalizing kidney purchase hinges on the key premise that individuals are entitled to control of their body parts even to the point of inducing risk of life. One approach to expanding the pool of kidney donors is to legalize payment of a fair market price of about 40,000 dollars to donors. Establishing a federal agency to manage marketing and purchase of donor kidneys in collaboration with the United Network for Organ Sharing might be financially self-sustaining as reduction in costs of dialysis balances the expense of payment to donors.

  7. [Horseshoe kidney: not a simple fusion anomaly]. (United States)

    Caccetta, Francesco; Caroppo, Maurizio; Musio, Fernando; Mudoni, Anna; Accogli, Antonella; Zacheo, Maria Dolores; Burzo, Domenica; Bramato, Daniele; Carluccio, Giancamillo; Nuzzo, Vitale


    The horseshoe kidney is a congenital anatomical defect of the kidney that occurs in 0,25% of the population and is generally characterized by the fusion of the lower poles of the two kidneys through an isthmus and to which may be associated with urogenital and renal vascular anomalies. Asymptomatic in 1/3 of the cases and, most of time, accidentally discovered during a radiological examination, promotes nephrolithiasis, ureteropelvic junction obstruction, hydronephrosis, vesicoureteral reflux and pyelonephritis. We report two cases of patients with kidney horseshoe, characterized by the abrupt onset of a septic state with oligo-anuric acute renal failure, electrolyte and acid-base abnormalities, rapid decay of the general conditions, with detection of nephrolithiasis, hydronephrosis and acute pyelonephritis and whose clinical management resulted in a significant and synergistic nefro-urology involvment. The kidney horseshoe not represent so only a simple fusion anomaly but rather an important anatomical condition that, once diagnosed, it would be worthy of a careful clinical, radiological and laboratory surveillance, in order to prevent the potential complications that may be also particularly severe.

  8. Oxymatrine attenuates CCl4-induced hepatic fibrosis via modulation of TLR4-dependent inflammatory and TGF-β1 signaling pathways. (United States)

    Zhao, Hong-Wei; Zhang, Zhen-Fang; Chai, Xuan; Li, Guang-Quan; Cui, He-Rong; Wang, Hong-Bo; Meng, Ya-Kun; Liu, Hui-Min; Wang, Jia-Bo; Li, Rui-Sheng; Bai, Zhao-Fang; Xiao, Xiao-He


    Oxymatrine (OMT) is able to effectively protect against hepatic fibrosis because of its anti-inflammatory property, while the underlying mechanism remains incompletely understood. In this study, forty rats were randomly divided into five groups: control group, model group (carbon tetrachloride, CCl4) and three OMT treatment groups (30, 60, 120mg/kg). After CCl4 alone, the fibrosis score was 20.2±0.8, and the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hydroxyproline content, and collagen I expression was elevated, but OMT blunted these parameters. Treatment with OMT prevented CCl4-induced increases in expression of pro-inflammatory and pro-fibrotic cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, meanwhile OMT promoted the expression of anti-inflammatory and anti-fibrotic factors such as interleukin (IL)-10 and bone morphogenetic protein and activin membrane-bound inhibitor (Bambi). Moreover, lipopolysaccharides (LPS) and high mobility group box-1 (HMGB1), which activates Toll-like receptor 4 (TLR4) and modulate hepatic fibrogenesis through hepatic stellate cells (HSCs) or Kupffer cells, were significantly decreased by OMT treatment. These results were further supported by in vitro data. First, OMT suppressed the expression of TLR4 and its downstream pro-inflammatory cytokines, lowered the level of HMGB1, TGF-β1 in macrophages. Then, OMT promoted Bambi expression and thereby inhibited activation of HSCs mediated by transforming growth factor (TGF)-β1. In conclusion, this study showed that OMT could effectively attenuate the CCl4-induced hepatic fibrosis, and this effect may be due to modulation of TLR4-dependent inflammatory and TGF-β1 signaling pathways.

  9. Relative renal function estimate by renal scintigraphy with 99mTc-DMSA: influence of attenuation correction methods

    Directory of Open Access Journals (Sweden)

    Andreia Amaro


    Full Text Available Introduction – The estimate of relative renal function (RRF through scintigraphy with dimercaptosuccinic acid labelled with Technetium-99 metastable (99mTc-DMSA may be influenced by kidney depth (KD, due to attenuation by soft tissue surrounding the kidneys. Considering that rarely this KD is known, several methods for attenuation correction (AC have been developed, namely those using empirical formulae, such as Raynaud, Taylor or Tonnesen methods, or by direct calculation of the geometric mean (GM. Objectives – To identify the influence of different AC methods on RRF estimateby scintigraphy with 99mTc-DMSA and to evaluate the respective KD variability. Methods: Thirty-one patients were referred for 99mTc-DMSA scintigraphy and underwent the same acquisition protocol. Processing was performed by 2 independent operators, three times per exam, changing for the same processing the methods for the FRR determination: Raynaud’s method, Taylor’s method, Tonnesen´s method, GM and without AC (WAC. Friedman’s test was used to identify the influence of the different AC methods on RRF estimate and Pearson’s correlation test was used to evaluate the association and significance between KD and the variables age, weight and height. Results – Friedman’s test indicated that there were significant differences between methods (p=0.000, except for WAC/Raynaud, Tonnesen/GM and Taylor/GM (p=1.000 comparisons, for both kidneys. Pearson’stest showed a strong positive correlation between weight and the three methods of KD estimation. Conclusions – Taylor’s method, regarding the three methods of KD calculation, is the closest to GM. The choice of the attenuation correction method influences significantly the quantitative parameters of FRR.

  10. Live attenuated vaccines for invasive Salmonella infections. (United States)

    Tennant, Sharon M; Levine, Myron M


    Salmonella enterica serovar Typhi produces significant morbidity and mortality worldwide despite the fact that there are licensed Salmonella Typhi vaccines available. This is primarily due to the fact that these vaccines are not used in the countries that most need them. There is growing recognition that an effective invasive Salmonella vaccine formulation must also prevent infection due to other Salmonella serovars. We anticipate that a multivalent vaccine that targets the following serovars will be needed to control invasive Salmonella infections worldwide: Salmonella Typhi, Salmonella Paratyphi A, Salmonella Paratyphi B (currently uncommon but may become dominant again), Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Choleraesuis (as well as other Group C Salmonella). Live attenuated vaccines are an attractive vaccine formulation for use in developing as well as developed countries. Here, we describe the methods of attenuation that have been used to date to create live attenuated Salmonella vaccines and provide an update on the progress that has been made on these vaccines.

  11. Research on Nanosecond Pulse Corona Discharge Attenuation

    Institute of Scientific and Technical Information of China (English)

    HE Zheng-hao; XU Huai-li; BAI Jing; YU Fu-sheng; HU Feng; LI Jin


    A line-to-plate reactor was set-up in the experimental study on the application of nanosecond pulsed corona discharge plasma technology in environmental pollution control.Investigation on the attenuation and distortion of the amplitude of the pulse wave front and the discharge image as well as the waveform along the corona wire was conducted.The results show that the wave front decreases sharply during the corona discharge along the corona wire.The higher the amplitude of the applied pulse is,the more the amplitude of the wave front decreased.The wave attenuation responds in a lower corona discharge inversely.To get a higher efficiency of the line-to-plate reactor a sharp attenuation of the corona has to be considered in practical design.

  12. Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury: The Role of Novel Biomarkers as Early and Accurate Diagnostics. (United States)

    Yerramilli, Murthy; Farace, Giosi; Quinn, John; Yerramilli, Maha


    Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and the presence of one is a risk for the other. CKD is an important predictor of AKI after exposure to nephrotoxic drugs or major surgery, whereas persistent or repetitive injury could result in the progression of CKD. This brings new perspectives to the diagnosis and monitoring of kidney diseases highlighting the need for a panel of kidney-specific biomarkers that reflect functional as well as structural damage and recovery, predict potential risk and provide prognosis. This article discusses the kidney-specific biomarkers, symmetric dimethylarginine (SDMA), clusterin, cystatin B, and inosine.

  13. Erythropoietin (EPO) in acute kidney injury. (United States)

    Moore, Elizabeth; Bellomo, Rinaldo


    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways, and promotion of recovery.In this article, we review the physiology of EPO, assess previous work that supports the role of EPO as a general tissue protective agent, and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on experimental and clinical data that suggest that EPO has a kidney protective effect.

  14. Technology innovation for patients with kidney disease. (United States)

    Mitsides, Nicos; Keane, David F; Lindley, Elizabeth; Mitra, Sandip


    The loss of kidney function is a life-changing event leading to life-long dependence on healthcare. Around 5000 people are diagnosed with kidney failure every year. Historically, technology in renal medicine has been employed for replacement therapies. Recently, a lot of emphasis has been placed on technologies that aid early identification and prevent progression of kidney disease, while at the same time empowering affected individuals to gain control over their chronic illness. There is a shift in diversity of technology development, driven by collaborative innovation initiatives such the National Institute's for Health Research Healthcare Technology Co-operative for Devices for Dignity. This has seen the emergence of the patient as a key figure in designing technologies that are fit for purpose, while business involvement has ensured uptake and sustainability of these developments. An embodiment of this approach is the first successful Small Business Research Initiative in the field of renal medicine in the UK.

  15. Kidney Modelling for FDG Excretion with PET

    Directory of Open Access Journals (Sweden)

    Huiting Qiao


    Full Text Available The purpose of this study was to detect the physiological process of FDG's filtration from blood to urine and to establish a mathematical model to describe the process. Dynamic positron emission tomography scan for FDG was performed on seven normal volunteers. The filtration process in kidney can be seen in the sequential images of each study. Variational distribution of FDG in kidney can be detected in dynamic data. According to the structure and function, kidney is divided into parenchyma and pelvis. A unidirectional three-compartment model is proposed to describe the renal function in FDG excretion. The time-activity curves that were picked up from the parenchyma, pelvis, and abdominal aorta were used to estimate the parameter of the model. The output of the model has fitted well with the original curve from dynamic data.

  16. Direct renin inhibition in chronic kidney disease

    DEFF Research Database (Denmark)

    Persson, Frederik; Rossing, Peter; Parving, Hans-Henrik


    that renin inhibition could hold potential for improved treatment in patients with chronic kidney disease, with diabetic nephropathy as an obvious group of patients to investigate, as the activity of the renin-angiotensin-aldosterone system is enhanced in these patients and as there is an unmet need....... In addition, combination treatment seemed safe and effective also in patients with impaired kidney function. These initial findings formed the basis for the design of a large morbidity and mortality trial investigating aliskiren as add-on to standard treatment. The study has just concluded, but was terminated...... early as a beneficial effect was unlikely and there was an increased frequency of side effects. Also in non-diabetic kidney disease a few intervention studies have been carried out, but there is no ongoing hard outcome study. In this review we provide the current evidence for renin inhibition in chronic...

  17. [Can man live with a pig kidney?]. (United States)

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


    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.

  18. Is there seismic attenuation in the mantle? (United States)

    Ricard, Y.; Durand, S.; Montagner, J.-P.; Chambat, F.


    The small scale heterogeneity of the mantle is mostly due to the mixing of petrological heterogeneities by a smooth but chaotic convection and should consist in a laminated structure (marble cake) with a power spectrum S(k) varying as 1/k, where k is the wavenumber of the anomalies. This distribution of heterogeneities during convective stirring with negligible diffusion, called Batchelor regime is documented by fluid dynamic experiments and corresponds to what can be inferred from geochemistry and seismic tomography. This laminated structure imposes density, seismic velocity and potentially, anisotropic heterogeneities with similar 1/k spectra. A seismic wave of wavenumber k0 crossing such a medium is partly reflected by the heterogeneities and we show that the scattered energy is proportional to k0S(2k0). The reduction of energy for the propagating wave appears therefore equivalent to a quality factor 1/Q∝k0S(2k0). With the specific 1/k spectrum of the mantle, the resulting apparent attenuation should therefore be frequency independent. We show that the total contribution of 6-9% RMS density, velocity and anisotropy would explain the observed S and P attenuation of the mantle. Although these values are large, they are not unreasonable and we discuss how they depend on the range of frequencies over which the attenuation is explained. If such a level of heterogeneity were present, most of the attenuation of the Earth would be due to small scale scattering by laminations, not by intrinsic dissipation. Intrinsic dissipation must certainly exist but might correspond to a larger, yet unobserved Q. This provocative result would explain the very weak frequency dependence of the attenuation, and the fact that bulk attenuation seems negligible, two observations that have been difficult to explain for 50 years.

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

    DEFF Research Database (Denmark)

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


    expressed in non-haematopoietic tissue and today, Epo is recognised as a cytokine with many pleiotropic effects. We hypothesize that hydrodynamic gene therapy with Epo can restore haemoglobin levels in anaemic transgenic mice and that this will attenuate the extracellular matrix accumulation in the kidneys....... The experiment is conducted by hydrodynamic gene transfer of a plasmid encoding murine Epo in a transgenic mouse model that overexpresses TGF-β1 locally in the kidneys. This model develops anaemia due to chronic kidney disease characterised by thickening of the glomerular basement membrane, deposition...... of mesangial matrix and mild interstitial fibrosis. A group of age matched wildtype littermates are treated accordingly. After a single hydrodynamic administration of plasmid DNA containing murine EPO gene, sustained high haemoglobin levels are observed in both transgenic and wildtype mice from 7.5 ± 0.6 mmol...

  20. Chronic kidney Disease and the Aging Population. (United States)

    Tonelli, Marcello; Riellae, Miguel


    Youth, which is forgiven everything, forgives itself nothing: age, which forgives itself everything, is forgiven nothing. George Bernard Shaw The proportion of older people in the general population is steadily increasing worldwide, with the most rapid growth in low-and middle-income countries [1]. This demographic change is to be celebrated, because it is the consequence of socioeconomic development and better life expectancy. However, population aging also has important implications for society - in diverse areas including health systems, labor markets, public policy, social programs, and family dynamics [2]. A successful response to the aging population will require capitalizing on the opportunities that this transition offers, as well as effectively addressing its challenges. Chronic kidney disease (CKD) is an important public health problem that is characterized by poor health outcomes and very high health care costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke - all of which are key causes of death and disability in older people [3]. Since the prevalence of CKD is higher in older people, the health impact of population aging will depend in part on how the kidney community responds. March 13, 2014 will mark the celebration of the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of kidney disease. The topic for WKD 2014 is "CKD in older people". This article reviews the key links between kidney function, age, health and illness - and discusses the implications of the aging population for the care of people with CKD.