Sample records for adult human kidney

  1. Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

    PubMed

    Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

    2015-06-01

    Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    PubMed

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

    2017-11-01

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

  3. Demonstration of human kidney differentiation antigens with monoclonal antibodies.

    PubMed

    Candelier, J J; Couillin, P; Bellon, G; Le Pendu, J; Eydoux, P; Boue, A

    1988-10-01

    Six human differentiation antigens (EE24.6, EG9.11, EG14.1, EI16.1, EK8.1, EK17.1) have been defined using monoclonal antibodies obtained from mice immunized with embryonic kidney cells. Their histologic distribution was determined on frozen sections of embryonic, fetal, and adult human kidneys by immunofluorescence assay. EE24.6, an ureteral bud marker, was detected only on the germ layer of mature kidney urothelium. EG9.11 and EG14.1 were detected on the S-shaped bodies and also on the adult proximal convoluted tubule for the former and the glomerular basement membrane for the latter. EI16.1, a marker of condensed mesenchyme, was detected only on epithelial cells of adult proximal convoluted tubule. EK8.1 was found in the mesangium, connective tissue, and with particularly dense labeling in the basement membranes. This labeling pattern was present throughout renal organogenesis. EK17.1 recognized both cell and plasma human fibronectins. Staining for all antibodies was nearly identical in mesonephros and metanephros. These results demonstate that some antigens follow their embryonic destiny. They indicate an antigenic similarity between the mesonephros and the metanephros and, therefore, a very early appearance of these antigens. During differentiation, these antigens concentrate on more defined structures, and staining became increased with an increased degree of differentiation.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Webb, Carol F., E-mail: carol-webb@omrf.org; Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK

    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:more » • 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.« less

  5. Reactivation of NCAM1 defines a subpopulation of human adult kidney epithelial cells with clonogenic and stem/progenitor properties.

    PubMed

    Buzhor, Ella; Omer, Dorit; Harari-Steinberg, Orit; Dotan, Zohar; Vax, Einav; Pri-Chen, Sara; Metsuyanim, Sally; Pleniceanu, Oren; Goldstein, Ronald S; Dekel, Benjamin

    2013-11-01

    The nephron is composed of a monolayer of epithelial cells that make up its various compartments. In development, these cells begin as mesenchyme. NCAM1, abundant in the mesenchyme and early nephron lineage, ceases to express in mature kidney epithelia. We show that, once placed in culture and released from quiescence, adult human kidney epithelial cells (hKEpCs), uniformly positive for CD24/CD133, re-express NCAM1 in a specific cell subset that attains a stem/progenitor state. Immunosorted NCAM1(+) cells overexpressed early nephron progenitor markers (PAX2, SALL1, SIX2, WT1) and acquired a mesenchymal fate, indicated by high vimentim and reduced E-cadherin levels. Gene expression and microarray analysis disclosed both a proximal tubular origin of these cells and molecules regulating epithelial-mesenchymal transition. NCAM1(+) cells generated clonal progeny when cultured in the presence of fetal kidney conditioned medium, differentiated along mesenchymal lineages but retained the unique propensity to generate epithelial kidney spheres and produce epithelial renal tissue on single-cell grafting in chick CAM and mouse. Depletion of NCAM1(+) cells from hKEpCs abrogated stemness traits in vitro. Eliminating these cells during the regenerative response that follows glycerol-induced acute tubular necrosis worsened peak renal injury in vivo. Thus, higher clone-forming and developmental capacities characterize a distinct subset of adult kidney-derived cells. The ability to influence an endogenous regenerative response via NCAM1 targeting may lead to novel therapeutics for renal diseases. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Decellularized Human Kidney Cortex Hydrogels Enhance Kidney Microvascular Endothelial Cell Maturation and Quiescence.

    PubMed

    Nagao, Ryan J; Xu, Jin; Luo, Ping; Xue, Jun; Wang, Yi; Kotha, Surya; Zeng, Wen; Fu, Xiaoyun; Himmelfarb, Jonathan; Zheng, Ying

    2016-10-01

    The kidney peritubular microvasculature is highly susceptible to injury from drugs and toxins, often resulting in acute kidney injury and progressive chronic kidney disease. Little is known about the process of injury and regeneration of human kidney microvasculature, resulting from the lack of appropriate kidney microvascular models that can incorporate the proper cells, extracellular matrices (ECMs), and architectures needed to understand the response and contribution of individual vascular components in these processes. In this study, we present methods to recreate the human kidney ECM (kECM) microenvironment by fabricating kECM hydrogels derived from decellularized human kidney cortex. The majority of native matrix proteins, such as collagen-IV, laminin, and heparan sulfate proteoglycan, and their isoforms were preserved in similar proportions as found in normal kidneys. Human kidney peritubular microvascular endothelial cells (HKMECs) became more quiescent when cultured on this kECM gel compared with culture on collagen-I-assessed using phenotypic, genotypic, and functional assays; whereas human umbilical vein endothelial cells became stimulated on kECM gels. We demonstrate for the first time that human kidney cortex can form a hydrogel suitable for use in flow-directed microphysiological systems. Our findings strongly suggest that selecting the proper ECM is a critical consideration in the development of vascularized organs on a chip and carries important implications for tissue engineering of all vascularized organs.

  7. Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification.

    PubMed

    Ehrlich, Lili E; Fahy, Gregory M; Wowk, Brian G; Malen, Jonathan A; Rabin, Yoed

    2018-01-01

    This study focuses on thermal analysis of the problem of scaling up from the vitrification of rabbit kidneys to the vitrification of human kidneys, where vitrification is the preservation of biological material in the glassy state. The basis for this study is a successful cryopreservation protocol for a rabbit kidney model, based on using a proprietary vitrification solution known as M22. Using the finite element analysis (FEA) commercial code ANSYS, heat transfer simulations suggest that indeed the rabbit kidney unquestionably cools rapidly enough to be vitrified based on known intrarenal concentrations of M22. Scaling up 21-fold, computer simulations suggest less favorable conditions for human kidney vitrification. In this case, cooling rates below -100 °C are sometimes slower than 1 °C/min, a rate that provides a clear-cut margin of safety at all temperatures based on the stability of rabbit kidneys in past studies. Nevertheless, it is concluded in this study that vitrifying human kidneys is possible without significant ice damage, assuming that human kidneys can be perfused with M22 as effectively as rabbit kidneys. The thermal analysis suggests that cooling rates can be further increased by a careful design of the cryogenic protocol and by tailoring the container to the shape of the kidney, in contrast to the present cylindrical container. This study demonstrates the critical need for the thermal analysis of experimental cryopreservation and highlights the unmet need for measuring the thermophysical properties of cryoprotective solutions under conditions relevant to realistic thermal histories.

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

    PubMed

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

    2018-03-01

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

  9. Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16.

    PubMed Central

    Reeders, S T; Breuning, M H; Corney, G; Jeremiah, S J; Meera Khan, P; Davies, K E; Hopkinson, D A; Pearson, P L; Weatherall, D J

    1986-01-01

    The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis. Images FIG 1 PMID:3008903

  10. Benefits of a transfer clinic in adolescent and young adult kidney transplant patients.

    PubMed

    McQuillan, Rory F; Toulany, Alene; Kaufman, Miriam; Schiff, Jeffrey R

    2015-01-01

    Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services. The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer. We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non-attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer. The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03). The median change in estimated glomerular filtration rate (eGFR) in the year following transfer

  11. Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

    PubMed Central

    Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

    2017-01-01

    Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

  12. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

    PubMed

    Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

    2016-05-01

    Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

  13. Effects of a restricted fetal growth environment on human kidney morphology, cell apoptosis and gene expression.

    PubMed

    Wang, Yan-Ping; Chen, Xu; Zhang, Zhi-Kun; Cui, Hong-Yan; Wang, Peng; Wang, Yue

    2015-12-01

    Kidney development is key to the onset of hypertension and cardiovascular diseases in adults, and in the fetal stage will be impaired by a lack of nutrients in utero in animal models. However, few human studies have been performed. Kidney samples from fetuses in a fetal growth restriction (FGR) environment were collected and the morphological characteristics were observed. Potentially molecular mechanisms were explored by analyzing apoptosis and kidney-development related gene expression. The results indicated that no malformations were observed in the kidney samples of the FGR group, but the mean kidney weight and volume were significantly decreased. Moreover, the ratio of apoptotic cells and Bax-positive cells was increased and the ratio of Bcl-2-positive cells was decreased in the FGR group, indicating potential apoptosis induction under an in utero FGR environment. Finally, aberrant expression of renin and angiotensinogen indicated potential kidney functional abnormalities in the FGR group. Our study suggested increased apoptosis and decreased renin and angiotensinogen expression during human kidney development in an FGR environment. The current results will be helpful to further explore the molecular mechanism of FGR and facilitate future studies of hypertension and cardiovascular diseases and the establishment of preventive methods. © The Author(s) 2014.

  14. Kidney enlargement and multiple liver cyst formation implicate mutations in PKD1/2 in adult sporadic polycystic kidney disease.

    PubMed

    Fujimaru, T; Mori, T; Sekine, A; Mandai, S; Chiga, M; Kikuchi, H; Ando, F; Mori, Y; Nomura, N; Iimori, S; Naito, S; Okado, T; Rai, T; Hoshino, J; Ubara, Y; Uchida, S; Sohara, E

    2018-07-01

    Distinguishing autosomal-dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease-causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed Central

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

    2012-01-01

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

  16. Anemia in new congenital adult type polycystic kidney mice.

    PubMed

    Koumegawa, J; Nagano, N; Arai, H; Wada, M; Kusaka, M; Takahashi, H

    1991-12-01

    Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.

  17. Impaired Kidney Function and Associated Factors Among Rural Adults With Disabilities in Taiwan.

    PubMed

    Chen, Chu-Yeh; Chiu, Wen-Nan; Lin, Yu-Chen; Jane, Sui-Hwi; Chiang, Hsin-Hung; Chen, Mei-Yen

    2017-04-01

    The results of numerous studies indicate that people with disabilities seek more healthcare than those who are not disabled, particularly for conditions such as chronic kidney disease, cardiovascular disease, and obesity. However, little is known about the incidence of impaired kidney function and its associated factors among adults with disabilities in Taiwan. The aim of this study was to explore the prevalence and factors associated with impaired kidney function among adults with disabilities. This descriptive study was nurse led and was conducted as part of a health promotion program for disadvantaged rural adults with disabilities in Chiayi County, Taiwan. Health screening and a health needs survey were conducted between July and December 2013. Kidney function, physiological biomarkers, health-related behaviors, and demographic characteristics were examined. Eight hundred ten rural adults with disabilities were enrolled. The most common disabilities included physical-related disability (33.1%), intellectual-related disability (26.7%), and hearing and vision impairment (18.6%). The prevalence of impaired kidney function in this population was 85%. According to classification for chronic kidney disease, 68.6% were in Stages 1-2, and 16.8% were in Stages 3-4. Univariate analysis showed that impaired kidney function was significantly associated with lower educational level (p < .001), hearing or vision impairment (p < .001), being overweight or obese (p < .05), high systolic blood pressure (p < .01), fasting blood glucose (p < .001), total cholesterol (p < .001), total triglyceride (p < .05), older age (p < .001), smoking (p < .05), chewing betel nuts (p = .001), and low levels of participation in social activities (p < .05). The final logistic regression model showed that residents with disabilities who were older or had less education, high fasting blood glucose, and high total cholesterol tended to have impaired kidney function after adjustment for other

  18. Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

    PubMed

    Lata, Sneh; Marasa, Maddalena; Li, Yifu; Fasel, David A; Groopman, Emily; Jobanputra, Vaidehi; Rasouly, Hila; Mitrotti, Adele; Westland, Rik; Verbitsky, Miguel; Nestor, Jordan; Slater, Lindsey M; D'Agati, Vivette; Zaniew, Marcin; Materna-Kiryluk, Anna; Lugani, Francesca; Caridi, Gianluca; Rampoldi, Luca; Mattoo, Aditya; Newton, Chad A; Rao, Maya K; Radhakrishnan, Jai; Ahn, Wooin; Canetta, Pietro A; Bomback, Andrew S; Appel, Gerald B; Antignac, Corinne; Markowitz, Glen S; Garcia, Christine K; Kiryluk, Krzysztof; Sanna-Cherchi, Simone; Gharavi, Ali G

    2018-01-16

    The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. To study the diagnostic utility of WES in a selected referral population of adults with CKD. Observational cohort. A major academic medical center. 92 adults with CKD of unknown cause or familial nephropathy or hypertension. The diagnostic yield of WES and its potential effect on clinical management. Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most identified cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy. The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population. Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted. New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of

  19. Endothelin-1 inactivating peptidase in the human kidney and urine.

    PubMed

    Janas, J; Sitkiewicz, D; Januszewicz, A; Szczesniak, C; Grenda, R; Janas, R M

    2000-04-01

    Recently, an apparently novel, specific endothelin-1 inactivating metalloendopeptidase (ET-1 peptidase) has been isolated from the rat kidney. In this study we attempted to determine whether the same or a similar peptidase is present in the human kidney, and whether the enzyme is excreted into the urine. The urinary ET-1 peptidase could serve as an indirect index of the renal endothelin system, both in physiology and pathophysiology. Kidney specimens were obtained from part of nephrectomized kidneys unaffected by any neoplastic process from six adult patients. The enzyme was purified using differential centrifugation, detergent solubilization of the membrane proteins, ultrafiltration and nondenaturing gel electrophoresis. The enzyme activity assays were performed at pH 5.5 and 37 degrees C in the presence of increasing concentrations of unlabelled peptides and inhibitors using a fixed amount of [125I]ET-1 as substrate. The degradation extent was quantified with trichloroacetic acid precipitation and high performance liquid chromatography. The degrading activity of ET-1 was determined in urine samples from adult patients with hypertension, children with chronic renal failure and those with stable renal allograft ET-1 peptidase from the human kidney displays characteristics close to that of the rat ET-1 peptidase we have recently described (J. Hypertens 1994; 12:1155-1162). The enzyme, a membrane-bound metalloendopeptidase, exhibits low electro- phoretical mobility on nondenaturing gel (Rf 0.08); it is an apparently heterologous structure comprising three enzymatically inactive subunits, it has a pH optimum at 5.5, a nanomolar range affinity to the ET-1 (KM 180 nmol/l) that is hydrolysed to two main degradation products, and a 10-100-fold lower affinity to big ET-1 (KM 11.5 micromol/l), endothelin 11 21 fragment (KM 15.3 micromol/l), endothelin antagonist Trp-Leu-Asp-Ile-Ile-Trp (KM 3.1 micromol/I), gastrin (KM 2.2 micromol/l) and cholecystokinin (KM 4.0 micromol

  20. Current status of pediatric donor en bloc kidney transplantation to young adult recipients.

    PubMed

    Lorente, D; Trilla, E; Serón, D; Moreso, J; Morote, J

    2013-06-01

    In recent years, despite the increased number of kidney transplants performed in Spain, we observed a gradual increase in waiting lists. The need to increase the number of transplants performed in our centers, forces us to accept as donors patients previously rejected. We performed a systematic review using PubMed of published articles in the last 10 years, that include the words transplant renal en bloque, "en bloc kidney transplantation" or its initials EBKT. The pediatric donor to adult recipient has been included in the expanded criteria donors group, being rejected nevertheless such donors in most centers. However, in recent published series comparing the en bloc kidney transplantation from pediatric donor to adult recipients with other transplanted groups, the authors observe similar results between this kind of transplantation and the "optimal" donor group or living kidney donor group, regarding renal function and graft survival, and better results than the transplanted kidneys with expanded criteria donors group. The results published in the current series lead us to consider this kind of transplant as an option to increase the number of transplants performed. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

  1. Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

    PubMed

    Stratta, Robert J; Farney, Alan C; Orlando, Giuseppe; Farooq, Umar; Al-Shraideh, Yousef; Palanisamy, Amudha; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; El-Hennawy, Hany; Khan, Muhammad; Rogers, Jeffrey

    2016-04-01

    The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from

  2. Stereological study of developing glomerular forms during human fetal kidney development.

    PubMed

    Dakovic Bjelakovic, Marija; Vlajkovic, Slobodan; Petrovic, Aleksandar; Bjelakovic, Marko; Antic, Milorad

    2018-05-01

    Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.

  3. Triglycerides in the human kidney cortex: relationship with body size.

    PubMed

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

    2014-01-01

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

  4. Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation

    PubMed Central

    Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

    2015-01-01

    Background Fetal exposure to hyperglycemia impacts negatively kidney development and function. Objective Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Design Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Results Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)—a key enzyme involved in gene expression during early development–was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Conclusion Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function. PMID:26258530

  5. Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation.

    PubMed

    Gautier, Jean-François; Porcher, Raphaël; Abi Khalil, Charbel; Bellili-Munoz, Naima; Fetita, Lila Sabrina; Travert, Florence; Choukem, Simeon-Pierre; Riveline, Jean-Pierre; Hadjadj, Samy; Larger, Etienne; Boudou, Philippe; Blondeau, Bertrand; Roussel, Ronan; Ferré, Pascal; Ravussin, Eric; Rouzet, François; Marre, Michel

    2015-01-01

    Fetal exposure to hyperglycemia impacts negatively kidney development and function. Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring. Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D) (case group) were matched with 28 offspring of T1D fathers (control group) for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium). In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) at baseline and during vasodilatation produced by amino acid infusion. Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1)--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls. Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function.

  6. Constraint, consent, and well-being in human kidney sales.

    PubMed

    Hughes, Paul M

    2009-12-01

    This paper canvasses recent arguments in favor of commercial markets in human transplant kidneys, raising objections to those arguments on grounds of the role of injustice, exploitation, and coercion in compromising the autonomy of those most likely to sell a kidney, namely, the least well off members of society.

  7. Density gradient electrophoresis of cultured human embryonic kidney cells

    NASA Technical Reports Server (NTRS)

    Plank, L. D.; Kunze, M. E.; Giranda, V.; Todd, P. W.

    1985-01-01

    Ground based confirmation of the electrophoretic heterogeneity of human embryonic kidney cell cultures, the general characterization of their electrophoretic migration, and observations on the general properties of cultures derived from electrophoretic subpopulations were studied. Cell migration in a density gradient electrophoresis column and cell electrophoretic mobility was determined. The mobility and heterogeneity of cultured human embryonic kidney cells with those of fixed rat erythrocytes as model test particle was compared. Electrophoretically separated cell subpopulations with respect to size, viability, and culture characteristics were examined.

  8. Self-management interventions for adults with chronic kidney disease: a scoping review

    PubMed Central

    Donald, Maoliosa; Kahlon, Bhavneet Kaur; Beanlands, Heather; Straus, Sharon; Ronksley, Paul; Herrington, Gwen; Tong, Allison; Grill, Allan; Waldvogel, Blair; Large, Chantel A; Large, Claire L; Harwood, Lori; Novak, Marta; James, Matthew T; Elliott, Meghan; Fernandez, Nicolas; Brimble, Scott; Samuel, Susan; Hemmelgarn, Brenda R

    2018-01-01

    Objective To systematically identify and describe self-management interventions for adult patients with chronic kidney disease (CKD). Setting Community-based. Participants Adults with CKD stages 1–5 (not requiring kidney replacement therapy). Interventions Self-management strategies for adults with CKD. Primary and secondary outcome measures Using a scoping review, electronic databases and grey literature were searched in October 2016 to identify self-management interventions for adults with CKD stages 1–5 (not requiring kidney replacement therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed method studies were included and study selection and data extraction were independently performed by two reviewers. Outcomes included behaviours, cognitions, physiological measures, symptoms, health status and healthcare. Results Fifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre-post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions were included. The most common intervention topic was diet/nutrition and interventions were regularly delivered face to face. Interventions were administered by a variety of providers, with nursing professionals the most common health professional group. Cognitions (ie, changes in general CKD knowledge, perceived self-management and motivation) were the most frequently reported outcome domain that showed improvement. Less than 1% of the interventions were co-developed with patients and 20% were based on a theory or framework. Conclusions There was a wide range of self-management interventions with considerable variability in outcomes for adults with CKD. Major gaps in the literature include lack of patient engagement in the design of the interventions, with the majority of interventions not applying a behavioural change theory to inform their development. This work highlights the need to involve patients to co-developed and evaluate a self-management intervention based on

  9. Self-management interventions for adults with chronic kidney disease: a scoping review.

    PubMed

    Donald, Maoliosa; Kahlon, Bhavneet Kaur; Beanlands, Heather; Straus, Sharon; Ronksley, Paul; Herrington, Gwen; Tong, Allison; Grill, Allan; Waldvogel, Blair; Large, Chantel A; Large, Claire L; Harwood, Lori; Novak, Marta; James, Matthew T; Elliott, Meghan; Fernandez, Nicolas; Brimble, Scott; Samuel, Susan; Hemmelgarn, Brenda R

    2018-03-22

    To systematically identify and describe self-management interventions for adult patients with chronic kidney disease (CKD). Community-based. Adults with CKD stages 1-5 (not requiring kidney replacement therapy). Self-management strategies for adults with CKD. Using a scoping review, electronic databases and grey literature were searched in October 2016 to identify self-management interventions for adults with CKD stages 1-5 (not requiring kidney replacement therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed method studies were included and study selection and data extraction were independently performed by two reviewers. Outcomes included behaviours, cognitions, physiological measures, symptoms, health status and healthcare. Fifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre-post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions were included. The most common intervention topic was diet/nutrition and interventions were regularly delivered face to face. Interventions were administered by a variety of providers, with nursing professionals the most common health professional group. Cognitions (ie, changes in general CKD knowledge, perceived self-management and motivation) were the most frequently reported outcome domain that showed improvement. Less than 1% of the interventions were co-developed with patients and 20% were based on a theory or framework. There was a wide range of self-management interventions with considerable variability in outcomes for adults with CKD. Major gaps in the literature include lack of patient engagement in the design of the interventions, with the majority of interventions not applying a behavioural change theory to inform their development. This work highlights the need to involve patients to co-developed and evaluate a self-management intervention based on sound theories and clinical evidence. © Article author(s) (or their employer(s) unless otherwise stated in the

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

    PubMed Central

    Zhang, Ai-Di; Dai, Shao-Xing; Huang, Jing-Fei

    2013-01-01

    With the advent of the high-throughput data production, recent studies of tissue-specific metabolic networks have largely advanced our understanding of the metabolic basis of various physiological and pathological processes. However, for kidney, which plays an essential role in the body, the available kidney-specific model remains incomplete. This paper reports the reconstruction and characterization of the human kidney metabolic network based on transcriptome and proteome data. In silico simulations revealed that house-keeping genes were more essential than kidney-specific genes in maintaining kidney metabolism. Importantly, a total of 267 potential metabolic biomarkers for kidney-related diseases were successfully explored using this model. Furthermore, we found that the discrepancies in metabolic processes of different tissues are directly corresponding to tissue's functions. Finally, the phenotypes of the differentially expressed genes in diabetic kidney disease were characterized, suggesting that these genes may affect disease development through altering kidney metabolism. Thus, the human kidney-specific model constructed in this study may provide valuable information for the metabolism of kidney and offer excellent insights into complex kidney diseases. PMID:24222897

  11. Increased risk of kidney damage among Chinese adults with simple renal cyst.

    PubMed

    Kong, Xianglei; Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Xu, Dongmei

    2018-05-04

    The presence of simple renal cyst (SRC) has been related to hypertension, the early and long-term allograft function, and aortic disease, but the relationship with kidney damage was still controversial. Accordingly, we conducted a large sample cross-sectional study to explore the association of SRC with indicators of kidney damage among Chinese adults. A total of 42,369 adults (aged 45.8 ± 13.67 years, 70.6% males) who visited the Health Checkup Clinic were consecutively enrolled. SRC was assessed by ultrasonography according to Bosniak category. Multiple regression models were applied to explore the relationships between SRC and indicators of kidney damage [proteinuria (dipstick urine protein ≥ 1+) and decreased estimated glomerular filtration rate (DeGFR) < 60 ml/min/1.73 m 2 ]. Among all participants in the study, the prevalence of SRC was 10.5%. As a categorical outcome, participants with more 1 cyst and with 1 cyst had higher percentage of proteinuria [53 (5.3%) and 93 (2.7%) vs. 596 (1.6%), p < 0.001] and DeGFR [57 (5.7%) and 85 (2.5%) vs. 278 (0.7%), p < 0.001] compared with participants with no cyst. SRC significantly correlated with proteinuria [OR 1.59 (95% CI 1.30-1.95)] and DeGFR [OR 1.97 (95% CI 1.56-2.47)] after adjusting for potential confounders. Furthermore, the results also demonstrated that maximum diameter (per 1 cm increase), bilateral location, and multiple cysts significantly correlated with DeGFR in the multiple logistic regression analysis. The study revealed that SRC significantly correlated with kidney damage and special attention should be paid among Chinese adults with SRC.

  12. Near-adult height in male kidney transplant recipients started on growth hormone treatment in late puberty.

    PubMed

    Gil, Silvia; Aziz, Mariana; Adragna, Marta; Monteverde, Marta; Belgorosky, Alicia

    2018-01-01

    Growth retardation and its impact on adult height is considered to be one of the most common complications in patients with chronic kidney disease (CKD). Treatment with recombinant human growth hormone (rhGH) has been effective in improving growth in kidney transplantation (KTx) patients, but little data are available on adult height in patients who began rhGh treatment in late puberty. Near-adult height was evaluated in 13 KTx patients treated with rhGH [growth hormone group (GHGr); dose 9.33 mg/m 2 per week] for a period of at least 18 months. At initiation of rhGH treatment, testicular volume was >8 ml and serum testosterone was >1 ng/ml compared with the control group (CGr) of ten KTx patients who did not receive rHGH. All subjects were of similar chronological age and bone age and had similar creatinine clearance (CrCl) levels, cumulative corticoid dose, height standard deviation score (SDS), target height SDS, and target height:initial height at the beginning of the study. Near-adult height was significantly greater in the GHGr than in the CGr (-1.8 ± 0.8 vs. -2.9 ± 1.1; p = 0.018). The difference between initial height and near-adult height in the GHGr revealed a significant height gain (initial height -3.1 ± 1.1; near-adult height -1.8 ± 0.8 SDS, respectively; delta 1.2 ± 0.3; p = 0.021). The CrCl level was not significantly different between the GHGr and CGr at either at study initiation or when attaining near-adult height (p = 0.74 and p = 0.23, respectively). Treatment with rhGH was effective in improving adult height in KTx patients who began treatment in late puberty, without any effect on renal function.

  13. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.

    PubMed

    Coresh, Josef; Astor, Brad C; Greene, Tom; Eknoyan, Garabed; Levey, Andrew S

    2003-01-01

    Recently developed clinical practice guidelines and calibration of the Third National Health and Nutrition Examination Survey (NHANES III) serum creatinine assay provide a basis for estimating the prevalence and distribution of chronic kidney disease (CKD) in the United States using standardized criteria based on estimated glomerular filtration rate (GFR) and persistent albuminuria. A nationally representative sample of 15,625 noninstitutionalized adults aged 20 years and older from the NHANES III was analyzed. Kidney function (GFR), kidney damage (albuminuria), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine level, spot urine albumin level, age, sex, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation and compared with the Cockcroft-Gault equation for creatinine clearance (CCr). The prevalence of CKD in the US adult population was 11% (19.2 million). By stage, an estimated 5.9 million individuals (3.3%) had stage 1 (persistent albuminuria with a normal GFR), 5.3 million (3.0%) had stage 2 (persistent albuminuria with a GFR of 60 to 89 mL/min/1.73 m(2)), 7.6 million (4.3%) had stage 3 (GFR, 30 to 59 mL/min/1.73 m(2)), 400,000 individuals (0.2%) had stage 4 (GFR, 15 to 29 mL/min/1.73 m(2)), and 300,000 individuals (0.2%) had stage 5, or kidney failure. Aside from hypertension and diabetes, age is a key predictor of CKD, and 11% of individuals older than 65 years without hypertension or diabetes had stage 3 or worse CKD. Compared with GFR estimates, CCr estimates showed a steeper decline with age and were lower in non-Hispanic blacks. CKD is common and warrants improved detection and classification using standardized criteria to improve outcomes. Am J Kidney Dis 41:1-12. Copyright 2003 by the National Kidney Foundation, Inc.

  14. World Kidney Day 2016: averting the legacy of kidney disease-focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-04-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. Sociedad Argentina de Pediatría.

  15. World Kidney Day 2016: Averting the legacy of kidney disease-focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early, or who are small-for-date newborns, have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy-makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  16. Metabolomic Perfusate Analysis during Kidney Machine Perfusion: The Pig Provides an Appropriate Model for Human Studies

    PubMed Central

    Nath, Jay; Guy, Alison; Smith, Thomas B.; Cobbold, Mark; Inston, Nicholas G.; Hodson, James; Tennant, Daniel A.

    2014-01-01

    Introduction Hypothermic machine perfusion offers great promise in kidney transplantation and experimental studies are needed to establish the optimal conditions for this to occur. Pig kidneys are considered to be a good model for this purpose and share many properties with human organs. However it is not established whether the metabolism of pig kidneys in such hypothermic hypoxic conditions is comparable to human organs. Methods Standard criteria human (n = 12) and porcine (n = 10) kidneys underwent HMP using the LifePort Kidney Transporter 1.0 (Organ Recovery Systems) using KPS-1 solution. Perfusate was sampled at 45 minutes and 4 hours of perfusion and metabolomic analysis performed using 1-D 1H-NMR spectroscopy. Results There was no inter-species difference in the number of metabolites identified. Of the 30 metabolites analysed, 16 (53.3%) were present in comparable concentrations in the pig and human kidney perfusates. The rate of change of concentration for 3-Hydroxybutyrate was greater for human kidneys (p<0.001). For the other 29 metabolites (96.7%), there was no difference in the rate of change of concentration between pig and human samples. Conclusions Whilst there are some differences between pig and human kidneys during HMP they appear to be metabolically similar and the pig seems to be a valid model for human studies. PMID:25502759

  17. Urine biomarkers informative of human kidney allograft rejection and tolerance.

    PubMed

    Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

    2018-05-01

    We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

  18. Age and treatment of kidney failure.

    PubMed

    Elliott, Meghan J; Tam-Tham, Helen; Hemmelgarn, Brenda R

    2013-05-01

    This review discusses issues related to treatment of chronic kidney disease, and kidney failure in particular, among older adults. A substantial proportion of older adults have chronic kidney disease and progress to kidney failure. There is considerable variability in treatment practices for advanced kidney disease among older adults, and evidence that treatment decisions such as dialysis initiation may be made without adequate preparation. When initiated, survival among older adults on chronic dialysis remains poor, and is associated with a significant decline in functional status. There is also evidence to suggest that dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners, and underdeveloped conservative care programs in many centers. Kidney failure is common among older adults. When considering treatment options for kidney failure, patient priorities, preferences, and symptoms should be taken into account, using a shared decision-making approach.

  19. Cellular and subcellular localization of uncoupling protein 2 in the human kidney.

    PubMed

    Nigro, Michelangelo; De Sanctis, Claudia; Formisano, Pietro; Stanzione, Rosita; Forte, Maurizio; Capasso, Giovambattista; Gigliotti, Giuseppe; Rubattu, Speranza; Viggiano, Davide

    2018-06-23

    The uncoupling protein-2 (UCP2) is an anion transporter that plays a key role in the control of intracellular oxidative stress. In animal models UCP2 downregulation has several pathological sequelae, particularly affecting the vasculature and the kidney. Specifically, in these models kidney damage is highly favored in the absence of UCP2 in the context of experimental hypertension. Confirmations of these data in humans awaits further information, as no data are yet available concerning the cell-type and subcellular expression in the human kidney. In the present study, we aimed to characterize the UCP2 protein distribution in human kidney biopsies. In humans UCP2 is mainly localized in proximal convoluted tubule cells, with an intracytoplasmic punctate staining. UCP2 positive puncta are often localized at the interface between the endoplasmic reticulum and the mitochondria. Glomerular structures do not express UCP2 at detectable levels. The expression of UCP2 in proximal tubular cells may explain their relative propensity to damage in pathological conditions including the hypertensive disease.

  20. Awareness level of kidney functions and diseases among adults in a Nigerian population

    PubMed Central

    Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

    2015-01-01

    The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

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

    PubMed

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

    2009-01-01

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

  2. Editorial: World Kidney Day 2016: Averting the Legacy of Kidney Disease--Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. Copyright © 2016. Published by Elsevier Inc.

  3. Candidacy for Kidney Transplantation of Older Adults

    PubMed Central

    Grams, Morgan E.; Kucirka, Lauren M.; Hanrahan, Colleen F.; Montgomery, Robert A.; Massie, Allan B.; Segev, Dorry L.

    2013-01-01

    OBJECTIVES To develop a prediction model for kidney transplantation (KT) outcomes specific to older adults with end-stage renal disease (ESRD) and to use this model to estimate the number of excellent older KT candidates who lack access to KT. DESIGN Secondary analysis of data collected by the United Network for Organ Sharing and U.S. Renal Disease System. SETTING Retrospective analysis of national registry data. PARTICIPANTS Model development: Medicare-primary older recipients (aged ≥ 65) of a first KT between 1999 and 2006 (N = 6,988). Model application: incident Medicare-primary older adults with ESRD between 1999 and 2006 without an absolute or relative contraindication to transplantation (N = 128,850). MEASUREMENTS Comorbid conditions were extracted from U.S. Renal Disease System Form 2728 data and Medicare claims. RESULTS The prediction model used 19 variables to estimate post-KT outcome and showed good calibration (Hosmer–Lemeshow P = .44) and better prediction than previous population-average models (P < .001). Application of the model to the population with incident ESRD identified 11,756 excellent older transplant candidates (defined as >87% predicted 3-year post-KT survival, corresponding to the top 20% of transplanted older adults used in model development), of whom 76.3% (n = 8,966) lacked access. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for KT. CONCLUSION A risk-prediction model specific to older adults can identify excellent KT candidates. Appropriate referral could result in significantly greater rates of KT in older adults. PMID:22239290

  4. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide

    PubMed Central

    Williams, Robert C.; Opelz, Gerhard; Weil, E. Jennifer; McGarvey, Chelsea J.; Chakkera, Harini A.

    2017-01-01

    Background Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Methods Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. Results There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. Conclusions These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible. PMID:28573187

  5. The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide.

    PubMed

    Williams, Robert C; Opelz, Gerhard; Weil, E Jennifer; McGarvey, Chelsea J; Chakkera, Harini A

    2017-05-01

    Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

  6. Outcomes of adult dual kidney transplants by KDRI in the United States.

    PubMed

    Klair, T; Gregg, A; Phair, J; Kayler, L K

    2013-09-01

    UNOS guidelines provide inadequate discriminatory criteria for kidneys that should be transplanted as single (SKT) versus dual (DKT). We evaluated the utility of the kidney donor risk index (KDRI) to define kidneys with better outcomes when transplanted as dual. Using SRTR data from 1995 to 2010 of de novo KTX recipients of adult deceased-donor kidneys, we examined outcomes of SKT and DKT stratified by KDRI group ≤1.4 (n = 49 294), 1.41-1.8 (n = 15 674), 1.81-2.2 (n = 6523) and >2.2 (n = 2791). DKT of kidneys with KDRI >2.2 was associated with significantly better overall graft survival [adjusted hazard ratio (aHR) 0.83, 95% confidence interval (CI) 0.72-0.96] compared to single kidneys with KDRI >2.2. DKT was associated with significantly decreased odds of delayed graft function (top 2 KDRI categories) and significantly decreased odds of 1-year serum creatinine level >2 mg/dL (top 3 KDRI categories). Among SKT and DKT from KDRI >2.2 there were 16.1 and 13.9 graft losses per 100 patient follow-up years, respectively. KDRI >2.2 is a useful discriminatory cut-off for the determination of graft survival benefit with the use of DKT; however, the benefit of increased graft years was less than half of single kidneys from donors in the same KDRI range. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  7. Studying Kidney Disease Using Tissue and Genome Engineering in Human Pluripotent Stem Cells.

    PubMed

    Garreta, Elena; González, Federico; Montserrat, Núria

    2018-01-01

    Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids. Kidney organoids are three-dimensional (3D) kidney-like tissues, which are able to partially recapitulate kidney structure and function in vitro. The current possibility to combine state-of-the art tissue engineering with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated systems 9 (Cas9)-mediated genome engineering provides an unprecedented opportunity for studying kidney disease with hPSCs. Recently, hPSCs with genetic mutations introduced through CRISPR/Cas9-mediated genome engineering have shown to produce kidney organoids able to recapitulate phenotypes of polycystic kidney disease and glomerulopathies. This mini review provides an overview of the most recent advances in differentiation of hPSCs into kidney lineages, and the latest implementation of the CRISPR/Cas9 technology in the organoid setting, as promising platforms to study human kidney development and disease. © 2017 S. Karger AG, Basel.

  8. Kidney stones and subclinical atherosclerosis in young adults: the CARDIA study.

    PubMed

    Reiner, Alexander P; Kahn, Arnold; Eisner, Brian H; Pletcher, Mark J; Sadetsky, Natalia; Williams, O Dale; Polak, Joseph F; Jacobs, David R; Stoller, Marshall L

    2011-03-01

    Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. To our knowledge there has been no previous examination of the relationship between kidney stones and subclinical atherosclerotic disease. We studied the relationship between nephrolithiasis, and carotid wall thickness and carotid stenosis assessed by B-mode ultrasound in the general community using data from the CARDIA study. The CARDIA study is a United States, population based, observational study of 5,115 white and African-American men and women between the ages of 18 and 30 years at recruitment in 1985 to 1986. By the year 20 examination 200 (3.9%) CARDIA participants had reported ever having kidney stones. Symptomatic kidney stones were associated with greater carotid wall thickness measured at the year 20 examination, particularly of the internal carotid/bulb region. Using a composite dichotomous end point of carotid stenosis and/or the upper quartile of internal carotid/bulb wall thickness, the association of kidney stones with carotid atherosclerosis was significant (OR 1.6, 95% CI 1.1-2.3, p=0.01), even after adjusting for major atherosclerotic risk factors. The association between a history of kidney stones and subclinical carotid atherosclerosis in young adults adds further support to the notion that nephrolithiasis and atherosclerosis share common systemic risk factors and/or pathophysiology. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Soft 3D-Printed Phantom of the Human Kidney with Collecting System.

    PubMed

    Adams, Fabian; Qiu, Tian; Mark, Andrew; Fritz, Benjamin; Kramer, Lena; Schlager, Daniel; Wetterauer, Ulrich; Miernik, Arkadiusz; Fischer, Peer

    2017-04-01

    Organ models are used for planning and simulation of operations, developing new surgical instruments, and training purposes. There is a substantial demand for in vitro organ phantoms, especially in urological surgery. Animal models and existing simulator systems poorly mimic the detailed morphology and the physical properties of human organs. In this paper, we report a novel fabrication process to make a human kidney phantom with realistic anatomical structures and physical properties. The detailed anatomical structure was directly acquired from high resolution CT data sets of human cadaveric kidneys. The soft phantoms were constructed using a novel technique that combines 3D wax printing and polymer molding. Anatomical details and material properties of the phantoms were validated in detail by CT scan, ultrasound, and endoscopy. CT reconstruction, ultrasound examination, and endoscopy showed that the designed phantom mimics a real kidney's detailed anatomy and correctly corresponds to the targeted human cadaver's upper urinary tract. Soft materials with a tensile modulus of 0.8-1.5 MPa as well as biocompatible hydrogels were used to mimic human kidney tissues. We developed a method of constructing 3D organ models from medical imaging data using a 3D wax printing and molding process. This method is cost-effective means for obtaining a reproducible and robust model suitable for surgical simulation and training purposes.

  10. Defining the Molecular Character of the Developing and Adult Kidney Podocyte

    PubMed Central

    Brunskill, Eric W.; Georgas, Kylie; Rumballe, Bree; Little, Melissa H.; Potter, S. Steven

    2011-01-01

    Background The podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease. Methodology/Principal Findings In this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined. Conclusions/Significance The complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells. PMID:21931791

  11. [Effects of kidney-tonifying Chinese herbal drugs on human osteoblast Ca2+ intake and mineralization in vitro].

    PubMed

    Li, Juan; Wu, Wei-kang; Sun, Wei; Yu, Ke-qiang

    2004-12-01

    To study the effects of kidney-tonifying Chinese herbal drugs on Ca2+ intake and mineralization of human osteoblasts in vitro. Human osteoblasts were isolated from the iliac trabecular bone followed by purification and culture at 37 degrees Celsius with 5% CO2. The cells were identified by cell morphology, calcium nodule formation and alkaline phosphatase (ALP) activity assay. The third passage of the cultured osteoblasts were treated with 10% scrum from rat fed with the decoction of the kidney-tonifying Chinese herbal drugs of different concentrations for 30 min, 3 d and 28 d, respectively. The cells treated with 10% rat serum without the drugs served as the control. Flow cytometry was used to observe the changes in cell proliferation and intracellular Ca2+ concentration, and von Kossa staining employed for quantification of the mineral nodules. The osteoblasts obtained were positive for ALP staining and could form calcium nodules in vitro. Flow cytometry showed that the drugs at different concentrations all increased Ca2+ influx, as compared with the control cells. The drugs also increased the relative proliferation index of the osteoblasts, and high concentration of the drugs resulted in greater number of the mineral nodules in the osteoblasts (P<0.05). The kidney-tonifying Chinese herbal drugs may increase Ca2+ influx and stimulate proliferation and differentiation of adult osteoblasts in vitro.

  12. Transition of adolescent and young adult patients with childhood-onset chronic kidney disease from pediatric to adult renal services: a nationwide survey in Japan.

    PubMed

    Hattori, Motoshi; Iwano, Masayuki; Sako, Mayumi; Honda, Masataka; Okada, Hirokazu; Akioka, Yuko; Ashida, Akira; Kawasaki, Yukihiko; Kiyomoto, Hideyasu; Terada, Yoshio; Hirano, Daishi; Fujieda, Mikiya; Fujimoto, Shouichi; Masaki, Takao; Maruyama, Shoichi; Mastuo, Seiich

    2016-12-01

    Transition of adolescent and young adult (AYA) patients with childhood-onset chronic kidney diseases (C-CKD) from pediatric to adult renal services has received increasing attention. However, information on transition of Japanese patients with C-CKD is limited. The Transition Medicine Working Group, in collaboration with the Japanese Society for Nephrology, the Japanese Society for Pediatric Nephrology and the Japanese Society of Pediatric Urology, conducted a retrospective cross-sectional study in 2014 on issues concerning the transition of Japanese patients with C-CKD. Few institutions in Japan had transition programs and/or transition coordinators for patients with C-CKD. Refusal to transfer by patients or their families, lack of concern about transition and inability to decide on transfer were common reasons for non-transfer of patients still followed by pediatric renal services. Around 25 % of patients who had ended or interrupted follow-up by pediatric renal services presented to adult renal services because of symptoms associated with C-CKD. Patients with various types of childhood-onset nephrourological diseases were transferred from pediatric to adult renal services. IgA nephropathy, minimal change nephrotic syndrome and congenital anomalies of the kidney and urinary tract were the most frequent primary kidney diseases in adult patients with C-CKD. These survey results indicate the need for introduction of transitional care for Japanese AYA patients with C-CKD. Consensus guidelines for the optimal clinical management of AYA patients with C-CKD are required to ensure the continuity of care from child to adult renal services.

  13. History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

    PubMed

    Calderon-Margalit, Ronit; Golan, Eliezer; Twig, Gilad; Leiba, Adi; Tzur, Dorit; Afek, Arnon; Skorecki, Karl; Vivante, Asaf

    2018-02-01

    The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

  14. Morphology of human embryonic kidney cells in culture after space flight

    NASA Technical Reports Server (NTRS)

    Todd, P.; Kunze, M. E.; Williams, K.; Morrison, D. R.; Lewis, M. L.; Barlow, G. H.

    1985-01-01

    The ability of human embyronic kidney cells to differentiate into small epithelioid, large epithelioid, domed, and fenestrated morphological cell types following space flight is examined. Kidney cells exposed to 1 day at 1 g, then 1 day in orbit, and a 12 minute passage through the electrophoretic separator are compared with control cultures. The data reveal that 70 percent of small epithelioid, 16 percent of large epithelioid, 9 percent of dome-forming, and 5 percent of fenestrated cells formed in the space exposed cells; the distributions correlate well with control data. The formation of domed cells from cells cultured from low electrophoretic mobility fractions and small epithelioid cells from high mobility fractions is unaffected by space flight conditions. It is concluded that storage under microgravity conditions does not influence the morphological differentiation of human embryonic kidney cells in low-passage culture.

  15. Survival among older adults with kidney failure is better in the first three years with chronic dialysis treatment than not.

    PubMed

    Tam-Tham, Helen; Quinn, Robert R; Weaver, Robert G; Zhang, Jianguo; Ravani, Pietro; Liu, Ping; Thomas, Chandra; King-Shier, Kathryn; Fruetel, Karen; James, Matt T; Manns, Braden J; Tonelli, Marcello; Murtagh, Fliss E M; Hemmelgarn, Brenda R

    2018-05-23

    Comparisons of survival between dialysis and nondialysis care for older adults with kidney failure have been limited to those managed by nephrologists, and are vulnerable to lead and immortal time biases. So we compared time to all-cause mortality among older adults with kidney failure treated vs. not treated with chronic dialysis. Our retrospective cohort study used linked administrative and laboratory data to identify adults aged 65 or more years of age in Alberta, Canada, with kidney failure (2002-2012), defined by two or more consecutive outpatient estimated glomerular filtration rates less than 10 mL/min/1.73m 2 , spanning 90 or more days. We used marginal structural Cox models to assess the association between receipt of dialysis and all-cause mortality by allowing control for both time-varying and baseline confounders. Overall, 838 patients met inclusion criteria (mean age 79.1; 48.6% male; mean estimated glomerular filtration rate 7.8 mL/min/1.73m 2 ). Dialysis treatment (vs. no dialysis) was associated with a significantly lower risk of death for the first three years of follow-up (hazard ratio 0.59 [95% confidence interval 0.46-0.77]), but not thereafter (1.22 [0.69-2.17]). However, dialysis was associated with a significantly higher risk of hospitalization (1.40 [1.16-1.69]). Thus, among older adults with kidney failure, treatment with dialysis was associated with longer survival up to three years after reaching kidney failure, though with a higher risk of hospital admissions. These findings may assist shared decision-making about treatment of kidney failure. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  16. Incidence and characteristics of kidney stones in patients with horseshoe kidney: A systematic review and meta-analysis

    PubMed Central

    Pawar, Aditya S.; Thongprayoon, Charat; Cheungpasitporn, Wisit; Sakhuja, Ankit; Mao, Michael A.; Erickson, Stephen B.

    2018-01-01

    Introduction: The horseshoe kidney (HSK) is the most common type of renal fusion anomaly. The incidence and characteristics of kidney stones in patients with HSK are not well studied. The aim of this meta-analysis was to evaluate the incidence and types of kidney stones in patients with HSK. Methods: A systematic literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the databases' inception through November 2016. Studies assessing the incidence and types of kidney stones in patients with HSK were included. We applied a random-effects model to estimate the incidence of kidney stones. The study protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016052037). Results: A total of 14 observational studies with 943 patients (522 adults and 421 pediatric) with HSK were enrolled. The estimated pooled incidence of kidney stones was 36% (95% confidence interval [CI], 15%–59%) in adults with the HSK. Kidney stones were less common in pediatric patients with HSK with an estimated pooled incidence of 3% (95% CI, 2%–5%). The mean age of adult stone formers with HSK was 44.9 ± 6.2 years, and 75% were males. Within reported studies, 89.2% of kidney stones were calcium-based stones (64.2% calcium oxalate [CaOx], 18.8% calcium phosphate [CaP], and 6.2% mixed CaOx/CaP), followed by struvite stones (4.2%), uric acid stones (3.8%), and others (2.8%). Conclusions: Kidney stones are very common in adult patients with HSK with an estimated incidence of 36%. Calcium-based stones are the most prevalent kidney stones in adults with HSKs. These findings may impact the prevention and clinical management of kidney stones in patients with HSK. PMID:29416282

  17. MECHANISMS OF HUMAN KIDNEY STONE FORMATION

    PubMed Central

    Evan, Andrew P.; Worcester, Elaine M.; Coe, Fredric L.; Williams, James; Lingeman, James E.

    2014-01-01

    The precise mechanisms of kidney stone formation and growth are not completely known, even though human stone disease appears to be one of the oldest diseases known to medicine. With the advent of the new digital endoscope and detailed renal physiological studies performed on well phenotyped stone formers, substantial advances have been made in our knowledge of the pathogenesis of the most common type of stone former, the idiopathic calcium oxalate stone former (ICSF) as well as nine other stone forming groups. The observations from our group on human stone formers and those of others on model systems have suggested four entirely different pathways for kidney stone formation. Calcium oxalate stone growth over sites of Randall’s plaque appear to be the primary mode of stone formation for those patients with hypercalciuria. Overgrowths off the ends of Bellini duct plugs have been noted in most stone phenotypes, do they result in a clinical stone? Micro-lith formation does occur within the lumens of dilated inner medullary collecting ducts of cystinuric stone formers and appear to be confined to this space. Lastly, cystinuric stone formers also have numerous small, oval, smooth yellow appearing calyceal stones suggestive of formation in free solution. The scientific basis for each of these four modes of stone formation are reviewed and used to explore novel research opportunities. PMID:25108546

  18. Regenerating the kidney using human pluripotent stem cells and renal progenitors.

    PubMed

    Becherucci, Francesca; Mazzinghi, Benedetta; Allinovi, Marco; Angelotti, Maria Lucia; Romagnani, Paola

    2018-06-25

    Introduction Chronic kidney disease is a major healthcare problem worldwide and its cost is becoming no longer affordable. Indeed, restoring damaged renal structures or building a new kidney represent an ambitious and ideal alternative to renal replacement therapy. Streams of research have explored the possible application of pluripotent SCs (embryonic SCs and induced pluripotent SCs) in different strategies aimed at regenerate functioning nephrons and at understanding the mechanisms of kidney regeneration. Areas covered In this review, we will focus on the main potential applications of human pluripotent SCs to kidney regeneration, including those leading to rebuilding new kidneys or part of them (organoids, scaffolds, biological microdevices) as well as those aimed at understanding the pathophysiological mechanisms of renal disease and regenerative processes (modeling of kidney disease, genome editing). Moreover, we will discuss the role of endogenous renal progenitors cells in order to understand and promote kidney regeneration, as an attractive alternative to pluripotent SCs. Expert opinion Opportunities and pitfalls of all these strategies will be underlined, finally leading to the conclusion that a deeper knowledge of the biology of pluripotent SCs is mandatory, in order to allow us to hypothesize their clinical application.

  19. Indoxyl Sulfate Induces Apoptosis and Hypertrophy in Human Kidney Proximal Tubular Cells.

    PubMed

    Ellis, Robert J; Small, David M; Ng, Keng Lim; Vesey, David A; Vitetta, Luis; Francis, Ross S; Gobe, Glenda C; Morais, Christudas

    2018-06-01

    Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with declining kidney function. Although generally thought of as a consequence of declining kidney function, emerging evidence demonstrates direct cytotoxic role of IS on endothelial cells and cardiomyocytes, largely through the expression of pro-inflammatory and pro-fibrotic factors. The direct toxicity of IS on human kidney proximal tubular epithelial cells (PTECs) remains a matter of debate. The current study explored the effect of IS on primary cultures of human PTECs and HK-2, an immortalized human PTEC line. Pathologically relevant concentrations of IS induced apoptosis and increased the expression of the proapoptotic molecule Bax in both cell types. IS impaired mitochondrial metabolic activity and induced cellular hypertrophy. Furthermore, statistically significant upregulation of pro-fibrotic (transforming growth factor-β, fibronectin) and pro-inflammatory molecules (interleukin-6, interleukin-8, and tumor necrosis factor-α) in response to IS was observed. Albumin had no influence on the toxicity of IS. The results of this study suggest that IS directly induced a pro-inflammatory and pro-fibrotic phenotype in proximal tubular cells. In light of the associated apoptosis, hypertrophy, and metabolic dysfunction, this study demonstrates that IS may play a role in the progression of chronic kidney disease.

  20. World Kidney Day 2016 Averting The Legacy of Kidney Disease-Focus On Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  1. The directed differentiation of human iPS cells into kidney podocytes.

    PubMed

    Song, Bi; Smink, Alexandra M; Jones, Christina V; Callaghan, Judy M; Firth, Stephen D; Bernard, Claude A; Laslett, Andrew L; Kerr, Peter G; Ricardo, Sharon D

    2012-01-01

    The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm's tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine.

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

    PubMed

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

    2016-04-30

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

  3. Evaluation of urine biomarkers of kidney injury in Polycystic Kidney Disease

    PubMed Central

    Parikh, Chirag R.; Dahl, Neera K.; Chapman, Arlene; Bost, James E.; Edelstein, Charles L.; Comer, Diane M.; Zeltner, Raoul; Tian, Xin; Grantham, Jared J.; Somlo, Stefan

    2012-01-01

    Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of ADPKD. Here we evaluated the effect of these processes on the expression of NGAL and IL-18, markers of tubular injury, in rodent models and in the cyst fluid and urine of patients with ADPKD. Two mouse models where Pkd2 was inactivated which resulted in early or adult onset cysts, were used to evaluate NGAL levels. Further, the Han:SPRD rat model of polycystic disease was used to study IL-18 levels. In four annual serial urine samples from 107 patients with ADPKD in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) study, NGAL and IL-18 excretion rates were determined in conjunction with measures of total kidney volume and estimated GFR (eGFR) by the MDRD equation. Kidneys from affected mice and rats showed prominent expression of NGAL and IL-18/IL-18R, respectively, in epithelial cells lining kidney cysts. In human ADPKD cyst fluid, both NGAL and IL-18 were elevated. In CRISP patients, the mean percentage increase in total kidney volume was 5.4 /year and the mean decline in eGFR 2.4 mL/min/year. The trend of increased mean urine NGAL and IL-18 over three years was statistically significant; however, there was no association of tertiles of IL-18 or quartiles of NGAL and the change in total kidney volume or eGFR over this period. Thus, urinary NGAL and IL-18 excretion are mildly and stably elevated in ADPKD, but do not correlate with changes in total kidney volume or kidney function. This may be due, in part, to the lack of communication between individual cysts and the urinary collecting system in this disorder. PMID:22258321

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

    PubMed

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

    2015-12-07

    CKD affects an estimated 14% of adults in sub-Saharan Africa, but very little research has been done on the cause, progression, and prevention of CKD there. As part of the Human Heredity and Health in Africa (H3Africa) Consortium, the H3Africa Kidney Disease Research Network was established to study prevalent forms of kidney disease in sub-Saharan Africa and increase the capacity for genetics and genomics research. The study is performing comprehensive phenotypic characterization and analyzing environmental and genetic factors from nine clinical centers in four African countries (Ghana, Nigeria, Ethiopia, and Kenya) over a 5-year period. Approximately 4000 participants with specified kidney disease diagnoses and 4000 control participants will be enrolled in the four African countries. In addition, approximately 50 families with hereditary glomerular disease will be enrolled. The study includes both pediatric and adult participants age <1 to 74 years across a broad spectrum of kidney diseases secondary to hypertension-attributed nephropathy, diabetes, HIV infection, sickle cell disease, biopsy-proven glomerular disease, and CKD of unknown origin. Clinical and demographic data with biospecimens are collected to assess clinical, biochemical, and genetic markers of kidney disease. As of March 2015, a total of 3499 patients and controls have been recruited and 1897 had complete entry data for analysis. Slightly more than half (50.2%) of the cohort is female. Initial quality control of clinical data collection and of biosample and DNA analysis is satisfactory, demonstrating that a clinical research infrastructure can be successfully established in Africa. This study will provide clinical, biochemical, and genotypic data that will greatly increase the understanding of CKD in sub-Saharan Africa. Copyright © 2015 by the American Society of Nephrology.

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

    PubMed Central

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

    2013-01-01

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

  6. Definition and Facts for Kidney Stones in Adults

    MedlinePlus

    ... Eating, Diet, & Nutrition Clinical Trials Definition & Facts for Kidney Stones What are kidney stones? Kidney stones are hard, pebble-like pieces ... stone may get stuck along the way. Do kidney stones have another name? The scientific name for ...

  7. Cross-cultural adaptation of the Kidney Transplant Questionnaire for Chinese adult kidney allograft recipients.

    PubMed

    Niu, Yujian; Zhang, Wenxin; Chen, Hong; Mao, Sha; Yue, Yang; Zhang, Hongying; Li, Li; Sun, Ping; Wang, Jianli; Zhu, Xiongwei

    2017-06-01

    To provide a disease-specific instrument for evaluating the health-related quality life of Chinese kidney allograft recipients. Cross-cultural adaptation of the Kidney Transplant Questionnaire (KTQ) was performed by forward translation of the original English version into Chinese, followed by back translation and evaluation of the Chinese version by health care professionals, language professionals, and the translators. A total of 297 patients (110 women and 187 men; mean age, 43.91 ± 11.38 y; average time since transplant, 40.36 ± 32.86 mo) completed the Chinese versions of the KTQ and 36-Item Short Form Health Survey, and the results were used to evaluate the validity and reliability of the Chinese KTQ. The Cronbach α values for all KTQ dimensions were satisfactory (physical symptoms, α = 0.876; fatigue, α = 0.896; uncertainty/fear, α = 0.686; appearance, α = 0.701; and emotions, α = 0.886) and similar to values reported for the English and Spanish versions. The correlation coefficients among the dimensions of the Chinese KTQ ranged from 0.26 to 0.69, and those between the KTQ and 36-Item Short Form Health Survey physical component summary and mental component summary subscales were low and moderate to high, respectively, except for the appearance dimension. A good fit of the data in the confirmatory factor analysis indicated that the individual items of the translated instrument indeed evaluated the intended concepts. The Chinese version of the KTQ was found to be similarly valid and reliable compared with the original version and, thus, can be used to evaluate health-related quality of life among Chinese adult kidney allograft recipients. © 2017 John Wiley & Sons, Ltd.

  8. Low protein diets for chronic kidney disease in non diabetic adults.

    PubMed

    Fouque, Denis; Laville, Maurice

    2009-07-08

    For more than fifty years, low protein diets have been proposed to patients with kidney failure. However, the effects of these diets in preventing severe kidney failure and the need for maintenance dialysis have not been resolved. To determine the efficacy of low protein diets in delaying the need to start maintenance dialysis. Cochrane Renal Group studies register, the Cochrane Central Register of Controlled studies, MEDLINE, and EMBASE. Congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987). Direct contacts with investigators. Randomised studies comparing two different levels of protein intake in adult patients suffering from moderate to severe kidney failure, followed for at least one year. Two authors independently selected studies and extracted data. Statistical analyses were performed using the random effects model and the results expressed as risk ratio (RR) for dichotomous outcomes with 95% confidence intervals (CI). Collection of the number of "renal deaths" defined as the need for starting dialysis, the death of a patient or a kidney transplant during the study. Ten studies were identified from over 40 studies. A total of 2000 patients were analysed, 1002 had received reduced protein intake and 998 a higher protein intake. There were 281 renal deaths recorded, 113 in the low protein diet and 168 in the higher protein diet group (RR 0.68, 95% CI 0.55 to 0.84, P = 0.0002). To avoid one renal death, 2 to 56 patients need to be treated with a low protein diet during one year. Reducing protein intake in patients with chronic kidney disease reduces the occurrence of renal death by 32% as compared with higher or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.

  9. The Content and Quality of Health Information on the Internet for Patients and Families on Adult Kidney Cancer.

    PubMed

    Alsaiari, Ahmed; Joury, Abdulaziz; Aljuaid, Mossab; Wazzan, Mohammed; Pines, Jesse M

    2017-12-01

    The Internet is one of the major sources for health information for patients and their families, particularly when patients face serious life-threatening conditions such as kidney cancer in adults. In this study, we evaluate the content and quality of health information on adult kidney cancer using several validated instruments. We accessed the three most popular search engines (Google, Yahoo, Bing), using two terms: "kidney cancer" and "renal cell carcinoma," and reviewed the top 30 hits. After exclusion of duplicated websites, websites targeting health care professionals, and unrelated websites, 35 websites were included. Content was assessed using a 22-item checklist adapted from the American Cancer Society. We assessed website quality using the DISCERN questionnaire, HONcode and JAMA benchmark criteria, readability using three readability scores, and ALEXA for global traffic ranking systems. The average website had 16 of 22 content items while 6 websites fulfilled all 22 items. Among all websites, the average DISCERN quality score was 42 out of 80, 15 (42.8 %) of websites had HONcode certification, and only 3 (8.5 %) fulfilled all JAMA benchmark criteria. The average website readability was at the ninth grade reading level. The content and quality of health-related information on the Internet for adult kidney cancer are variable in comprehensiveness and quality. Many websites are difficult to read without a high school education. A standardized approach to presenting cancer information on the Internet for patients and families may be warranted.

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

    NASA Astrophysics Data System (ADS)

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

    2016-02-01

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

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

    PubMed Central

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

    2015-01-01

    The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. PMID:25568173

  12. Kidney (Renal Cell) Cancer—Patient Version

    Cancer.gov

    Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

  13. Averting the Legacy of Kidney Disease-Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-02-08

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy, including dialysis and transplantation, while only a minority of children may require this ultimate intervention.  Since there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. "For in every adult there dwells the child that was, and in every child there lies the adult that will be."-John Connolly, The Book of Lost Things.

  14. Urokinase production by electrophoretically separated cultured human embryonic kidney cells

    NASA Technical Reports Server (NTRS)

    Kunze, M. E.; Plank, L. D.; Giranda, V.; Sedor, K.; Todd, P. W.

    1985-01-01

    Urokinase is a plasminogen activator found in urine. Relatively pure preparations have been tested in Europe, Japan and the United States for the treatment of deep vein thrombosis and other dangerous blood clots. Human embryonic kidney cell cultures have been found to produce urokinase at much higher concentrations, but less than 5% of the cells in typical cultures are producers. Since human diploid cells become senescent in culture the selection of clones derived from single cells will not provide enough material to be useful, so a bulk purification method is needed for the isolation of urokinase producing cell populations. Preparative cell electrophoresis was chosen as the method, since evidence exists that human embryonic cell cultures are richly heterogeneous with respect to electrophoretic mobility, and preliminary electrophoretic separations on the Apollo-Soyuz space flight produced cell populations that were rich in urokinase production. Similarly, erythropoietin is useful in the treatment of certain anemias and is a kidney cell duct, and electrophoretically enriched cell populations producing this product have been reported. Thus, there is a clear need for diploid human cells that produce these products, and there is evidence that such cells should be separable by free-flow cell electrophoresis.

  15. Creatine synthesis: production of guanidinoacetate by the rat and human kidney in vivo.

    PubMed

    Edison, Erica E; Brosnan, Margaret E; Meyer, Christian; Brosnan, John T

    2007-12-01

    A fraction of the body's creatine and creatine phosphate spontaneously degrades to creatinine, which is excreted by the kidneys. In humans, this amounts to approximately 1-2 g/day and demands a comparable rate of de novo creatine synthesis. This is a two-step process in which l-arginine:glycine amidinotransferase (AGAT) catalyzes the conversion of glycine and arginine to ornithine and guanidinoacetate (GAA); guanidinoacetate methyltransferase (GAMT) then catalyzes the S-adenosylmethionine-dependent methylation of GAA to creatine. AGAT is found in the kidney and GAMT in the liver, which implies an interorgan movement of GAA from the kidney to the liver. We studied the renal production of this metabolite in both rats and humans. In control rats, [GAA] was 5.9 microM in arterial plasma and 10.9 microM in renal venous plasma for a renal arteriovenous (A-V) difference of -5.0 microM. In the rat, infusion of arginine or citrulline markedly increased renal GAA production but infusion of glycine did not. Rats fed 0.4% creatine in their diet had decreased renal AGAT activity and mRNA, an arterial plasma [GAA] of 1.5 microM, and a decreased renal A-V difference for GAA of -0.9 microM. In humans, [GAA] was 2.4 microM in arterial plasma, with a renal A-V difference of -1.1 microM. These studies show, for the first time, that GAA is produced by both rat and human kidneys in vivo.

  16. (Re)Building a Kidney

    PubMed Central

    Carroll, Thomas J.; Cleaver, Ondine; Gossett, Daniel R.; Hoshizaki, Deborah K.; Hubbell, Jeffrey A.; Humphreys, Benjamin D.; Jain, Sanjay; Jensen, Jan; Kaplan, David L.; Kesselman, Carl; Ketchum, Christian J.; Little, Melissa H.; McMahon, Andrew P.; Shankland, Stuart J.; Spence, Jason R.; Valerius, M. Todd; Wertheim, Jason A.; Wessely, Oliver; Zheng, Ying; Drummond, Iain A.

    2017-01-01

    (Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function. Projects within the consortium will answer fundamental questions regarding human gene expression in the developing kidney, essential signaling crosstalk between distinct cell types of the developing kidney, how to derive the many cell types of the kidney through directed differentiation of human pluripotent stem cells, which bioengineering or scaffolding strategies have the most potential for kidney tissue formation, and basic parameters of the regenerative response to injury. As these projects progress, the consortium will incorporate systematic investigations in physiologic function of in vitro and in vivo differentiated kidney tissue, strategies for engraftment in experimental animals, and development of therapeutic approaches to activate innate reparative responses. PMID:28096308

  17. Mutations in GREB1L Cause Bilateral Kidney Agenesis in Humans and Mice.

    PubMed

    De Tomasi, Lara; David, Pierre; Humbert, Camille; Silbermann, Flora; Arrondel, Christelle; Tores, Frédéric; Fouquet, Stéphane; Desgrange, Audrey; Niel, Olivier; Bole-Feysot, Christine; Nitschké, Patrick; Roume, Joëlle; Cordier, Marie-Pierre; Pietrement, Christine; Isidor, Bertrand; Khau Van Kien, Philippe; Gonzales, Marie; Saint-Frison, Marie-Hélène; Martinovic, Jelena; Novo, Robert; Piard, Juliette; Cabrol, Christelle; Verma, Ishwar C; Puri, Ratna; Journel, Hubert; Aziza, Jacqueline; Gavard, Laurent; Said-Menthon, Marie-Hélène; Heidet, Laurence; Saunier, Sophie; Jeanpierre, Cécile

    2017-11-02

    Congenital anomalies of the kidney and urinary tract (CAKUT) constitute a major cause of chronic kidney disease in children and 20% of prenatally detected anomalies. CAKUT encompass a spectrum of developmental kidney defects, including renal agenesis, hypoplasia, and cystic and non-cystic dysplasia. More than 50 genes have been reported as mutated in CAKUT-affected case subjects. However, the pathophysiological mechanisms leading to bilateral kidney agenesis (BKA) remain largely elusive. Whole-exome or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L (growth regulation by estrogen in breast cancer 1-like), a gene reported as a target of retinoic acid signaling. Four loss-of-function and 12 damaging missense variants, 14 being absent from GnomAD, were identified. Twelve of them were present in familial or simplex BKA-affected case subjects. Female BKA-affected fetuses also displayed uterus agenesis. We demonstrated a significant association between GREB1L variants and BKA. By in situ hybridization, we showed expression of Greb1l in the nephrogenic zone in developing mouse kidney. We generated a Greb1l knock-out mouse model by CRISPR-Cas9. Analysis at E13.5 revealed lack of kidneys and genital tract anomalies in male and female Greb1l -/- embryos and a slight decrease in ureteric bud branching in Greb1l +/- embryos. We showed that Greb1l invalidation in mIMCD3 cells affected tubulomorphogenesis in 3D-collagen culture, a phenotype rescued by expression of the wild-type human protein. This demonstrates that GREB1L plays a major role in early metanephros and genital development in mice and humans. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Nutritional Status in Adults with Predialysis Chronic Kidney Disease: KNOW-CKD Study.

    PubMed

    Hyun, Young Youl; Lee, Kyu Beck; Han, Seung Hyeok; Kim, Yeong Hoon; Kim, Yong Soo; Lee, Sung Woo; Oh, Yun Kyu; Chae, Dong Wan; Ahn, Curie

    2017-02-01

    Adverse changes in nutrition are prevalent and are strong indicators of adverse outcomes in patients with chronic kidney disease (CKD). The International Society of Renal Nutrition and Metabolism (ISRNM) proposed a common nomenclature and diagnostic criteria to identify protein-energy wasting (PEW) in CKD patients. We examined the nutritional status in 1,834 adults with predialysis CKD enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) study. As there was a need for further understanding of nutritional status and associated factors in CKD, we evaluated the prevalence and associated factors of PEW in adults with predialysis CKD. The prevalence of PEW was about 9.0% according to ISRNM criteria and tended to increase with advanced stage in predialysis CKD. Those who concurrently had PEW, inflammation, and CVD were a small proportion (0.4%). In multivariate logistic regression model, PEW was independently associated with estimated glomerular filtration rate (eGFR) (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-0.99), total CO₂ (OR, 0.93; 95% CI, 0.87-0.99), physical activity (OR, 0.43; 95% CI, 0.26-0.69), comorbid diabetes (OR, 1.68; 95% CI, 1.09-2.59), and high sensitivity C-reactive protein (hs-CRP) (OR, 1.03; 95% CI, 1.01-1.06). Our study suggests that PEW increases with advanced CKD stage. PEW is independently associated with renal function, low total CO₂, low physical activity, comorbid diabetes, and increased hs-CRP in adults with predialysis CKD.

  19. Clinical-Grade Isolated Human Kidney Perivascular Stromal Cells as an Organotypic Cell Source for Kidney Regenerative Medicine.

    PubMed

    Leuning, Daniëlle G; Reinders, Marlies E J; Li, Joan; Peired, Anna J; Lievers, Ellen; de Boer, Hetty C; Fibbe, Willem E; Romagnani, Paola; van Kooten, Cees; Little, Melissa H; Engelse, Marten A; Rabelink, Ton J

    2017-02-01

    Mesenchymal stromal cells (MSCs) are immunomodulatory and tissue homeostatic cells that have shown beneficial effects in kidney diseases and transplantation. Perivascular stromal cells (PSCs) identified within several different organs share characteristics of bone marrow-derived MSCs (BM-MSCs). These PSCs may also possess tissue-specific properties and play a role in local tissue homeostasis. We hypothesized that human kidney-derived PSCs (hkPSCs) would elicit improved kidney repair in comparison with BM-MSCs. Here we introduce a novel, clinical-grade isolation method of hkPSCs from cadaveric kidneys by enriching for the perivascular marker, NG2. hkPSCs show strong transcriptional similarities to BM-MSCs but also show organotypic expression signatures, including the HoxD10 and HoxD11 nephrogenic transcription factors. Comparable to BM-MSCs, hkPSCs showed immunosuppressive potential and, when cocultured with endothelial cells, vascular plexus formation was supported, which was specifically in the hkPSCs accompanied by an increased NG2 expression. hkPSCs did not undergo myofibroblast transformation after exposure to transforming growth factor-β, further corroborating their potential regulatory role in tissue homeostasis. This was further supported by the observation that hkPSCs induced accelerated repair in a tubular epithelial wound scratch assay, which was mediated through hepatocyte growth factor release. In vivo, in a neonatal kidney injection model, hkPSCs reintegrated and survived in the interstitial compartment, whereas BM-MSCs did not show this potential. Moreover, hkPSCs gave protection against the development of acute kidney injury in vivo in a model of rhabdomyolysis-mediated nephrotoxicity. Overall, this suggests a superior therapeutic potential for the use of hkPSCs and their secretome in the treatment of kidney diseases. Stem Cells Translational Medicine 2017;6:405-418. © 2016 The Authors Stem Cells Translational Medicine published by Wiley

  20. Averting the legacy of kidney disease--focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and chronic kidney disease in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of chronic kidney disease later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced chronic kidney disease in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplant, whereas only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. Copyright © 2016 World Kidney Day 2016 Steering Committee. Published by Elsevier Inc. All rights reserved.

  1. Polycystic kidney disease in a European roe deer (Capreolus capreolus).

    PubMed

    Blutke, Andreas; März, Kristian; Matenaers, Cyrill; Oswald, Karl; Hermanns, Walter; Wanke, Rüdiger

    2013-06-01

    A severe case of polycystic nephropathy was seen in an adult European roe deer (Capreolus capreolus), culled in a German hunting district. The doe had bilaterally drastically enlarged kidneys, completely riddled with variably sized, fluid-filled cysts of up to 4 cm in diameter. Histopathologic and ultrastructural examination revealed disseminated formation of cysts with flattened epithelial cell linings in the entire renal parenchyma, as well as severe dilations of renal tubules, marked interstitial fibrosis, nephron atrophy, and chronic interstitial lymphoplasmacytic infiltrations in the intercystic kidney tissue. These morphologic findings most likely resemble the hallmarks of autosomal dominant polycystic disease in humans, and present the first detailed description of a case of polycystic kidney disease in a roe deer.

  2. Effect of Coaching to Increase Water Intake on Kidney Function Decline in Adults With Chronic Kidney Disease: The CKD WIT Randomized Clinical Trial.

    PubMed

    Clark, William F; Sontrop, Jessica M; Huang, Shih-Han; Gallo, Kerri; Moist, Louise; House, Andrew A; Cuerden, Meaghan S; Weir, Matthew A; Bagga, Amit; Brimble, Scott; Burke, Andrew; Muirhead, Norman; Pandeya, Sanjay; Garg, Amit X

    2018-05-08

    In observational studies, increased water intake is associated with better kidney function. To determine the effect of coaching to increase water intake on kidney function in adults with chronic kidney disease. The CKD WIT (Chronic Kidney Disease Water Intake Trial) randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 (last day of follow-up, May 25, 2017). Patients had stage 3 chronic kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m2 and microalbuminuria or macroalbuminuria) and a 24-hour urine volume of less than 3.0 L. Patients in the hydration group (n = 316) were coached to drink more water, and those in the control group (n = 315) were coached to maintain usual intake. The primary outcome was change in kidney function (eGFR from baseline to 12 months). Secondary outcomes included 1-year change in plasma copeptin concentration, creatinine clearance, 24-hour urine albumin, and patient-reported overall quality of health (0 [worst possible] to 10 [best possible]). Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group [n = 5]; control group [n = 7]). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was -2.2 mL/min/1.73 m2 in the hydration group and -1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, -0.3 mL/min/1.73 m2 [95% CI, -1.8 to 1.2; P = .74]). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, -2.2 pmol/L (95% CI, -3.9 to -0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, -4 to 51; P = .11); and quality of health, 0.2 points (95% CI, -0

  3. Averting the legacy of kidney disease - Focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  4. Averting the legacy of kidney disease: focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-04-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  5. Averting the Legacy of Kidney Disease - Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 S. Karger AG, Basel.

  6. Averting the legacy of kidney disease - focus on childhood.

    PubMed

    Ingelfinger, J R; Kalantar-Zadeh, K; Schaefer, F

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  7. Averting the Legacy of Kidney Disease - Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 S. Karger AG, Basel.

  8. Averting the Legacy of Kidney Disease: Focus on Childhood.

    PubMed

    Ingelfinger, J R; Kalantar-Zadeh, K; Schaefer, F

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policymakers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  9. Averting the legacy of kidney disease: focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-06-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  10. Averting the legacy of kidney disease - focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-04-08

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group amongst children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertensionand CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help to detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, whilst only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic oreconomic circumstances. Our hope is that World Kidney Day will inform the general public, policymakers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  11. Averting the Legacy of Kidney Disease - Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-04-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

  12. Averting the Legacy of Kidney Disease--Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. © 2016 S. Karger AG, Basel.

  13. Averting the legacy of kidney disease-focus on childhood.

    PubMed

    Ingelfinger, Julie R; Schaefer, Franz; Kalantar-Zadeh, Kamyar

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duangtum, Natapol; Department of Anatomy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700; Junking, Mutita

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

  15. Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction

    PubMed Central

    ASAHINA, Makoto; SHIMIZU, Fumi; OHTA, Masayuki; TAKEYAMA, Michiyasu; TOZAWA, Ryuichi

    2015-01-01

    Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome. PMID:25912321

  16. Human apolipoprotein B transgenic SHR/NDmcr-cp rats show exacerbated kidney dysfunction.

    PubMed

    Asahina, Makoto; Shimizu, Fumi; Ohta, Masayuki; Takeyama, Michiyasu; Tozawa, Ryuichi

    2015-01-01

    Nephropathy frequently co-occurs with metabolic syndrome in humans. Metabolic syndrome is a cluster of metabolic diseases including obesity, diabetes, hypertension, and dyslipidemia, and some previous studies revealed that dyslipidemia contributes to the progression of kidney dysfunction. To establish a new nephropathy model with metabolic syndrome, we produced human apolipoprotein B (apoB) transgenic (Tg.) SHR/NDmcr-cp (SHR-cp/cp) rats, in which dyslipidemia is exacerbated more than in an established metabolic syndrome model, SHR-cp/cp rats. Human apoB Tg. SHR-cp/cp rats showed obesity, hyperinsulinemia, hypertension, and severe hyperlipidemia. They also exhibited exacerbated early-onset proteinuria, accompanied by increased kidney injury and increased oxidative and inflammatory markers. Histological analyses revealed the characteristic features of human apoB Tg. SHR-cp/cp rats including prominent glomerulosclerosis with lipid accumulation. Our newly established human apoB Tg. SHR-cp/cp rat could be a useful model for the nephropathy in metabolic syndrome and for understanding the interaction between dyslipidemia and renal dysfunction in metabolic syndrome.

  17. Community-acquired acute kidney injury in adults in Africa.

    PubMed

    Adu, Dwomoa; Okyere, Perditer; Boima, Vincent; Matekole, Michael; Osafo, Charlotte

    We review recent published data on demographics, causes, diagnoses, treatment, and outcome of acute kidney injury (AKI) in Africa. A review of the incidence, etiology, diagnoses, and treatment of AKI in adults in Africa from studies published between the years 2000 and 2015. The incidence of AKI in hospitalized patients in Africa ranges from 0.3 to 1.9% in adults. Between 70 and 90% of cases of AKI are community acquired. Most patients with AKI are young with a weighted mean age of 41.3 standard deviation (SD) 9.3 years, and a male to female ratio of 1.2 : 1.0. Medical causes account for between 65 and 80% of causes of AKI. This is followed by obstetric causes in 5 - 27% of cases and surgical causes in 2 - 24% of cases. In the reported studies, between 17 and 94% of patients who needed dialysis received this. The mortality of AKI in adults in Africa ranged from 11.5 to 43.5%. Most reported cases of AKI in Africa originate in the community. The low incidence of hospital-acquired AKI is likely to be due to under ascertainment. Most patients with AKI in Africa are young and have a single precipitating cause. Prominent among these are infection, pregnancy complications and nephrotoxins. Early treatment can improve clinical outcomes.

  18. Impact of end-stage kidney disease on academic achievement and employment in young adults: a mixed methods study.

    PubMed

    Murray, Peter D; Dobbels, Fabienne; Lonsdale, Daniel C; Harden, Paul N

    2014-10-01

    Young adult kidney patients are at an important stage of development when end-stage kidney disease (ESKD) may adversely influence progress in education and employment. This study is designed to assess the impact of ESKD on education and employment outcomes in young adults. This cross-sectional study was a mixed methods design. Education and career achievements in young adults with ESKD were recorded quantitatively using a questionnaire survey (n = 57): 14 of 57 representative participants were subsequently selected for semistructured interview. Questionnaire survey was conducted in 57 young adults (median age 25): 8.8% (n = 5) were predialysis; 14.0% (n = 8) dialysis; and 78.9% (n = 45) were kidney transplant recipients. Median school-leaving age was 16 (interquartile range = 15-19). Of 57 young adults, 10 (17.5%) were still studying, 43 (75.4%) had completed education, 34 (59.7%) were employed (23 full time and 11 part time), and 19 (33.3%) were unemployed. Twenty-seven of 45 transplanted patients were employed (60.0%). Of these 27, 21 were full time (77.8%). Five of eight dialysis patients were employed: only one of eight was full-time employed (12.5%). Themes impacting on education and employment included low energy levels, time missed, loss of self-esteem, and feelings of loneliness and isolation, which may progress to depression and recreational drug use. Lack of understanding from educators and employers resulting in lost work, and career ambitions changed or limited because of dialysis. Dialysis has a major negative impact on education and reduced employment rates of young adults. There is a general lack of understanding among educators and employers of the impact of ESKD. Low energy levels, lack of self-esteem, and depression are key factors. There is a need for health care providers to recognize this issue and invest in supporting young adults with ESKD. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights

  19. [Calcium and magnesium concentrations in "Healthy" and lithiasic human kidney (author's transl)].

    PubMed

    Terhorst, B; Stoeppler, M

    1976-07-01

    Calcium and magnesium levels in the cortex, medulla, and papilla of human kidney from 32 so-called healthy patients and from eleven patients with calcium-oxalate lithiasis were determined by atom-absorption spectralphotometry. A positive calcium gradient with the highest calcium concentration in the papilla was found in all kidneys. Compared to the control group, that calcium concentration in the lithiasic kidneys was reduced by 50% in the papilla, but in the cortex and medulla, the levels were the same. A relative depletion of calcium in the papilla in hypercalciuria goes against the theory that the papilla is the main center of development of calcium-containing stones. The magnesium concentration was practically the same in cortex, medulla, and papilla, and no significant difference was found between lithiasic and healthy kidneys. These findings underline the central role of calcium in the genesis of calcium-containing stones.

  20. 9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

    PubMed

    Asciak, C P; Domazet, Z

    1975-02-20

    1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

  1. Dual kidneys from marginal adult donors as a source for cadaveric renal transplantation in the United States.

    PubMed

    Bunnapradist, Suphamai; Gritsch, H Albin; Peng, Alice; Jordan, Stanley C; Cho, Yong W

    2003-04-01

    The current organ shortage has led to the utilization of double kidney transplants from marginal adult donors, but outcomes data are limited. The United Network for Organ Sharing registry database was used to compare the outcomes of 403 dual adult kidney transplantations (DKT) and 11,033 single kidney transplantations (SKT) from 1997 to 2000. Graft and patient survival and the effect of multiple risk factors were evaluated. It was found that DKT patients were older, less sensitized, and received grafts from older, more mismatched donors with longer cold ischemia times. There was also a greater percentage of donors with a history of diabetes or hypertension and African-American recipients and donors in the DKT group. Graft survival was inferior in the DKT group, with a 7% lower graft survival rate at 1 yr. There was a higher incidence of primary nonfunction in the DKT group, although the incidence of delayed graft function, early rejection treatment, and graft thrombosis did not differ. Multivariate analysis was used to identify African-American recipient ethnicity and retransplant as risk factors for graft loss. Graft survival was comparable in DKT and SKT with donors over 55 yr of age. DKT resulted in inferior graft outcomes compared with SKT. When compared with SKT with donors over 55 yr of age, DKT resulted in similar graft outcomes. These otherwise discarded kidneys should be cautiously considered as a source of marginal donors.

  2. The State of the Human Proteome in 2013 as viewed through PeptideAtlas: Comparing the Kidney, Urine, and Plasma Proteomes for the Biology and Disease-driven Human Proteome Project

    PubMed Central

    Farrah, Terry; Deutsch, Eric W.; Omenn, Gilbert S.; Sun, Zhi; Watts, Julian D.; Yamamoto, Tadashi; Shteynberg, David; Harris, Micheleen M.; Moritz, Robert L.

    2014-01-01

    The kidney, urine, and plasma proteomes are intimately related: proteins and metabolic waste products are filtered from the plasma by the kidney and excreted via the urine, while kidney proteins may be secreted into the circulation or released into the urine. Shotgun proteomics datasets derived from human kidney, urine, and plasma samples were collated and processed using a uniform software pipeline, and relative protein abundances were estimated by spectral counting. The resulting PeptideAtlas builds yielded 4005, 2491, and 3553 nonredundant proteins at 1% FDR for the kidney, urine, and plasma proteomes, respectively—for kidney and plasma, the largest high-confidence protein sets to date. The same pipeline applied to all available human data yielded a 2013 Human PeptideAtlas build containing 12,644 nonredundant proteins and at least one peptide for each of ~14,000 Swiss-Prot entries, an increase over 2012 of ~7.5% of the predicted human proteome. We demonstrate that abundances are correlated between plasma and urine, examine the most abundant urine proteins not derived from either plasma or kidney, and consider the biomarker potential of proteins associated with renal decline. This analysis forms part of the Biology and Disease-driven Human Proteome Project (B/D-HPP) and a contribution to the Chromosome-centric Human Proteome Project (C-HPP) special issue. PMID:24261998

  3. Cyclosporine and Vancomycin + Amikacin Induced Hot Kidney Appearance in a Young Adult and a Pediatric Patient.

    PubMed

    Çayır, Derya; Araz, Mine; Filik, Mustafa; Erdoğan, Mehmet

    2017-10-03

    The appearance of a hot kidney on bone scintigraphy is rare and can be seen due to various factors. In our clinic, we observed hot kidney appearance in two patients to whom technetium-99m methylene diphosphonate (Tc-99m MDP) whole body scan has been performed: a young male adult at the age of 18 who was diagnosed with acute lymphocytic leukemia with a presumptive diagnosis of avascular necrosis, and a 9-year-old girl with cystitis for a pre-diagnosis of osteomyelitis. The first patient had a history of cyclosporine usage and the second patient was being treated with amikacin + vancomycin. To the best of our knowledge, we present the first cases where hot-kidney appearance on Tc-99m MDP whole body scan due to the use of cyclosporin and amikacin + vancomycin is demonstrated.

  4. Ghrelin and cachexia in chronic kidney disease.

    PubMed

    Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; Nakamura, Norifumi; Inui, Akio

    2013-04-01

    Ghrelin is a growth hormone (GH) secretagogue and a potent orexigenic factor that stimulates feeding by interacting with hypothalamic feeding-regulatory nuclei. Its multifaceted effects are potentially beneficial as a treatment in human disease states. In both adult and pediatric chronic kidney disease (CKD) patients, decreased appetite plays a major role in wasting, which in turn is linked to morbidity and mortality; wasting has also been linked to high levels of leptin and proinflammatory cytokines. The beneficial effects of ghrelin treatment in CKD are potentially mediated by multiple concurrent actions, including the stimulation of appetite-regulating centers, anti-inflammatory effects, and direct kidney effects. Further evaluation of this appetite-regulating hormone in CKD is needed to confirm previous findings and to determine the underlying mechanisms.

  5. At Risk for Kidney Disease?

    MedlinePlus

    ... in Adults Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Pour les personnes atteintes de diabète ou d’hypertension artérielle Heart Disease Mineral & Bone Disorder Causes of Chronic Kidney ...

  6. Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010

    PubMed Central

    Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K.; Kramer, Holly; Rosas, Sylvia E.; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L.

    2016-01-01

    Objective Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. Methods We analyzed data from the NHANES 1999–2010 for 6918 young adults ages 20–40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Results Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6–12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Conclusion Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease. PMID:27224643

  7. MicroRNA profiling of human kidney cancer subtypes.

    PubMed

    Petillo, David; Kort, Eric J; Anema, John; Furge, Kyle A; Yang, Ximing J; Teh, Bin Tean

    2009-07-01

    Although the functions of most of the identified microRNAs (miRNAs) have yet to be determined, their use as potential biomarkers has been considered in several human diseases and cancers. In order to understand their role in renal tumorigenesis, we screened the expression levels of miRNAs in four subtypes of human renal neoplasms: clear cell, papillary, and chromophobe renal cell carcinomas (RCC) as well as benign renal oncocytomas. We found a unique miRNA signature for each subtype of renal tumor. Furthermore, we identified unique patterns of miRNA expression distinguishing clear cell RCC cases with favorable vs. unfavorable outcome. Specifically, we documented the overexpression of miRs 424 and 203 in clear cell RCC relative to papillary RCC, as well as the inversion of expression of miR-203 in the benign oncocytomas (where it is underexpressed relative to normal kidney) as compared to the malignant chromophobe RCC (where it is overexpressed relative to normal kidney). Our results further suggest that overexpression of S-has-miR-32 is associated with poor outcome. While previous studies have identified unique miRNA expression pattern distinguishing tumors from different anatomical locations, here we extend this principle to demonstrate the utility of miRNA expression profiling to identify a signature unique to various tumor subtypes at a single anatomic locus.

  8. Access to kidney transplantation in European adults aged 75-84 years and related outcomes: an analysis of the European Renal Association-European Dialysis and Transplant Association Registry.

    PubMed

    Pippias, Maria; Stel, Vianda S; Kramer, Anneke; Abad Diez, Jose M; Aresté-Fosalba, Nuria; Ayav, Carole; Buturovic, Jadranka; Caskey, Fergus J; Collart, Frederic; Couchoud, Cécile; De Meester, Johan; Heaf, James G; Helanterä, Ilkka; Hemmelder, Marc H; Kostopoulou, Myrto; Noordzij, Marlies; Pascual, Julio; Palsson, Runolfur; Reisaeter, Anna Varberg; Traynor, Jamie P; Massy, Ziad; Jager, Kitty J

    2018-05-01

    To what extent access to, and allocation of kidney transplants and survival outcomes in patients aged ≥75 years have changed over time in Europe is unclear. We included patients aged ≥75-84 years (termed older adults) receiving renal replacement therapy in thirteen European countries between 2005 and 2014. Country differences and time trends in access to, and allocation of kidney transplants were examined. Survival outcomes were determined by Cox regression analyses. Between 2005 and 2014, 1392 older adult patients received 1406 transplants. Access to kidney transplantation varied from ~0% (Slovenia, Greece and Denmark) to ~4% (Norway and various Spanish regions) of all older adult dialysis patients, and overall increased from 0.3% (2005) to 0.9% (2014). Allocation of kidney transplants to older adults overall increased from 0.8% (2005) to 3.2% (2014). Seven-year unadjusted patient and graft survival probabilities were 49.1% (95% confidence interval, 95% CI: 43.6; 54.4) and 41.7% (95% CI: 36.5; 46.8), respectively, with a temporal trend towards improved survival outcomes. In conclusion, in the European dialysis population aged ≥75-84 years access to kidney transplantation is low, and allocation of kidney transplants remains a rare event. Though both are increasing with time and vary considerably between countries. The trend towards improved survival outcomes is encouraging. This information can aid informed decision-making regarding treatment options. © 2018 Steunstichting ESOT.

  9. In vitro regeneration of kidney from pluripotent stem cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Osafune, Kenji, E-mail: osafu@cira.kyoto-u.ac.jp; PRESTO, Japan Science and Technology Agency; JST Yamanaka iPS Cell Special Project, Japan Science and Technology Agency

    2010-10-01

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

  10. Acute Kidney Injury in the Elderly

    PubMed Central

    Abdel-Kader, Khaled; Palevsky, Paul

    2009-01-01

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

  11. Nitraria retusa fruit prevents penconazole-induced kidney injury in adult rats through modulation of oxidative stress and histopathological changes.

    PubMed

    Chaâbane, Mariem; Koubaa, Mohamed; Soudani, Nejla; Elwej, Awatef; Grati, Malek; Jamoussi, Kamel; Boudawara, Tahia; Ellouze Chaabouni, Semia; Zeghal, Najiba

    2017-12-01

    Nitraria retusa (Forssk.) Asch. (Nitrariaceae) is a medicinal plant which produces edible fruits whose antioxidant activity has been demonstrated. The current study elucidates the potential protective effect of N. retusa fruit aqueous extract against nephrotoxicity induced by penconazole, a triazole fungicide, in the kidney of adult rats. Adult Wistar rats were exposed either to penconazole (67 mg/kg body weight), or to N. retusa extract (300 mg/kg body weight) or to their combination. Penconazole was administered by intra-peritoneal injection every 2 days from day 7 until day 15, the sacrifice day, while N. retusa extract was administered daily by gavage during 15 days. Oxidative stress parameters, kidney biomarkers and histopathological examination were determined. Nitraria retusa extract administration to penconazole treated rats decreased kidney levels of malondialdehyde (-10%), hydrogen peroxide (-12%), protein carbonyls (PCOs, -11%) and advanced oxidation protein products (AOPP, -16%); antioxidant enzyme activities: catalase (-13%), superoxide dismutase (-8%) and glutathione peroxidase (GPx, -14%), and the levels of non-enzymatic antioxidants: non-protein thiols (-9%), glutathione (-7%) and metallothionein (-12%). Furthermore, this plant extract prevented kidney biomarker changes by reducing plasma levels of creatinine, urea, uric acid and LDH and increasing those of ALP and GGT. Histopathological alterations induced by penconazole (glomeruli fragmentation, Bowman's space enlargement, tubular epithelial cells necrosis and infiltration of inflammatory leucocytes) were attenuated following N. retusa administration. Our results indicated that N. retusa fruit extract had protective effects against penconazole-induced kidney injury, which could be attributed to its phenolic compounds.

  12. Kidney regeneration and stem cells.

    PubMed

    Takaori, Koji; Yanagita, Motoko

    2014-01-01

    The kidney has the capacity to recover from ischemic and toxic insults. Although there has been debate about the origin of cells that replace injured epithelial cells, it is now widely recognized that intrinsic surviving tubular cells are responsible for the repair. On the other hand, the cells, which have stem cell-like characteristics, have been isolated in the kidney using various methods, but it remains unknown if these stem cells actually exist in the adult kidney and if they are involved in kidney regeneration. This review will focus on the pathophysiology of kidney regeneration and the contribution of renal stem cells. We also discuss possible therapeutic applications to kidney disease. Copyright © 2013 Wiley Periodicals, Inc.

  13. AAV9-mediated engineering of autotransplanted kidney of non-human primates.

    PubMed

    Tomasoni, S; Trionfini, P; Azzollini, N; Zentilin, L; Giacca, M; Aiello, S; Longaretti, L; Cozzi, E; Baldan, N; Remuzzi, G; Benigni, A

    2017-05-01

    Ex vivo gene transfer to the graft before transplantation is an attractive option for circumventing systemic side effects of chronic antirejection therapy. Gene delivery of the immunomodulatory protein cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) prevented chronic kidney rejection in a rat model of allotransplantation without the need for systemic immunosuppression. Here we generated adeno-associated virus type 2 (AAV2) and AAV9 vectors encoding for LEA29Y, an optimized version of CTLA4-Ig. Both LEA29Y vectors were equally efficient for reducing T-cell proliferation in vitro. Serotype 9 was chosen for in vivo experiments owing to a lower frequency of preformed antibodies against the AAV9 capsid in 16 non-human primate tested sera. AAV9-LEA29Y was able to transduce the kidney of non-human primates in an autotransplantation model. Expression of LEA29Y mRNA by renal cells translated into the production of the corresponding protein, which was confined to the graft but not detected in serum. Results in non-human primates represent a step forward in maintaining the portability of this strategy into clinics.

  14. Ultrasensitive sensor for detection of early stage chronic kidney disease in human.

    PubMed

    Desai, Dignya; Kumar, Ashok; Bose, Debajyoti; Datta, Manali

    2018-05-15

    A facile label free, ultrasensitive platform for a rapid detection of chronic kidney disease has been fabricated. Early intervention in patients with chronic kidney disease has the potential to delay, or even prevent, the development of end stage renal disease and complications, leading to a marked impact on life expectancy and quality of life. Thus, a potable electrochemical diagnostic biosensor has become an attractive option as electrochemical analysis is feasible to use for on-site detection of samples. In human, Cystatin C present in human body fluids is freely filtered by the glomerulus, but reabsorbed and catabolised by the renal tubules. Trace detectable amount is eliminated in urine, giving this molecular marker an edge over serum creatinine's disadvantages. A carboxyl functionalized multiwalled carbon nanotubes screen printed electrode was immobilized with papain (cysteine protease) where amino group of papain covalently bound carboxyl group on electrode surface by EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) and NHS (N-hydroxysuccinimide) chemistry. The modifications on sensor surface were characterized by field emission scanning electron microscopy. Interaction between papain and chronic kidney disease specific biomarker, Cystatin C was detected by cyclic voltammetry and differential pulse voltammetry within 10min. The sensor is highly specific to Cystatin C and showed negligible response to non-specific macromolecules present in urine. The sensitivity of the sensor was 1583.49µAcm -2 µg -1 and lower limit of detection of Cystatin C was found 0.58ngL -1 which presents as a promising platform for designing potable kidney disease detector. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. [The history of kidney transplantation].

    PubMed

    Hatzinger, M; Stastny, M; Grützmacher, P; Sohn, M

    2016-10-01

    The history of kidney transplantation is a history of many unsuccessful efforts and setbacks, but also the history of perseverance, pioneering spirit, and steadfast courage. The first successful transplantation of a dog kidney was done by the Austrian Emerich Ullmann (1861-1937) in 1902. The kidney was connected to the carotid artery of the dog and the ureter ended freely. The organ produced urine for a couple of days before it died. In 1909, there were efforts to transplant human kidneys from deceased patients to monkeys and in the following year the first xenotransplantation in humans was completed. Different kinds of donors were tried: dogs, monkeys, goats and lambs, all without success. In 1939, the first transplantation from a deceased human donor was done by the Russion Yurii Voronoy, the patient survived for only a couple of days, and the organ never worked. In 1953, the first temporarily successful transplantation of a human kidney was performed by Jean Hamburger in Paris. A 16-year-old boy received the kidney of his mother as living donor transplantation. Then in 1954, a milestone was made with the first long-term successful kidney transplantation by Joseph Murray: the transplantation was done between monozygotic twins; the organ survived for 8 years. For his efforts in kidney transplantation, Murray was honored with the Nobel Prize in medicine in 1990. In 1962, the first kidney transplantation between genetically nonrelated patients was done using immunosuppression and in 1963 the first kidney transplantation in Germany was done by Reinhard Nagel and Wilhelm Brosig in Berlin. The aim of this article is to present the history of kidney transplantation from the beginning until today.

  16. Polycystic kidney disease at Howard University Hospital.

    PubMed

    Hosten, A O; Cummings, Y

    1977-08-01

    Adult polycystic kidney disease treatment at Howard University Hospital is summarized. The cases are taken from autopsies performed between January 1955 and November 1975 and from the Hospital's dialysis population. Polycystic kidney disease was identified in six adults and four infants. Only two dialysis patients were clinically thought to have the disease. A review of the major clinical features of the disease is presented.

  17. Molecular markers of trichloroethylene-induced toxicity in human kidney cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lash, Lawrence H.; Putt, David A.; Hueni, Sarah E.

    Difficulties in evaluation of trichloroethylene (TRI)-induced toxicity in humans and extrapolation of data from laboratory animals to humans are due to the existence of multiple target organs, multiple metabolic pathways, sex-, species-, and strain-dependent differences in both metabolism and susceptibility to toxicity, and the lack or minimal amount of human data for many target organs. The use of human tissue for mechanistic studies is thus distinctly advantageous. The kidneys are one target organ for TRI and metabolism by the glutathione (GSH) conjugation pathway is responsible for nephrotoxicity. The GSH conjugate is processed further to produce the cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC),more » which is the penultimate nephrotoxic species. Confluent, primary cultures of human proximal tubular (hPT) cells were used as the model system. Although cells in log-phase growth, which are undergoing more rapid DNA synthesis, would give lower LD{sub 50} values, confluent cells more closely mimic the in vivo proximal tubule. DCVC caused cellular necrosis only at relatively high doses (>100 {mu}M) and long incubation times (>24 h). In contrast, both apoptosis and enhanced cellular proliferation occurred at relatively low doses (10-100 {mu}M) and early incubation times (2-8 h). These responses were associated with prominent changes in expression of several proteins that regulate apoptosis (Bcl-2, Bax, Apaf-1, Caspase-9 cleavage, PARP cleavage) and cellular growth, differentiation and stress response (p53, Hsp27, NF-{kappa}B). Effects on p53 and Hsp27 implicate function of protein kinase C, the mitogen activated protein kinase pathway, and the cytoskeleton. The precise pattern of expression of these and other proteins can thus serve as molecular markers for TRI exposure and effect in human kidney.« less

  18. GDF11 induces kidney fibrosis, renal cell epithelial-to-mesenchymal transition, and kidney dysfunction and failure.

    PubMed

    Pons, Marianne; Koniaris, Leonidas G; Moe, Sharon M; Gutierrez, Juan C; Esquela-Kerscher, Aurora; Zimmers, Teresa A

    2018-05-03

    GDF11 modulates embryonic patterning and kidney organogenesis. Herein, we sought to define GDF11 function in the adult kidney and in renal diseases. In vitro renal cell lines, genetic, and murine in vivo renal injury models were examined. Among tissues tested, Gdf11 was highest in normal adult mouse kidney. Expression was increased acutely after 5/6 nephrectomy, ischemia-reperfusion injury, kanamycin toxicity, or unilateral ureteric obstruction. Systemic, high-dose GDF11 administration in adult mice led to renal failure, with accompanying kidney atrophy, interstitial fibrosis, epithelial-to-mesenchymal transition of renal tubular cells, and eventually death. These effects were associated with phosphorylation of SMAD2 and could be blocked by follistatin. In contrast, Gdf11 heterozygous mice showed reduced renal Gdf11 expression, renal fibrosis, and expression of fibrosis-associated genes both at baseline and after unilateral ureteric obstruction compared with wild-type littermates. The kidney-specific consequences of GDF11 dose modulation are direct effects on kidney cells. GDF11 induced proliferation and activation of NRK49f renal fibroblasts and also promoted epithelial-to-mesenchymal transition of IMCD-3 tubular epithelial cells in a SMAD3-dependent manner. Taken together, these data suggest that GDF11 and its downstream signals are critical in vivo mediators of renal injury. These effects are through direct actions of GDF11 on renal tubular cells and fibroblasts. Thus, regulation of GDF11 presents a therapeutic target for diseases involving renal fibrosis and impaired tubular function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Young adults' perspectives on living with kidney failure: a systematic review and thematic synthesis of qualitative studies.

    PubMed

    Bailey, Phillippa K; Hamilton, Alexander J; Clissold, Rhian L; Inward, Carol D; Caskey, Fergus J; Ben-Shlomo, Yoav; Owen-Smith, Amanda

    2018-01-10

    Young adults fare worse than younger adolescents or older adults on a broad range of health indicators. Those with a chronic illness such as renal failure are a particularly vulnerable group, who experience poor outcomes compared with both children and older adults. Understanding how being in receipt of renal replacement therapy (RRT) affects the lives of young adults might help us to better prepare and support these individuals for and on RRT, and improve outcomes. This study aimed to synthesise research describing young adults' experiences of the psychosocial impact of kidney failure and RRT. A systematic literature review identified qualitative research reporting the perspectives of people aged 16-30 years receiving RRT on the psychosocial impact of renal failure. Electronic databases (including Medline/EMBASE/PsycINFO/ASSIA) were searched to November 2017 for full-text papers. The transparency of reporting of each study was assessed using the Consolidated Criteria for Reporting Qualitative Health Research (COREQ) framework. Quality was assessed using the Critical Appraisal Skills Programme qualitative checklist. An inductive thematic synthesis was undertaken. Seven studies from five different countries were included, comprising 123 young adults receiving RRT. Comprehensiveness of reporting was variable: studies reported 9-22 of the 32 COREQ-checklist items.Three global themes about the impact of kidney failure on young adults were identified: (1) difference desiring normality, (2) thwarted or moderated dreams and ambitions, and (3) uncertainty and liminality. These reflected five organising themes: (1) physical appearance and body image, (2) activity and participation, (3) educational disruption and underachievement, (4) career ambitions and employment difficulties, and (5) social isolation and intimate relationships. Across different countries and different healthcare settings, young adults on RRT experience difference and liminality, even after

  20. Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors.

    PubMed

    Locke, Jayme E; Sawinski, Deirdre; Reed, Rhiannon D; Shelton, Brittany; MacLennan, Paul A; Kumar, Vineeta; Mehta, Shikha; Mannon, Roslyn B; Gaston, Robert; Julian, Bruce A; Carr, John J; Terry, James G; Kilgore, Meredith; Massie, Allan B; Segev, Dorry L; Lewis, Cora E

    2018-06-01

    The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs). We identified a cohort of young adults (18-30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60 mL/min/1.73 m) were identified and assigned weighted points to calculate risk scores. A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5-25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men. Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.

  1. Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

    PubMed

    Dobrowolski, Linn C; van Huis, Maike; van der Lee, Johanna H; Peters Sengers, Hessel; Liliën, Marc R; Cransberg, Karlien; Cornelissen, Marlies; Bouts, Antonia H; de Fijter, Johan W; Berger, Stefan P; van Zuilen, Arjan; Nurmohamed, Shaikh A; Betjes, Michiel H G; Hilbrands, Luuk; Hoitsma, Andries J; Bemelman, Frederike J; Krediet, C T Paul; Groothoff, Jaap W

    2016-11-01

    Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres. Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (≥18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres. Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment. Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT. © The Author 2016. Published by Oxford University Press on behalf of ERA

  2. Determination of Single-Kidney Glomerular Filtration Rate in Human Subjects by Using CT

    PubMed Central

    Kwon, Soon Hyo; Saad, Ahmed; Herrmann, Sandra M.; Textor, Stephen C.

    2015-01-01

    Purpose To test the hypothesis that computed tomography (CT)–derived measurements of single-kidney glomerular filtration rate (GFR) obtained in human subjects with 64-section CT agree with those obtained with iothalamate clearance, a rigorous reference standard. Materials and Methods The institutional review board approved this HIPAA-compliant study, and written informed consent was obtained. Ninety-six patients (age range, 51–73 years; 46 men, 50 women) with essential (n = 56) or renovascular (n = 40) hypertension were prospectively studied in controlled conditions (involving sodium intake and renin-angiotensin blockade). Single-kidney perfusion, volume, and GFR were measured by using multidetector CT time-attenuation curves and were compared with GFR measured by using iothalamate clearance, as assigned to the right and left kidney according to relative volumes. The reproducibility of CT GFR over a 3-month period (n = 21) was assessed in patients with renal artery stenosis who were undergoing stable medical treatment. Statistical analysis included the t test, Wilcoxon signed rank test, linear regression, and Bland-Altman analysis. Results CT GFR values were similar to those of iothalamate clearance (mean ± standard deviation, 38.2 mL/min ± 18 vs 41.6 mL/min ± 17; P = .062). Stenotic kidney CT GFR in patients with renal artery stenosis was lower than contralateral kidney GFR or essential hypertension single-kidney GFR (mean, 23.1 mL/min ± 13 vs 36.9 mL/min ± 17 [P = .0008] and 45.2 mL/min ± 16 [P = .019], respectively), as was iothalamate clearance (mean, 26.9 mL/min ± 14 vs 38.5 mL/min ± 15 [P = .0004] and 49.0 mL/min ± 14 [P = .001], respectively). CT GFR correlated well with iothalamate GFR (linear regression, CT GFR = 0.88*iothalamate GFR, r2 = 0.89, P < .0001), and Bland-Altman analysis was used to confirm the agreement. CT GFR was also moderately reproducible in medically treated patients with renal artery stenosis (concordance coefficient

  3. Serum Calcitriol Concentrations and Kidney Function Decline, Heart Failure, and Mortality in Elderly Community-Living Adults: The Health, Aging, and Body Composition Study.

    PubMed

    Selamet, Umut; Katz, Ronit; Ginsberg, Charles; Rifkin, Dena E; Fried, Linda F; Kritchevsky, Stephen B; Hoofnagle, Andrew N; Bibbins-Domingo, Kirsten; Drew, David; Harris, Tamara; Newman, Anne; Gutiérrez, Orlando M; Sarnak, Mark J; Shlipak, Michael G; Ix, Joachim H

    2018-06-06

    Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. Case-cohort study. Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. Major kidney function decline (≥30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. Lower

  4. Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip

    PubMed Central

    Musah, Samira; Mammoto, Akiko; Ferrante, Thomas C.; Jeanty, Sauveur S. F.; Hirano-Kobayashi, Mariko; Mammoto, Tadanori; Roberts, Kristen; Chung, Seyoon; Novak, Richard; Ingram, Miles; Fatanat-Didar, Tohid; Koshy, Sandeep; Weaver, James C.; Church, George M.; Ingber, Donald E.

    2017-01-01

    An in vitro model of the human kidney glomerulus — the major site of blood filtration — could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes — the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2−) and that exhibit primary and secondary foot processes. We also show that the hiPS-cell-derived podocytes produce glomerular basement-membrane collagen and recapitulate the natural tissue/tissue interface of the glomerulus, as well as the differential clearance of albumin and inulin, when co-cultured with human glomerular endothelial cells in an organ-on-a-chip microfluidic device. The glomerulus-on-a-chip also mimics adriamycin-induced albuminuria and podocyte injury. This in vitro model of human glomerular function with mature human podocytes may facilitate drug development and personalized-medicine applications. PMID:29038743

  5. Donor brain death predisposes human kidney grafts to a proinflammatory reaction after transplantation.

    PubMed

    de Vries, D K; Lindeman, J H N; Ringers, J; Reinders, M E J; Rabelink, T J; Schaapherder, A F M

    2011-05-01

    Donor brain death has profound effects on post-transplantation graft function and survival. We hypothesized that changes initiated in the donor influence the graft's response to ischemia and reperfusion. In this study, human brain dead donor kidney grafts were compared to living and cardiac dead donor kidney grafts. Pretransplant biopsies of brain dead donor kidneys contained notably more infiltrating T lymphocytes and macrophages. To assess whether the different donor conditions result in a different response to reperfusion, local cytokine release from the reperfused kidney was studied by measurement of paired arterial and renal venous blood samples. Reperfusion of kidneys from brain dead donors was associated with the instantaneous release of inflammatory cytokines, such as G-CSF, IL-6, IL-9, IL-16 and MCP-1. In contrast, kidneys from living and cardiac dead donors showed a more modest cytokine response with release of IL-6 and small amounts of MCP-1. In conclusion, this study shows that donor brain death initiates an inflammatory state of the graft with T lymphocyte and macrophage infiltration and massive inflammatory cytokine release upon reperfusion. These observations suggest that brain dead donors require a novel approach for donor pretreatment aimed at preventing this inflammatory response to increase graft survival. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2017-12-05

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

  8. Women and kidney disease: reflections on World Kidney Day 2018.

    PubMed

    Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

    2018-02-01

    Chronic kidney disease affects ∼10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health, and specifically their kidney health, to the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women, so that we may apply those learnings more broadly. Girls and women, who make up ∼50% of the world's population, are important contributors to society as a whole and to their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, and also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and for the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health and kidney disease, and what we might learn in the future to improve outcomes worldwide.

  9. Women and kidney disease: reflections on World Kidney Day 2018

    PubMed Central

    Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena

    2018-01-01

    Abstract Chronic kidney disease affects ∼10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health, and specifically their kidney health, to the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women, so that we may apply those learnings more broadly. Girls and women, who make up ∼50% of the world’s population, are important contributors to society as a whole and to their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, and also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and for the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health and kidney disease, and what we might learn in the future to improve outcomes worldwide. PMID:29435267

  10. Women and Kidney Disease: Reflections on World Kidney Day 2018.

    PubMed

    Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

    2018-03-01

    : Chronic kidney disease aff ects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus off ering an opportunity to refl ect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Sex diff erences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, off ering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have diff erent complications on dialysis than men and are more likely to be donors than recipients of kidney transplants.In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

  11. The effects of body mass index on graft survival in adult recipients transplanted with single pediatric kidneys.

    PubMed

    Balamuthusamy, Saravanan; Paramesh, Anil; Zhang, Rubin; Florman, Sander; Shenava, Rajesh; Islam, Tareq; Wagner, Janis; Killackey, Mary; Alper, Brent; Simon, Eric E; Slakey, Douglas

    2009-01-01

    There is insufficient data on the impact of recipient body mass index (BMI) on the long-term graft survival of adult patients transplanted with single pediatric kidneys. We performed a retrospective analysis of adult patients transplanted with single pediatric kidneys at our center. The recipients were classified into 2 groups: group 1 (BMI > or =30) and group 2 (BMI <30). Donor/recipient demographics, postoperative outcomes and survival rates were compared between the 2 groups. There was no significant difference in donor/recipient demographics between the 2 groups. In group 1, the death-censored graft survival (DCGS) at 1, 3 and 5 years was 90% at all 3 time points, and in group 2 it was 86, 68 and 60%, respectively (p = 0.05). The mean glomerular filtration rate (with standard deviation in parentheses) at 1, 3 and 5 years was, respectively, 55 (15), 59 (19) and 55 (28) ml/min for group 1, compared to 65 (28), 69 (23) and 67 (20) ml/min in group 2 (p = NS). Multivariate analysis revealed a hazard ratio of 5.12 (95% confidence interval 1.06-24.7; p = 0.04) for graft loss in nonobese patients when compared to obese patients. Obese patients had an increased risk for acute rejections within the first month of transplant (p = 0.02). Patients with a BMI > or =30 transplanted with single pediatric kidneys have better DCGS rates when compared to nonobese patients. Copyright (c) 2008 S. Karger AG, Basel.

  12. Low protein diets for chronic kidney disease in non diabetic adults.

    PubMed

    Fouque, D; Laville, M; Boissel, J P

    2006-04-19

    For more than fifty years, low protein diets have been proposed to patients with kidney failure. However, the effects of these diets in preventing severe renal failure and the need for maintenance dialysis have not been resolved. To determine the efficacy of low protein diets in delaying the need to start maintenance dialysis. Cochrane Renal Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987). Direct contacts with investigators. Date of most recent search: December 2004. Randomised trials comparing two different levels of protein intake in adult patients suffering from moderate to severe renal failure, followed for at least one year. Two reviewers independently selected studies and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Collection of the number of "renal deaths" defined as the need for starting dialysis, the death of a patient or a kidney transplant during the trial. Eight trials were identified from over 40 studies. A total of 1524 patients were analysed, 763 had received reduced protein intake and 761 a higher protein intake. Two hundred and fifty one renal deaths were recorded, 103 in the low protein diet and 148 in the higher protein diet group (RR 0.69, 95% CI 0.56 to 0.86, P = 0.0007). To avoid one renal death, 2 to 56 patients need to be treated with a low protein diet during one year. Reducing protein intake in patients with chronic kidney disease reduces the occurrence of renal death by 31% as compared with higher or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.

  13. Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity.

    PubMed

    Kharasch, E D; Hankins, D C; Thummel, K E

    1995-03-01

    Methoxyflurane nephrotoxicity is mediated by cytochrome P450-catalyzed metabolism to toxic metabolites. It is historically accepted that one of the metabolites, fluoride, is the nephrotoxin, and that methoxyflurane nephrotoxicity is caused by plasma fluoride concentrations in excess of 50 microM. Sevoflurane also is metabolized to fluoride ion, and plasma concentrations may exceed 50 microM, yet sevoflurane nephrotoxicity has not been observed. It is possible that in situ renal metabolism of methoxyflurane, rather than hepatic metabolism, is a critical event leading to nephrotoxicity. We tested whether there was a metabolic basis for this hypothesis by examining the relative rates of methoxyflurane and sevoflurane defluorination by human kidney microsomes. Microsomes and cytosol were prepared from kidneys of organ donors. Methoxyflurane and sevoflurane metabolism were measured with a fluoride-selective electrode. Human cytochrome P450 isoforms contributing to renal anesthetic metabolism were identified by using isoform-selective inhibitors and by Western blot analysis of renal P450s in conjunction with metabolism by individual P450s expressed from a human hepatic complementary deoxyribonucleic acid library. Sevoflurane and methoxyflurane did undergo defluorination by human kidney microsomes. Fluoride production was dependent on time, reduced nicotinamide adenine dinucleotide phosphate, protein concentration, and anesthetic concentration. In seven human kidneys studied, enzymatic sevoflurane defluorination was minima, whereas methoxyflurane defluorination rates were substantially greater and exhibited large interindividual variability. Kidney cytosol did not catalyze anesthetic defluorination. Chemical inhibitors of the P450 isoforms 2E1, 2A6, and 3A diminished methoxyflurane and sevoflurane defluorination. Complementary deoxyribonucleic acid-expressed P450s 2E1, 2A6, and 3A4 catalyzed methoxyflurane and sevoflurane metabolism, in diminishing order of activity

  14. A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

    PubMed

    Spector, Reynold; Robert Snodgrass, S; Johanson, Conrad E

    2015-11-01

    In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. Copyright © 2015. Published by Elsevier Inc.

  15. Urinary Virome Perturbations in Kidney Transplantation.

    PubMed

    Sigdel, Tara K; Mercer, Neil; Nandoe, Sharvin; Nicora, Carrie D; Burnum-Johnson, Kristin; Qian, Wei-Jun; Sarwal, Minnie M

    2018-01-01

    The human microbiome is important for health and plays a role in essential metabolic functions and protection from certain pathogens. Conversely, dysbiosis of the microbiome is seen in the context of various diseases. Recent studies have highlighted that a complex microbial community containing hundreds of bacteria colonizes the healthy urinary tract, but little is known about the human urinary viruses in health and disease. To evaluate the human urinary virome in the context of kidney transplantation (tx), variations in the composition of the urinary virome were evaluated in urine samples from normal healthy volunteers as well as patients with kidney disease after they had undergone kidney tx. Liquid chromatography-mass spectrometry/mass spectrometry analysis was undertaken on a selected cohort of 142 kidney tx patients and normal healthy controls, from a larger biobank of 770 kidney biopsy matched urine samples. In addition to analysis of normal healthy control urine, the cohort of kidney tx patients had biopsy confirmed phenotype classification, coincident with the urine sample analyzed, of stable grafts (STA), acute rejection, BK virus nephritis, and chronic allograft nephropathy. We identified 37 unique viruses, 29 of which are being identified for the first time in human urine samples. The composition of the human urinary virome differs in health and kidney injury, and the distribution of viral proteins in the urinary tract may be further impacted by IS exposure, diet and environmental, dietary, or cutaneous exposure to various insecticides and pesticides.

  16. Autosomal dominant polycystic kidney disease in children

    PubMed Central

    Cadnapaphornchai, Melissa A.

    2015-01-01

    Purpose of review Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, affecting one in 500 individuals. The cardinal manifestation of ADPKD is progressive cystic dilatation of renal tubules with kidney enlargement and progression to end-stage renal disease in approximately half of cases by 60 years of age. Although previously considered a condition of adults, it is clear that children and young adults are subject to the complications of ADPKD. Recent findings It has been increasingly recognized that interventions early in life are necessary in order to confer the best long-term outcome in this common condition. Therefore, it is imperative for pediatricians to recognize the manifestations and complications of this disease. Until recently ADPKD management focused on general principles of chronic kidney disease. However, several recent clinical trials in children and adults with ADPKD have focused on disease-specific therapies. Summary This review will highlight the clinical manifestations, diagnosis, and appropriate management of ADPKD in childhood and will review recent relevant clinical trials in children and adults with this condition. PMID:25635587

  17. Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients.

    PubMed

    Wolf, Mattie F; George, Roshan P; Warshaw, Barry; Wang, Elizabeth; Greenbaum, Larry A

    2016-12-01

    To quantify physical activity and grip strength in pediatric kidney transplant recipients and describe attitudes about exercise and exercise counseling given concerns about allograft injury. This was a cross-sectional analysis of 101 kidney transplant recipients (7-21 years old) >6 months post-transplant. Patients completed the Physical Activity Questionnaire (PAQ). Grip strength was measured with a dynamometer. We asked about activity limitations and provider counseling. Univariate analysis and multiple linear regression were used to determine independent predictors of PAQ score and grip strength z score. We enrolled 101 of 122 eligible patients. Median PAQ score was 2.2 (range 0-5) and was lower compared with controls (P < .001). The average grip strength z score was -1.1 and -0.7 in the right and left hand, respectively. Predictors of lower grip strength were younger age (P = .036), non-African American race (P = .029), lower height z score (P = .010), and longer percentage of lifetime with kidney disease (P = .029). Although 49% and 67% limited exercise before and after transplant, respectively, 67% reported increased activity after transplant. By parent report, provider counseling included limiting certain activities (71%) and encouraging regular exercise (45%). Physical activity and grip strength are low after kidney transplant. Patients perceive an emphasis on exercise limitations rather than the benefits of regular exercise. Interventions that encourage physical activity may be beneficial. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

    Raza, Mohsen; Skordis-Worrall, Jolene

    2012-01-01

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

  19. Giant kidney worm (Dioctophyma renale) infection mimicking retroperitoneal neoplasm.

    PubMed

    Sun, T; Turnbull, A; Lieberman, P H; Sternberg, S S

    1986-07-01

    A 50-year-old Chinese man was found by ultrasound and computed tomography to have a retroperitoneal mass in the right upper quadrant of the abdomen. At operation, a hemorrhagic cyst was detected at the upper pole of the right kidney adjacent to the adrenal gland. Microscopic examination revealed that the cyst wall was composed of granulomatous tissue loaded with eggs and cross-sections of parasites, identified as Dioctophyma renale. The eggs were characterized by a birefringent striated double wall. The presence of cross sections of adult worms of D. renale in human tissue has not been previously described. Another unique feature of this case was that the right kidney was intact, as examined grossly at laparotomy and by intravenous pyelography. Eggs were not detected in the urine.

  20. Rabbit antithymocyte globulin–induced serum sickness disease and human kidney graft survival

    PubMed Central

    Couvrat-Desvergnes, Grégoire; Salama, Apolline; Le Berre, Ludmilla; Evanno, Gwénaëlle; Viklicky, Ondrej; Hruba, Petra; Vesely, Pavel; Guerif, Pierrick; Dejoie, Thomas; Rousse, Juliette; Nicot, Arnaud; Bach, Jean-Marie; Ang, Evelyn; Foucher, Yohann; Brouard, Sophie; Castagnet, Stéphanie; Giral, Magali; Harb, Jean; Perreault, Hélène; Charreau, Béatrice; Lorent, Marine; Soulillou, Jean-Paul

    2015-01-01

    BACKGROUND. Rabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and α-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment. METHODS. We analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD+] and 803 without SSD [SSD–]) from the Données Informatisées et Validées en Transplantation data bank. Two subgroups of SSD+ and SSD– patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation. RESULTS. SSD was significantly associated with long-term graft loss (>10 years, P = 0.02). Moreover, SSD+ patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD– recipients. CONCLUSION. In conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD+ patients. FUNDING. This study was funded by Société d’Accélération du Transfert de Technologies Ouest Valorisation, the European FP7 “Translink” research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation. PMID

  1. Electrophoretic mobilities of cultured human embryonic kidney cells in various buffers

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Data on the electrophoretic mobility distributions of cells in the new D-1 buffer and the interlaboratory standardization of urokinase assay methods are presented. A table of cell strains and recent data on cell dispersal methods are also included. It was decided that glycerol in A-1 electrophoretic mobility data on cultured human embryonic kidney cells subjected to electrophoresis in this buffer. The buffer composition is presented.

  2. Women and kidney disease: Reflections on world kidney day 2018.

    PubMed

    Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

    2018-03-01

    Chronic Kidney Disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the foetus. Low birth weight children have increased risk of metabolic diseases, CVD and CKD. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. There is little data to guide best practice and limited research in the area. In this editorial, we focus on what we do and do not know about women, kidney health and kidney disease, and what we might learn in the future to improve outcomes worldwide. © 2018 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  3. Stem cells for kidney repair: useful tool for acute renal failure?

    PubMed

    Yokoo, Takashi; Kawamura, Tetsuya; Kobayashi, Eiji

    2008-10-01

    Several cell types isolated from adult tissues have been reported to differentiate into mature kidney cells that may participate in renal repair after systemic administration. Chen et al. report that local mesenchymal stem cells derived from adult mouse kidneys are another source of cells with similar properties. Although these cells have the potential to differentiate into endothelial-lineage cell types, their therapeutic benefit to the ischemic kidney is mainly via the production of renoprotective factors.

  4. Loss of executive function after dialysis initiation in adults with chronic kidney disease.

    PubMed

    Kurella Tamura, Manjula; Vittinghoff, Eric; Hsu, Chi-Yuan; Tam, Karman; Seliger, Stephen L; Sozio, Stephen; Fischer, Michael; Chen, Jing; Lustigova, Eva; Strauss, Louise; Deo, Rajat; Go, Alan S; Yaffe, Kristine

    2017-04-01

    The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, we enrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort in a prospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20 ml/min/1.73m 2 or less, or dialysis initiation within the past two years. We evaluated cognitive function by a validated telephone battery at regular intervals over two years and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52 transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated net difference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60, -0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation. Published by Elsevier Inc.

  5. Androgens for the anaemia of chronic kidney disease in adults.

    PubMed

    Yang, Qianchun; Abudou, Minawaer; Xie, Xi Sheng; Wu, Taixiang

    2014-10-09

    Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial. The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD. We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014. All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion. Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2

  6. Hypertension in pediatric patients with chronic kidney disease: management challenges.

    PubMed

    Gallibois, Claire M; Jawa, Natasha A; Noone, Damien G

    2017-01-01

    In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem.

  7. Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

    PubMed

    Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

    2017-12-01

    The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

  8. Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry.

    PubMed

    Mekahli, Djalila; van Stralen, Karlijn J; Bonthuis, Marjolein; Jager, Kitty J; Balat, Ayşe; Benetti, Elisa; Godefroid, Nathalie; Edvardsson, Vidar O; Heaf, James G; Jankauskiene, Augustina; Kerecuk, Larissa; Marinova, Svetlana; Puteo, Flora; Seeman, Tomas; Zurowska, Aleksandra; Pirenne, Jacques; Schaefer, Franz; Groothoff, Jaap W

    2016-11-01

    The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults. Cohort study. We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries. Liver transplantation. Transplantation and patient survival. 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9%-100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex-adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver-kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4). No data for liver disease of kidney therapy recipients. Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal

  9. Geographic determinants of access to pediatric deceased donor kidney transplantation.

    PubMed

    Reese, Peter P; Hwang, Hojun; Potluri, Vishnu; Abt, Peter L; Shults, Justine; Amaral, Sandra

    2014-04-01

    Children receive priority in the allocation of deceased donor kidneys for transplantation in the United States, but because allocation begins locally, geographic differences in population and organ supply may enable variation in pediatric access to transplantation. We assembled a cohort of 3764 individual listings for pediatric kidney transplantation in 2005-2010. For each donor service area, we assigned a category of short (<180 days), medium (181-270 days), or long (>270 days) median waiting time and calculated the ratio of pediatric-quality kidneys to pediatric candidates and the percentage of these kidneys locally diverted to adults. We used multivariable Cox regression analyses to examine the association between donor service area characteristics and time to deceased donor kidney transplantation. The Kaplan-Meier estimate of median waiting time to transplantation was 284 days (95% confidence interval, 263 to 300 days) and varied from 14 to 1313 days across donor service areas. Overall, 29% of pediatric-quality kidneys were locally diverted to adults. Compared with areas with short waiting times, areas with long waiting times had a lower ratio of pediatric-quality kidneys to candidates (3.1 versus 5.9; P<0.001) and more diversions to adults (31% versus 27%; P<0.001). In multivariable regression, a lower kidney to candidate ratio remained associated with longer waiting time (hazard ratio, 0.56 for areas with <2:1 versus reference areas with ≥5:1 kidneys/candidates; P<0.01). Large geographic variation in waiting time for pediatric deceased donor kidney transplantation exists and is highly associated with local supply and demand factors. Future organ allocation policy should address this geographic inequity.

  10. Summary electrophoretic data base on human embryonic kidney cell strain 8514

    NASA Technical Reports Server (NTRS)

    Plank, L. D.; Kunze, M. E.; Arquiza, M. V.; Morrison, D. R.; Todd, P. W.

    1985-01-01

    To properly plan the electrophoresis equipment verification test (EEVT) and continuous flow electrophoresis system (CFES) experiments with human embryonic kidney cells, first a candidate cell lot had to be chosen on the basis of electrophoretic heterogeneity, growth potential, cytogenetics, and urokinase production. Cell lot 8514 from MA Bioproducts, Inc. was chosen for this purpose, and several essential analytical electrophoresis experiments were performed to test its final suitability for these experiments.

  11. Medical nutrition therapy in adults with chronic kidney disease: integrating evidence and consensus into practice for the generalist registered dietitian nutritionist.

    PubMed

    Beto, Judith A; Ramirez, Wendy E; Bansal, Vinod K

    2014-07-01

    Chronic kidney disease is classified in stages 1 to 5 by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative depending on the level of renal function by glomerular filtration rate and, more recently, using further categorization depending on the level of glomerular filtration rate and albuminuria by the Kidney Disease Improving Global Outcomes initiative. Registered dietitian nutritionists can be reimbursed for medical nutrition therapy in chronic kidney disease stages 3 to 4 for specific clients under Center for Medicare and Medicaid Services coverage. This predialysis medical nutrition therapy counseling has been shown to both potentially delay progression to stage 5 (renal replacement therapy) and decrease first-year mortality after initiation of hemodialysis. The Joint Standards Task Force of the American Dietetic Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition Dietetic Practice Group, and the National Kidney Foundation Council on Renal Nutrition collaboratively published 2009 Standards of Practice and Standards of Professional Performance for generalist, specialty, and advanced practice registered dietitian nutritionists in nephrology care. The purpose of this article is to provide an update on current recommendations for screening, diagnosis, and treatment of adults with chronic kidney disease for application in clinical practice for the generalist registered dietitian nutritionist using the evidence-based library of the Academy of Nutrition and Dietetics, published clinical practice guidelines (ie, National Kidney Foundation Council on Renal Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition Care Process model, and peer-reviewed literature. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  12. Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

    PubMed Central

    Tain, You-Lin; Hsu, Chien-Ning

    2017-01-01

    Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

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

    PubMed

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

    2009-03-01

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

  14. Pkd1 transgenic mice: adult model of polycystic kidney disease with extrarenal and renal phenotypes

    PubMed Central

    Kurbegovic, Almira; Côté, Olivier; Couillard, Martin; Ward, Christopher J.; Harris, Peter C.; Trudel, Marie

    2010-01-01

    While high levels of Pkd1 expression are detected in tissues of patients with autosomal dominant polycystic kidney disease (ADPKD), it is unclear whether enhanced expression could be a pathogenetic mechanism for this systemic disorder. Three transgenic mouse lines were generated from a Pkd1-BAC modified by introducing a silent tag via homologous recombination to target a sustained wild-type genomic Pkd1 expression within the native tissue and temporal regulation. These mice specifically overexpressed the Pkd1 transgene in extrarenal and renal tissues from ∼2- to 15-fold over Pkd1 endogenous levels in a copy-dependent manner. All transgenic mice reproducibly developed tubular and glomerular cysts leading to renal insufficiency. Interestingly, Pkd1TAG mice also exhibited renal fibrosis and calcium deposits in papilla reminiscent of nephrolithiasis as frequently observed in ADPKD. Similar to human ADPKD, these mice consistently displayed hepatic fibrosis and ∼15% intrahepatic cysts of the bile ducts affecting females preferentially. Moreover, a significant proportion of mice developed cardiac anomalies with severe left-ventricular hypertrophy, marked aortic arch distention and/or valvular stenosis and calcification that had profound functional impact. Of significance, Pkd1TAG mice displayed occasional cerebral lesions with evidence of ruptured and unruptured cerebral aneurysms. This Pkd1TAG mouse model demonstrates that overexpression of wild-type Pkd1 can trigger the typical adult renal and extrarenal phenotypes resembling human ADPKD. PMID:20053665

  15. Conserved and Divergent Features of Mesenchymal Progenitor Cell Types within the Cortical Nephrogenic Niche of the Human and Mouse Kidney.

    PubMed

    Lindström, Nils O; Guo, Jinjin; Kim, Albert D; Tran, Tracy; Guo, Qiuyu; De Sena Brandine, Guilherme; Ransick, Andrew; Parvez, Riana K; Thornton, Matthew E; Basking, Laurence; Grubbs, Brendan; McMahon, Jill A; Smith, Andrew D; McMahon, Andrew P

    2018-03-01

    Cellular interactions among nephron, interstitial, and collecting duct progenitors drive mammalian kidney development. In mice, Six2 + nephron progenitor cells (NPCs) and Foxd1 + interstitial progenitor cells (IPCs) form largely distinct lineage compartments at the onset of metanephric kidney development. Here, we used the method for analyzing RNA following intracellular sorting (MARIS) approach, single-cell transcriptional profiling, in situ hybridization, and immunolabeling to characterize the presumptive NPC and IPC compartments of the developing human kidney. As in mice, each progenitor population adopts a stereotypical arrangement in the human nephron-forming niche: NPCs capped outgrowing ureteric branch tips, whereas IPCs were sandwiched between the NPCs and the renal capsule. Unlike mouse NPCs, human NPCs displayed a transcriptional profile that overlapped substantially with the IPC transcriptional profile, and key IPC determinants, including FOXD1 , were readily detected within SIX2 + NPCs. Comparative gene expression profiling in human and mouse Six2/SIX2 + NPCs showed broad agreement between the species but also identified species-biased expression of some genes. Notably, some human NPC-enriched genes, including DAPL1 and COL9A2 , are linked to human renal disease. We further explored the cellular diversity of mesenchymal cell types in the human nephrogenic niche through single-cell transcriptional profiling. Data analysis stratified NPCs into two main subpopulations and identified a third group of differentiating cells. These findings were confirmed by section in situ hybridization with novel human NPC markers predicted through the single-cell studies. This study provides a benchmark for the mesenchymal progenitors in the human nephrogenic niche and highlights species-variability in kidney developmental programs. Copyright © 2018 by the American Society of Nephrology.

  16. Knowledge, Attitudes, and Practices Associated with Chronic Kidney Disease in Northern Tanzania: A Community-Based Study

    PubMed Central

    Stanifer, John W.; Turner, Elizabeth L.; Egger, Joseph R.; Thielman, Nathan; Karia, Francis; Maro, Venance; Kilonzo, Kajiru; Patel, Uptal D.; Yeates, Karen

    2016-01-01

    Background Non-communicable diseases (NCDs) are a leading cause of death among adults in sub-Saharan Africa, and chronic kidney disease (CKD) is a growing public health threat. Understanding knowledge, attitudes, and practices associated with NCDs is vital to informing optimal policy and public health responses in the region, but few community-based assessments have been performed for CKD. To address this gap, we conducted a cross-sectional survey of adults in northern Tanzania using a validated instrument. Methods Between January and June 2014, we administered a structured survey to a random sample of adults from urban and rural communities. The validated instrument consisted of 25 items designed to measure knowledge, attitudes, and practices associated with kidney disease. Participants were also screened for CKD, diabetes, hypertension, and human immunodeficiency virus. Results We enrolled 606 participants from 431 urban and rural households. Knowledge of the etiologies, symptoms, and treatments for kidney disease was low (mean score 3.28 out of 10; 95% CI 2.94, 3.63). There were no significant differences by CKD status. Living in an urban setting and level of education had the strongest independent associations with knowledge score. Attitudes were characterized by frequent concern about the health (27.3%; 20.2, 36.0%), economic (73.1%; 68.2, 77.5%), and social impact (25.4%; 18.6, 33.6%) of kidney disease. Practices included the use of traditional healers (15.2%; 9.1, 24.5%) and traditional medicines (33.8%; 25.0, 43.9%) for treatment of kidney disease as well as a willingness to engage with mobile-phone technology in CKD care (94.3%; 90.1, 96.8%). Conclusions Community-based adults in northern Tanzania have limited knowledge of kidney disease. However, there is a modest knowledge base upon which to build public health programs to expand awareness and understanding of CKD, but these programs must also consider the variety of means by which adults in this

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

    PubMed Central

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

    2018-01-01

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

  18. Chronic epithelial kidney injury molecule-1 expression causes murine kidney fibrosis.

    PubMed

    Humphreys, Benjamin D; Xu, Fengfeng; Sabbisetti, Venkata; Grgic, Ivica; Movahedi Naini, Said; Wang, Ningning; Chen, Guochun; Xiao, Sheng; Patel, Dhruti; Henderson, Joel M; Ichimura, Takaharu; Mou, Shan; Soeung, Savuth; McMahon, Andrew P; Kuchroo, Vijay K; Bonventre, Joseph V

    2013-09-01

    Acute kidney injury predisposes patients to the development of both chronic kidney disease and end-stage renal failure, but the molecular details underlying this important clinical association remain obscure. We report that kidney injury molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed transiently after acute injury and chronically in fibrotic renal disease, promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal epithelial vacuolization at birth, but otherwise normal tubule histology and kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and progressive interstitial kidney inflammation with fibrosis, leading to renal failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac hypertrophy, and death, analogous to progressive kidney disease in humans. Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant, truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1. Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link between acute and recurrent injury with progressive chronic kidney disease.

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

    PubMed

    Süsal, Caner; Pelzl, Steffen; Opelz, Gerhard

    2003-10-27

    The influence of human leukocyte antigen (HLA) matching on graft survival is greater in patients with preformed lymphocytotoxic antibodies than in nonsensitized patients. Pretransplant serum soluble CD30 (sCD30) affects graft outcome independently of presensitization status. The impact of HLA compatibility on kidney transplant survival was analyzed in 3980 nonsensitized first cadaveric kidney recipients in relation to the pretransplant serum sCD30 content. Although HLA compatibility influenced graft outcome only marginally in nonsensitized recipients with low sCD30 (at 3 years: P=0.0095; at 5 years: P=0.1033), a strong HLA matching effect was observed in nonsensitized recipients with high sCD30 (at 3 years: P<0.0001; at 5 years: P=0.0001). Nonsensitized patients with high pretransplant sCD30 benefit from an HLA well-matched kidney. Patients should be tested for sCD30 while on the waiting list for a kidney transplant, and HLA well-matched kidneys should be allocated to patients with high sCD30.

  20. CT of trauma to the abnormal kidney

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rhyner, P.; Federle, M.P.; Jeffrey, R.B.

    Traumatic injuries to already abnormal kidneys are difficult to assess by excretory urography and clinical evaluation. Bleeding and urinary extravasation may accompany minor trauma; conversely, underlying tumors, perirenal hemorrhage, and extravasation may be missed on urography. Computed tomography (CT) was performed in eight cases including three neoplasms, one adult polycystic disease, one simple renal cyst, two hydronephrotic kidneys, and one horseshoe kidney. CT provided specific and clinically useful information in each case that was not apparent on excretory urography.

  1. Pharmacological management of acute kidney injury and chronic kidney disease in neonates.

    PubMed

    Jetton, Jennifer G; Sorenson, Mark

    2017-04-01

    Both acute kidney injury (AKI) and chronic kidney disease (CKD) are seen more frequently in the neonatal intensive care unit (NICU) as advances in supportive care improve the survival of critically ill infants as well as those with severe, congenital kidney and urinary tract anomalies. Many aspects of the infant's care, including fluid balance, electrolyte and mineral homeostasis, acid-base balance, and growth and nutrition require close monitoring by and collaboration among neonatologists, nephrologists, dieticians, and pharmacologists. This educational review summarizes the therapies widely used for neonates with AKI and CKD. Use of these therapies is extrapolated from data in older children and adults or based on clinical experience and case series. There is a critical need for more research on the use of therapies in infants with kidney disease as well as for the development of drug delivery systems and preparations scaled more appropriately for these small patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Dual Kidney Allocation Score: A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults.

    PubMed

    Johnson, Adam P; Price, Thea P; Lieby, Benjamin; Doria, Cataldo

    2016-09-08

    BACKGROUND Dual kidney transplantation (DKT) of expanded-criteria donors is a cost-intensive procedure that aims to increase the pool of available deceased organ donors and has demonstrated equivalent outcomes to expanded-criteria single kidney transplantation (eSKT). The objective of this study was to develop an allocation score based on predicted graft survival from historical dual and single kidney donors. MATERIAL AND METHODS We analyzed United Network for Organ Sharing (UNOS) data for 1547 DKT and 26 381 eSKT performed between January 1994 and September 2013. We utilized multivariable Cox regression to identify variables independently associated with graft survival in dual and single kidney transplantations. We then derived a weighted multivariable product score from calculated hazard ratios to model the benefit of transplantation as dual kidneys. RESULTS Of 36 donor variables known at the time of listing, 13 were significantly associated with graft survival. The derived dual allocation score demonstrated good internal validity with strong correlation to improved survival in dual kidney transplants. Donors with scores less than 2.1 transplanted as dual kidneys had a worsened median survival of 594 days (24%, p-value 0.031) and donors with scores greater than 3.9 had improved median survival of 1107 days (71%, p-value 0.002). There were 17 733 eSKT (67%) and 1051 DKT (67%) with scores in between these values and no differences in survival (p-values 0.676 and 0.185). CONCLUSIONS We have derived a dual kidney allocation score (DKAS) with good internal validity. Future prospective studies will be required to demonstrate external validity, but this score may help to standardize organ allocation for dual kidney transplantation.

  3. Whole kidney engineering for clinical translation.

    PubMed

    Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

    2015-04-01

    Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

  4. Targeted Nanoparticles for Kidney Cancer Therapy

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81XWH-10-1-0434 TITLE: Targeted Nanoparticles for Kidney Cancer Therapy PRINCIPAL...Targeted Nanoparticles for Kidney Cancer Therapy 5b. GRANT NUMBER W81XWH-10-1-0434 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...lines following treatment with D5 nanotubes. Tthermoablation will be studied initially. Human kidney cancer cells will be injected into the kidney

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

    NASA Astrophysics Data System (ADS)

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

    2017-11-01

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

  6. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

    PubMed Central

    2013-01-01

    Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]

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

    PubMed

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

    2013-10-01

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

  8. Calcium Balance in Chronic Kidney Disease.

    PubMed

    Hill Gallant, Kathleen M; Spiegel, David M

    2017-06-01

    The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

  9. THE EFFECT OF A TARGETED KNOCKOUT MUTATION ON THE TRANSCRIPTIONAL PROFILE OF THE KIDNEY IN TSC2 MUTANT (EKER) RATS.

    EPA Science Inventory

    Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting for up to 80% of malignant renal neoplasms. Hereditary RCC in the Eker rat, which bear a number of cellular, molecular and phenotypic similarities to human RCC, results from an inherited insertion...

  10. Male infertility associated with adult dominant polycystic kidney disease: a case series.

    PubMed

    Shefi, Shai; Levron, Jacob; Nadu, Andrei; Raviv, Gil

    2009-09-01

    Although described earlier, the association of male infertility with adult dominant polycystic kidney disease (ADPKD) is quite rare and unfamiliar to some of the multidisciplinary team members caring for affected men. Infertile men diagnosed to have ADPKD were evaluated by clinical characteristics including testis volume, as well as serum hormone levels, semen analysis, and transrectal ultrasonography (TRUS) because of low volume ejaculate. Semen analysis revealed low-normal volume, normal pH, and azoospermia/virtual azoospermia. Serum hormones were within the normal range. Transrectal ultrasonography demonstrated cystic dilatation of the seminal vesicles in all three men. Patients should be referred for andrological evaluation of a presentation similar to obstructive azoospermia. Their potential to achieve paternity by surgical sperm retrieval combined with assisted reproductive technology is another example of cooperation between andrologists and gynecologists.

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

    PubMed

    Stenvinkel, Peter; Johnson, Richard J

    2013-11-01

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

  12. Reprogramming: A Preventive Strategy in Hypertension Focusing on the Kidney

    PubMed Central

    Tain, You-Lin; Joles, Jaap A.

    2015-01-01

    Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension. Common pathways, whereby both genetic and acquired developmental programming converge into the same phenotype, have been recognized. For instance, the same reprogramming interventions aimed at shifting nitric oxide (NO)-reactive oxygen species (ROS) balance, such as perinatal citrulline or melatonin supplements, can be protective in both genetic and developmentally programmed hypertension. Furthermore, a significantly increased expression of gene Ephx2 (soluble epoxide hydrolase) was noted in both genetic and acquired animal models of hypertension. Since a suboptimal environment is often multifactorial, such common reprogramming pathways are a practical finding for translation to the clinic. This review provides an overview of potential clinical applications of reprogramming strategies to prevent programmed hypertension. We emphasize the kidney in the following areas: mechanistic insights from human studies and animal models to interpret programmed hypertension; identified risk factors of human programmed hypertension from mother-child cohorts; and the impact of reprogramming strategies on programmed hypertension from animal models. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies. PMID

  13. Microsomal and Cytosolic Scaling Factors in Dog and Human Kidney Cortex and Application for In Vitro-In Vivo Extrapolation of Renal Metabolic Clearance

    PubMed Central

    Scotcher, Daniel; Billington, Sarah; Brown, Jay; Jones, Christopher R.; Brown, Colin D. A.; Rostami-Hodjegan, Amin

    2017-01-01

    In vitro-in vivo extrapolation of drug metabolism data obtained in enriched preparations of subcellular fractions rely on robust estimates of physiologically relevant scaling factors for the prediction of clearance in vivo. The purpose of the current study was to measure the microsomal and cytosolic protein per gram of kidney (MPPGK and CPPGK) in dog and human kidney cortex using appropriate protein recovery marker and evaluate functional activity of human cortex microsomes. Cytochrome P450 (CYP) content and glucose-6-phosphatase (G6Pase) activity were used as microsomal protein markers, whereas glutathione-S-transferase activity was a cytosolic marker. Functional activity of human microsomal samples was assessed by measuring mycophenolic acid glucuronidation. MPPGK was 33.9 and 44.0 mg/g in dog kidney cortex, and 41.1 and 63.6 mg/g in dog liver (n = 17), using P450 content and G6Pase activity, respectively. No trends were noted between kidney, liver, and intestinal scalars from the same animals. Species differences were evident, as human MPPGK and CPPGK were 26.2 and 53.3 mg/g in kidney cortex (n = 38), respectively. MPPGK was 2-fold greater than the commonly used in vitro-in vivo extrapolation scalar; this difference was attributed mainly to tissue source (mixed kidney regions versus cortex). Robust human MPPGK and CPPGK scalars were measured for the first time. The work emphasized the importance of regional differences (cortex versus whole kidney–specific MPPGK, tissue weight, and blood flow) and a need to account for these to improve assessment of renal metabolic clearance and its extrapolation to in vivo. PMID:28270564

  14. Human kidney stone matrix: Latent potential to restrain COM induced cytotoxicity and inflammatory response.

    PubMed

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

    2017-12-25

    Kidney stone disease is a multi-factorial disorder resulting from the interplay of various risk factors including lifestyle, environment and genetics along with metabolic activities inside the body. However, it is difficult to determine how these factors converge to promote stone disease. Extensive investigations of kidney stone composition at the molecular level have been carried out however; its impact on the complex mechanism of stone formation is still obscure. Hence, an in vitro study was designed to investigate the attenuation of calcium oxalate toxicity by human kidney stone matrix proteins on NRK-52E cells using flowcytometry, Western blotting, RT-PCR and immunofluorescence assays. Morphological alterations in cell-crystal interaction were assessed using scanning electron microscopy. Microscopic studies showed profound impairment of COM crystal structure as a consequence of protein-crystal interactions. RT-PCR analysis and immunocytochemistry of NRK-52E cells revealed the up-regulation of inflammatory and stress biomarkers OPN and HSP-70, respectively, in response to COM toxicity; which diminished significantly in the presence of kidney stone matrix proteins. The results of present study propose that the mechanism undertaken by matrix proteins to attenuate COM induced cytotoxicity could be attributed to the modulation of crystal structure, which subsequently restraint the inflammatory response and apoptotic cell death. The inference drawn through this study could provide better understanding of the intricate process of kidney stone formation. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2010-12-14

    To study the protection of gene transfer-induced human heme oxygenase-1 over-expression against renal ischemia reperfusion injury in rats. The model of kidney ischemia-reperfusion injury was established with Sprague-Dawley rats. In the therapy group (n=18), the left kidney was perfused and preserved with Ad-hHO-1 at 2.5×10(9) pfu/1.0 ml after flushed with 0-4°C HC-A organ storage solution via donor renal aorta. The rats in control groups were perfused with 0.9% saline solution (n=12) or the vector carrying no interest gene Ad-EGFP 2.5×10(9) pfu/1.0 ml (n=18) instead of Ad-hHO-1. BUN and Cr in serum were measured by slide chemical methods. The kidney samples of rats were harvested for assay of histology, immunohistochemistry and quantification of HO enzymatic activity. Apoptosis cells in the kidney were measured by TUNEL. Ad-hHO-1 via donor renal aorta could transfect renal cells of rats effectively, enzymatic activity of HO in treated group [(1.62±0.07) nmol×mg(-1)×min(-1)] is higher than in control groups treated with saline solution team [(1.27±0.07) nmol×mg(-1)×min(-1)] and vector EGFP team [(1.22±0.06) nmol×mg(-1)×min(-1)] (P<0.01). Immunohistochemically, we found that the rats treated with Ad-hHO-1 expressed hHO-1 in kidneys at a high level. Corresponding to this, the level of BUN and Cr, as well as the number of apoptosis cells, were decreased, and the damage in histology by HE staining was ameliorated. Over-expression of human HO-1 can protect the kidney from ischemia/reperfusion injury in rats.

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

    PubMed

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

    2017-10-06

    Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p <0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

  17. Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants.

    PubMed

    Müller-Deile, Janina; Bräsen, Jan Hinrich; Pollheimer, Marion; Ratschek, Manfred; Haller, Hermann; Pape, Lars; Schiffer, Mario

    2017-10-01

    Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that most likely hyperfiltration is the key trigger inducing the

  18. Effect of passage number on electrophoretic mobility distributions of cultured human embryonic kidney cells

    NASA Technical Reports Server (NTRS)

    Kunze, M. E.

    1985-01-01

    A systematic investigation was undertaken to characterize population shifts that occur in cultured human embryonic kidney cells as a function of passage number in vitro after original explantation. This approach to cell population shift analysis follows the suggestion of Mehreshi, Klein and Revesz that perturbed cell populations can be characterized by electrophoretic mobility distributions if they contain subpopulations with different electrophoretic mobilities. It was shown that this is the case with early passage cultured human embryo cells.

  19. Living Donor Kidney Transplantation: Overcoming Disparities in Live Kidney Donation in the US—Recommendations from a Consensus Conference

    PubMed Central

    Rodrigue, James R.; Kazley, Abby Swanson; Mandelbrot, Didier A.; Hays, Rebecca; LaPointe Rudow, Dianne

    2015-01-01

    Despite its superior outcomes relative to chronic dialysis and deceased donor kidney transplantation, live donor kidney transplantation (LDKT) is less likely to occur in minorities, older adults, and poor patients than in those who are white, younger, and have higher household income. In addition, there is considerable geographic variability in LDKT rates. Concomitantly, in recent years, the rate of living kidney donation (LKD) has stopped increasing and is declining, after decades of consistent growth. Particularly noteworthy is the decline in LKD among black, younger, male, and lower-income adults. The Live Donor Community of Practice within the American Society of Transplantation, with financial support from 10 other organizations, held a Consensus Conference on Best Practices in Live Kidney Donation in June 2014. The purpose of this meeting was to identify LKD best practices and knowledge gaps that might influence LDKT, with a focus on patient and donor education, evaluation efficiencies, disparities, and systemic barriers to LKD. In this article, we discuss trends in LDKT/LKD and emerging novel strategies for attenuating disparities, and we offer specific recommendations for future clinical practice, education, research, and policy from the Consensus Conference Workgroup focused on disparities. PMID:25883072

  20. Effect of glycemic index and carbohydrate intake on kidney function in healthy adults.

    PubMed

    Juraschek, Stephen P; Chang, Alex R; Appel, Lawrence J; Anderson, Cheryl A M; Crews, Deidra C; Thomas, Letitia; Charleston, Jeanne; Miller, Edgar R

    2016-07-08

    Replacing carbohydrate with protein acutely increases glomerular filtration rate (GFR) but is associated with faster, long-term kidney disease progression. The effects of carbohydrate type (i.e. glycemic index, GI) on kidney function are unknown. We conducted an ancillary study of a randomized, crossover feeding trial in overweight/obese adults without diabetes or kidney disease (N = 163). Participants were fed each of four healthy, DASH-like diets for 5 weeks, separated by 2-week washout periods. Weight was kept constant. The four diets were: high GI (GI ≥65) with high %carb (58 % kcal) (reference diet), low GI (≤45) with low %carb (40 % kcal), low GI with high %carb; and high GI with low %carb. Plasma was collected at baseline and after each feeding period. Study outcomes were cystatin C, β2-microglobulin (β2M), and estimated GFR based on cystatin C (eGFRcys). Mean (SD) age was 52 (11) years; 52 % were women; 50 % were black. At baseline, mean (SD) cystatin C, β2M, and eGFRcys were 0.8 (0.1) mg/L, 1.9 (0.4) mg/L, and 104 (16) mL/min/1.73 m(2). Compared to the high GI/high %carb diet, reducing GI, %carb, or both increased eGFRcys by 1.9 mL/min/1.73 m(2) (95 % CI: 1.1, 2.7; P < 0.001), 3.0 mL/min/1.73 m(2) (1.9, 4.0; P < 0.001), and 4.5 mL/min/1.73 m(2) (3.5, 5.4; P < 0.001), respectively. Increases in eGFRcys from reducing GI were significantly associated with increases in eGFRcys from reducing %carb (P < 0.001). Results for cystatin C and β2M reflected eGFRcys. Reducing GI increased GFR. Reducing %carb by increasing calories from protein and fat, also increased GFR. Future studies on GI should examine the long-term effects of this increase in GFR on kidney injury markers and clinical outcomes. Clinical Trials.gov, number: NCT00608049 (first registered January 23, 2008).

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

    PubMed

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

    2018-01-01

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

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

    PubMed Central

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

    2018-01-01

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

  3. Liesegang rings in tissue. How to distinguish Liesegang rings from the giant kidney worm, Dioctophyma renale.

    PubMed

    Tuur, S M; Nelson, A M; Gibson, D W; Neafie, R C; Johnson, F B; Mostofi, F K; Connor, D H

    1987-08-01

    Liesegang rings (LRs) are periodic precipitation zones from supersaturated solutions in colloidal systems. They are formed by a process that involves an interplay of diffusion, nucleation, flocculation or precipitation, and supersaturation. Examples include LRs of calcium carbonate in oölitic limestone (in nature), LRs of silver chromate in gelatin (in vitro), and LRs of glycoprotein in pulmonary corpora amylacea (in vivo). Here we describe LRs in lesions from 29 patients--mostly lesions of the kidney, synovium, conjunctiva, and eyelid. The LRs formed in cysts, or in fibrotic, inflamed, or necrotic tissue. The LRs in this study varied greatly in shape and size, measuring 7-800 microns. Special stains and energy-dispersive radiographic analysis or scanning electron microscopy revealed that some LRs contained calcium, iron (hemosiderin), silicon, and sulfur. Some pathologists have mistaken LRs for eggs, larvae, or adults of the giant kidney worm, Dioctophyma renale. D. renale is a large blood-red nematode that infects a variety of fish-eating mammals, especially mink. Fourteen documented infections of humans have been recorded, usually with adult worms expelled from the urethra. The adult worms are probably the largest helminth to parasitize humans. Eggs of D. renale are constant in size (60-80 microns X 39-47 microns), contain an embryo, and have characteristic sculpturing of the shell. Liesegang rings should not be mistaken for eggs, larvae, or adults of D. renale, or for any other helminth.

  4. Occupational risk and chronic kidney disease: a population-based study in the United States adult population.

    PubMed

    Rubinstein, Sofia; Wang, Chengwei; Qu, Wenchun

    2013-01-01

    Previous studies on occupational risk for chronic kidney disease (CKD) have analyzed a limited range of occupations and focused on nephrotoxins. The primary purpose of this study was to examine the relative risk for the occurrence of CKD between different occupations in the US adult population. This was a population-based survey study of 91,340 participants in the US, who completed the National Health Interview Survey, 2004 through 2008. The outcome variable, CKD, was defined as having weakening/failing kidneys in the past 12 months, as diagnosed by a physician. The predictor variable, occupation, was obtained using the census occupational codes, regrouped according to North American Industrial Classification System. After controlling for age, gender, hypertension, and education, and with the category Life, Physical, and Social Science Occupations as a reference group, the likelihood of developing CKD was 4.3 times higher in respondents working in Building, Grounds Cleaning and Maintenance Occupations, 4.4 times higher in Healthcare Practitioners and Technical Occupations, 4.7 times higher in Transportation and Material Moving Occupations and in Computer and Mathematical Occupations, 4.8 times higher in Production Occupations, 5.3 times higher in Food Preparation and Serving Related Occupations, and 6.1 times higher in Healthcare Support Occupations and in Legal Occupations. This study identified occupation groups in US adult population with increased risk for CKD. Alleviation of workplace stress is suggested as a goal for behavioral intervention in high-risk occupations.

  5. Kidney function and population-based outcomes of initiating oral atenolol versus metoprolol tartrate in older adults.

    PubMed

    Fleet, Jamie L; Weir, Matthew A; McArthur, Eric; Ozair, Sundus; Devereaux, Philip J; Roberts, Matthew A; Jain, Arsh K; Garg, Amit X

    2014-12-01

    Atenolol and metoprolol tartrate are commonly prescribed β-blockers. Atenolol elimination depends on kidney function, whereas metoprolol tartrate does not. We hypothesized that compared to metoprolol tartrate, initiating oral atenolol treatment would be associated with more adverse events in older adults, with the association most pronounced in patients with lower baseline estimated glomerular filtration rates (eGFRs). Population-based matched retrospective cohort study. Older adults (mean age, 75 years) in Ontario, Canada, prescribed oral atenolol versus metoprolol tartrate from April 2002 through December 2011. The 2 groups were well matched (n=75,257 in each group), with no difference in 31 measured baseline characteristics. Patients with end-stage renal disease were ineligible, and 4.6% of patients had chronic kidney disease (median eGFR, 38mL/min/1.73m(2) assessed through a database algorithm). β-Blocker type and eGFR. A composite outcome of hospitalization with bradycardia or hypotension and all-cause mortality were assessed in 90-day follow-up. Compared to metoprolol tartrate, initiating atenolol treatment was not associated with higher risk of hospitalization with bradycardia or hypotension (incidence, 0.71% vs 0.79%; relative risk, 0.90; 95%CI, 0.80-1.01). Atenolol treatment initiation was associated with lower 90-day risk of mortality than metoprolol tartrate (incidence, 0.97% vs 1.44%; relative risk, 0.68; 95%CI, 0.61-0.74). Lower eGFR did not modify either association (P for interaction=0.5 and 0.6, respectively). Heart rate and blood pressure were not available in our data sources, and effects ascertained from observational studies are subject to residual confounding. Contrary to our expectation, we found that atenolol versus metoprolol tartrate was associated with lower 90-day risk of mortality in patients regardless of eGFR, with no difference in risk of hospitalization with bradycardia or hypotension. Copyright © 2014 National Kidney Foundation

  6. Neurocognitive Outcomes in Children with Chronic Kidney Disease: Current Findings and Contemporary Endeavors

    ERIC Educational Resources Information Center

    Gerson, Arlene C.; Butler, Robert; Moxey-Mims, Marva; Wentz, Alicia; Shinnar, Shlomo; Lande, Marc B.; Mendley, Susan R.; Warady, Bradley A.; Furth, Susan L.; Hooper, Stephen R.

    2006-01-01

    Given the rise in chronic kidney disease (CKD) in both children and adults, CKD has recently been targeted as a public health priority. Childhood onset kidney disease is generally a noncurable and progressive condition that leads to kidney failure by early adulthood. Fortunately, improved identification of kidney problems allows for early…

  7. A human anti-dsDNA monoclonal antibody caused hyaline thrombi formation in kidneys of ‘leaky’ SCID mice

    PubMed Central

    Mason, L J; Ravirajan, C T; Latchman, D S; Isenberg, D A

    2001-01-01

    There are few studies assessing the pathogenicity of human monoclonal anti-DNA antibodies. The use of SCID mice avoids the problem of rejection of the human hybridoma cells thus allowing in vivo assessment of human immunoglobulins. Using electron microscopy we have shown that the human IgG anti-dsDNA monoclonal antibody, RH14, is nephritogenic in SCID mice, causing morphological changes in the kidney due to immunoglobulin deposition. The problem with using SCID mice is that they have an abnormal immune system; normally they are used at about 2 months of age, at which time they have virtually no functional T or B cells. It is known that older SCID mice become increasingly ‘leaky’, that is they develop some mature lymphocyte clones. Our aim was to assess if implanting anti-DNA antibodies into older ‘leaky’ SCID mice would result in pathology which was observable by light microscopy. Eight-month-old SCID mice were implanted with human hybridoma cells secreting either RH14 an anti-dsDNA IgG, CL24, an antiphospholipid antibody or an irrelevant human IgG control. As previously, RH14 deposited in the kidney and caused proteinuria but unexpectedly we also observed hyaline thrombi in the kidney glomeruli and peritubular capillaries. These thrombi occurred only in the case of RH14 implanted mice and were found to stain positively for human IgG and fibrin. However, apart from the interesting thrombi, we did not observe any greater pathological damage resulting from the anti-dsDNA antibody deposition than we had seen in the younger mice; indeed, the electron microscopic findings were more limited. PMID:11678910

  8. The assessment of cognitive function in older adult patients with chronic kidney disease: an integrative review.

    PubMed

    Hannan, Mary; Steffen, Alana; Quinn, Lauretta; Collins, Eileen G; Phillips, Shane A; Bronas, Ulf G

    2018-05-25

    Chronic kidney disease (CKD) is a common chronic condition in older adults that is associated with cognitive decline. However, the exact prevalence of cognitive impairment in older adults with CKD is unclear likely due to the variety of methods utilized to assess cognitive function. The purpose of this integrative review is to determine how cognitive function is most frequently assessed in older adult patients with CKD. Five electronic databases were searched to explore relevant literature related to cognitive function assessment in older adult patients with CKD. Inclusion and exclusion criteria were created to focus the search to the assessment of cognitive function with standardized cognitive tests in older adults with CKD, not on renal replacement therapy. Through the search methods, 36 articles were found that fulfilled the purpose of the review. There were 36 different types of cognitive tests utilized in the included articles, with each study utilizing between one and 12 tests. The most commonly utilized cognitive test was the Mini Mental State Exam (MMSE), followed by tests of digit symbol substitution and verbal fluency. The most commonly assessed aspect of cognitive function was global cognition. The assessment of cognitive function in older adults with CKD with standardized tests is completed in various ways. Unfortunately, the common methods of assessment of cognitive function may not be fully examining the domains of impairment commonly found in older adults with CKD. Further research is needed to identify the ideal cognitive test to best assess older adults with CKD for cognitive impairment.

  9. Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

    PubMed Central

    Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

  10. Congenital ureteropelvic junction obstruction: human disease and animal models

    PubMed Central

    Klein, Julie; Gonzalez, Julien; Miravete, Mathieu; Caubet, Cécile; Chaaya, Rana; Decramer, Stéphane; Bandin, Flavio; Bascands, Jean-Loup; Buffin-Meyer, Bénédicte; Schanstra, Joost P

    2011-01-01

    Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation/apoptosis, renin–angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major short-coming is the absence of data on the impact of UPJ obstruction on long-term adult renal function to elucidate whether these animal data are also valid in humans. PMID:20681980

  11. Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

    PubMed

    Bansal, Nisha; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen; Lima, Joao; Kramer, Holly; Shlipak, Michael; Bibbins-Domingo, Kirsten

    2016-02-01

    Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Observational study. We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year 25. eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). LVMI measured at year 25. We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n = 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n = 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (β coefficient, 1.48; 95% CI, 0.11-2.83; P = 0.03) after adjustment for confounders. There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated

  12. Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients.

    PubMed

    Luo, Jinmei; Wang, Fen; Wan, Jianxin; Ye, Zhuangjian; Huang, Chumei; Cai, Yuesu; Liu, Min; Wu, Ben-Quan; Li, Laisheng

    2018-05-05

    Renal fibrosis remains an important cause of kidney allograft failure. The objective of this study was to evaluate the performance of serum human epididymis secretory protein 4 (HE4) as a biomarker for renal fibrosis in kidney transplant recipients. A total of 103 kidney transplantation patients were enrolled in this study, and serum HE4 concentrations were detected using the chemiluminescent microparticle immunoassay. Renal biopsy was carried out, and histological findings were assessed by immunohistochemistry. Median serum HE4 concentrations were significantly increased in kidney transplant recipients (186.2 pmol/l, interquartile range [IQR] 125.6-300.2) compared with control subjects (34.3 pmol/l, IQR 30.4-42.3, p < 0.0001). Meanwhile, serum HE4 concentrations were significantly increased along with disease severity (p < 0.0001). In addition, we found serum HE4 concentrations to be strongly correlated with the severity of fibrosis (IF/TA 0, 1, 2, and 3: 114.3, 179.0, 197.8, and 467.8 pmol/l, respectively; p < 0.0001) and serum HE4 concentrations significantly correlated with HE4 tissue expression concentrations in renal biopsy. Serum HE4 was increased in kidney transplant recipients with decreased kidney function and renal fibrosis and was correlated with the severity of the disease, suggesting that HE4 has the potential to be used as a novel clinical biomarker for evaluating kidney function and predicting renal fibrosis in kidney transplant recipients. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. CD74 in Kidney Disease

    PubMed Central

    Valiño-Rivas, Lara; Baeza-Bermejillo, Ciro; Gonzalez-Lafuente, Laura; Sanz, Ana Belen; Ortiz, Alberto; Sanchez-Niño, Maria Dolores

    2015-01-01

    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. PMID:26441987

  14. A Review of the Diagnosis and Treatment of Ochratoxin A Inhalational Exposure Associated with Human Illness and Kidney Disease including Focal Segmental Glomerulosclerosis

    PubMed Central

    Hope, Janette H.; Hope, Bradley E.

    2012-01-01

    Ochratoxin A (OTA) exposure via ingestion and inhalation has been described in the literature to cause kidney disease in both animals and humans. This paper reviews Ochratoxin A and its relationship to human health and kidney disease with a focus on a possible association with focal segmental glomerulosclerosis (FSGS) in humans. Prevention and treatment strategies for OTA-induced illness are also discussed, including cholestyramine, a bile-acid-binding resin used as a sequestrant to reduce the enterohepatic recirculation of OTA. PMID:22253638

  15. Acute kidney injury after percutaneous nephrolithotomy for stones in solitary kidneys.

    PubMed

    El-Nahas, Ahmed R; Taha, Diaa-Eldin; Ali, Hussien M; Elshal, Ahmed M; Zahran, Mohamed H; El-Tabey, Nasr A; El-Assmy, Ahmed M; Harraz, Ahmed M; Moawad, Hazem E; Othman, Mahmoud M

    2017-04-01

    The aim of this study was to report the incidence, severity, outcome and risk factors of acute kidney injury (AKI) following percutaneous nephrolithotomy (PNL) in solitary kidneys. The study included consecutive adult patients who underwent PNL for treatment of calculi in a solitary kidney between May 2012 and July 2015. Patients with congenital renal anomalies or with stages 4 and 5 chronic kidney disease (CKD) were excluded. Serum creatinine levels were measured the day before PNL, daily after PNL for 2-5 days and after 3 months. AKI was depicted according to changes in early postoperative serum creatinine levels and its severity was determined based on the Acute Kidney Injury Network (AKIN) classification. The outcome of AKI was evaluated after 3 months by changes in the stage of CKD. Univariate and multivariate statistical analyses were conducted to determine risk factors for developing AKI. The study included 100 patients (62 males) with a mean ± SD age of 50 ± 11.7 years. Complications were reported for 27 patients. AKI developed in 25 patients; at the 3 month follow-up, 23 of them (92%) had completely recovered from AKI and two (8%) had developed stage 4 CKD. Independent risk factors for developing AKI were multiple PNL tracts and postoperative ureteric obstruction (relative risks were 14 and 22, respectively). The incidence of AKI was 25% after PNL for a solitary kidney. The likelihood of renal function recovery was 92%. Multiple PNL tracts and postoperative ureteric obstruction were risk factors for developing AKI.

  16. Apical Plasma Membrane Mispolarization of NaK-ATPase in Polycystic Kidney Disease Epithelia Is Associated with Aberrant Expression of the β2 Isoform

    PubMed Central

    Wilson, Patricia D.; Devuyst, Olivier; Li, Xiaohong; Gatti, Laura; Falkenstein, Doris; Robinson, Shawn; Fambrough, Douglas; Burrow, Christopher R.

    2000-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease of the kidney, characterized by cystic enlargement of renal tubules, aberrant epithelial proliferation, and ion and fluid secretion into the lumen. Previous studies have shown abnormalities in polarization of membrane proteins, including mislocalization of the NaK-ATPase to the apical plasma membranes of cystic epithelia. Apically located NaK-ATPase has previously been shown to be fully functional in vivo and in membrane-grown ADPKD epithelial cells in vitro, where basal-to-apical 22Na transport was inhibited by application of ouabain to the apical membrane compartment. Studies were conducted with polymerase chain reaction-generated specific riboprobes and polyclonal peptide antibodies against human sequences of α1, α3, β1, and β2 subunits of NaK-ATPase. High levels of expression of α1 and β1 messenger RNA were detected in ADPKD and age-matched normal adult kidneys in vivo, whereas β2 messenger RNA was detected only in ADPKD kidneys. Western blot analysis and immunocytochemical studies showed that, in normal adult kidneys, peptide subunit-specific antibodies against α1 and β1 localized to the basolateral membranes of normal renal tubules, predominantly thick ascending limbs of Henle’s loop. In ADPKD kidneys, α1 and β2 subunits were localized to the apical epithelial cell membranes, whereas β1 was distributed throughout the cytoplasm and predominantly in the endoplasmic reticulum, but was not seen associated with cystic epithelial cell membranes or in cell membrane fractions. Polarizing, renal-derived epithelial Madin Darby canine kidney cells, stably expressing normal or N-terminally truncated chicken β1 subunits, showed selective accumulation in the basolateral Madin Darby canine kidney cell surface, whereas c-myc epitope-tagged chicken β2 or human β2 subunits accumulated selectively in the apical cell surface. Similarly, human ADPKD epithelial cell lines, which

  17. Peroxisome Proliferator-Activated Receptors Alpha, Beta, and Gamma mRNA and Protein Expression in Human Fetal Tissues

    PubMed Central

    Abbott, Barbara D.; Wood, Carmen R.; Watkins, Andrew M.; Das, Kaberi P.; Lau, Christopher S.

    2010-01-01

    Peroxisome proliferator-activated receptors (PPARs) regulate lipid and glucose homeostasis, are targets of pharmaceuticals, and are also activated by environmental contaminants. Almost nothing is known about expression of PPARs during human fetal development. This study examines expression of PPARα, β, and γ mRNA and protein in human fetal tissues. With increasing fetal age, mRNA expression of PPARα and β increased in liver, but PPARβ decreased in heart and intestine, and PPARγ decreased in adrenal. Adult and fetal mean expression of PPARα, β, and γ mRNA did not differ in intestine, but expression was lower in fetal stomach and heart. PPARα and β mRNA in kidney and spleen, and PPARγ mRNA in lung and adrenal were lower in fetal versus adult. PPARγ in liver and PPARβ mRNA in thymus were higher in fetal versus adult. PPARα protein increased with fetal age in intestine and decreased in lung, kidney, and adrenal. PPARβ protein in adrenal and PPARγ in kidney decreased with fetal age. This study provides new information on expression of PPAR subtypes during human development and will be important in evaluating the potential for the developing human to respond to PPAR environmental or pharmaceutical agonists. PMID:20706641

  18. Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity.

    PubMed

    Awadalla, Eatemad A

    2012-07-01

    Paraquat has been demonstrated to be a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The current experiment aimed to examine if vitamin C (ascorbic acid) alleviates the morphological changes induced by paraquat (PQ) administration in the liver and kidney of male albino rats. Male adult rats received paraquat (PQ) (1.5 mg/kg body weight) daily for three weeks. Vitamin C (VC) at a dose of 20 mg/kg body weight was given concomitantly with PQ to rats. Animals were divided into three groups in this experiment (control, PQ and PQ+VC). The morphopathological manifestations were investigated in tissues from liver and kidney. As expected, PQ administration induced marked changes in the morphological structure of the liver and kidney in PQ demonstrated animals. Importantly, vitamin C administration restored PQ-induced changes in the studied organs. Vitamin C administration attenuated the morphological damages induced by PQ in the liver and kidney of experimental animals. Our results suggest an antitoxic effect of vitamin C against paraquat. Copyright © 2010 Elsevier GmbH. All rights reserved.

  19. Effect of a High-Protein Diet on Kidney Function in Healthy Adults: Results From the OmniHeart Trial

    PubMed Central

    Juraschek, Stephen P.; Appel, Lawrence J.; Anderson, Cheryl A.M.; Miller, Edgar R.

    2013-01-01

    Background Consumption of a diet high in protein can cause glomerular hyperfiltration, a potentially maladaptive response, which may accelerate the progression of kidney disease. Study Design An ancillary study of the OmniHeart trial, a randomized 3-period crossover feeding trial testing the effects of partial replacement of carbohydrate with protein on kidney function. Setting & Participants Healthy adults (N=164) with prehypertension or stage 1 hypertension at a community-based research clinic with a metabolic kitchen. Intervention Participants were fed each of 3 diets for 6 weeks. Feeding periods were separated by a 2- to 4-week washout period. Weight was held constant on each diet. The 3 diets emphasized carbohydrate, protein, or unsaturated fat; dietary protein was either 15% (carbohydrate and unsaturated fat diets) or 25% (protein diet) of energy intake. Outcomes Fasting serum creatinine, cystatin C, and β2-microglobulin levels, estimated glomerular filtration rate (eGFR). Measurements Serum creatinine, cystatin C, and β2-microglobulin collected at the end of each feeding period. Results Baseline cystatin C-based eGFR was 92.0±16.3 (SD) mL/min/1.73 m2. Compared with the carbohydrate and unsaturated fat diets, the protein diet increased cystatin C-based eGFR by ~4 mL/min/1.73 m2 (P < 0.001). The effects of the protein diet on kidney function were independent of changes in blood pressure. There was no significant difference between the carbohydrate and unsaturated fat diets. Limitations Participants did not have kidney disease at baseline. Conclusions A healthy diet rich in protein increased eGFR. Whether long-term consumption of a high-protein diet leads to kidney disease is uncertain. PMID:23219108

  20. Safety and complications of percutaneous kidney biopsies in 715 children and 8573 adults in Norway 1988-2010.

    PubMed

    Tøndel, Camilla; Vikse, Bjørn Egil; Bostad, Leif; Svarstad, Einar

    2012-10-01

    Skepticism about performing renal biopsies is often because of uncertainty regarding risk of complications. The aim of this study was to evaluate safety and relevant complications of renal biopsies in pediatric and adult patients in a large national registry study. Kidney biopsies reported in the Norwegian Kidney Biopsy Registry from 1988 to 2010 were included. Risk factors for major complications (blood transfusion and/or surgical or catheter intervention) were analyzed using logistic regression statistics. Of the 9288 biopsies included, 715 were from children, and 8573 were from adults (≥18 years). Median age was 49 years (range=2 weeks to 94 years). Gross hematuria appeared after biopsy in 1.9% of the patients; 0.9% of patients needed blood transfusion, and 0.2% of patients needed surgical intervention/catheterization. The frequencies were 1.9%, 0.9%, and 0.2% in adults and 1.7%, 0.1% and 0.1% in children, respectively; 97.9% of the biopsies were without complications. In unadjusted analyses, risk factors for major complications were age>60 years, estimated GFR<60 ml/min per 1.73 m(2), systolic hypertension, acute renal failure, and smaller clinical center size (<30 biopsies/yr). Adjusted analyses (adjusted for age and/or estimated GFR) showed higher odds ratios (OR) only for smaller clinical center (OR=1.60 [1.02-2.50]) and low estimated GFR (estimated GFR=30-59 ml/min per 1.73 m(2) [OR=4.90 (1.60-14.00)] and estimated GFR<30 ml/min per 1.73 m(2) [OR 15.50 (5.60-43.00)]). Percutaneous renal biopsy is a low-risk procedure in all ages. Reduced estimated GFR and smaller center size are associated with an increased risk of major complications.

  1. Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants

    PubMed Central

    Müller-Deile, Janina; Bräsen, Jan Hinrich; Pollheimer, Marion; Ratschek, Manfred; Haller, Hermann; Pape, Lars; Schiffer, Mario

    2017-01-01

    Background Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. Methods We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. Results We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Conclusions Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that most likely

  2. Kidney stones and kidney function loss: a cohort study.

    PubMed

    Alexander, R Todd; Hemmelgarn, Brenda R; Wiebe, Natasha; Bello, Aminu; Morgan, Catherine; Samuel, Susan; Klarenbach, Scott W; Curhan, Gary C; Tonelli, Marcello

    2012-08-29

    To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes. A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years. Alberta, Canada, between 1997 and 2009. 3,089,194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1,954,836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level. One or more kidney stones during follow-up. Incident ESRD, development of stage 3b-5 chronic kidney disease (estimated glomerular filtration rate <45 mL/min/1.73 m(2)), and sustained doubling of serum creatinine concentration from baseline. 23,706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68,525 (4%) developed stage 3b-5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b-5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged <50 years than in those aged ≥ 50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones. Even a single kidney stone

  3. Women and kidney disease: reflections on World Kidney Day 2018: Kidney Health and Women's Health: a case for optimizing outcomes for present and future generations.

    PubMed

    Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

    2018-02-01

    Chronic kidney disease (CKD) affects ∼10% of the world's adult population: it is one of the top 20 causes of death worldwide and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day coincide in 2018, thus offering an opportunity to reflect on the importance of women's health, and specifically their kidney health, on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply these learnings more broadly. Girls and women, who make up ∼50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for the diagnosis of kidney disease, and also a state where acute and chronic kidney diseases may manifest and that may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing and on the fetus. Women have different complications on dialysis than men and are more likely to be donors than recipients of kidney transplants. In this editorial we focus on what we do and do not know about women, kidney health and kidney disease and what we might learn in the future to improve outcomes worldwide. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  4. Immune System and Kidney Transplantation.

    PubMed

    Shrestha, Badri Man

    2017-01-01

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

  5. Beyond Income: A Social Justice Approach to Assessing Poverty among Older Adults with Chronic Kidney Disease.

    PubMed

    Caplan, Mary A; Washington, Tiffany R; Swanner, Lauren

    2017-01-01

    How social workers define and assess poverty is a matter of economic and social justice. Recent conceptual and measurement advances point to a multidimensional definition of poverty which captures material, social, and political deprivations. Using data from a survey, this article describes how nephrology social workers assess poverty among older adults living with a chronic kidney disease (N = 52). Results suggest respondents already conceive of poverty as a multidimensional experience, support awareness-raising about poverty, and primarily assess poverty by employment status, income, access to transportation, and education. Opportunities to expand poverty assessment in future work are promising.

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

    PubMed Central

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

    2014-01-01

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

  7. Graft and patient outcomes of zero-human leucocyte-antigen-mismatched deceased and live donor kidney transplant recipients.

    PubMed

    Lim, Wai H; Gray, Nicholas A; Chadban, Steven J; Pilmore, Helen; Wong, Germaine

    2015-05-01

    Greater compatibility of human leucocyte antigen (HLA) alleles between kidney donors and recipients may lead to improved graft outcomes. This study aimed to compare the incidence of acute rejection and graft failure in zero-HLA-mismatched recipients of living-related (LD) and deceased donor (DD) kidney transplants. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we compared the risk of any acute rejection and biopsy-proven acute rejection (BPAR) and graft failure in recipients of zero-HLA-mismatched kidneys between LD and DD using logistic and Cox regression models. Of the 931 zero-HLA-mismatched recipients transplanted between 1990 and 2012, 19 (2.0%) received kidneys from monozygotic/dizygotic twins (twin), 500 (53.7%) from nontwin LD and 412 (44.3%) from DD. Twin kidney transplant recipients did not experience rejection. Compared to DD transplant recipients, the risk of any acute rejection (adjusted odds ratio 0.52, 95%CI 0.34-0.79, P = 0.002) and overall graft failure (adjusted hazard ratio 0.55, 95%CI 0.41-0.73, P < 0.001) was significantly lower in LD recipients independent of initial immunosuppression, but not for BPAR (adjusted odds ratio 0.52, 95%CI 0.16-1.64, P = 0.263). Zero-HLA-mismatched DD kidney transplant recipients have a significantly higher risk of any acute rejection episodes and graft loss compared to zero-HLA-mismatched LD kidney transplant recipients. A cautious and careful approach in reducing immunosuppression appears to be warranted in this group of transplant recipients. © 2015 Steunstichting ESOT.

  8. Human Adult Neurogenesis: Evidence and Remaining Questions.

    PubMed

    Kempermann, Gerd; Gage, Fred H; Aigner, Ludwig; Song, Hongjun; Curtis, Maurice A; Thuret, Sandrine; Kuhn, H Georg; Jessberger, Sebastian; Frankland, Paul W; Cameron, Heather A; Gould, Elizabeth; Hen, Rene; Abrous, D Nora; Toni, Nicolas; Schinder, Alejandro F; Zhao, Xinyu; Lucassen, Paul J; Frisén, Jonas

    2018-04-18

    Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2017-01-01

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

  10. Have you got any cholesterol? Adults' views of human nutrition

    NASA Astrophysics Data System (ADS)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  11. Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.

    PubMed

    Raaij, Sanne van; Swelm, Rachel van; Bouman, Karlijn; Cliteur, Maaike; Heuvel, Marius van den; Pertijs, Jeanne; Patel, Dominic; Bass, Paul; Goor, Harry van; Unwin, Robert; Srai, Surjit Kaila; Swinkels, Dorine

    2018-06-19

    Iron is suggested to play a detrimental role in the progression of chronic kidney disease (CKD). The kidney recycles iron back into the circulation. However, the localization of proteins relevant for physiological tubular iron handling and their potential role in CKD remain unclear. We examined associations between iron deposition, expression of iron handling proteins and tubular injury in kidney biopsies from CKD patients and healthy controls using immunohistochemistry. Iron was deposited in proximal (PT) and distal tubules (DT) in 33% of CKD biopsies, predominantly in pathologies with glomerular dysfunction, but absent in controls. In healthy kidney, PT contained proteins required for iron recycling including putative iron importers ZIP8, ZIP14, DMT1, iron storage proteins L- and H-ferritin and iron exporter ferroportin, while DT only contained ZIP8, ZIP14, and DMT1. In CKD, iron deposition associated with increased intensity of iron importers (ZIP14, ZIP8), storage proteins (L-, H-ferritin), and/or decreased ferroportin abundance. This demonstrates that tubular iron accumulation may result from increased iron uptake and/or inadequate iron export. Iron deposition associated with oxidative injury as indicated by heme oxygenase-1 abundance. In conclusion, iron deposition is relatively common in CKD, and may result from altered molecular iron handling and may contribute to renal injury.

  12. Concise Review: Kidney Stem/Progenitor Cells: Differentiate, Sort Out, or Reprogram?

    PubMed Central

    Pleniceanu, Oren; Harari-Steinberg, Orit; Dekel, Benjamin

    2010-01-01

    End-stage renal disease (ESRD) is defined as the inability of the kidneys to remove waste products and excess fluid from the blood. ESRD progresses from earlier stages of chronic kidney disease (CKD) and occurs when the glomerular filtration rate (GFR) is below 15 ml/minute/1.73 m2. CKD and ESRD are dramatically rising due to increasing aging population, population demographics, and the growing rate of diabetes and hypertension. Identification of multipotential stem/progenitor populations in mammalian tissues is important for therapeutic applications and for understanding developmental processes and tissue homeostasis. Progenitor populations are ideal targets for gene therapy, cell transplantation, and tissue engineering. The demand for kidney progenitors is increasing due to severe shortage of donor organs. Because dialysis and transplantation are currently the only successful therapies for ESRD, cell therapy offers an alternative approach for kidney diseases. However, this approach may be relevant only in earlier stages of CKD, when kidney function and histology are still preserved, allowing for the integration of cells and/or for their paracrine effects, but not when small and fibrotic end-stage kidneys develop. Although blood- and bone marrow-derived stem cells hold a therapeutic promise, they are devoid of nephrogenic potential, emphasizing the need to seek kidney stem cells beyond known extrarenal sources. Moreover, controversies regarding the existence of a true adult kidney stem cell highlight the importance of studying cell-based therapies using pluripotent cells, progenitor cells from fetal kidney, or dedifferentiated/reprogrammed adult kidney cells. Stem Cells 2010; 28:1649–1660. PMID:20652959

  13. Serum creatinine elevation after switch to dolutegravir in a human immunodeficiency virus-positive kidney transplant recipient

    PubMed Central

    Lee, D.H.; Malat, G.E.; Bias, T.E.; Harhay, M.N.; Ranganna, K.; Doyle, A.M.

    2017-01-01

    Dolutegravir is a preferred antiretroviral drug for human immunodeficiency virus (HIV)-infected patients following solid organ transplantation. It has potent antiretroviral activity and does not interact with calcineurin inhibitors. We describe a case of an HIV-infected kidney transplant patient, who was noted to have a rising serum creatinine following initiation of dolutegravir. At first an acute rejection episode was suspected, but this finding was later attributed to inhibition of creatinine secretion by dolutegravir. We suggest that an awareness of this potential effect of dolutegravir is important for providers who take care of HIV-positive kidney transplant recipients, in order to prevent potentially unnecessary testing. PMID:27159656

  14. Properties of electrophoretic fractions of human embryonic kidney cells separated on space shuttle flight STS-8

    NASA Technical Reports Server (NTRS)

    Morrison, D. R.; Lewis, M. L.; Barlow, G. H.; Todd, P. W.; Kunze, M. E.; Sarnoff, B. E.; Li, Z. K.

    1985-01-01

    Suspensions of cultured primary human embryonic kidney cells were subjected to continuous flow electrophoresis on Space Shuttle flight STS-8. The objectives of the experiments were to obtain electrophoretically separated fractions of the original cell populations and to test these fractions for the amount and kind of urokinase (a kidney plasminogen activator that is used medically for digesting blood clots), the morphologies of cells in the individual fractions, and their cellular electrophoretic mobilities after separation and subsequent proliferation. Individual fractions were successfully cultured after return from orbit, and they were found to differ substantially from one another and from the starting sample with respect to all of these properties.

  15. Development and Testing of an LED-Based Near-Infrared Sensor for Human Kidney Tumor Diagnostics

    PubMed Central

    Zabarylo, Urszula; Kirsanov, Dmitry; Belikova, Valeria; Ageev, Vladimir; Usenov, Iskander; Galyanin, Vladislav; Minet, Olaf; Sakharova, Tatiana; Danielyan, Georgy; Feliksberger, Elena; Artyushenko, Viacheslav

    2017-01-01

    Optical spectroscopy is increasingly used for cancer diagnostics. Tumor detection feasibility in human kidney samples using mid- and near-infrared (NIR) spectroscopy, fluorescence spectroscopy, and Raman spectroscopy has been reported (Artyushenko et al., Spectral fiber sensors for cancer diagnostics in vitro. In Proceedings of the European Conference on Biomedical Optics, Munich, Germany, 21–25 June 2015). In the present work, a simplification of the NIR spectroscopic analysis for cancer diagnostics was studied. The conventional high-resolution NIR spectroscopic method of kidney tumor diagnostics was replaced by a compact optical sensing device constructively represented by a set of four light-emitting diodes (LEDs) at selected wavelengths and one detecting photodiode. Two sensor prototypes were tested using 14 in vitro clinical samples of 7 different patients. Statistical data evaluation using principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) confirmed the general applicability of the LED-based sensing approach to kidney tumor detection. An additional validation of the results was performed by means of sample permutation. PMID:28825612

  16. Incidence and mortality of kidney cancer and its relationship with HDI (Human Development Index) in the world in 2012.

    PubMed

    Mohammadian, Maryam; Pakzad, Reza; Towhidi, Farhad; Makhsosi, Behnam Reza; Ahmadi, Abbas; Salehiniya, Hamid

    2017-01-01

    Kidney cancer is among the cancers that have the highest growth rate in all age and racial groups in the world and is as the most deadly type of urinary tract cancer. Since awareness about this cancer incidence status and mortality is essential for better planning, this study aimed to investigate the incidence and mortality rate of kidney cancer and its relationship with the development index in the world in 2012. This study was an ecological study conducted based on GLOBOCAN project of the World Health Organization (WHO) for the countries in the world. The correlation between Standardized Incidence Rates (SIRs) and Standardized Mortality Rates (SMRs) of kidney cancer with HDI and its components was assessed using SPSS18. In total, 337,860 incidence cases (213,924 were men and 123,936 women) and 143,406 deaths (90,802 cases in men and 52,604 in women) of kidney cancer were recorded in 2012. A positive correlation of 0.731 was seen between SIR of kidney cancer and HDI (p≤0.001). Also, a negative correlation of 0.627 was seen between SMR of kidney cancer and HDI (p≤0.001). The incidence and mortality rate of kidney cancer is higher in developed countries. A significant positive correlation has been seen between the standardized incidence and mortality rate of kidney cancer with the Human Development Index and its components. We need more studies to examine variation in incidence and mortality of kidney cancer and its related factors in the world.

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

    PubMed

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

    2008-10-01

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

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

    PubMed Central

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

    2008-01-01

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

  19. Nocturnal Hypoxia and Loss of Kidney Function

    PubMed Central

    Ahmed, Sofia B.; Ronksley, Paul E.; Hemmelgarn, Brenda R.; Tsai, Willis H.; Manns, Braden J.; Tonelli, Marcello; Klarenbach, Scott W.; Chin, Rick; Clement, Fiona M.; Hanly, Patrick J.

    2011-01-01

    Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function. PMID:21559506

  20. Pediatric Inflammatory Bowel Diseases: Should We Be Looking for Kidney Abnormalities?

    PubMed

    Lauritzen, Didde; Andreassen, Bente Utoft; Heegaard, Niels Henrik H; Klinge, Lone Gabriels; Walsted, Anne-Mette; Neland, Mette; Nielsen, Rasmus Gaardskær; Wittenhagen, Per

    2018-04-26

    Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56 children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease. The median kidney size compared with normal children was significantly reduced. In a multivariate linear mixed model, small kidneys significantly correlated with the use of infliximab, whereas the use of enteral nutritional therapy was associated with larger kidneys. Children with IBD are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease.

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

    PubMed Central

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

    2017-01-01

    Background The incidence and mortality of kidney cancer have steadily increased by 2%- 3% per decade worldwide, and an increased risk of kidney cancer has been observed in many Asian countries. The information on the incidence and mortality of a disease and its distribution is essential for better planning for prevention and further studies. Objectives This study aimed to assess the incidence and mortality of kidney cancer and their correlation with the human development index (HDI) in Asia. Materials and Methods This ecological study was based on GLOBOCAN data Asia for assessment the correlation between age-specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its details that include life expectancy at birth, mean years of schooling and gross national income (GNI) per capita. We use of correlation bivariate method for assessment the correlation between ASIR and ASMR with HDI and its components. Results A total of 121 099 kidney cancer cases were recorded in Asian countries in 2012.Overall, 80 080 cases (66.12%) were males. Sex ratio was 1.95. The three countries with the highest number of new patients were china (66 466 cases), Japan (16 830 cases), India(9658 cases), respectively. Positive correlation were seen between HDI and ASIR of kidney cancer 0.655 (P = 0.001), and HDI and ASMR of kidney cancer 0.285 (P = 0.055). Conclusions A positive relationship between ASIR and the HDI was seen. The relationship is due to risk factors in countries with high development such as older age, smoking, hypertension, obesity, and diet. However, ASMR showed no significant relationship with HDI. PMID:28042551

  2. Polycystic kidneys in the red panda (Ailurus fulgens).

    PubMed

    Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Koeppel, Katja N; Groenewald, Hermanus B

    2013-09-01

    An intact adult male 14.3-yr-old red panda (Ailurus fulgens) presented for health examination with a history of slowly progressing loss of body condition. Abdominal radiographs revealed a truncated abdomen with poor serosal abdominal detail and multiple areas of spondylosis with some collapsed intervertebral disc spaces. On computed tomography, multiple ovoid hypoattenuating lesions were seen in the left and right kidneys. Gross pathology and histopathology revealed multiple cystic lesions in the kidneys concurrent with pancreatic cysts on histopathology. To the best of the authors' knowledge, polycystic kidneys have not been reported in this species.

  3. Quantitative Large-Scale Three-Dimensional Imaging of Human Kidney Biopsies: A Bridge to Precision Medicine in Kidney Disease.

    PubMed

    Winfree, Seth; Dagher, Pierre C; Dunn, Kenneth W; Eadon, Michael T; Ferkowicz, Michael; Barwinska, Daria; Kelly, Katherine J; Sutton, Timothy A; El-Achkar, Tarek M

    2018-06-05

    Kidney biopsy remains the gold standard for uncovering the pathogenesis of acute and chronic kidney diseases. However, the ability to perform high resolution, quantitative, molecular and cellular interrogation of this precious tissue is still at a developing stage compared to other fields such as oncology. Here, we discuss recent advances in performing large-scale, three-dimensional (3D), multi-fluorescence imaging of kidney biopsies and quantitative analysis referred to as 3D tissue cytometry. This approach allows the accurate measurement of specific cell types and their spatial distribution in a thick section spanning the entire length of the biopsy. By uncovering specific disease signatures, including rare occurrences, and linking them to the biology in situ, this approach will enhance our understanding of disease pathogenesis. Furthermore, by providing accurate quantitation of cellular events, 3D cytometry may improve the accuracy of prognosticating the clinical course and response to therapy. Therefore, large-scale 3D imaging and cytometry of kidney biopsy is poised to become a bridge towards personalized medicine for patients with kidney disease. © 2018 S. Karger AG, Basel.

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

    PubMed Central

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

    2015-01-01

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

  5. Prevalence of kidney stones in China: an ultrasonography based cross-sectional study.

    PubMed

    Zeng, Guohua; Mai, Zanlin; Xia, Shujie; Wang, Zhiping; Zhang, Keqin; Wang, Li; Long, Yongfu; Ma, Jinxiang; Li, Yi; Wan, Show P; Wu, Wenqi; Liu, Yongda; Cui, Zelin; Zhao, Zhijian; Qin, Jing; Zeng, Tao; Liu, Yang; Duan, Xiaolu; Mai, Xin; Yang, Zhou; Kong, Zhenzhen; Zhang, Tao; Cai, Chao; Shao, Yi; Yue, Zhongjin; Li, Shujing; Ding, Jiandong; Tang, Shan; Ye, Zhangqun

    2017-07-01

    To investigate the prevalence and associated factors of kidney stones among adults in China. A nationwide cross-sectional survey was conducted among individuals aged ≥18 years across China, from May 2013 to July 2014. Participants underwent urinary tract ultrasonographic examinations, completed pre-designed and standardised questionnaires, and provided blood and urine samples for analysis. Kidney stones were defined as particles of ≥4 mm. Prevalence was defined as the proportion of participants with kidney stones and binary logistic regression was used to estimate the associated factors. A total of 12 570 individuals (45.2% men) with a mean (sd, range) age of 48.8 (15.3, 18-96) years were selected and invited to participate in the study. In all, 9310 (40.7% men) participants completed the investigation, with a response rate of 74.1%. The prevalence of kidney stones was 6.4% [95% confidence interval (CI) 5.9, 6.9], and the age- and sex-adjusted prevalence was 5.8% (95% CI 5.3, 6.3; 6.5% in men and 5.1% in women). Binary logistic regression analysis showed that male gender, rural residency, age, family history of urinary stones, concurrent diabetes mellitus and hyperuricaemia, increased consumption of meat, and excessive sweating were all statistically significantly associated with a greater risk of kidney stones. By contrast, consumption of more tea, legumes, and fermented vinegar was statistically significantly associated with a lesser risk of kidney stone formation. Kidney stones are common among Chinese adults, with about one in 17 adults affected currently. Some Chinese dietary habits may lower the risk of kidney stone formation. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  6. Antioxidants and self-reported history of kidney stones: the National Health and Nutrition Examination Survey.

    PubMed

    Holoch, Peter A; Tracy, Chad R

    2011-12-01

    Animal studies have demonstrated the likely role of oxidative tissue damage in the pathophysiology of stone disease; however, the effect of antioxidants on stone formation in the human population is unknown. We evaluated the association between serum antioxidant levels and the self-reported prevalence of kidney stones in a large cross-sectional population in a retrospective cohort study. Serum levels of antioxidants among adult participants in the National Health and Nutrition Examination Survey (NHANES III) 1988-1994 were compared between those with and without a self-reported history of kidney stones, adjusting for covariates of age, sex, body mass index (BMI), race/ethnicity, diabetes, and hypertension. The prevalence of kidney stones was 5.25% (95% confidence interval: 4.60%, 5.90%). The prevalence of kidney stones was higher in males, white/non-Hispanics, diabetics, and those with hypertension. The prevalence of kidney stones increased with BMI. After adjusting for covariates, mean levels of alpha-carotene, beta-carotene, and beta-cryptoxanthin were significantly lower in those with kidney stones (-9.36%, -10.79%, and -8.48%, respectively). When analyzed by quartile, higher serum levels of beta-carotene and beta-cryptoxanthin,, trended toward a decreasing prevalence of stones (P=0.007 and P=0.03, respectively), indicating that the highest levels of these antioxidants may protect against the formation of kidney stones. Lower levels of alpha-carotene, beta-carotene, and beta-cryptoxanthin are associated with a history of kidney stones and may indicate a role for these antioxidants in preventing stone formation.

  7. Glomerular parietal epithelial cells of adult murine kidney undergo EMT to generate cells with traits of renal progenitors

    PubMed Central

    G, Swetha; Chandra, Vikash; Phadnis, Smruti; Bhonde, Ramesh

    2011-01-01

    Abstract Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic phenotype in response to renal injury. However, the mechanism of de-differentiation in GPECs and the underlying cellular processes are not fully understood. In the present study, we show that cultured GPECs of adult murine kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and immunostaining of these clonogenic cells demonstrate that they exhibit metastable phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7, C-Ret) genes in these cells, indicating their bipotent progenitor status. Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression of renal progenitor markers reflecting the correlation between EMT and acquired stemness in these cells. Additional in vitro renal commitment assays confirmed their functional staminality. When injected into E13.5 kidney rudiments, the cells incorporated into the developing kidney primordia and co-culture with E13.5 spinal cord resulted in branching and tubulogenesis in these cells. When implanted under renal capsule of unilaterally nephrectomized mice, these cells differentiated into immature glomeruli and vascular ducts. Our study demonstrates that EMT plays a major role in imparting plasticity to terminally differentiated GPECs by producing metastable cells with traits of kidney progenitors. The present study would improve our understanding on epithelial cell plasticity, furthering our knowledge of its role in renal repair and regeneration. PMID:19840197

  8. Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease.

    PubMed

    Reza-Zaldívar, E E; Sandoval-Avila, S; Gutiérrez-Mercado, Y K; Vázquez-Méndez, E; Canales-Aguirre, A A; Esquivel-Solís, H; Gómez-Pinedo, U; Márquez-Aguirre, A L

    2017-11-10

    Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Four decades of kidney transplantation in Cuba.

    PubMed

    Alfonzo, Jorge P

    2013-01-01

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

  10. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

    PubMed

    Camarata, Troy; Howard, Alexis; Elsey, Ruth M; Raza, Sarah; O'Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

    2016-01-01

    New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

  11. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney

    PubMed Central

    Camarata, Troy; Howard, Alexis; Elsey, Ruth M.; Raza, Sarah; O’Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

    2016-01-01

    New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population. PMID:27144443

  12. First in Human Clinical Trial of Ultrasonic Propulsion of Kidney Stones.

    PubMed

    Harper, Jonathan D; Cunitz, Bryan W; Dunmire, Barbrina; Lee, Franklin C; Sorensen, Mathew D; Hsi, Ryan S; Thiel, Jeff; Wessells, Hunter; Lingeman, James E; Bailey, Michael R

    2016-04-01

    Ultrasonic propulsion is a new technology using focused ultrasound energy applied transcutaneously to reposition kidney stones. We report what are to our knowledge the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones. Subjects underwent ultrasonic propulsion while awake without sedation in clinic, or during ureteroscopy while anesthetized. Ultrasound and a pain questionnaire were completed before, during and after propulsion. The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controllable movement of stones and movement of stones less than 5 mm and 5 mm or greater. Adverse events were assessed weekly for 3 weeks. Kidney stones were repositioned in 14 of 15 subjects. Of the 43 targets 28 (65%) showed some level of movement while 13 (30%) were displaced greater than 3 mm to a new location. Discomfort during the procedure was rare, mild, brief and self-limited. Stones were moved in a controlled direction with more than 30 fragments passed by 4 of the 6 subjects who had previously undergone a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of a large stone at the ureteropelvic junction. In 4 subjects a seemingly large stone was determined to be a cluster of small passable stones after they were moved. Ultrasonic propulsion was able to successfully reposition stones and facilitate the passage of fragments in humans. No adverse events were associated with the investigational procedure. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

    PubMed Central

    Ahlstedt, Jonas; Tran, Thuy A.; Strand, Sven-Erik; Gram, Magnus; Åkerström, Bo

    2015-01-01

    Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies. PMID:26694383

  14. Severe acute dehydration in a desert rodent elicits a transcriptional response that effectively prevents kidney injury.

    PubMed

    MacManes, Matthew David

    2017-08-01

    Animals living in desert environments are forced to survive despite severe heat, intense solar radiation, and both acute and chronic dehydration. These animals have evolved phenotypes that effectively address these environmental stressors. To begin to understand the ways in which the desert-adapted rodent Peromyscus eremicus survives, reproductively mature adults were subjected to 72 h of water deprivation, during which they lost, on average, 23% of their body weight. The animals reacted via a series of changes in the kidney, which included modulating expression of genes responsible for reducing the rate of transcription and maintaining water and salt balance. Extracellular matrix turnover appeared to be decreased, and apoptosis was limited. In contrast to the canonical human response, serum creatinine and other biomarkers of kidney injury were not elevated, suggesting that changes in gene expression related to acute dehydration may effectively prohibit widespread kidney damage in the cactus mouse. Copyright © 2017 the American Physiological Society.

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

    PubMed

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

    2011-01-01

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

  16. A Review of Organ Transplantation: Heart, Lung, Kidney, Liver, and Simultaneous Liver-Kidney.

    PubMed

    Scheuher, Cynthia

    2016-01-01

    Heart, lung, kidney, liver, and simultaneous liver-kidney transplants share many features. They all follow the same 7-step process, the same 3 immunosuppressant medications, and the same reason for organ transplantation. Organs are transplanted because of organ failure. The similarities end there. Each organ has its unique causes for failure. Each organ also has its own set of criteria that must be met prior to transplantation. Simultaneous liver-kidney transplant criteria vary per transplant center but are similar in nature. Both the criteria required and the 7-step process are described by the United Network of Organ Sharing, which is a private, nonprofit organization, under contract with the US Department of Health and Human Services. Its function is to increase the number of transplants, improve survival rates after transplantation, promote safe transplant practices, and endorse efficiency. The purpose of this article is to review the reasons transplant is needed, specifically heart, lung, kidney, liver, and simultaneous liver-kidney, and a brief overview of the transplant process including criteria used, contraindications, and medications prescribed.

  17. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    ERIC Educational Resources Information Center

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  18. Dietary Potential Renal Acid Load and Risk of Albuminuria and Reduced Kidney Function in the Jackson Heart Study.

    PubMed

    Banerjee, Tanushree; Tucker, Katherine; Griswold, Michael; Wyatt, Sharon B; Harman, Jane; Young, Bessie; Taylor, Herman; Powe, Neil R

    2018-07-01

    Diets high in sulfur-rich protein and low in fruit and vegetables affect human acid-base balance adversely and may have a harmful effect on progression of chronic kidney disease (CKD). Little is known about the relationship of participant characteristics, dietary acid load (DAL), and kidney injury in African-Americans with high risk of CKD progression. We examined the association of DAL with CKD in 3,257 African-Americans aged >20 years in Jackson Heart Study. DAL was measured with nutrient intakes assessed with a food frequency questionnaire, using a model described by Remer and Manz. We tested associations of participant characteristics with DAL using median regression, and associations of DAL with albuminuria (>17 mg/g for men, >25 mg/g for women), reduced kidney function (eGFR <60 mL/minute/1.73 m 2 ), or CKD defined as albuminuria or reduced kidney function using logistic regression. We further explored whether endothelin and aldosterone production in participants with hypertension mediated risk of albuminuria or reduced kidney function due to the intake of an acid-inducing diet. Younger adults, men, and those with higher body mass index had higher DAL. Higher DAL, compared with lower, was associated with greater odds of reduced kidney function (OR [95% CI]: 2.82 [1.40-4.75]). Higher DAL was also associated with greater risk of CKD, and this persisted after adjustment for confounders. Results were similar in adults with hypertension; the OR [95% CI] for highest, versus lowest, tertile of DAL with albuminuria was 1.66 [1.01-2.59]. Aldosterone and endothelin mediated the association between DAL and albuminuria; the OR [95% CI] in the highest tertile was no longer significant 1.53 [0.97-2.40] after their inclusion. Higher DAL was associated with higher prevalence of CKD and with reduced kidney function. DAL may be an important target for future interventions in African-Americans at high risk of CKD. Copyright © 2018 National Kidney Foundation, Inc

  19. Phase composition and morphological characterization of human kidney stones using IR spectroscopy, scanning electron microscopy and X-ray Rietveld analysis.

    PubMed

    Chatterjee, Paramita; Chakraborty, Arup; Mukherjee, Alok K

    2018-07-05

    Pathological calcification in human urinary tract (kidney stones) is a common problem affecting an increasing number of people around the world. Analysis of such minerals or compounds is of fundamental importance for understanding their etiology and for the development of prophylactic measures. In the present study, structural characterization, phase quantification and morphological behaviour of thirty three (33) human kidney stones from eastern India have been carried out using IR spectroscopy (FT-IR), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). Quantitative phase composition of kidney stones has been analyzed following the Rietveld method. Based on the quantitative estimates of constituent phases, the calculi samples have been classified into oxalate (OX), uric acid (UA), phosphate (PH) and mixed (MX) groups. Rietveld analysis of PXRD patterns showed that twelve (36%) of the renal calculi were composed exclusively of whewellite (calcium oxalate monohydrate, COM). The remaining twenty one (64%) stones were mixture of phases with oxalate as the major constituent in fourteen (67%) of these stones. The average crystallite size of whewellite in oxalate stones, as determined from the PXRD analysis, varies between 93 (1) nm and 202 (3) nm, whereas the corresponding sizes for the uric acid and struvite crystallites in UA and PH stones are 79 (1)-155 (4) nm and 69 (1)-123(1) nm, respectively. The size of hydroxyapatite crystallites, 10 (1)-21 (1) nm, is smaller by about one order of magnitude compared to other minerals in the kidney stones. A statistical analysis using fifty (50) kidney stones (33 calculi from the present study and 17 calculi reported earlier from our laboratory) revealed that the oxalate group (whewellite, weddellite or mixture of whewellite and weddellite as the major constituent) is the most prevalent (82%) kidney stone type in eastern India. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. MRI quantification of non-Gaussian water diffusion in normal human kidney: a diffusional kurtosis imaging study.

    PubMed

    Huang, Yanqi; Chen, Xin; Zhang, Zhongping; Yan, Lifen; Pan, Dan; Liang, Changhong; Liu, Zaiyi

    2015-02-01

    Our aim was to prospectively evaluate the feasibility of diffusional kurtosis imaging (DKI) in normal human kidney and to report preliminary DKI measurements. Institutional review board approval and informed consent were obtained. Forty-two healthy volunteers underwent diffusion-weighted imaging (DWI) scans with a 3-T MR scanner. b values of 0, 500 and 1000 s/mm(2) were adopted. Maps of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (D⊥), axial diffusivity (D||), mean kurtosis (MK), radial kurtosis (K⊥) and axial kurtosis (K||) were produced. Three representative axial slices in the upper pole, mid-zone and lower pole were selected in the left and right kidney. On each selected slice, three regions of interest were drawn on the renal cortex and another three on the medulla. Statistical comparison was performed with t-test and analysis of variance. Thirty-seven volunteers successfully completed the scans. No statistically significant differences were observed between the left and right kidney for all metrics (p values in the cortex: FA, 0.114; MD, 0.531; D⊥, 0.576; D||, 0.691; MK, 0.934; K⊥, 0.722; K||, 0.891; p values in the medulla: FA, 0.348; MD, 0.732; D⊥, 0.470; D||, 0.289; MK, 0.959; K⊥, 0.780; K||, 0.287). Kurtosis metrics (MK, K||, K⊥) obtained in the renal medulla were significantly (p <0.001) higher than those in the cortex (0.552 ± 0.04, 0.637 ± 0.07 and 0.530 ± 0.08 in the medulla and 0.373 ± 0.04, 0.492 ± 0.06 and 0.295 ± 0.06 in the cortex, respectively). For the diffusivity measures, FA of the medulla (0.356 ± 0.03) was higher than that of the cortex (0.179 ± 0.03), whereas MD, D⊥ and D|| (mm(2) /ms) were lower in the medulla than in the cortex (3.88 ± 0.09, 3.50 ± 0.23 and 4.65 ± 0.29 in the cortex and 2.88 ± 0.11, 2.32 ± 0.20 and 3.47 ± 0.31 in the medulla, respectively). Our results indicate that DKI is feasible in the human kidney. We

  1. Germline stem cells and neo-oogenesis in the adult human ovary.

    PubMed

    Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

    2007-06-01

    It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

  2. Silicate calculi, a rare cause of kidney stones in children.

    PubMed

    Taşdemir, Mehmet; Fuçucuoğlu, Dilara; Özman, Oktay; Sever, Lale; Önal, Bülent; Bilge, Ilmay

    2017-02-01

    Urinary silicate calculi in humans are extremely rare. Reported cases of silicate calculi are mostly documented in adults and are commonly related to an excessive intake of magnesium trisilicate in food or drugs. Published studies on the presence of silicate calculi in children are scarce. Three cases of silicate kidney stones without prior silicate intake are reported. Two patients underwent surgical treatment, and the third patient was treated using conservative methods. Urinalysis revealed no underlying metabolic abnormalities. Analyses revealed that silicate was the major component of the stones. Siliceous deposits in urinary stones may be more common than anticipated, and the underlying pathophysiology remains to be clarified.

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

    PubMed

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

    2018-05-15

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

  4. The kidneys in the Bible: what happened?

    PubMed

    Eknoyan, Garabed

    2005-12-01

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

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

    PubMed

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

    2016-01-01

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

  6. 78 FR 43218 - Notice of Kidney Interagency Coordinating Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Notice of Kidney Interagency Coordinating Committee Meeting SUMMARY: The Kidney Interagency Coordinating Committee (KICC) will hold a meeting on September 27, 2013, about interagency collaboration to improve outcomes in Chronic Kidney...

  7. Quantitative Enzymatic and Immunologic Histophotometry of Diseased Human Kid-Ney Tissues Using Tv-Camera and Computer Assisted Image Processing Systems.

    NASA Astrophysics Data System (ADS)

    Heinert, G.; Mondorf, W.

    1982-11-01

    High speed image processing was used to analyse morphologic and metabolic characteristics of clinically relevant kidney tissue alterations.Qualitative computer-assisted histophotometry was performed to measure alterations in levels of the enzymes alkaline phosphatase (Ap),alanine aminopeptidase (AAP),g-glutamyltranspepti-dase (GGTP) and A-glucuronidase (B-G1) and AAP and GGTP immunologically determined in prepared renal and cancer tissue sections. A "Mioro-Videomat 2" image analysis system with a "Tessovar" macroscope,a computer-assisted "Axiomat" photomicroscope and an "Interactive Image Analysis System (IBAS)" were employed for analysing changes in enzyme activities determined by changes in absorbance or transmission.Diseased kidney as well as renal neoplastic tissues could be distinguished by significantly (wilcoxon test,p<0,05) decreased enzyme concentrations as compared to those found in normal human kidney tissues.This image analysis techniques might be of potential use in diagnostic and prognostic evaluation of renal cancer and diseased kidney tissues.

  8. Experience with dual kidney transplants from donors at the extremes of age.

    PubMed

    Moore, Phillip S; Farney, Alan C; Sundberg, Aimee K; Rohr, Michael S; Hartmann, Erica L; Iskandar, Samy S; Gautreaux, Michael D; Rogers, Jeffrey; Doares, William; Anderson, Teresa K; Adams, Patricia L; Stratta, Robert J

    2006-10-01

    Dual kidney transplantation (DKT) from donors at the extremes of age represents one approach to expanding the organ donor pool. The purpose of this study was to review our experience with DKT from older donors and en bloc KT (EBKT) from small pediatric donors. Deceased donor KTs performed at our center between October 2001 and November 2005, were reviewed retrospectively. If the calculated creatinine clearance in an expanded criteria donor was <65 mL/min, then the kidneys were transplanted dually into a single adult recipient. If a pediatric donor weighed <15 kg, then the kidneys were transplanted en bloc. In both instances, low-risk recipients were chosen (primary transplant, low sensitization, body mass index <25 kg/m(2), human leukocyte antigen matching). Donor, recipient, and transplant characteristics, waiting time, and outcomes were examined. Of a total of 279 deceased donor KTs during the 49-month study period, 15 (5%) recipients underwent DKT and 5 (2%) underwent EBKT. Mean donor age was 65.4 years and 21.4 months in the DKT and EBKT groups, respectively. Patient survival rates in both groups were 100% with a mean follow-up of 22 months (minimum, 6 months). Kidney graft survival rates were 80% (12/15) and 60% (3/5) in the DKT and EBKT groups, respectively. The combined incidence of delayed graft function was 10%. Mean 12-month glomerular filtration rates were 46 mL/min and 66 mL/min in the DKT and EBKT groups, respectively. DKT using kidneys from marginal elderly donors and EBKT from small pediatric donors appear to offer a viable option to counteract the shortage of acceptable kidney donors.

  9. Targeting Iron Homeostasis in Acute Kidney Injury

    PubMed Central

    Walker, Vyvyca J.; Agarwal, Anupam

    2017-01-01

    Summary Iron is an essential metal involved in several major cellular processes required to maintain life. Because of iron’s ability to cause oxidative damage, its transport, metabolism, and storage is strictly controlled in the body, especially in the small intestine, liver, and kidney. Iron plays a major role in acute kidney injury and has been a target for therapeutic intervention. However, the therapies that have been effective in animal models of acute kidney injury have not been successful in human beings. Targeting iron trafficking via ferritin, ferroportin, or hepcidin may offer new insights. This review focuses on the biology of iron, particularly in the kidney, and its implications in acute kidney injury. PMID:27085736

  10. Characterization of kidney lesions in Indian adults: towards a renal biopsy registry.

    PubMed

    Narasimhan, Balakrishnan; Chacko, Bobby; John, George T; Korula, Anila; Kirubakaran, Meshach G; Jacob, Chakko K

    2006-01-01

    In the absence of a renal biopsy registry, there is a paucity of data on the renal disease pattern seen in India. This study reviews the changing pattern of renal disease seen at a single center over the last 30 yrs. Histopathological data of 5415 adequate native kidney biopsies performed on consecutive adult Indian patients presenting to our hospital from 1986-2002 were analyzed. This pathological demography classified according to the modified World Health Organization (WHO) classification was compared to the earlier published cohort collected from 1971-1985 (n=2827) to ascertain the changing trends. The indications for renal biopsy were comparable between the cohorts and included nephrotic syndrome (65%), nephritic syndrome (13%) and chronic renal failure (10.2%). Primary glomerular disease accounted for 71% of all biopsies. Non-immunoglobulin A (IgA) mesangio proliferative glomerulonephritis as a group was the predominant pathology (20.2%), followed by idiopathic focal segmental glomerulosclerosis (FSGS) (17%), minimal change disease (MCD) (11.6%), membranous glomerulopathy (MN) (9.8%), IgA nephropathy (8.6%) and membranoproliferative glomerulonephritis (MPGN) (3.7%). Of the patients with secondary kidney diseases, lupus nephritis (6.5%), diabetic nephropathy (2.5%), interstitial nephropathy (2.5%) and benign nephrosclerosis (2.2%) were notable. During the 31 yrs of the study period, there was a steady increase in FSGS prevalence (p<0.001), MN (p<0.0001), and post infectious glomerulonephritis (PIGN) (p<0.001). A reduction in the frequency of MPGN (p<0.001) and MCD (p<0.001) was observed. This is the largest series of renal biopsy data from India; and therefore, could reflect the demographic picture of renal diseases in this country. It discusses evolving patterns over 30 yrs and highlights differences with the developed world. This report represents the basis for the future of a renal biopsy registry in India.

  11. Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults.

    PubMed

    Tamura, Manjula Kurella; Pajewski, Nicholas M; Bryan, R Nick; Weiner, Daniel E; Diamond, Matthew; Van Buren, Peter; Taylor, Addison; Beddhu, Srinivasan; Rosendorff, Clive; Jahanian, Hesamoddin; Zaharchuk, Greg

    2016-03-29

    To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults. We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics. There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g). Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV. © 2016 American Academy of Neurology.

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

    PubMed

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

    2013-09-01

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

  13. Synthetic marijuana and acute kidney injury: an unforeseen association.

    PubMed

    Kazory, Amir; Aiyer, Ravi

    2013-06-01

    Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations.

  14. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia

    PubMed Central

    Garrido, Patrícia; Ribeiro, Sandra; Fernandes, João; Vala, Helena; Rocha-Pereira, Petronila; Bronze-da-Rocha, Elsa; Belo, Luís; Costa, Elísio; Santos-Silva, Alice; Reis, Flávio

    2015-01-01

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue (kidney, liver and/or duodenum) protein and/or gene expression of mediators of erythropoiesis, iron metabolism and tissue hypoxia, inflammation, and fibrosis. Long-term treatment with a high rHuEPO dose is associated with development of resistance to therapy as a result of antibodies formation. In this condition, serum EPO levels are not deficient and iron availability is recovered by increased duodenal absorption. However, erythropoiesis is not stimulated, and the resistance to endogenous EPO effect and to rHuEPO therapy results from the development of a hypoxic, inflammatory and fibrotic milieu in the kidney tissue. This study provides new insights that could be important to ameliorate the current therapeutic strategies used to treat patients with CKD-associated anemia, in particular those that become resistant to rHuEPO therapy. PMID:26712750

  15. The importance of total kidney volume in evaluating progression of polycystic kidney disease

    PubMed Central

    Grantham, Jared J.; Torres, Vicente E.

    2017-01-01

    The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue. PMID:27694979

  16. Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).

    PubMed

    Mace, T F

    1976-01-01

    Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.

  17. [Case report of rhabdoid tumor of the kidney occurring in own kidney following kidney transplantation from the living relative].

    PubMed

    Sato, Yasuyuki; Iizuka, Jyunpei; Imai, Kenji; Sawada, Yugo; Komatsu, Tomonori; Yago, Rie; Kondo, Tsunenori; Ishida, Hideki; Tanabe, Kazunari

    2010-07-01

    The patient was a 30-year-old man who had undergone living-donor kidney transplantation for renal failure caused by IgA nephropathy at age 29. On post-transplantation day 83, he visited our department with a chief complaint of asymptomatic hematuria. CT performed on post-transplantation day 95 revealed a tumor (size, 4 cm) in the right native kidney that had not been observed at the time of transplantation. CT performed on post-transplantation day 153 showed that the tumor had enlarged to 6 cm, while retrograde pyelogram performed on post-transplantation day 171 was negative for renal pelvic tumor. On post-transplantation day 193, radical right nephrectomy was performed. The tumor had directly invaded the diaphragm and the lower surface of the liver, and was histopathologically diagnosed as rhabdoid tumor of the kidney. As the pathological tissue was extremely malignant, hepatic posterior segmentectomy, right adrenalectomy, and lymph node dissection were further performed for metastases on post-transplantation day 200. On the 23rd day after radical right nephrectomy (post-transplantation day 216), the patient developed dyspnea. Chest CT showed pleural effusion, hemothorax in right lung and metastases in both lungs. The patient's general status gradually worsened thereafter, and he died on the 53rd day after radical right nephrectomy (post-transplantation day 246). Rhabdoid tumor of the kidney is a rare renal tumor that affects children, and only four adult cases have been reported to date. We report our experience with this rare case.

  18. Impact of chronic kidney disease on mortality in older adults treated with pacemaker implantation

    PubMed Central

    Fabbian, Fabio; De Giorgi, Alfredo; Guarino, Matteo; Malagù, Michele; Bertini, Matteo

    2017-01-01

    Objective To investigate whether chronic kidney disease could negatively impact survival in older adults needing pacemaker implantation after admission for bradyarrhythmias. Methods This retrospective observational study considered 538 older adults consecutively admitted, who had been followed-up for 31 ± 20 months. Subjects with poor short-term prognosis were excluded. Charlson comorbidity index (CCI) and estimated glomerular filtration rate (eGFR) was calculated, along with the independent relationship between all-cause mortality and clinical data. Hazard Ratio (HR) was calculated by Cox regression analysis. Results Mean age of the population was 85 ± 3.7 years, and causes for implantation were atrioventricular block in 51.9% and other bradyarrhythmias in 48.1% of cases. Mean eGFR was 58.3 ± 24 mL/min per 1.73 m2, and mean CCI was 3.65 ± 2.28. Death for all-causes was recorded in 213 subjects. Deceased patients were older, had lower eGFR, higher comorbidity, higher prevalence of myocardial infarction, congestive heart failure, cerebrovascular disease, dementia and chronic pulmonary disease. Age (HR: 1.081, 95% CI: 1.044–1.119; P < 001), CCI (HR: 1.651, 95% CI: 1.286–2.121, P < 001) and eGFR ≤ 45 mL/min per 1.73 m2 (HR: 1.360, 95% CI: 1.024–1.806; P = 0.033) were predictors of death. Conclusions Renal dysfunction, as well as comorbidity, impacts negatively survival of older adults treated with pacemaker implantation because of bradyarrhythmias. PMID:29238360

  19. Human pancreatic polypeptide in children and young adults.

    PubMed

    Hanukoglu, A; Chalew, S; Kowarski, A A

    1990-01-01

    Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults.

  20. Perceived Discrimination and Longitudinal Change in Kidney Function Among Urban Adults.

    PubMed

    Beydoun, May A; Poggi-Burke, Angedith; Zonderman, Alan B; Rostant, Ola S; Evans, Michele K; Crews, Deidra C

    2017-09-01

    Perceived discrimination has been associated with psychosocial distress and adverse health outcomes. We examined associations of perceived discrimination measures with changes in kidney function in a prospective cohort study, the Healthy Aging in Neighborhoods of Diversity across the Life Span. Our study included 1620 participants with preserved baseline kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m) (662 whites and 958 African Americans, aged 30-64 years). Self-reported perceived racial discrimination and perceived gender discrimination (PGD) and a general measure of experience of discrimination (EOD) ("medium versus low," "high versus low") were examined in relation to baseline, follow-up, and annual rate of change in eGFR using multiple mixed-effects regression (γbase, γrate) and ordinary least square models (γfollow). Perceived gender discrimination "high versus low PGD" was associated with a lower baseline eGFR in all models (γbase = -3.51 (1.34), p = .009 for total sample). Among white women, high EOD was associated with lower baseline eGFR, an effect that was strengthened in the full model (γbase = -5.86 [2.52], p = .020). Overall, "high versus low" PGD was associated with lower follow-up eGFR (γfollow = -3.03 [1.45], p = .036). Among African American women, both perceived racial discrimination and PGD were linked to lower follow-up kidney function, an effect that was attenuated with covariate adjustment, indicating mediation through health-related, psychosocial, and lifestyle factors. In contrast, EOD was not linked to follow-up eGFR in any of the sex by race groups. Perceived racial and gender discrimination are associated with lower kidney function assessed by glomerular filtration rate and the strength of associations differ by sex and race groups. Perceived discrimination deserves further investigation as a psychosocial risk factors for kidney disease.

  1. In search of adult renal stem cells.

    PubMed

    Anglani, F; Forino, M; Del Prete, D; Tosetto, E; Torregrossa, R; D'Angelo, A

    2004-01-01

    The therapeutic potential of adult stem cells in the treatment of chronic degenerative diseases has becoming increasingly evident over the last few years. Significant attention is currently being paid to the development of novel treatments for acute and chronic kidney diseases too. To date, promising sources of stem cells for renal therapies include adult bone marrow stem cells and the kidney precursors present in the early embryo. Both cells have clearly demonstrated their ability to differentiate into the kidney's specialized structures. Adult renal stem cells have yet to be identified, but the papilla is where the stem cell niche is probably located. Now we need to isolate and characterize the fraction of papillary cells that constitute the putative renal stem cells. Our growing understanding of the cellular and molecular mechanisms behind kidney regeneration and repair processes - together with a knowledge of the embryonic origin of renal cells - should induce us, however, to bear in mind that in the kidney, as in other mesenchymal tissues, the need for a real stem cell compartment might be less important than the phenotypic flexibility of tubular cells. Thus, by displaying their plasticity during kidney maintenance and repair, terminally differentiated cells may well function as multipotent stem cells despite being at a later stage of maturation than adult stem cells. One of the major tasks of Regenerative Medicine will be to disclose the molecular mechanisms underlying renal tubular plasticity and to exploit its biological and therapeutic potential.

  2. In Utero Bisphenol A Concentration, Metabolism, and Global DNA Methylation Across Matched Placenta, Kidney, and Liver in the Human Fetus

    PubMed Central

    Nahar, Muna S.; Liao, Chunyang; Kannan, Kurunthachalam; Harris, Craig; Dolinoy, Dana C.

    2014-01-01

    While urine has been an easily accessible and feasible matrix for human biomonitoring, analytical measurements in internal tissues and organs can provide more accurate exposure assessments to understand disease etiology. This is especially important for the endocrine active compound, bisphenol A (BPA), where studies investigating internal doses at sensitive periods of human development are currently lacking. Herein, BPA concentrations, BPA-specific metabolizing enzyme gene expression, and global DNA methylation were characterized across three matched tissues from elective pregnancy terminations of 2nd trimester human fetuses: the placenta, liver, and kidney (N=12 each; N=36 total). Compared to liver (free: 0.54-50.5 ng/g), BPA concentrations were lower in matched placenta (<0.05-25.4 ng/g) and kidney (0.08-11.1 ng/g) specimens. BPA-specific metabolism gene expression of GUSB, UGT2B15, STS, and SULT1A1 differed across each tissue type; however, conjugation and deconjugation expression patterns were similar across the fetus. Average LINE1 and CCGG global methylation were 58.3 and 59.2% in placenta, 79.5 and 66.4% in fetal liver, and 77.9 and 77.0% in fetal kidney, with significant tissue-specific DNA methylation differences in both LINE1 (p-value <0.001) and CCGG content (p-value <0.001). Total BPA concentrations were positively associated with global methylation for the placenta only using the LINE1 assay (p-value: 0.002), suggesting organ-specific biological effects after fetal exposure. Utilizing sensitive human clinical specimens, results are informative for BPA toxicokinetics and toxicodynamics assessment in the developing human fetus. PMID:25434263

  3. Wavelet-based segmentation of renal compartments in DCE-MRI of human kidney: initial results in patients and healthy volunteers.

    PubMed

    Li, Sheng; Zöllner, Frank G; Merrem, Andreas D; Peng, Yinghong; Roervik, Jarle; Lundervold, Arvid; Schad, Lothar R

    2012-03-01

    Renal diseases can lead to kidney failure that requires life-long dialysis or renal transplantation. Early detection and treatment can prevent progression towards end stage renal disease. MRI has evolved into a standard examination for the assessment of the renal morphology and function. We propose a wavelet-based clustering to group the voxel time courses and thereby, to segment the renal compartments. This approach comprises (1) a nonparametric, discrete wavelet transform of the voxel time course, (2) thresholding of the wavelet coefficients using Stein's Unbiased Risk estimator, and (3) k-means clustering of the wavelet coefficients to segment the kidneys. Our method was applied to 3D dynamic contrast enhanced (DCE-) MRI data sets of human kidney in four healthy volunteers and three patients. On average, the renal cortex in the healthy volunteers could be segmented at 88%, the medulla at 91%, and the pelvis at 98% accuracy. In the patient data, with aberrant voxel time courses, the segmentation was also feasible with good results for the kidney compartments. In conclusion wavelet based clustering of DCE-MRI of kidney is feasible and a valuable tool towards automated perfusion and glomerular filtration rate quantification. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

    PubMed Central

    Bansal, Nisha; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen; Lima, Joao; Kramer, Holly; Shlipak, Michael; Bibbins-Domingo, Kirsten

    2015-01-01

    Background Left ventricular hypertrophy (LVH) is common and is associated with cardiovascular events and death among patients with known chronic kidney disease (CKD). However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Study Design Observational study Setting & Participants We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys >60 ml/min/1.73 m2 at Year 15 and who had an echocardiogram performed at Year 25. Predictor eGFRcys at Year 15 and rapid decline of eGFRcys (defined as >3% per year over 5 years from Years 15 to 20) Outcome LVMI measured at Year 25 Measurements We adjusted for age, sex, race, diabetes, body mass index, LDL and HDL cholesterol, cumulative systolic blood pressure, and albuminuria. Results Mean age was 40 ±4 (SD) years, 58% were female and 43% were Black. After 10 years of follow-up, mean LVMI was 39.6 ±13.4 g/m2.7. Compared with eGFRcys >90 ml/min/1.73 m2 (n=2228), eGFRcys 60-75 ml/min/1.73 m2 (n=29) was associated with 5.63 (95% CI, 0.90-10.36) g/m2.7 greater LVMI (p=0.02), but there was no association of eGFR 76-90 ml/min/1.73 m2 (n=153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared to participants without a rapid GFR decline (β-coefficient, 1.48; 95% CI, 0.11-2.83; p=0.03) after adjustment for confounders. Limitations There were a limited number of participants with eGFR 60-90 ml/min/1.73 m2. Conclusions Among young and middle-aged adults with preserved kidney function, eGFRcys 60-75 ml/min/1.73 m2 and rapid decline of eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the

  5. Prevalence of chronic kidney disease defined by using CKD-EPI equation and albumin-to-creatinine ratio in the Korean adult population.

    PubMed

    Ji, Eunhee; Kim, Yon Su

    2016-11-01

    An updated chronic kidney disease (CKD) definition and classification were proposed by Kidney Disease: Improving Global Outcomes (KDIGO), with adoption of a new equation to estimate glomerular filtration rate (GFR) and albuminuria to evaluate kidney structural damage. This study was performed to estimate the prevalence of CKD in the Korean adult population as defined and classified by the KDIGO guidelines. Cross-sectional samples of the fifth Korean National Health and Nutrition Examination Survey for 2011 to 2012 were examined for adults aged ≥ 19 years. CKD prevalence was determined based on decreased GFR and albuminuria. The GFR was estimated using the CKD Epidemiology Collaboration creatinine equation, and albuminuria was evaluated using the albumin-to-creatinine ratio (ACR) in spot urine. Of the 16,576 subjects participating in the survey, 10,636 (4,758 men, 5,878 women) were included in the present study. The prevalence of CKD was estimated as 7.9% (7.8% in 2011 and 8.0% in 2012, p = 0.770). The prevalence of low, moderately increased, high, and very high CKD risk prognosis was 92.0%, 6.3%, 1.1%, and 0.6%, respectively. The prevalence of albuminuria (ACR ≥ 30 mg/g) in individuals with GFR ≥ 60 mL/min/1.73 m 2 has reached 5.7%. The odds ratios of hypertension and diabetes to CKD were 3.4 and 3.1 in men, and 2.9 and 2.0 in women (all p < 0.001), respectively. A large percentage of CKD patients had albuminuria prior to a decrease in GFR. Regular laboratory tests for albuminuria for the high-risk group, and especially for hypertensive or diabetic patients, might improve detection of CKD at an early stage.

  6. Exertional rhabdomyolysis leading to acute kidney injury: when genetic defects are diagnosed in adult life.

    PubMed

    Cucchiari, David; Colombo, Irene; Amato, Ottavia; Podestà, Manuel Alfredo; Reggiani, Francesco; Valentino, Rossella; Faravelli, Irene; Testolin, Silvia; Moggio, Maurizio; Badalamenti, Salvatore

    2018-05-01

    Rhabdomyolysis is a common cause of acute kidney injury (AKI) that is usually triggered by trauma. However, less common causes of rhabdomyolysis may precipitate AKI as well, possibly representing a diagnostic challenge even for the experienced nephrologist. Genetic defects of muscle metabolism represent one of these causes and can be overlooked in adults, since these diseases usually become apparent in childhood. We present here a case in which an adult patient with severe exertional rhabdomyolysis leading to AKI was finally diagnosed with a genetic defect of lipid metabolism. A 41-year-old patient was brought to our attention because of AKI and pigmenturia after strenuous physical effort. At admission, the patient was over-hydrated with a weight increase of 3 kg in few days. Laboratory examination showed creatinine of 8.7 mg/dl, along with increased myoglobin and CPK. Urinalysis was positive for haemoglobin and proteins, while urinary sediment analysis did not demonstrate any red blood cell but rather "muddy-brown" casts and tubular cells. Urine output was forced and the patient completely recovered renal function. Genetic analysis later demonstrated the presence of a common mutation of Carnitine Palmitoyl-Transferase II (CPTII). When facing rhabdomyolysis of obscure origin, nephrologists must keep in mind the possibility that even adult patients may have a genetic defect of energy metabolism. In these cases, patients usually experience rhabdomyolysis during exertion, fasting, or infection. CPTII deficiency often has a subtle presentation and might be unrecognized until AKI develops. Therefore, it is important to consider a genetic defect of muscle metabolism even in adult patients when a history of rhabdomyolysis of unclear origin is present.

  7. Flow cytometry of human embryonic kidney cells: A light scattering approach

    NASA Technical Reports Server (NTRS)

    Kunze, M. E.; Goolsby, C. L.; Todd, P. W.; Morrison, D. R.; Lewis, M. L.

    1985-01-01

    The mammalian kidney contains cells that transport water, convert vitamin D to active forms, synthesize hormones such a renin and erythropoietin, and produce enzymes such as urokinase, a plasminogen activator. Several of these functions are maintained by human embryonic kidney cells (HEK) cultivated in vitro. Biochemical study of these functions in their individual cell types in vitro requires purified populations of cells. Light-scattering activated cell sorting (LACS) was explored as a means of achieving such purifications. It was found that HEK cells at the first 1 to 5 passages in culture were heterogeneous with respect to 2-parameter light scattering intensity distribution, in which combined measurements included forward angle scattering (2.5 to 19 deg), 90 deg scattering, and time-of-flight size measurements. Size was measured at a resolution of 0.15 microns/channel in 256 channels using pulse-height independent pulse-width measurements. Two-parameter distributions combining these measurements were obtained for HEK cell subpopulations that had been purified by microgravity electrophoresis and subsequently propagated in culture. These distributions contained at least 3 subpopulations in all purified fractions, and results of experiments with prepurified cultured HEK cells indicated that subpopulations of living cells that were high in plasminogen-activator activity also contained the highest per cent of cells with high 90 deg light scatter intensity.

  8. Kidney Dysplasia

    MedlinePlus

    ... 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 ...

  9. Chronic Kidney Disease Awareness Among Individuals with Clinical Markers of Kidney Dysfunction

    PubMed Central

    Plantinga, Laura C.; Hsu, Chi-yuan; Jordan, Regina; Burrows, Nilka Ríos; Hedgeman, Elizabeth; Yee, Jerry; Saran, Rajiv; Powe, Neil R.

    2011-01-01

    Summary Background and objectives Awareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness. Design, setting, participants, & measurements CKD awareness was assessed in 1852 adults with an estimated GFR <60 ml/min per 1.73 m2 using 1999 to 2008 National Health and Nutrition Examination Survey data. CKD awareness was a “yes” answer to “Have you ever been told you have weak or failing kidneys?” Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression. Results Among individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P < 0.01) than those without. Odds of CKD awareness increased with each additional manifested clinical marker of CKD (adjusted odds ratio, 1.3, P = 0.05). Nonetheless, 90% of individuals with two to four markers of CKD and 84% of individuals with ≥5 markers of CKD were unaware of their disease. Conclusions Although individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications. PMID:21784832

  10. Graded Association Between Kidney Function and Impaired Orthostatic Blood Pressure Stabilization in Older Adults.

    PubMed

    Canney, Mark; O'Connell, Matthew D L; Sexton, Donal J; O'Leary, Neil; Kenny, Rose Anne; Little, Mark A; O'Seaghdha, Conall M

    2017-05-04

    Impaired orthostatic blood pressure (BP) stabilization is highly prevalent in older adults and is a predictor of end-organ injury, falls, and mortality. We sought to characterize the relationship between postural BP responses and the kidney. We performed a cross-sectional analysis of 4204 participants from The Irish Longitudinal Study on Ageing, a national cohort of community-dwelling adults aged ≥50 years. Beat-to-beat systolic and diastolic BP were measured during a 2-minute active stand test. The primary predictor was cystatin C estimated glomerular filtration rate (eGFR) categorized as follows (mL/min per 1.73 m 2 ): ≥90 (reference, n=1414); 75 to 89 (n=1379); 60 to 74 (n=942); 45 to 59 (n=337); <45 (n=132). We examined the association between eGFR categories and (1) sustained orthostatic hypotension, defined as a BP drop exceeding consensus thresholds (systolic BP drop ≥20 mm Hg±diastolic BP drop ≥10 mm Hg) at each 10-second interval from 60 to 110 seconds inclusive; (2) pattern of BP stabilization, characterized as the difference from baseline in mean systolic BP/diastolic BP at 10-second intervals. The mean age of subjects was 61.6 years; 47% of subjects were male, and the median eGFR was 82 mL/min per 1.73 m 2 . After multivariable adjustment, participants with eGFR <60 mL/min per 1.73 m 2 were approximately twice as likely to have sustained orthostatic hypotension ( P =0.008 for trend across eGFR categories). We observed a graded association between eGFR categories and impaired orthostatic BP stabilization, particularly within the first minute of standing. We report a novel, graded relationship between diminished eGFR and impaired orthostatic BP stabilization. Mapping the postural BP response merits further study in kidney disease as a potential means of identifying those at risk of hypotension-related events. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  11. Kidney regeneration by xeno-embryonic nephrogenesis.

    PubMed

    Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Kawamura, Tetsuya

    2008-03-01

    Establishment of a functional whole kidney de novo has not received much attention because of the formidable challenges and the slow pace of advances in this field of research. This situation has changed recently with publication of data revealing the catastrophic nature of Medicaid costs for dialysis-related diseases. An innovative approach is needed in our search for therapies for kidney diseases and to provide a substitute for dialysis as soon as possible. Regenerative medicine offers great hope for realizing this goal. We established a system by which human mesenchymal stem cells can differentiate into a functional renal unit using a program of nephrogenesis in a developing xeno-embryo. In this article, recent research in the field of developing whole kidneys is reviewed, and possible therapeutic applications for kidney diseases are proposed in combination with our knowledge of the emerging field of kidney stem cell biology.

  12. A scoping review of adult chronic kidney disease clinical pathways for primary care.

    PubMed

    Elliott, Meghan J; Gil, Sarah; Hemmelgarn, Brenda R; Manns, Braden J; Tonelli, Marcello; Jun, Min; Donald, Maoliosa

    2017-05-01

    Chronic kidney disease (CKD) affects ∼10% of the adult population. The majority of patients with CKD are managed by primary care physicians, and despite the availability of effective treatment options, the use of evidence-based interventions for CKD in this setting remains suboptimal. Clinical pathways have been identified as effective tools to guide primary care physicians in providing evidence-based care. We aimed to describe the availability, characteristics and credibility of clinical pathways for adult CKD using a scoping review methodology. We searched Medline, Embase, CINAHL and targeted Internet sites from inception to 31 October 2014 to identify studies and resources that identified adult CKD clinical pathways for primary care settings. Study selection and data extraction were independently performed by two reviewers. From 487 citations, 41 items were eligible for review: 7 published articles and 34 grey literature resources published between 2001 and 2014. Of the 41 clinical pathways, 32, 24 and 22% were from the UK, USA and Canada, respectively. The majority (66%, n = 31) of clinical pathways were static in nature (did not have an online interactive feature). The majority (76%) of articles/resources reported using one or more clinical practice guidelines as a resource to guide the clinical pathway content. Few articles described a dissemination and evaluation plan for the clinical pathway, but most reported the targeted end-users. Our scoping review synthesized available literature on CKD clinical pathways in the primary care setting. We found that existing clinical pathways are diverse in their design, content and implementation. These results can be used by researchers developing or testing new or existing clinical pathways and by practitioners and health system stakeholders who aim to implement CKD clinical pathways in clinical practice. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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

    PubMed

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

    2015-07-01

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

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

    PubMed Central

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

    2015-01-01

    Background Multiple modifications of the porcine genome are required to prevent rejection after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout of the α1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase-1 and A20, and investigated their xenoprotective properties. Methods The GGTA1-KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1 gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by quantitative reverse-transcription polymerase chain reaction, flow cytometry, and sequencing. The biological function of the genetic modifications was tested in a 51Chromium release assay and by ex vivo kidney perfusions with human blood. Results Disruption of the GGTA1 gene by deletion of few basepairs was demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA expression was confirmed by quantitative reverse-transcription polymerase chain reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum experimental time of 240 minutes without symptoms of rejection. Conclusions Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and could serve as a background for further genetic modifications toward the production of a donor pig that is clinically relevant for xenotransplantation. PMID:27500225

  15. Blood Cadmium and Lead and Chronic Kidney Disease in US Adults: A Joint Analysis

    PubMed Central

    Navas-Acien, Ana; Tellez-Plaza, Maria; Guallar, Eliseo; Muntner, Paul; Silbergeld, Ellen; Jaar, Bernard

    2009-01-01

    Environmental cadmium and lead exposures are widespread, and both metals are nephrotoxic at high exposure levels. Few studies have evaluated the associations between low-level cadmium and clinical renal outcomes, particularly with respect to joint cadmium and lead exposure. The geometric mean levels of blood cadmium and lead were 0.41 μg/L (3.65 nmol/L) and 1.58 μg/dL (0.076 μmol/L), respectively, in 14,778 adults aged ≥20 years who participated in the National Health and Nutrition Examination Survey (1999–2006). After adjustment for survey year, sociodemographic factors, chronic kidney disease risk factors, and blood lead, the odds ratios for albuminuria (≥30 mg/g creatinine), reduced estimated glomerular filtration rate (eGFR) (<60 mL/minute/1.73 m2), and both albuminuria and reduced eGFR were 1.92 (95% confidence interval (CI): 1.53, 2.43), 1.32 (95% CI: 1.04, 1.68), and 2.91 (95% CI: 1.76, 4.81), respectively, comparing the highest with the lowest blood cadmium quartiles. The odds ratios comparing participants in the highest with the lowest quartiles of both cadmium and lead were 2.34 (95% CI: 1.72, 3.18) for albuminuria, 1.98 (95% CI: 1.27, 3.10) for reduced eGFR, and 4.10 (95% CI: 1.58, 10.65) for both outcomes. These findings support consideration of cadmium and lead as chronic kidney disease risk factors in the general population and provide novel evidence of risk with environmental exposure to both metals. PMID:19700501

  16. A Pilot Randomized Controlled Trial to Promote Immunosuppressant Adherence in Adult Kidney Transplant Recipients.

    PubMed

    Cukor, Daniel; Ver Halen, Nisha; Pencille, Melissa; Tedla, Fasika; Salifu, Moro

    2017-01-01

    Nonadherence to immunosuppressant medication is a prevalent practice among kidney transplant recipients and has been associated with increased risk for graft failure and economic burden. The aim of this pilot study was to test whether a culturally sensitive cognitive-behavioral adherence promotion program could significantly improve medication adherence to tacrolimus prescription as measured by telephone pill counts among kidney transplant recipients. Thirty-three adult transplant recipients were less than 98% adherent to tacrolimus prescription based on 3 telephone pill counts and were randomized either to the 2-session cognitive-behavioral adherence promotion program or to standard care. The curriculum was developed from an iterative process with transplant recipients into a 2-session group program that provided psychoeducation, addressed barriers to adherence, fostered motivation to improve adherence behavior, and discussed cultural messages on adherence behavior. The intervention group displayed significantly higher levels of adherence when compared to the control group (t = 2.2, p = 0.04) and. similarly, when the amount of change was compared between the groups, the intervention group showed more change than the control condition (F (22,1) = 12.005, p = 0.003). Tacrolimus trough concentration levels were used as a secondary measure of adherence and, while there were no significant between-group differences for mean trough concentration levels, the variability in the trough levels did significantly decrease over time indicating more consistent pill-taking behavior in the intervention group. There is preliminary support for the pilot program as a successful intervention in helping patients with their immunosuppressant medication. © 2016 S. Karger AG, Basel.

  17. Ectopic Kidney

    MedlinePlus

    ... 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 ...

  18. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  19. Reestablishment of radiographic kidney size in Miniature Schnauzer dogs

    PubMed Central

    SOHN, Jungmin; YUN, Sookyung; LEE, Jeosoon; CHANG, Dongwoo; CHOI, Mincheol; YOON, Junghee

    2016-01-01

    Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly. PMID:27594274

  20. Reestablishment of radiographic kidney size in Miniature Schnauzer dogs.

    PubMed

    Sohn, Jungmin; Yun, Sookyung; Lee, Jeosoon; Chang, Dongwoo; Choi, Mincheol; Yoon, Junghee

    2017-01-10

    Kidney size may be altered in renal diseases, and the detection of kidney size alteration has diagnostic and prognostic values. We hypothesized that radiographic kidney size, the kidney length to the second lumbar vertebra (L2) length ratio, in normal Miniature Schnauzer dogs may be overestimated due to their shorter vertebral length. This study was conducted to evaluate radiographic and ultrasonographic kidney size and L2 length in clinically normal Miniature Schnauzers and other dog breeds to evaluate the effect of vertebral length on radiographic kidney size and to reestablish radiographic kidney size in normal Miniature Schnauzers. Abdominal radiographs and ultrasonograms from 49 Miniature Schnauzers and 54 other breeds without clinical evidence of renal disease and lumbar vertebral abnormality were retrospectively evaluated. Radiographic kidney size, in the Miniature Schnauzer (3.31 ± 0.26) was significantly larger than that in other breeds (2.94 ± 0.27). Relative L2 length, the L2 length to width ratio, in the Miniature Schnauzer (1.11 ± 0.06) was significantly shorter than that in other breeds (1.21 ± 0.09). However, ultrasonographic kidney sizes, kidney length to aorta diameter ratios, were within or very close to normal range both in the Miniature Schnauzer (6.75 ± 0.67) and other breeds (7.16 ± 1.01). Thus, Miniature Schnauzer dogs have breed-specific short vertebrae and consequently a larger radiographic kidney size, which was greater than standard reference in normal adult dogs. Care should be taken when evaluating radiographic kidney size in Miniature Schnauzers to prevent falsely diagnosed renomegaly.

  1. [Social representations of illness among people with chronic kidney disease].

    PubMed

    Campos, Caroline Gonçalves Pustiglione; Mantovani, Maria de Fátima; Nascimento, Maria Elisa Brum do; Cassi, Cristiam Carla

    2015-06-01

    To describe the social representations of illness among people with chronic kidney disease undergoing haemodialysis. Descriptive, qualitative research, anchored on the social representations theory. This study was conducted in the municipality of Ponta Grossa, Paraná State, Brazil, with 23 adults with chronic kidney disease. Data were collection between February and November 2012 by means of a semi-structured interview, and analyzed using Content Analysis. The interviews led to the categories "the meaning of kidney disease": awareness of finitude, and "survival": the visible with chronic kidney disease. The representation of illness unveiled a difference and interruption in life projects, and haemodialysis meant loss of freedom, imprisonment and stigma. Family ties and the individuals´ social role are determining representations for healthcare.

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

    PubMed

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

    2014-10-01

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

  3. Vitamin D in the Pathophysiology of Hypertension, Kidney Disease, and Diabetes: Examining the Relationship Between Vitamin D and the Renin-Angiotensin System in Human Diseases

    PubMed Central

    Vaidya, Anand; Williams, Jonathan S.

    2011-01-01

    Objective Vitamin D has been implicated in the pathophysiology of extra-skeletal conditions such as hypertension, kidney disease, and diabetes, via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. Methods Literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes. Results Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25(OH)2D mediated down-regulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β–cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well designed prospective human interventional studies to definitively assess clinical outcomes. Conclusion Animal studies implicate vitamin D receptor agonist therapy to lower RAS activity as a potential method to reduce the risk of hypertension, kidney disease, and diabetes. There is a need for more well designed prospective interventional studies to validate this hypothesis in human clinical outcomes. PMID:22075270

  4. Disease Progression Modeling to Evaluate the Effects of Enzyme Replacement Therapy on Kidney Function in Adult Patients with the Classic Phenotype of Fabry Disease.

    PubMed

    Nowak, Albina; Koch, Gilbert; Huynh-Do, Uyen; Siegenthaler, Martin; Marti, Hans-Peter; Pfister, Marc

    2017-01-01

    Fabry disease (FD) is a rare inherited lysosomal storage disease with common and serious kidney complications. Enzyme replacement therapies (ERT) with agalsidase-α and -β were investigated to characterize their therapeutic effect on kidney function in FD patients with Classic phenotype. The prospective FD cohort consisted of 98 genetically confirmed patients (females, n = 61, males, n = 37). The median [interquartile range] follow-up time (time difference from first to last visit) was 9 [6, 12] years. The median age of ERT start was 36 [21 - 54] years for females and 39 [28 - 49] years for males. A disease progression model was developed to (i) characterize the time course of estimated glomerular filtration rate (eGFR) and (ii) evaluate therapeutic effects of ERT on kidney function. Change in eGFR over time was best described by the linear model. Females had stable kidney function with and without ERT (eGFR slopes of -0.07 ml/min/1.73m^2 per year and 0.52 ml/min/1.73m^2 per year, respectively). Males with ERT showed an eGFR decrease of -3.07 ml/min/1.73m^2 per year. Mathematical disease progression modeling indicates that there is no clear therapeutic effect of ERT on kidney function in adult patients with Classic Phenotype of FD. Interpretation of these findings should take into account that the study is not randomized and lacks a placebo controlled group. Further investigations are warranted to clarify whether earlier ERT initiation before 18 years of age, higher ERT dose or more intensive therapies can preserve kidney function. © 2017 The Author(s)Published by S. Karger AG, Basel.

  5. Application of Hanging Drop Technique for Kidney Tissue Culture.

    PubMed

    Wang, Shaohui; Wang, Ximing; Boone, Jasmine; Wie, Jin; Yip, Kay-Pong; Zhang, Jie; Wang, Lei; Liu, Ruisheng

    2017-01-01

    The hanging drop technique is a well-established method used in culture of animal tissues. However, this method has not been used in adult kidney tissue culture yet. This study was to explore the feasibility of using this technique for culturing adult kidney cortex to study the time course of RNA viability in the tubules and vasculature, as well as the tissue structural integrity. In each Petri dish with the plate covered with sterile buffer, a section of mouse renal cortex was cultured within a drop of DMEM culture medium on the inner surface of the lip facing downward. The tissue were then harvested at each specific time points for Real-time PCR analysis and histological studies. The results showed that the mRNA level of most Na+ related transporters and cotransporters were stably maintained within 6 hours in culture, and that the mRNA level of most receptors found in the vasculature and glomeruli were stably maintained for up to 9 days in culture. Paraffin sections of the cultured renal cortex indicated that the tubules began to lose tubular integrity after 6 hours, but the glomeruli and vasculatures were still recognizable up to 9 days in culture. We concluded that adult kidney tissue culture by hanging drop method can be used to study gene expressions in vasculature and glomeruli. © 2017 The Author(s). Published by S. Karger AG, Basel.

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

    PubMed

    Minuth, Will W

    2018-01-01

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

  7. [Fitness and quality of life in kidney transplant recipients: case-control study].

    PubMed

    Hernández Sánchez, Sonsoles; Carrero, Juan J; García López, David; Herrero Alonso, Juan Azael; Menéndez Alegre, Héctor; Ruiz, Jonatan R

    2016-04-15

    We analyzed the levels of fitness, muscle structure and quality of life of adults after kidney transplant and healthy adults. A total of 16 kidney transplant patients and 21 healthy controls performed several fitness test, isokinetic evaluation of knee flexion and extension and ultrasonography muscle thickness assessment. They also completed the quality of life questionnaire SF-36. Physical fitness, muscle structure and quality of life of the kidney transplant recipients were significantly poorer than the controls. The transplant patients performed less well in the "get up and go" and "sit to stand" test (p<.001) as well as in assessments of muscle structure, strength and power. The patients had a poorer score in their quality of life assessments, differing from the controls in domains of physical function, physical role, general health and social function (p<.001). Fitness, strength and muscle mass are diminished in kidney transplant patients, resulting in a poorer quality of life which might entail an increased risk to their health. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. Perspectives on using a multiplex human kidney safety biomarker panel to detect cisplatin-induced tubular toxicity in male and female Cynomolgus monkeys.

    PubMed

    Chen, Yafei; Dale Thurman, J; Kinter, Lewis B; Bialecki, Russell; Eric McDuffie, J

    2017-12-01

    Multiplex biomarker panel assays would enable early de-risking of discovery compound related kidney safety liabilities. The objective of this study was to evaluate the usefulness of the Myriad RBM Human KidneyMAP (Multi-Analyte Profile)® v.1.0 panel to detect experimental nephrotoxicity in Cynomolgus monkeys following a single intravenous administration of cisplatin (2.5mg/kg). Urine samples were collected at baseline on day -2; at approximately 4hr post-dose on day 1; and on days 4, 9, 15 and/or 20. Blood samples were collected at predose on day -2; at 4hr post-dose on day 1; and on days 2, 5, 10 and/or 21. Changes in toxicokinetic and biochemistry parameters in plasma, qualitative/quantitative urinalysis parameters, and urinary kidney safety biomarkers were assessed. Kidney tissues were collected on days 2, 5, 10 and 21 for routine microscopy. Cisplatin-induced tubular alterations were characterized by acute and progressive cortical tubular degeneration/necrosis, regeneration, tubular dilation and proteinaceous cast in the absence of statistically significant changes in traditional plasma biochemistry and urinalysis parameters. When normalized to urinary creatinine, cisplatin-induced significant increases in urinary levels of kidney injury molecule 1 (females on day 4), increases in calbindin D28k (males and females on day 4), decreases in Tamm-Horsfall glycoprotein (males on days 1, 4 and 9), and increases in clusterin (females and males on days 15 and 20, respectively), when compared to concurrent controls. This study revealed the usefulness of the Human KidneyMAP® multiplex panel when measuring changes in urine-based biomarkers to reliably detect cisplatin-induced acute/progressive cortical tubular injury in male and female Cynomolgus monkeys. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

    Grisk, Olaf

    2017-05-01

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

  10. Kidney Facts

    MedlinePlus

    ... Page Transplant Living > Kidney KIDNEY TRANSPLANT LEARNING CENTER Kidney The kidneys are a vital organ in the ... your body. Location of the kidneys How the kidney works Your kidneys play a vital role in ...

  11. Using Zebrafish to Study Podocyte Genesis During Kidney Development and Regeneration

    PubMed Central

    Kroeger, Paul T.; Wingert, Rebecca A.

    2014-01-01

    SUMMARY During development, vertebrates form a progression of up to three different kidneys that are comprised of functional units termed nephrons. Nephron composition is highly conserved across species, and an increasing appreciation of the similarities between zebrafish and mammalian nephron cell types has positioned the zebrafish as a relevant genetic system for nephrogenesis studies. A key component of the nephron blood filter is a specialized epithelial cell known as the podocyte. Podocyte research is of the utmost importance as a vast majority of renal diseases initiate with the dysfunction or loss of podocytes, resulting in a condition known as proteinuria that causes nephron degeneration and eventually leads to kidney failure. Understanding how podocytes develop during organogenesis may elucidate new ways to promote nephron health by stimulating podocyte replacement in kidney disease patients. In this review, we discuss how the zebrafish model can be used to study kidney development, and how zebrafish research has provided new insights into podocyte lineage specification and differentiation. Further, we discuss the recent discovery of podocyte regeneration in adult zebrafish, and explore how continued basic research using zebrafish can provide important knowledge about podocyte genesis in embryonic and adult environments. PMID:24920186

  12. Association Between High Environmental Heat and Risk of Acute Kidney Injury Among Older Adults in a Northern Climate: A Matched Case-Control Study.

    PubMed

    McTavish, Rebecca K; Richard, Lucie; McArthur, Eric; Shariff, Salimah Z; Acedillo, Rey; Parikh, Chirag R; Wald, Ron; Wilk, Piotr; Garg, Amit X

    2018-02-01

    An association between high heat and acute kidney injury (AKI) has been reported in warm climates. However, whether this association generalizes to a northern climate, with more variable temperatures, is unknown. Matched case-control study. Our study focused on older adults (mean age, 80 years) in the northern climate of Ontario, Canada. 52,913 case patients who had a hospital encounter with AKI in April through September 2005 to 2012 were matched with 174,222 controls for exact date, age, sex, rural residence, income, and history of chronic kidney disease. Heat periods were defined as 3 consecutive days exceeding the 95th percentile of area-specific maximum temperature. Hospital encounter (inpatient admission or emergency department visit) with a diagnosis of AKI. ORs (95% CIs) were used to assess the association between heat periods and AKI. To quantify the effect in absolute terms, we multiplied the population incidence rate of AKI in the absence of heat periods by our adjusted OR (an approximate of relative risk). Heat periods were significantly associated with higher risk for AKI (adjusted OR, 1.11; 95% CI, 1.00-1.23). Heat periods in absolute terms were associated with an additional 182 cases of AKI per 100,000 person-years during the warm season. We did not know how long persons were outside or if they had access to air conditioning. In a northern climate, periods of higher environmental heat were associated with a modestly higher risk for hospital encounter with AKI among older adults. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  13. De novo Uroplakin IIIa heterozygous mutations cause human renal adysplasia leading to severe kidney failure.

    PubMed

    Jenkins, Dagan; Bitner-Glindzicz, Maria; Malcolm, Sue; Hu, Chih-Chi A; Allison, Jennifer; Winyard, Paul J D; Gullett, Ambrose M; Thomas, David F M; Belk, Rachel A; Feather, Sally A; Sun, Tung-Tien; Woolf, Adrian S

    2005-07-01

    Human renal adysplasia usually occurs sporadically, and bilateral disease is the most common cause of childhood end-stage renal failure, a condition that is lethal without intervention using dialysis or transplantation. De novo heterozygous mutations in Uroplakin IIIa (UPIIIa) are reported in four of 17 children with kidney failure caused by renal adysplasia in the absence of an overt urinary tract obstruction. One girl and one boy in unrelated kindreds had a missense mutation at a CpG dinucleotide in the cytoplasmic domain of UPIIIa (Pro273Leu), both of whom had severe vesicoureteric reflux, and the girl had persistent cloaca; two other patients had de novo mutations in the 3' UTR (963 T-->G; 1003 T-->C), and they had renal adysplasia in the absence of any other anomaly. The mutations were absent in all sets of parents and in siblings, none of whom had radiologic evidence of renal adysplasia, and mutations were absent in two panels of 192 ethnically matched control chromosomes. UPIIIa was expressed in nascent urothelia in ureter and renal pelvis of human embryos, and it is suggested that perturbed urothelial differentiation may generate human kidney malformations, perhaps by altering differentiation of adjacent smooth muscle cells such that the metanephros is exposed to a functional obstruction of urine flow. With advances in renal replacement therapy, children with renal failure, who would otherwise have died, are surviving to adulthood. Therefore, although the mechanisms of action of the UPIIIa mutations have yet to be determined, these findings have important implications regarding genetic counseling of affected individuals who reach reproductive age.

  14. Not the Usual Viral Suspects: Parvovirus B19, West Nile Virus, and Human T-Cell Lymphotrophic Virus Infections After Kidney Transplantation.

    PubMed

    Razonable, Raymund R

    2016-09-01

    Kidney transplant recipients are at increased risk of developing clinical disease due to uncommon opportunistic viral pathogens. Refractory anemia is classically associated with parvovirus B19 infection. West Nile virus has the propensity to cause fever and neurologic symptoms, while spastic paresis and lymphoma can be triggered by human T cell lymphotrophic virus. In this review article, the epidemiology, clinical manifestations, diagnosis and treatment of less common viruses are discussed in the setting of kidney transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Solitary Kidney

    MedlinePlus

    ... Solitary Kidney Your Kidneys & How They Work Solitary Kidney What is a solitary kidney? When a person has only one kidney or ... ureter are removed (bottom right). What are the kidneys and what do they do? The kidneys are ...

  16. Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species

    PubMed Central

    Ju, Wenjun; Brosius, Frank C.

    2010-01-01

    Animal models have long been useful in investigating both normal and abnormal human physiology. Systems biology provides a relatively new set of approaches to identify similarities and differences between animal models and humans that may lead to a more comprehensive understanding of human kidney pathophysiology. In this review, we briefly describe how genome-wide analyses of mouse models have helped elucidate features of human kidney diseases, discuss strategies to achieve effective network integration, and summarize currently available web-based tools that may facilitate integration of data across species. The rapid progress in systems biology and orthology, as well as the advent of web-based tools to facilitate these processes, now make it possible to take advantage of knowledge from distant animal species in targeted identification of regulatory networks that may have clinical relevance for human kidney diseases. PMID:21044762

  17. Contemporary rates and predictors of fast progression of chronic kidney disease in adults with and without diabetes mellitus.

    PubMed

    Go, Alan S; Yang, Jingrong; Tan, Thida C; Cabrera, Claudia S; Stefansson, Bergur V; Greasley, Peter J; Ordonez, Juan D

    2018-06-22

    Chronic kidney disease (CKD) is highly prevalent but identification of patients at high risk for fast CKD progression before reaching end-stage renal disease in the short-term has been challenging. Whether factors associated with fast progression vary by diabetes status is also not well understood. We examined a large community-based cohort of adults with CKD to identify predictors of fast progression during the first 2 years of follow-up in the presence or absence of diabetes mellitus. Within a large integrated healthcare delivery system in northern California, we identified adults with estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m 2 by CKD-EPI equation between 2008 and 2010 who had no previous dialysis or renal transplant, who had outpatient serum creatinine values spaced 10-14 months apart and who did not initiate renal replacement therapy, die or disenroll during the first 2 years of follow-up. Through 2012, we calculated the annual rate of change in eGFR and classified patients as fast progressors if they lost > 4 ml/min/1.73 m 2 per year. We used multivariable logistic regression to identify patient characteristics that were independently associated with fast CKD progression stratified by diabetes status. We identified 36,195 eligible adults with eGFR 30-59 ml/min/1.73 m 2 and mean age 73 years, 55% women, 11% black, 12% Asian/Pacific Islander and 36% with diabetes mellitus. During 24-month follow-up, fast progression of CKD occurred in 23.0% of patients with diabetes vs. 15.3% of patients without diabetes. Multivariable predictors of fast CKD progression that were similar by diabetes status included proteinuria, age ≥ 80 years, heart failure, anemia and higher systolic blood pressure. Age 70-79 years, prior ischemic stroke, current or former smoking and lower HDL cholesterol level were also predictive in patients without diabetes, while age 18-49 years was additionally predictive in those with diabetes. In a large

  18. Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation

    PubMed Central

    Stratta, Robert J.; Rohr, Michael S.; Sundberg, Aimee K.; Farney, Alan C.; Hartmann, Erica L.; Moore, Phillip S.; Rogers, Jeffrey; Iskandar, Samy S.; Gautreaux, Michael D.; Kiger, David F.; Doares, William; Anderson, Teresa K.; Hairston, Gloria; Adams, Patricia L.

    2006-01-01

    Objective: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the

  19. Zoonotic bacterial meningitis in human adults.

    PubMed

    van Samkar, Anusha; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

    2016-09-13

    To describe the epidemiology, etiology, clinical characteristics, treatment, outcome, and prevention of zoonotic bacterial meningitis in human adults. We identified 16 zoonotic bacteria causing meningitis in adults. Zoonotic bacterial meningitis is uncommon compared to bacterial meningitis caused by human pathogens, and the incidence has a strong regional distribution. Zoonotic bacterial meningitis is mainly associated with animal contact, consumption of animal products, and an immunocompromised state of the patient. In a high proportion of zoonotic bacterial meningitis cases, CSF analysis showed only a mildly elevated leukocyte count. The recommended antibiotic therapy differs per pathogen, and the overall mortality is low. Zoonotic bacterial meningitis is uncommon but is associated with specific complications. The suspicion should be raised in patients with bacterial meningitis who have recreational or professional contact with animals and in patients living in regions endemic for specific zoonotic pathogens. An immunocompromised state is associated with a worse prognosis. Identification of risk factors and underlying disease is necessary to improve treatment. © 2016 American Academy of Neurology.

  20. Polycythemia in transgenic mice expressing the human erythropoietin gene

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Semenza, G.L.; Traystman, M.D.; Gearhart, J.D.

    1989-04-01

    Erythropoietin is a glycoprotein hormone that regulates mammalian erythropoiesis. To study the expression of the human erythropoietin gene, EPO, 4 kilobases of DNA encompassing the gene with 0.4 kilobase of 5{prime} flanking sequence and 0.7 kilobase of 3{prime} flanking sequence was microinjected into fertilized mouse eggs. Transgenic mice were generated that are polycythemic, with increased erythrocytic indices in peripheral blood, increased numbers of erythroid precursors in hematopoietic tissue, and increased serum erythropoietin levels. Transgenic homozygotes show a greater degree of polycythemia than do heterozygotes as well as striking extramedullary erythropoiesis. Human erythropoietin RNA was found not only in fetal liver,more » adult liver, and kidney but also in all other transgenic tissues analyzed. Anemia induced increased human erythropoietin RNA levels in liver but not kidney. These transgenic mice represent a unique model of polycythemia due to increased erythropoietin levels.« less

  1. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

    PubMed

    Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

    2016-08-01

    End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations

  2. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

    PubMed Central

    Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

    2016-01-01

    BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI

  3. [The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study: To better understand chronic kidney disease].

    PubMed

    Stengel, Bénédicte; Combe, Christian; Jacquelinet, Christian; Briançon, Serge; Fouque, Denis; Laville, Maurice; Frimat, Luc; Pascal, Christophe; Herpe, Yves-Édouard; Morel, Pascal; Deleuze, Jean-François; Schanstra, Joost P; Pisoni, Ron L; Robinson, Bruce M; Massy, Ziad A

    2016-04-01

    Preserving kidney function and improving the transition from chronic kidney disease to end stage is a research and healthcare challenge. The national Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort was established to identify the determinants, biomarkers and practice patterns associated with chronic kidney disease outcomes. The study will include more than 3000 adult patients with moderate to advanced chronic kidney disease from a representative sample of 40 nephrology clinics with respect to regions and legal status, public or private. Patients are recruited during a routine visit and followed for 5 years, before and after starting renal replacement therapy. Patient-level clinical, biological, and lifestyle data are collected annually, as well as provider-level data on clinical practices, coordinated with the International Chronic Kidney Disease Outcomes and Practice Pattern Study. Blood and urine samples are stored in a biobank. Major studied outcomes include survival, patient-reported outcomes, disease progression and hospitalizations. More than 13,000 eligible patients with chronic kidney disease were identified, 60% with stage 3 and 40% with stage 4. Their median age is 72 years [interquartile range, 62-80 years], 60% are men and 38% have diabetes. By the end of December 2015, 2885 patients were included. The CKD-REIN cohort will serve to improve our understanding of chronic kidney disease and provide evidence to improve patient survival and quality of life as well as health care system performances. Copyright © 2016 Association Société de néphrologie. All rights reserved.

  4. LMX1B is essential for the maintenance of differentiated podocytes in adult kidneys.

    PubMed

    Burghardt, Tillmann; Kastner, Jürgen; Suleiman, Hani; Rivera-Milla, Eric; Stepanova, Natalya; Lottaz, Claudio; Kubitza, Marion; Böger, Carsten A; Schmidt, Sarah; Gorski, Mathias; de Vries, Uwe; Schmidt, Helga; Hertting, Irmgard; Kopp, Jeffrey; Rascle, Anne; Moser, Markus; Heid, Iris M; Warth, Richard; Spang, Rainer; Wegener, Joachim; Mierke, Claudia T; Englert, Christoph; Witzgall, Ralph

    2013-11-01

    Mutations of the LMX1B gene cause nail-patella syndrome, a rare autosomal-dominant disorder affecting the development of the limbs, eyes, brain, and kidneys. The characterization of conventional Lmx1b knockout mice has shown that LMX1B regulates the development of podocyte foot processes and slit diaphragms, but studies using podocyte-specific Lmx1b knockout mice have yielded conflicting results regarding the importance of LMX1B for maintaining podocyte structures. In order to address this question, we generated inducible podocyte-specific Lmx1b knockout mice. One week of Lmx1b inactivation in adult mice resulted in proteinuria with only minimal foot process effacement. Notably, expression levels of slit diaphragm and basement membrane proteins remained stable at this time point, and basement membrane charge properties also did not change, suggesting that alternative mechanisms mediate the development of proteinuria in these mice. Cell biological and biophysical experiments with primary podocytes isolated after 1 week of Lmx1b inactivation indicated dysregulation of actin cytoskeleton organization, and time-resolved DNA microarray analysis identified the genes encoding actin cytoskeleton-associated proteins, including Abra and Arl4c, as putative LMX1B targets. Chromatin immunoprecipitation experiments in conditionally immortalized human podocytes and gel shift assays showed that LMX1B recognizes AT-rich binding sites (FLAT elements) in the promoter regions of ABRA and ARL4C, and knockdown experiments in zebrafish support a model in which LMX1B and ABRA act in a common pathway during pronephros development. Our report establishes the importance of LMX1B in fully differentiated podocytes and argues that LMX1B is essential for the maintenance of an appropriately structured actin cytoskeleton in podocytes.

  5. Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.

    PubMed

    Chen, C L; Chou, K J; Fang, H C; Hsu, C Y; Huang, W C; Huang, C W; Huang, C K; Chen, H Y; Lee, P T

    2015-12-02

    Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-β-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell

  6. Incident Atrial Fibrillation and Risk of End-Stage Renal Disease in Adults with Chronic Kidney Disease

    PubMed Central

    Bansal, Nisha; Fan, Dongjie; Hsu, Chi-yuan; Ordonez, Juan D.; Marcus, Gregory M.; Go, Alan S.

    2013-01-01

    Background Atrial fibrillation (AF) frequently occurs in patients with chronic kidney disease (CKD). However, the long-term impact of development of AF on the risk of adverse renal outcomes in patients with CKD is unknown. In this study, we determined the association between incident AF and risk of end-stage renal disease (ESRD) among adults with CKD. Methods and Results We studied adults with CKD (defined as persistent glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 by the CKD-EPI equation) enrolled in Kaiser Permanente Northern California who were identified between 2002–2010 and who did not have prior ESRD or previously documented AF. Incident AF was identified using primary hospital discharge diagnoses and/or two or more outpatient visits for AF. Incident ESRD was ascertained from a comprehensive health plan registry for dialysis and renal transplant. Among 206,229 adults with CKD, 16,463 developed incident AF. During a mean follow-up of 5.1± 2.5 years, there were 345 cases of ESRD that occurred after development of incident AF (74 per 1000 person-years) compared with 6505 cases of ESRD during periods without AF (64 per 1000 person-years, P<0.001). After adjustment for potential confounders, incident AF was associated with a 67% increase in rate of ESRD (hazard ratio 1.67, 95% confidence interval: 1.46–1.91). Conclusions Incident AF is independently associated with increased risk of developing ESRD in adults with CKD. Further study is needed to identify potentially modifiable pathways through which AF leads to a higher risk of progression to ESRD. PMID:23275377

  7. Pre-flight report on cultured human embryonic kidney cell handling and cell electrophoresis. Prepared prior to continuous-flow electrophoretic separation experiments aboard space shuttle flight STS-8

    NASA Technical Reports Server (NTRS)

    Todd, P. W.; Sarnoff, B. E.; Li, Z. K.

    1985-01-01

    Studies of the physical properties of continuous-flow zero-G electrophoretic separator (CFES) buffer, the electrokinetic properties of human erythrocytes in the CFES buffer, the electrokinetic properties of human embryonic kidney cells in the CFES buffer, and the viability and yield of human embryonc kidney cells subjected to flight handling procedures are discussed. In general, the procedure for cell handling and electrophoresis of HEK-8514 cells in 1st or 2nd passage on STS-8 is acceptable if executed properly. The CFES buffer has ionic strength that is barely compatible with cell viability and membrane stability, as seen in experiments with human erythrocytes and trypan-blue staining of human kidney cells. Cells suspended in 10% dialysed horse serum for 3 days in the cold appear to be more stable than freshly trypsinized cells. 10% horse serum appears to be superior to 5% horse serum for this purpose. The mean absolute raw mobility of HEK-8514 cells in CFES buffer at 6 degrees, conductivity 0.055 mmho/cm, is 1.1 to 1.4 um-cm/V-sec, with a range of nearly a whole mobility unit.

  8. Scattered Deletion of PKD1 in Kidneys Causes a Cystic Snowball Effect and Recapitulates Polycystic Kidney Disease

    PubMed Central

    Leonhard, Wouter N.; Zandbergen, Malu; Veraar, Kimberley; van den Berg, Susan; van der Weerd, Louise; Breuning, Martijn; de Heer, Emile

    2015-01-01

    In total, 1 in 1000 individuals carries a germline mutation in the PKD1 or PKD2 gene, which leads to autosomal dominant polycystic kidney disease (ADPKD). Cysts can form early in life and progressively increase in number and size during adulthood. Extensive research has led to the presumption that somatic inactivation of the remaining allele initiates the formation of cysts, and the progression is further accelerated by renal injury. However, this hypothesis is primarily on the basis of animal studies, in which the gene is inactivated simultaneously in large percentages of kidney cells. To mimic human ADPKD in mice more precisely, we reduced the percentage of Pkd1-deficient kidney cells to 8%. Notably, no pathologic changes occurred for 6 months after Pkd1 deletion, and additional renal injury increased the likelihood of cyst formation but never triggered rapid PKD. In mildly affected mice, cysts were not randomly distributed throughout the kidney but formed in clusters, which could be explained by increased PKD-related signaling in not only cystic epithelial cells but also, healthy-appearing tubules near cysts. In the majority of mice, these changes preceded a rapid and massive onset of severe PKD that was remarkably similar to human ADPKD. Our data suggest that initial cysts are the principal trigger for a snowball effect driving the formation of new cysts, leading to the progression of severe PKD. In addition, this approach is a suitable model for mimicking human ADPKD and can be used for preclinical testing. PMID:25361818

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

    PubMed

    Balat, Ayse

    2016-02-01

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

  10. Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

    PubMed

    Przybylowski, P; Koc-Zorawska, E; Malyszko, J S; Kozlowska, S; Mysliwiec, M; Malyszko, J

    2011-10-01

    Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function

  11. Trends in Hospitalizations for Acute Kidney Injury - United States, 2000-2014.

    PubMed

    Pavkov, Meda E; Harding, Jessica L; Burrows, Nilka R

    2018-03-16

    Acute kidney injury is a sudden decrease in kidney function with or without kidney damage, occurring over a few hours or days. Diabetes, hypertension, and advanced age are primary risk factors for acute kidney injury. It is increasingly recognized as an in-hospital complication of sepsis, heart conditions, and surgery (1,2). Its most severe stage requires treatment with dialysis. Acute kidney injury is also associated with higher likelihood of long-term care, incidence of chronic kidney disease and hospital mortality, and health care costs (1,2). Although a number of U.S. studies have indicated an increasing incidence of dialysis-treated acute kidney injury since the late 1990s (3), no data are available on national trends in diabetes-related acute kidney injury. To estimate diabetes- and nondiabetes-related acute kidney injury trends, CDC analyzed 2000-2014 data from the National Inpatient Sample (NIS) (4) and the National Health Interview Survey (NHIS) (5). Age-standardized rates of acute kidney injury hospitalizations increased by 139% (from 23.1 to 55.3 per 1,000 persons) among adults with diagnosed diabetes, and by 230% (from 3.5 to 11.7 per 1,000 persons) among those without diabetes. Improving both patient and provider awareness that diabetes, hypertension, and advancing age are frequently associated with acute kidney injury might reduce its occurrence and improve management of the underlying diseases in an aging population.

  12. Comparative anatomical study of the kidney position in amniotes using the origin of the renal artery as a landmark.

    PubMed

    Yokota, Eri; Kawashima, Tomokazu; Ohkubo, Fumie; Sasaki, Hiroshi

    2005-03-01

    The anatomical relationship between the kidney position and its arterial supply was investigated in 21 mammals, 1 bird, and 3 reptiles (n = 1 for each species) and in 43 human cadavers. The following observations were made. (1) Although the right kidney was located caudal to the left kidney in 29 out of 43 human cadavers (67.4%), the origin of the right renal artery from the aorta was located cranial to the origin of the left renal artery in 36 human cadavers (83.7%). Therefore, the relative positions of the kidneys do not correspond with the relative origins of the renal arteries in humans. (2) Among the mammals that were examined, the position of the kidney and the branching level of the renal artery on the right side were usually cranial to those on the left side. (3) In the bird and most reptiles that were examined, kidneys were typically located in the pelvic region and were supplied by segmental arterial branches. These results suggest that the right kidney and its arterial supply are generally located cranial to the left kidney in phylogeny of mammals. While the presence of a human accessory renal artery in 9 out of 86 sides (10.5%) and a cranial origin of the left renal artery relative to the right renal artery in 7 out of 43 cadavers (16.3%), shows some variation in the arterial supply to the kidneys, the origin of the renal arteries can generally be used as phylogenetic landmarks indicating the relative positions of the kidneys. Hence, from an ontological perspective, the human right kidney may be initially situated cranial to the left kidney during the early stages of development. Thereafter, the human right kidney may shift downwards secondary.

  13. Citrate salts for preventing and treating calcium containing kidney stones in adults.

    PubMed

    Phillips, Rebecca; Hanchanale, Vishwanath S; Myatt, Andy; Somani, Bhaskar; Nabi, Ghulam; Biyani, C Shekhar

    2015-10-06

    Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain. The objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones. We searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months. Two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. We included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to

  14. Morphology of the kidney of adult bowfin, Amia calva, with emphasis on "renal chloride cells" in the tubule.

    PubMed

    Youson, J H; Butler, D G

    1988-05-01

    The nephron of adult bowfin, Amia calva, was described using light and electron microscopic techniques. The kidney of the bowfin possesses an abundant supply of renal corpuscles with each consisting of a glomerulus and a Bowman's capsule of visceral (podocyte) and parietal layers. No juxtaglomerular apparatus is present. The epithelium of the tubule is continuous with the parietal epithelium and is divisible in descending order into neck, first proximal, second proximal, first distal, second distal, and collecting segments. The tubules drain into a complex system of collecting ducts that ultimately unite with the main excretory duct, the archinephric duct. Mucous cells are the dominant cell throughout the entire ductular system. Nephrostomes are dispersed along the kidney capsule. The neck segment has a ciliated epithelium, and while both proximal segments possess a prominent brush border, the fine structure of the first implies involvement in protein absorption and the second in the transport and reabsorption of solutes. The cells of the first distal segment are characterized by deep infolding of the plasma membrane and a rich supply of mitochondria suggesting the presence of a mechanism for ion transport. The second distal segment is composed of cells resembling the chloride cells of fishes and these cells are present in progressively decreasing numbers in the collecting segment and duct system so that only a few are present in the epithelium of the archinephric duct. The "renal chloride cells" possess an abundant network of smooth tubules and numerous mitochondria with a rich supply of cristae. Glycogen is also a conspicuous component of these cells. The presence of "renal chloride cells" in this freshwater holostean, in other relatively primitive freshwater teleosts, and in larval and adult lampreys is discussed with reference to both phylogeny and the need for a special mechanism for renal ion conservation through absorption.

  15. Performance of the Cockcroft-Gault and MDRD equations in adult Nigerians with chronic kidney disease.

    PubMed

    Agaba, Emmanuel I; Wigwe, Chinyere M; Agaba, Patricia A; Tzamaloukas, Antonios H

    2009-01-01

    Estimation of the glomerular filtration rate (GFR) is required in the assessment of patients with chronic kidney disease (CKD) in order to provide information regarding the functional status of the kidneys. Current guidelines advocate the use of prediction equations, such as the Cockcroft-Gault (CG) formula and the Modification of Diet in Renal Disease (MDRD) study-derived equations, over clearance of endogenous creatinine (Ccr) in achieving this aim. We were interested in knowing the accuracy of these equations in predicting the GFR in adult Nigerians with CKD. We conducted a review of records of patients who were evaluated for CKD at the Nephrology Clinic of the Jos University Teaching Hospital between 2001 and 2003. We compared the CG and MDRD equations against the Ccr in predicting the GFR in 130 patients (88 males and 42 females) with CKD. The means +/- standard deviation (SD) for the measured and predicted GFR by the CG and MDRD equations were similar (17.6 +/- 25.8 ml/min, 19.9 +/- 24.0 ml/min and 21.5 +/- 28.2 ml/min, respectively; analysis of variance [ANOVA], F = 0.68, P = 0.5). The mean difference between CG and Ccr was -2.2 +/- 14.8 ml/min, with discordance at Ccr values >25 ml/min. The mean difference between MDRD and Ccr was -3.9 +/- 18.1 ml/min, with discordance at Ccr values >40 ml/min. The CG and MDRD equations provide reliable alternatives to measured Ccr in the estimation of the GFR in Nigerian patients with CKD.

  16. Screening for asymptomatic bacteruria at one month after adult kidney transplantation: Clinical factors and implications.

    PubMed

    Goh, Yen Seow Benjamin; Deng, Zhaolong; Cheong, Pei Shan Cassandra; Raman, Lata; Goh, Ting Hui Angeline; Vathsala, Anatharaman; Tiong, Ho Yee

    2017-05-01

    Urinary tract infections (UTIs) account for significant morbidity after kidney transplantation (KT). Screening for asymptomatic bacteruria (AB) has proven to be beneficial in certain population including pregnant women; however, it is not well-studied in KT population. We reviewed the incidence, clinical features, and implications of asymptomatic bacteruria one month after KT. A total of 171 adult KT patients (86 [50.3%] living transplants, 87 [50.9%] males, mean age 47.3 ± 13.7 years), between 2005 and 2012, were analyzed. Immunosuppression induction and maintenance were as per protocol. Protocol urine cultures were taken at 1 month post-transplantation. Patients were stratified for presence of AB and analyzed for demographics and clinical parameters. Outcomes of hospitalization for symptomatic UTIs, graft, and patient survival were ascertained. Forty-one (24%) KT recipients had AB at 30 days post-transplant. Multiresistant organisms accounted for 43.9% of these infections. Logistic regression confirms female sex and deceased donor recipients as independent predictors of 30-day bacteruria, which predicts subsequent hospitalization for symptomatic UTI. One-year patient and graft survival were similar in recipient with or without AB. Asymptomatic bacteruria 30 days post-transplant can be predicted in female recipients and kidneys from deceased donors probably due to anatomical and functional differences respectively. There is increased morbidity of subsequent hospitalization for symptomatic UTI and more research in prevention of UTI is needed, particularly non-antibiotic prophylaxis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    PubMed

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

    1989-02-28

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

  18. No evidence of persisting unrepaired nuclear DNA single strand breaks in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT.

    PubMed

    Korr, Hubert; Angstman, Nicholas B; Born, Tatjana B; Bosse, Kerstin; Brauns, Birka; Demmler, Martin; Fueller, Katja; Kántor, Orsolya; Kever, Barbara M; Rahimyar, Navida; Salimi, Sepideh; Silny, Jiri; Schmitz, Christoph

    2014-01-01

    It has been hypothesized in the literature that exposure to extremely low frequency electromagnetic fields (50 or 60 Hz) may lead to human health effects such as childhood leukemia or brain tumors. In a previous study investigating multiple types of cells from brain and kidney of the mouse (Acta Neuropathologica 2004; 107: 257-264), we found increased unrepaired nuclear DNA single strand breaks (nDNA SSB) only in epithelial cells of the choroid plexus in the brain using autoradiographic methods after a continuous eight-week 50 Hz magnetic field (MF) exposure of adult mice with flux density of 1.5 mT. In the present study we tested the hypothesis that MF exposure with lower flux densities (0.1 mT, i.e., the actual exposure limit for the population in most European countries, and 1.0 mT) shows similar results to those in the previous study. Experiments and data analysis were carried out in a similar way as in our previous study. Continuous eight-week 50 Hz MF exposure with 0.1 mT or 1.0 mT did not result in increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice. MF exposure with 1.0 mT led to reduced unscheduled DNA synthesis (UDS) in epithelial cells in the choroid plexus of the fourth ventricle in the brain (EC-CP) and epithelial cells of the cortical collecting duct in the kidney, as well as to reduced mtDNA synthesis in neurons of the caudate nucleus in the brain and in EC-CP. No evidence was found for increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT.

  19. Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults

    PubMed Central

    Tong, Ann-Jay; Kollmann, Tobias R.; Smale, Stephen T.

    2015-01-01

    A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development. PMID:26147648

  20. Pediatric Acute Kidney Injury.

    PubMed

    Fragasso, Tiziana; Ricci, Zaccaria; Goldstein, Stuart L

    2018-01-01

    Acute kidney injury (AKI) in children is a serious condition with an important impact on morbidity and mortality. Onset can be insidious and it is frequently unrecognized in the early phase when the therapeutic opportunities are theoretically more effective. The present review focuses on the most recent epidemiology studies and the progress in pediatric AKI (pAKI) research. Standardization of definition (presented in the Kidney Disease: Improving Global Outcomes) and novel biomarkers have been developed to help clinicians recognize kidney injury in a timely manner, both in adult and pediatric populations. Strengths and weaknesses of these diagnostic tools are discussed and the clinical scoring system (Renal Angina Index), which aims to provide a rational context for biomarker utilization, is also presented. Even if effective treatments are not currently available for established AKI, specific preventive approaches and some promising pharmacological treatments will be detailed. Renal replacement therapy is currently considered the most effective way to manage fluid balance when severe AKI occurs. Key Messages: Great efforts in pAKI research have today led to new strategies for early AKI detection and prevention strategies. Further studies have to be conducted in the next future in order to definitely improve the outcomes of pediatric patients experiencing this deadly syndrome. © 2018 S. Karger AG, Basel.

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

    PubMed

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

    2015-01-01

    Although kidney cancer incidence and nephrectomy rates have risen in tandem, clinical advances have generated new uncertainty regarding the optimal management of patients with small renal tumors, especially the elderly. To clarify existing practice patterns, we assessed contemporary trends in the incidence and management of patients with early-stage kidney cancer. Using Surveillance, Epidemiology, and End Results data, we identified adult patients diagnosed with T1aN0M0 kidney cancer from 2000 to 2010. We determined age-adjusted and age-specific incidence and management rates (i.e., nonoperative, ablation, partial nephrectomy [PN], and radical nephrectomy) per 100,000 adults and determined the average annual percent change (AAPC). Finally, we compared management groups using multinomial logistic regression accounting for patient characteristics, cancer information, and county-level measures for health. From 2000 to 2010, we identified 41,645 adults diagnosed with T1aN0M0 kidney cancer. Overall incidence increased from 3.7 to 7.0 per 100,000 adults (AAPC = 7.0%, P<0.001). Over the study interval, rates of PN (AAPC = 13.1%, P<0.001) increased substantially, becoming the most used treatment by 2010. Among the elderly, rates of nonoperative management and ablation approached nephrectomy rates for those aged 75 to 84 years and became the predominant strategy for patients older than 84 years. Adjusting for clinical, oncological, and environmental factors, older patients less frequently underwent PN and more often received ablative or nonoperative management (P<0.001). As the incidence of early-stage kidney cancer rises, patients are increasingly treated with nonoperative and nephron-sparing strategies, especially among the most elderly. The broader array of treatment options suggests opportunities to better personalize kidney cancer care for seniors. Published by Elsevier Inc.

  2. Two-dimensional electrophoretic profiling of normal human kidney glomerulus proteome and construction of an extensible markup language (XML)-based database.

    PubMed

    Yoshida, Yutaka; Miyazaki, Kenji; Kamiie, Junichi; Sato, Masao; Okuizumi, Seiji; Kenmochi, Akihisa; Kamijo, Ken'ichi; Nabetani, Takuji; Tsugita, Akira; Xu, Bo; Zhang, Ying; Yaoita, Eishin; Osawa, Tetsuo; Yamamoto, Tadashi

    2005-03-01

    To contribute to physiology and pathophysiology of the glomerulus of human kidney, we have launched a proteomic study of human glomerulus, and compiled a profile of proteins expressed in the glomerulus of normal human kidney by two-dimensional gel electrophoresis (2-DE) and identification with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Kidney cortices with normal appearance were obtained from patients under surgical nephrectomy due to renal tumor, and glomeruli were highly purified by a standard sieving method followed by picking-up under a phase-contrast microscope. The glomerular proteins were separated by 2-DE with 24 cm immobilized pH gradient strips in the 3-10 range in the first dimension and 26 x 20 cm sodium dodecyl sulfate polyacrylamide electrophoresis gels of 12.5% in the second dimension. Gels were silver-stained, and valid spots were processed for identification through an integrated robotic system that consisted of a spot picker, an in-gel digester, and a MALDI-TOF MS and / or a LC-MS/MS. From 2-DE gel images of glomeruli of four subjects with no apparent pathologic manifestations, a synthetic gel image of normal glomerular proteins was created. The synthetic gel image contained 1713 valid spots, of which 1559 spots were commonly observed in the respective 2-DE gels. Among the 1559 spots, 347 protein spots, representing 212 proteins, have so far been identified, and used for the construction of an extensible markup language (XML)-based database. The database is deposited on a web site (http://www.sw.nec.co.jp/bio/rd/hgldb/index.html) in a form accessible to researchers to contribute to proteomic studies of human glomerulus in health and disease.

  3. Prevalence of Barriers and Facilitators to Enhancing Conservative Kidney Management for Older Adults in the Primary Care Setting.

    PubMed

    Tam-Tham, Helen; King-Shier, Kathryn M; Thomas, Chandra M; Quinn, Robert R; Fruetel, Karen; Davison, Sara N; Hemmelgarn, Brenda R

    2016-11-07

    Conservative management of adults with stage 5 CKD (eGFR<15 ml/min per 1.73 m 2 ) is increasingly being provided in the primary care setting. We aimed to examine perceived barriers and facilitators for conservative management of older adults by primary care physicians. In 2015, we conducted a cross-sectional, population-based survey of all primary care physicians in Alberta, Canada. Eligible participants had experience caring for adults ages ≥75 years old with stage 5 CKD not planning on initiating dialysis. Questionnaire items were on the basis of a qualitative descriptive study informed by the Behavior Change Wheel and tested for face and content validity. Physicians were contacted via postal mail and/or fax on the basis of a modified Dillman method. Four hundred nine eligible primary care physicians completed the questionnaire (9.6% response rate). The majority of respondents were men (61.6%), were ages 40-60 years old (62.6%), and practiced in a large/medium population center (68.0%). The most common barrier to providing conservative care in the primary care setting was the inability to access support to maintain patients in the home setting (39.1% of respondents; 95% confidence interval, 34.6% to 43.6%). The second most common barrier was working with nonphysician providers with limited kidney-specific clinical expertise (32.3%; 95% confidence interval, 28.0% to 36.7%). Primary care physicians indicated that the two most common strategies that would enhance their ability to provide conservative management would be the ability to use the telephone to contact a nephrologist or clinical staff from the conservative care clinic (86.9%; 95% confidence interval, 83.7% to 90.0% and 85.6%; 95% confidence interval, 82.4% to 88.9%, respectively). We identified important areas to inform clinical programs to reduce barriers and enhance facilitators to improve primary care physicians' provision of conservative kidney care. In particular, primary care physicians require

  4. Social participation after successful kidney transplantation.

    PubMed

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

    2007-03-30

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

  5. ELECTROLYTE DISTURBANCE AND KIDNEY DYSFUNCTION IN DENGUE VIRAL INFECTION.

    PubMed

    Vachvanichsanong, Prayong; McNeil, Edward

    2015-01-01

    Dengue virus infection (DVI) is endemic in tropical countries in both children and adults. The classical presentation includes fever, hepatomegaly, thrombocytopenia-related bleeding disorders, and plasma leakage. Multi-organ involvement, including kidneys is found in complex cases. Asymptomatic electrolyte disturbances, abnormal urinalysis, and more severe manifestation such as acute kidney injury (AKI) usually indicate kidney involvement. Such manifestations are not rare in DVI, but are often not recognized and can cause the physician to misread the real situation of the patient. The prevalence of electrolyte disturbances or kidney involvement reported in studies varies widely by country and mainly depends on the severity of DVI and age of the patients. The prevalence of DVI-induced AKI ranges from 0.2%-10.0% in children and 2.2%-35.7% in adults. The prevalence among all age groups appears to be increasing in the last decade. Dengue shock syndrome (DSS) has been reported to be an independent risk factor for AKI development. The mechanism of DVI-induced AKI is complex and the details are to date undetermined. Urinalysis, serum electrolytes and creatinine measurements should be performed to document renal involvement in DVI patients for early detection and initiation of appropriate fluid therapy with close monitoring. Renal replacement therapy may be required in some cases. The presence of AKI dramatically increases the mortality rate among both childhood and adulthood DVI from 12%-44% to more than 60%.

  6. Fourier transform infrared spectroscopy for analysis of kidney stones.

    PubMed

    Khan, Aysha Habib; Imran, Sheharbano; Talati, Jamsheer; Jafri, Lena

    2018-01-01

    To compare the results of a chemical method of kidney stone analysis with the results of Fourier transform infrared (FT-IR) spectroscopy. Kidney stones collected between June and October 2015 were simultaneously analyzed by chemical and FT-IR methods. Kidney stones (n=449) were collected from patients from 1 to 81 years old. Most stones were from adults, with only 11.5% from children (aged 3-16 years) and 1.5% from children aged <2 years. The male to female ratio was 4.6. In adults, the calcium oxalate stone type, calcium oxalate monohydrate (COM, n=224), was the most common crystal, followed by uric acid and calcium oxalate dihydrate (COD, n=83). In children, the most frequently occurring type was predominantly COD (n=21), followed by COM (n=11), ammonium urate (n=10), carbonate apatite (n=6), uric acid (n=4), and cystine (n=1). Core composition in 22 stones showed ammonium urate (n=2), COM (n=2), and carbonate apatite (n=1) in five stones, while uric acid crystals were detected (n=13) by FT-IR. While chemical analysis identified 3 stones as uric acid and the rest as calcium oxalate only. Agreement between the two methods was moderate, with a kappa statistic of 0.57 (95% confidence interval, 0.5-0.64). Disagreement was noted in the analysis of 77 stones. FT-IR analysis of kidney stones can overcome many limitations associated with chemical analysis.

  7. Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease*

    PubMed Central

    Good, David M.; Zürbig, Petra; Argilés, Àngel; Bauer, Hartwig W.; Behrens, Georg; Coon, Joshua J.; Dakna, Mohammed; Decramer, Stéphane; Delles, Christian; Dominiczak, Anna F.; Ehrich, Jochen H. H.; Eitner, Frank; Fliser, Danilo; Frommberger, Moritz; Ganser, Arnold; Girolami, Mark A.; Golovko, Igor; Gwinner, Wilfried; Haubitz, Marion; Herget-Rosenthal, Stefan; Jankowski, Joachim; Jahn, Holger; Jerums, George; Julian, Bruce A.; Kellmann, Markus; Kliem, Volker; Kolch, Walter; Krolewski, Andrzej S.; Luppi, Mario; Massy, Ziad; Melter, Michael; Neusüss, Christian; Novak, Jan; Peter, Karlheinz; Rossing, Kasper; Rupprecht, Harald; Schanstra, Joost P.; Schiffer, Eric; Stolzenburg, Jens-Uwe; Tarnow, Lise; Theodorescu, Dan; Thongboonkerd, Visith; Vanholder, Raymond; Weissinger, Eva M.; Mischak, Harald; Schmitt-Kopplin, Philippe

    2010-01-01

    Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides. PMID:20616184

  8. IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury.

    PubMed

    Lefaucheur, Carmen; Viglietti, Denis; Bentlejewski, Carol; Duong van Huyen, Jean-Paul; Vernerey, Dewi; Aubert, Olivier; Verine, Jérôme; Jouven, Xavier; Legendre, Christophe; Glotz, Denis; Loupy, Alexandre; Zeevi, Adriana

    2016-01-01

    Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury. Copyright © 2016 by the American Society of Nephrology.

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

    PubMed

    Aldur, Muhammet M

    2005-01-01

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

  10. CRISPR Gene Editing in the Kidney.

    PubMed

    Cruz, Nelly M; Freedman, Benjamin S

    2018-06-01

    CRISPR is a nuclease guidance system that enables rapid and efficient gene editing of specific DNA sequences within genomes. We review applications of CRISPR for the study and treatment of kidney disease. CRISPR enables functional experiments in cell lines and model organisms to validate candidate genes arising from genetic studies. CRISPR has furthermore been used to establish the first models of genetic disease in human kidney organoids derived from pluripotent stem cells. These gene-edited organoids are providing new insight into the cellular mechanisms of polycystic kidney disease and nephrotic syndrome. CRISPR-engineered cell therapies are currently in clinical trials for cancers and immunologic syndromes, an approach that may be applicable to inflammatory conditions such as lupus nephritis. Use of CRISPR in large domestic species such as pigs raises the possibility of farming kidneys for transplantation to alleviate the shortage of donor organs. However, significant challenges remain, including how to effectively deliver CRISPR to kidneys and how to control gene editing events within the genome. Thorough testing of CRISPR in preclinical models will be critical to the safe and efficacious translation of this powerful young technology into therapies. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  11. Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta-analysis.

    PubMed

    He, Yuan-Mei; Feng, Li; Huo, Dong-Mei; Yang, Zhen-Hua; Liao, Yun-Hua

    2013-09-01

    Both enalapril and losartan are effective and widely used in patients with chronic kidney disease (CKD). This review aimed to evaluate the benefits of enalapril and losartan in adults with CKD. PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, without language limitations, for randomized controlled trials (RCT), in which enalapril and losartan were compared in adults with CKD. Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, ver. 5.2, was used for meta-analysis. Of 318 citations retrieved, 17 RCT (14 parallel-group and three cross-over) met our inclusion criteria. The pooled analysis for parallel RCT showed that the effects of enalapril and losartan on blood pressure, renal function and serum uric acid (UA) were similar. Meta-analysis indicated that patients taking enalapril had a higher risk of dry cough (risk ratio, 2.88; 95% CI, 1.11-7.48; P=0.03). Sensitivity analysis showed good robustness of these findings. Enalapril has similar effects to losartan on systemic blood pressure, renal function and serum UA in patients with CKD, but carries a higher risk of dry cough. Larger trials are required to evaluate the effects of these medications on clinical outcomes. © 2013 The Authors. Nephrology © 2013 Asian Pacific Society of Nephrology.

  12. Dietary acid load and chronic kidney disease in elderly adults: Protein and potassium intake.

    PubMed

    Ko, Byung-Joon; Chang, Yoosoo; Ryu, Seungho; Kim, Eun Mi; Lee, Mi Yeon; Hyun, Young Youl; Lee, Kyu-Beck

    2017-01-01

    Dietary net endogenous acid production (NEAP), which represents total dietary load of nonvolatile acid, may affect kidney function. Estimated NEAP (eNEAP) is calculated indirectly by the ratio of protein and potassium intake. A few studies are available assessing the association between eNEAP and chronic kidney disease (CKD), and its relation to dietary protein and potassium intake in the elderly. A total 1,369 community-dwelling elderly Koreans in the Kangbuk Samsung Cohort Study (KSCS) were evaluated using a food frequency questionnaire (FFQ) and comprehensive health examination. We evaluated the association between eNEAP and the CKD. We also examined their relation to protein and potassium intake. eNEAP was correlated with potassium intake (r = -0.410, P < 0.001), but was not correlated with protein intake (r = -0.004, P = 0.879). In a full multivariate adjustment for sociodemographic factors, dietary factors, and comorbidities, the participants with higher eNEAP quartiles (Q2, Q3, Q4) had higher odds of CKD compared to the lowest eNEAP quartile (Q1); OR (95% CI) were 1.47 (0.78-2.72), 1.66 (0.85-3.23), and 2.30 (1.16-4.60) respectively (P for trend = 0.019). The odds of CKD decreased for participants with higher potassium intake quartiles (Q2, Q3, Q4) compared to the lowest potassium intake quartile (Q1); OR (95% CI) were 0.52 (0.28-0.95), 0.50 (0.26-0.96), and 0.50 (0.21-0.99) respectively (P for trend = 0.050). Protein intake was not associated with CKD. The association between eNEAP and CKD was similar in subgroup analysis. Dietary acid load was associated with CKD. Among the nutrients related to dietary acid load, potassium intake was negatively associated with CKD, but protein intake was not associated with CKD in elderly adults.

  13. Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors.

    PubMed

    Moore, Phillip S; Farney, Alan C; Sundberg, Aimee K; Rohr, Michael S; Hartmann, Erica L; Iskandar, Samy S; Gautreaux, Michael D; Rogers, Jeffrey; Doares, William; Anderson, Teresa K; Adams, Patricia L; Stratta, Robert J

    2007-06-27

    The purpose of this study was to perform a case-matched cohort analysis of dual kidney transplantation (DKT) from expanded criteria donors (ECDs) compared to single kidney transplantation (SKT) from concurrent ECDs and standard criteria donors (SCDs, defined as non-ECD). Deceased donor (DD) kidney transplants (KTs) performed at a single center between October 2001 and February 2006 were reviewed retrospectively. If the calculated DD creatinine clearance (CrCl) was <65 mL/min, then the kidneys were transplanted dually into a single patient. In the case of DKT and SKT from ECDs, low risk patients were chosen and informed consent was obtained. Patients in each group were matched for age, gender, race, transplant number, and time of transplant. Of 294 adult DD KTs performed, 16 (5%) were DKTs, which were matched with 16 concurrent SCD and 16 ECD SKT patients. Mean donor age in years (65 DKT vs. 33 SCD vs. 61 ECD; P<0.0001) and mean donor CrCl in ml/min (54 DKT vs. 91 SCD vs. 76 ECD; P=0.002) were different between groups. Patient survival was 100% in the DKT and SCD SKT groups and 94% in the ECD SKT group (mean follow up 23-28 months); graft survival rates in the DKT, SCD, and ECD groups were 81%, 81%, and 94%, respectively (P=NS). Graft function, rejection, and morbidity were similar between groups. DKT using kidneys from marginal ECDs is a viable option to counteract the growing shortage of available organs. Excellent short-term results and renal function can be achieved with older, low nephron mass donors provided that both kidneys are transplanted into a single recipient.

  14. Expression of human oxoguanine glycosylase 1 or formamidopyrimidine glycosylase in human embryonic kidney 293 cells exacerbates methylmercury toxicity in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ondovcik, Stephanie L.; Preston, Thomas J.; McCallum, Gordon P.

    Exposure to methylmercury (MeHg) acutely at high levels, or via chronic low-level dietary exposure from daily fish consumption, can lead to adverse neurological effects in both the adult and developing conceptus. To determine the impact of variable DNA repair capacity, and the role of reactive oxygen species (ROS) and oxidatively damaged DNA in the mechanism of toxicity, transgenic human embryonic kidney (HEK) 293 cells that stably express either human oxoguanine glycosylase 1 (hOgg1) or its bacterial homolog, formamidopyrimidine glycosylase (Fpg), which primarily repair the oxidative lesion 8-oxo-2′-deoxyguanosine (8-oxodG), were used to assess the in vitro effects of MeHg. Western blottingmore » confirmed the expression of hOgg1 or Fpg in both the nuclear and mitochondrial compartments of their respective cell lines. Following acute (1–2 h) incubations with 0–10 μM MeHg, concentration-dependent decreases in clonogenic survival and cell growth accompanied concentration-dependent increases in lactate dehydrogenase (LDH) release, ROS formation, 8-oxodG levels and apurinic/apyrimidinic (AP) sites, consistent with the onset of cytotoxicity. Paradoxically, hOgg1- and Fpg-expressing HEK 293 cells were more sensitive than wild-type cells stably transfected with the empty vector control to MeHg across all cellular and biochemical parameters, exhibiting reduced clonogenic survival and cell growth, and increased LDH release and DNA damage. Accordingly, upregulation of specific components of the base excision repair (BER) pathway may prove deleterious potentially due to the absence of compensatory enhancement of downstream processes to repair toxic intermediary abasic sites. Thus, interindividual variability in DNA repair activity may constitute an important risk factor for environmentally-initiated, oxidatively damaged DNA and its pathological consequences. - Highlights: • hOgg1 and Fpg repair oxidatively damaged DNA. • hOgg1- and Fpg-expressing cells are more

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

    PubMed

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

    2017-09-26

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

  16. Notes on the Problems of the Transplantation of Kidneys in Dogs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Puza, A.; Drahovsky, V.; Neubauer, E.

    1963-01-01

    In a group of 29 mongrel dogs kidney homotransplantation was performed. In five dogs an autograft was performed to check the suitability of the surgical technique. In the remaining 24 dogs kidney homografts were carried out, Five dogs served as controls; in these animals the functioning of the homografted kidney stopped after 8 days on the average, In 12 animals an attempt at the induction of immunological tolerance by exsanguinotransfusion, whole-body irradiation and 6-MP-administration was made. Induction of immunological tolerance by total exsanguinotransfusion immediately after birth may render possible a successful homograft even in adult life. The transplanted organ thenmore » exhibits a permanent take and takes over the function of the recipient's removed kidneys. One dog is alive with its single kidney homograft after almost two years. 6-MP administration may lead to such a degree of induced tolerance that the function of a kidney homograft is prolonged by a factor of two to three. Whole-body irradiation within a range of 400 rad (Co 60 source) does not significantly prolong homograft survival.« less

  17. Simple Kidney Cysts

    MedlinePlus

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

  18. Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development.

    PubMed

    Barker, Nick; Rookmaaker, Maarten B; Kujala, Pekka; Ng, Annie; Leushacke, Marc; Snippert, Hugo; van de Wetering, Marc; Tan, Shawna; Van Es, Johan H; Huch, Meritxell; Poulsom, Richard; Verhaar, Marianne C; Peters, Peter J; Clevers, Hans

    2012-09-27

    Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5(+ve) cells via in vivo lineage tracing. The appearance and localization of Lgr5(+ve) cells coincided with that of the S-shaped body around embryonic day 14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until postnatal day 7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  19. What we know and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman's Day.

    PubMed

    Piccoli, G B; Al Rukhaimi, M; Liu, Zhi-Hong; Zakharova, E; Levin, A

    2018-01-01

    Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically women's kidney health on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. Various autoimmune and other conditions are more likely to impact women, with profound consequences for child bearing and the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we know and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

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

    PubMed

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

    2003-09-01

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

  1. The Genetics and Epigenetics of Kidney Development

    PubMed Central

    Patel, Sanjeevkumar R.; Dressler, Gregory R.

    2013-01-01

    The development of the mammalian kidney has been studied at the genetic, biochemical, and cell biological level for more than 40 years. As such, detailed mechanisms governing early patterning, cell lineages, and inductive interactions are well described. How genes interact to specify the renal epithelial cells of the nephrons and how this specification is relevant to maintaining normal renal function is discussed. Implicit in the development of the kidney are epigenetic mechanisms that mark renal cell types and connect certain developmental regulatory factors to chromatin modifications that control gene expression patterns and cellular physiology. In adults, such regulatory factors and their epigenetic pathways may function in regeneration and may be disturbed in disease processes. PMID:24011574

  2. Evolutionary trade-offs in kidney injury and repair.

    PubMed

    Lei, Yutian; Anders, Hans-Joachim

    2017-11-01

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

  3. Uric acid and progression of chronic kidney disease.

    PubMed

    Weaver, Donald J

    2018-06-21

    The association between serum uric acid levels and human disease has garnered intense interest over the last decade including chronic kidney disease. Animal studies have provided evidence for a potential mechanistic role of uric acid in promoting progression of chronic kidney disease. Epidemiologic studies have also suggested an association between elevated serum uric acid levels and worsening renal function in the general population as well as in patients with chronic kidney disease. However, there is currently insufficient evidence to recommend the use of uric acid-lowering therapy to delay progression of chronic kidney disease in this patient population. Adequately powered, randomized, placebo-controlled trials are required to more precisely evaluate the risk and benefits of uric acid-lowering therapy in pediatric patients.

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

    PubMed

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

    2018-01-01

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

  5. HILDA/LIF urinary excretion during acute kidney rejection.

    PubMed

    Taupin, J L; Morel, D; Moreau, J F; Gualde, N; Potaux, L; Bezian, J H

    1992-03-01

    Recently, a new lymphokine called HILDA (human interleukin for DA cells) has been described and cloned. This cytokine, initially described to be produced by alloreactive T lymphocyte clones grown from a rejected human kidney allograft, is identical to other factors termed D-factor, differentiation-inducing factor, differentiation inhibitory activity, hepatocyte-stimulating factor III, and leukemia inhibitory factor. HILDA/LIF induces various effects on neural, hemopoietic, embryonic cells as well as on bone remodeling and acute phase protein synthesis in hepatocyte. In this study we demonstrate the presence of HILDA/LIF in the urine but not in the serum of kidney graft recipients during acute rejection episodes, whereas this lymphokine was detectable neither in the serum nor in the urine of kidney transplanted patients with stable renal function. These data reinforce the notion of a possible role for this lymphokine in the inflammatory and/or the immune response.

  6. Chronic Kidney Disease in Kidney Stone Formers

    PubMed Central

    Krambeck, Amy E.; Lieske, John C.

    2011-01-01

    Summary Recent population studies have found symptomatic kidney stone formers to be at increased risk for chronic kidney disease (CKD). Although kidney stones are not commonly identified as the primary cause of ESRD, they still may be important contributing factors. Paradoxically, CKD can be protective against forming kidney stones because of the substantial reduction in urine calcium excretion. Among stone formers, those with rare hereditary diseases (cystinuria, primary hyperoxaluria, Dent disease, and 2,8 dihydroxyadenine stones), recurrent urinary tract infections, struvite stones, hypertension, and diabetes seem to be at highest risk for CKD. The primary mechanism for CKD from kidney stones is usually attributed to an obstructive uropathy or pyelonephritis, but crystal plugs at the ducts of Bellini and parenchymal injury from shockwave lithotripsy may also contribute. The historical shift to less invasive surgical management of kidney stones has likely had a beneficial impact on the risk for CKD. Among potential kidney donors, past symptomatic kidney stones but not radiographic stones found on computed tomography scans were associated with albuminuria. Kidney stones detected by ultrasound screening have also been associated with CKD in the general population. Further studies that better classify CKD, better characterize stone formers, more thoroughly address potential confounding by comorbidities, and have active instead of passive follow-up to avoid detection bias are needed. PMID:21784825

  7. Stress associated proteins metallothionein, HO-1 and HSP 70 in human zero-hour biopsies of transplanted kidneys.

    PubMed

    August, Christian; Brockmann, Jens; Vowinkel, Thorsten; Wolters, Heiner; Dietl, Karl-Heinz; Levkau, Bodo; Heidenreich, Stefan; Lang, Detlef; Baba, Hideo A

    2006-08-01

    Light microscopic alterations reflecting both previous and preservation-induced changes in the donor organ are usually not very distinctive. The ischemia/reperfusion-associated injury depends primarily on the conditions of donor organ preservation. The present study examined human kidney biopsies with special attention paid to the molecular mechanisms of preservation-induced injury preceding reperfusion. Stress-associated proteins hemeoxygenase-1 (HO-1), heat shock protein 70 (HSP 70), and metallothionein (MT) were studied in human zero-hour biopsies of transplanted kidneys prior to reperfusion in 29 patients. Protein expression was evaluated by semiquantitative immunohistochemistry and Western blotting for HO-1 and HSP 70. These findings were correlated with terminal deoxynucleotidyltransferase-mediated 2'-deoxyuridine 5'-triphosphate-digoxigenin nick end labeling (TUNEL) staining and follow up. Compared to controls, MT and HSP 70 expression was significantly higher at zero hour. In contrast, HO-1 and the number of TUNEL-positive cells were not elevated. MT and HO-1 immunoexpression were inversely associated with graft function, and hence, were of prognostic relevance. MT and HSP 70 were sensitive to the duration of cold ischemia. MT and HO-1 are suitable indicators for tissue injury during ischemia and may serve as new predictive markers that need to be validated in further independent studies.

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

    PubMed

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

    1989-03-15

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

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

    PubMed

    Gentili, Marc E

    2015-11-01

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

  10. Metabolomics Reveals Signature of Mitochondrial Dysfunction in Diabetic Kidney Disease

    PubMed Central

    Karl, Bethany; Mathew, Anna V.; Gangoiti, Jon A.; Wassel, Christina L.; Saito, Rintaro; Pu, Minya; Sharma, Shoba; You, Young-Hyun; Wang, Lin; Diamond-Stanic, Maggie; Lindenmeyer, Maja T.; Forsblom, Carol; Wu, Wei; Ix, Joachim H.; Ideker, Trey; Kopp, Jeffrey B.; Nigam, Sanjay K.; Cohen, Clemens D.; Groop, Per-Henrik; Barshop, Bruce A.; Natarajan, Loki; Nyhan, William L.; Naviaux, Robert K.

    2013-01-01

    Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of diabetic kidney disease are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM without CKD (DM–CKD), and in healthy controls. Compared with levels in healthy controls, 13 metabolites were significantly reduced in the DM+CKD cohorts (P≤0.001), and 12 of the 13 remained significant when compared with the DM–CKD cohort. Many of the differentially expressed metabolites were water-soluble organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice expressed a similar pattern of reduced levels of urinary organic acids, and human kidney tissue from patients with diabetic nephropathy demonstrated lower gene expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of the 13 differentially expressed metabolites are linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in diabetic kidney disease. Supporting this analysis, human diabetic kidney sections expressed less mitochondrial protein, urine exosomes from patients with diabetes and CKD had less mitochondrial DNA, and kidney tissues from patients with diabetic kidney disease had lower gene expression of PGC1α (a master regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a reliable source for biomarkers of diabetic complications, and our data suggest that renal organic ion transport and mitochondrial function are dysregulated in diabetic kidney disease. PMID:23949796

  11. Nutrient requirements and other factors involved in the culture of human kidney cells on microcarrier beads

    NASA Technical Reports Server (NTRS)

    Lewis, Marian L.; Morrison, Dennis R.

    1987-01-01

    The culture of human kidney cells on microcarrier beads in the Bioprocessing Laboratory at the Johnson Space Center is described. These were the first series of studies performed before and during 1983 to determine optimum conditions, including medium type, bead type and density. The composition of several medium types and the molecular weights of some common culture medium supplements and cellular proteins are included. The microgravity cell-to-bead attachment experiment performed on Space Transportation System Flight 8 is described.

  12. Nutrition and dietary intake and their association with mortality and hospitalisation in adults with chronic kidney disease treated with haemodialysis: protocol for DIET-HD, a prospective multinational cohort study.

    PubMed

    Palmer, Suetonia C; Ruospo, Marinella; Campbell, Katrina L; Garcia Larsen, Vanessa; Saglimbene, Valeria; Natale, Patrizia; Gargano, Letizia; Craig, Jonathan C; Johnson, David W; Tonelli, Marcello; Knight, John; Bednarek-Skublewska, Anna; Celia, Eduardo; Del Castillo, Domingo; Dulawa, Jan; Ecder, Tevfik; Fabricius, Elisabeth; Frazão, João Miguel; Gelfman, Ruben; Hoischen, Susanne Hildegard; Schön, Staffan; Stroumza, Paul; Timofte, Delia; Török, Marietta; Hegbrant, Jörgen; Wollheim, Charlotta; Frantzen, Luc; Strippoli, G F M

    2015-03-20

    Adults with end-stage kidney disease (ESKD) treated with haemodialysis experience mortality of between 15% and 20% each year. Effective interventions that improve health outcomes for long-term dialysis patients remain unproven. Novel and testable determinants of health in dialysis are needed. Nutrition and dietary patterns are potential factors influencing health in other health settings that warrant exploration in multinational studies in men and women treated with dialysis. We report the protocol of the "DIETary intake, death and hospitalisation in adults with end-stage kidney disease treated with HaemoDialysis (DIET-HD) study," a multinational prospective cohort study. DIET-HD will describe associations of nutrition and dietary patterns with major health outcomes for adults treated with dialysis in several countries. DIET-HD will recruit approximately 10,000 adults who have ESKD treated by clinics administered by a single dialysis provider in Argentina, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden and Turkey. Recruitment will take place between March 2014 and June 2015. The study has currently recruited 8000 participants who have completed baseline data. Nutritional intake and dietary patterns will be measured using the Global Allergy and Asthma European Network (GA(2)LEN) food frequency questionnaire. The primary dietary exposures will be n-3 and n-6 polyunsaturated fatty acid consumption. The primary outcome will be cardiovascular mortality and secondary outcomes will be all-cause mortality, infection-related mortality and hospitalisation. The study is approved by the relevant Ethics Committees in participating countries. All participants will provide written informed consent and be free to withdraw their data at any time. The findings of the study will be disseminated through peer-reviewed journals, conference presentations and to participants via regular newsletters. We expect that the DIET-HD study will inform large pragmatic

  13. Fluoroquinolones inhibit human polyomavirus BK (BKV) replication in primary human kidney cells.

    PubMed

    Sharma, Biswa Nath; Li, Ruomei; Bernhoff, Eva; Gutteberg, Tore Jarl; Rinaldo, Christine Hanssen

    2011-10-01

    Reactivation of human polyomavirus BK (BKV) may cause polyomavirus-associated nephropathy or polyomavirus-associated hemorrhagic cystitis in renal- or bone marrow-transplant patients, respectively. Lack of treatment options has led to exploration of fluoroquinolones that inhibit topoisomerase II and IV in prokaryotes and possibly large T-antigen (LT-ag) helicase activity in polyomavirus. We characterized the effects of ofloxacin and levofloxacin on BKV replication in the natural host cells - primary human renal proximal tubular epithelial cells (RPTECs). Ofloxacin and levofloxacin inhibited BKV load in a dose-dependent manner yielding a ∼90% inhibition at 150 μg/ml. Ofloxacin at 150 μg/ml inhibited LT-ag mRNA and protein expression from 24h post infection (hpi). BKV genome replication was 77% reduced at 48 hpi and a similar reduction was found in VP1 and agnoprotein expression. At 72 hpi, the reduction in genome replication and protein expression was less pronounced. A dose-dependent cytostatic effect was noted. In infected cells, 150 μg/ml ofloxacin led to a 26% and 6% inhibition of cellular DNA replication and total metabolic activity, respectively while 150 μg/ml levofloxacin affected this slightly more, particularly in uninfected cells. Cell counting and xCELLigence results revealed that cell numbers were not reduced. In conclusion, ofloxacin and levofloxacin inhibit but do not eradicate BKV replication in RPTECs. At a concentration of ofloxacin giving ∼90% inhibition in BKV load, no significant cytotoxicity was observed. This concentration can be achieved in urine and possibly in the kidneys. Our results support a mechanism involving inhibition of LT-ag expression or functions but also suggest inhibition of cellular enzymes. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Further analyses of human kidney cell populations separated on the Space Shuttle

    NASA Technical Reports Server (NTRS)

    Stewart, Robin M.; Todd, Paul; Cole, Kenneth D.; Morrison, Dennis R.

    1992-01-01

    Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120 C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantization of plasminogen activators in these samples. These assays of frozen-culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator-producing cells from nonproducing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one other.

  15. Fell-Muir lecture: connective tissue growth factor (CCN2) – a pernicious and pleiotropic player in the development of kidney fibrosis

    PubMed Central

    Mason, Roger M

    2013-01-01

    Connective tissue growth factor (CTGF, CCN2) is a member of the CCN family of matricellular proteins. It interacts with many other proteins, including plasma membrane proteins, modulating cell function. It is expressed at low levels in normal adult kidney cells but is increased in kidney diseases, playing important roles in inflammation and in the development of glomerular and interstitial fibrosis in chronic disease. This review reports the evidence for its expression in human and animal models of chronic kidney disease and summarizes data showing that anti-CTGF therapy can successfully attenuate fibrotic changes in several such models, suggesting that therapies targeting CTGF and events downstream of it in renal cells may be useful for the treatment of human kidney fibrosis. Connective tissue growth factor stimulates the development of fibrosis in the kidney in many ways including activating cells to increase extracellular matrix synthesis, inducing cell cycle arrest and hypertrophy, and prolonging survival of activated cells. The relationship between CTGF and the pro-fibrotic factor TGFβ is examined and mechanisms by which CTGF promotes signalling by the latter are discussed. No specific cellular receptors for CTGF have been discovered but it interacts with and activates several plasma membrane proteins including low-density lipoprotein receptor-related protein (LRP)-1, LRP-6, tropomyosin-related kinase A, integrins and heparan sulphate proteoglycans. Intracellular signalling and downstream events triggered by such interactions are reviewed. Finally, the relationships between CTGF and several anti-fibrotic factors, such as bone morphogenetic factor-4 (BMP4), BMP7, hepatocyte growth factor, CCN3 and Oncostatin M, are discussed. These may determine whether injured tissue heals or progresses to fibrosis. PMID:23110747

  16. Can sleep deprivation studies explain why human adults sleep?

    PubMed

    Brown, Lee K

    2012-11-01

    This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.

  17. Kidney Transplant

    MedlinePlus

    ... Events Advocacy Donate A to Z Health Guide Kidney Transplant Print Email When your kidneys fail, treatment ... doctor, nurse and family members. What is a kidney transplant? When you get a kidney transplant, a ...

  18. Kidney Failure

    MedlinePlus

    ... store Donate Now Give Monthly Give In Honor Kidney Failure (ESRD) Causes, Symptoms, & Treatments www.kidneyfund.org > ... Disaster preparedness Kidney failure/ESRD diet What causes kidney failure? In most cases, kidney failure is caused ...

  19. Kidney Problems

    MedlinePlus

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

  20. What we know and do not know about women and kidney diseases; Questions unanswered and answers unquestioned: Reflection on World Kidney Day and International Woman’s Day

    PubMed Central

    Piccoli, G.B.; Al Rukhaimi, M.; Liu, Zhi-Hong; Zakharova, E.; Levin, A.

    2018-01-01

    Chronic kidney disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically women’s kidney health on the community and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state in which acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. Various autoimmune and other conditions are more likely to impact women, with profound consequences for child bearing and the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we know and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide. PMID:29791583

  1. MicroRNAs and Drug-induced Kidney Injury

    PubMed Central

    Pavkovic, Mira; Vaidya, Vishal S.

    2016-01-01

    Drug-induced kidney injury (DIKI) is a severe complication in hospitalized patients associated with higher probabilities of developing progressive chronic kidney disease or end-stage renal diseases. Furthermore, DIKI is a problem during preclinical and clinical phases of drug development leading to high rates of project terminations. Understanding the molecular perturbations caused by DIKI would pave the way for a new class of therapeutics to mitigate the damage. Yet, another approach to ameliorate DIKI is identifying sensitive and specific translational biomarkers that outperform the current diagnostic analytes like serum creatinine and facilitate early diagnosis. MicroRNAs (miRNAs), a class of non-coding RNAs, are increasingly being recognized to have a two-pronged approach towards DIKI management: 1) miRNAs have a regulatory role in gene expression and signaling pathways thereby making them novel interventional targets and 2) miRNAs enable diagnosis and prognosis of DIKI because of their stable presence in biofluids. In this review, apart from summarizing the literature on miRNAs in DIKI, we report small RNA sequencing results showing miRNA expression profiles at baseline in normal kidney samples from mice and humans. Additionally, we also compared the miRNA expression in biopsies of normal human kidneys to patients with acute tubular necrosis, and found 76 miRNAs significantly downregulated and 47 miRNAs upregulated (FDR adjusted p<0.05, +/−2-fold change). In summary, we highlight the transformative potential of miRNAs in therapeutics and translational medicine with a focus on drug-induced kidney damage. PMID:27126472

  2. Effect of Sirolimus on Native Total Kidney Volume After Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease: A Randomized Controlled Pilot Study.

    PubMed

    Davis, S; Gralla, J; Chan, L; Wiseman, A; Edelstein, C L

    2018-06-01

    The mammalian target of rapamycin (mTOR) pathway has been shown to be central to cyst formation and growth in patients with autosomal dominant polycystic kidney disease (ADPKD). Drugs that suppress mTOR signaling are frequently used as antiproliferative agents for maintenance immunosuppression in patients who have undergone kidney transplantation. The aim of this study was to determine the effect of sirolimus, an mTOR inhibitor, on cyst volume regression in patients with ADPKD who have undergone renal transplantation. In this single-center, prospective, open-label, parallel-group, randomized trial, 23 adult patients with ADPKD who successfully underwent renal transplantation from 2008 to 2012 were subsequently randomized (on a 1:1 basis) to a maintenance immunosuppression regimen with either sirolimus (sirolimus, tacrolimus, prednisone) or mycophenolate (mycophenolate, tacrolimus, prednisone). Total kidney volumes were measured by means of high-resolution magnetic resonance imaging within 2 weeks after transplantation and at 1 year. The primary end point was change in total kidney volume at 1 year. Sixteen patients completed the 1-year study (8 patients in each group). There was a decrease in kidney volume in both the sirolimus group (percentage change from baseline, 20.5%; P < .001) and mycophenolate group (percentage change from baseline, 17%; P = .048), but there was no significant difference in percentage change of total kidney volume between the groups (P = .665). In ADPKD patients at 1 year after kidney transplantation, there was a similar decrease in polycystic kidney volume in patients receiving an immunosuppression regimen containing sirolimus compared with patients receiving mycophenolate. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Tryptophan Intake in the US Adult Population Is Not Related to Liver or Kidney Function but Is Associated with Depression and Sleep Outcomes.

    PubMed

    Lieberman, Harris R; Agarwal, Sanjiv; Fulgoni, Victor L

    2016-12-01

    Tryptophan is an indispensable amino acid and is a precursor of the neurotransmitter serotonin. Tryptophan metabolites, such as serotonin and melatonin, are thought to participate in the regulation of mood and sleep and tryptophan is used to treat insomnia, sleep apnea, and depression. This study examined the intake of tryptophan and its associations with biochemical, behavioral, sleep, and health and safety outcomes in adults in a secondary analysis of a large, publicly available database of the US population. Data from the NHANES 2001-2012 (n = 29,687) were used to determine daily intakes of tryptophan and its associations with biochemical markers of health- and safety-related outcomes, self-reported depression, and sleep-related variables. Data were adjusted for demographic factors and protein intake. Linear trends were computed across deciles of intake for each outcome variable, and P-trends were determined. The usual tryptophan intake by US adults was 826 mg/d, severalfold higher than the Estimated Average Requirement for adults of 4 mg/(kg ⋅ d) (∼280 mg/d for a 70-kg adult). Most health- and safety-related biochemical markers of liver function, kidney function, and carbohydrate metabolism were not significantly (P-trend > 0.05) associated with deciles of tryptophan intake and were well within normal ranges, even for individuals in the 99th percentile of intake. Usual intake deciles of tryptophan were inversely associated with self-reported depression measured by the Patient Health Questionnaire raw score (0-27; P-trend < 0.01) and calculated level (1 = no depression, 5 = severe depression; P-trend < 0.01) and were positively associated with self-reported sleep duration (P-trend = 0.02). Tryptophan intake was not related to most markers of liver function, kidney function or carbohydrate metabolism. Levels of tryptophan intake in the US population appear to be safe as shown by the absence of abnormal laboratory findings. Tryptophan intake was inversely

  4. RNA Sequencing Identifies Novel Translational Biomarkers of Kidney Fibrosis

    PubMed Central

    Craciun, Florin L.; Bijol, Vanesa; Ajay, Amrendra K.; Rao, Poornima; Kumar, Ramya K.; Hutchinson, John; Hofmann, Oliver; Joshi, Nikita; Luyendyk, James P.; Kusebauch, Ulrike; Moss, Christopher L.; Srivastava, Anand; Himmelfarb, Jonathan; Waikar, Sushrut S.; Moritz, Robert L.

    2016-01-01

    CKD is the gradual, asymptomatic loss of kidney function, but current tests only identify CKD when significant loss has already happened. Several potential biomarkers of CKD have been reported, but none have been approved for preclinical or clinical use. Using RNA sequencing in a mouse model of folic acid-induced nephropathy, we identified ten genes that track kidney fibrosis development, the common pathologic finding in patients with CKD. The gene expression of all ten candidates was confirmed to be significantly higher (approximately ten- to 150-fold) in three well established, mechanistically distinct mouse models of kidney fibrosis than in models of nonfibrotic AKI. Protein expression of these genes was also high in the folic acid model and in patients with biopsy-proven kidney fibrosis. mRNA expression of the ten genes increased with increasing severity of kidney fibrosis, decreased in response to therapeutic intervention, and increased only modestly (approximately two- to five-fold) with liver fibrosis in mice and humans, demonstrating specificity for kidney fibrosis. Using targeted selected reaction monitoring mass spectrometry, we detected three of the ten candidates in human urine: cadherin 11 (CDH11), macrophage mannose receptor C1 (MRC1), and phospholipid transfer protein (PLTP). Furthermore, urinary levels of each of these three proteins distinguished patients with CKD (n=53) from healthy individuals (n=53; P<0.05). In summary, we report the identification of urinary CDH11, MRC1, and PLTP as novel noninvasive biomarkers of CKD. PMID:26449608

  5. African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era

    PubMed Central

    Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi

    2015-01-01

    Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era. PMID:25949944

  6. Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Corley, R.A., E-mail: rick.corley@pnl.gov; Saghir, S.A.; Bartels, M.J.

    2011-02-01

    A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrationsmore » exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.« less

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

    PubMed

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

    2016-11-01

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

  8. Acute Kidney Injury Incidence in Noncritically Ill Hospitalized Children, Adolescents, and Young Adults: A Retrospective Observational Study

    PubMed Central

    McGregor, Tracy L.; Jones, Deborah P.; Wang, Li; Danciu, Ioana; Bridges, Brian C.; Fleming, Geoffrey M.; Shirey-Rice, Jana; Chen, Lixin; Byrne, Daniel W.; Van Driest, Sara L.

    2015-01-01

    Background Acute kidney injury (AKI) has been characterized in young high-risk inpatients, in whom AKI is frequent and associated with increased mortality, morbidity, and length of stay. The incidence of AKI among patients not requiring intensive care is unknown. Study Design Retrospective cohort study Setting & Participants 13,914 noncritical admissions during 2011–2012 at our tertiary referral pediatric hospital were evaluated. Patients <28 days or >21 years of age, or with chronic kidney disease (CKD), were excluded. Admissions with ≥2 serum creatinine measurements were evaluated. Factors Demographic features, laboratory measurements, medication exposures, and length of stay. Outcome AKI defined by increased serum creatinine in accordance with KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Based on time of admission, time interval requirements were met in 97% of cases, but KDIGO time window criteria were not strictly enforced to allow implementation using clinically-obtained data. Results Two or more creatinine measurements (one baseline before or during admission, and a second during admission) in 2,374 of 13,914 (17%) patients allowed for AKI evaluation. A serum creatinine difference of ≥0.3 mg/dL or ≥1.5 times baseline was seen in 722 of 2,374 (30%) patients. A minimum of 5% of all noncritical inpatients without CKD in pediatric wards have an episode of AKI during routine hospital admission. Limitations Urine output, glomerular filtration rate, and time interval criteria for AKI were not applied secondary to study design and available data. The evaluated cohort was restricted to patients with ≥2 clinically obtained serum creatinine measurements, and baseline creatinine may have been measured after the AKI episode. Conclusions AKI occurs in at least 5% of all non-critically ill hospitalized children, adolescents, and young adults without known CKD. Physicians should increase their awareness of AKI and improve surveillance strategies with

  9. Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic Reticulum Stress and Attenuates Kidney Injury

    PubMed Central

    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

    2016-01-01

    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. PMID:26195817

  10. Kidney Disease

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Kidney Disease KidsHealth / For Teens / Kidney Disease What's in ... Coping With Kidney Conditions Print What Do the Kidneys Do? You might never think much about some ...

  11. Predonation Direct and Indirect Costs Incurred by Adults Who Donated a Kidney: Findings From the KDOC Study.

    PubMed

    Rodrigue, J R; Schold, J D; Morrissey, P; Whiting, J; Vella, J; Kayler, L K; Katz, D; Jones, J; Kaplan, B; Fleishman, A; Pavlakis, M; Mandelbrot, D A

    2015-09-01

    Limited information exists on the predonation costs incurred by eventual living kidney donors (LKDs). Expenses related to completion of the donation evaluation were collected from 194 LKDs participating in the multi-center, prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one or more direct costs, including ground transportation (80%), healthcare (24%), lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523 ± 942). Excluding paid vacation or sick leave, donor and companion lost wages totaled $35 918 (mean = $187 ± 556) and $14 378 (mean = $76 ± 311), respectively. One-third of LKDs used paid vacation or sick leave to avoid incurring lost wages. Few LKDs reported receiving financial support from the transplant candidate (6%), transplant candidate's family (3%), a nonprofit organization (3%), the National Living Donor Assistance Center (7%), or transplant center (3%). Higher total costs were significantly associated with longer distance traveled to the transplant center (p < 0.001); however, total costs were not associated with age, sex, race/ethnicity, household income, marital status, insurance status, or transplant center. Moderate predonation direct and indirect costs are common for adults who complete the donation evaluation. Potential LKDs should be advised of these possible costs, and the transplant community should examine additional strategies to reimburse donors for them. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. Contact and perspective taking improve humanness standards and perceptions of humanness of older adults and people with dementia: a cross-sectional survey study.

    PubMed

    Miron, Anca M; McFadden, Susan H; Hermus, Nathan J; Buelow, Jennifer; Nazario, Amanda S; Seelman, Katarena

    2017-10-01

    No empirical work has systematically explored perceptions of humanness of people with dementia and of older adults and the variables that could improve these perceptions. We thus investigated the role of contact and perspective taking in improving perceptions of humanness of these social groups. To do so, we developed a new concept, humanness standards, defined as the amount of evidence of ability impairment needed to conclude that elderly people and those with dementia have lost personhood. We used a cross-sectional survey design (n = 619) to assess participants' humanness standards and perceptions of uniquely human characteristics and human nature characteristics of two social groups (people with dementia and older adults). Half the participants (n = 311) completed a survey about people with dementia and half (n = 308) assessed older adults. People with dementia were perceived as possessing humanness characteristics to a lesser extent than were older adults. For both groups, contact predicted enhanced perceptions of humanness characteristics. Participants' degree of contact with individuals with dementia also predicted humanness standards, but only under low perspective-taking conditions. As predicted, for older adults, participants set the highest humanness impairment thresholds in the high contact/high perspective-taking condition. We conclude that while social programs that bring persons with dementia and other individuals in contact could change humanness standards and perceptions of humanness characteristics of people with dementia, in the case of elderly adults, the contact must be supplemented by variables that facilitate taking the perspective of the person.

  13. [En bloc renal transplant from infant donors to adults].

    PubMed

    Gómez Vegas, A; Blázquez Izquierdo, J; Pérez Contín, M J; Grimalt Alvarez, J; Rabadán Marina, M; Hermida Gutiérrez, J F; Prats, D; Resel Estévez, L

    1998-12-01

    To analyze the medium-term outcome of en bloc transplantation of pediatric kidneys into adult patients, including the incidence and type of surgical complications. From November 1991 to December 1997, we performed 37 en bloc transplantation of pediatric kidneys into adult patients. The kidneys were harvested from donors less that 3 years old and/or weighing 15 kg. The mean follow-up was 24 months. Grafting was achieved by end-to-side anastomosis of the donor cava to the receptor external iliac and the aortic patch to the external iliac artery. Three grafts failed, probably due to hilar torsion; the remaining were initially functioning well. Seven transplant removal were performed; 6 were due to thrombosis. The actuarial graft survival was 89.1% at one month, 80.83% at 12 months and 80.83% at 24 months. The medium-term results of en bloc transplantation of pediatric kidneys into adult patients were excellent and demonstrate the efficacy of this type of grafts. Arterial and venous thrombosis were the most important complications, quantitatively and qualitatively.

  14. Kidney Biopsy

    MedlinePlus

    ... Series Urinary Tract Imaging Urodynamic Testing Virtual Colonoscopy Kidney Biopsy What is a kidney biopsy? A kidney biopsy is a procedure that ... performs procedures using imaging equipment Why is a kidney biopsy performed? A health care provider will perform ...

  15. Kidney Disease Basics

    MedlinePlus

    ... My Kidneys Fail? Clinical Trials What Is Chronic Kidney Disease? Chronic kidney disease (CKD) means your kidneys ... work, be active, and enjoy life. Will my kidneys get better? Kidney disease is often “progressive”, which ...

  16. Dermatoglyphics in kidney diseases: a review.

    PubMed

    Wijerathne, Buddhika T B; Meier, Robert J; Salgado, Sujatha S; Agampodi, Suneth B

    2016-01-01

    Kidney diseases are becoming a major cause of global burden with high mortality and morbidity. The origins of most kidney diseases are known, but for some the exact aetiology is not yet understood. Dermatoglyphics is the scientific study of epidermal ridge patterns and it has been used as a non-invasive diagnostic tool to detect or predict different medical conditions that have foetal origin. However, there have been a limited number of studies that have evaluated a dermatoglyphic relationship in different kidney diseases. The aim of this review was to systematically identify, review and appraise available literature that evaluated an association of different dermatoglyphic variables with kidney diseases. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The PubMed(®) (Medline), POPLINE, Cochrane Library and Trip Database and grey literature sources such as OpenGrey, Google Scholar, and Google were searched to earliest date to 17 April 2014. Of the 36 relevant publications, 15 were included in the review. Of these studies, there are five case reports, seven case series and three comparative studies. Possible association of dermatoglyphics with Wilms tumor (WT) had been evaluated in two comparative studies and one case series that found fewer whorls and a lower mean total ridge count (TRC). Another study evaluated adult polycystic kidney disease (APCD) type III that revealed lower TRC means in all cases. All other case series and case reports describe dermatoglyphics in various kidney disease such as acro-renal-ocular syndrome, potter syndrome, kabuki makeup syndrome, neurofaciodigitorenal syndrome, syndactyly type V, ring chromosome 13 syndrome, trisomy 13 syndrome and sirenomelia. It is evident that whorl pattern frequency and TRC have been used widely to investigate the uncertainty related to the origin of several kidney diseases such as WT and APCD type III. However, small sample sizes

  17. Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation.

    PubMed

    Taner, Timucin; Park, Walter D; Stegall, Mark D

    2017-05-01

    Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match-positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match-negative kidney transplants. These changes were not found in cross-match-positive simultaneous liver-kidney transplant biopsies when compared to cross-match-negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match-positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match-negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match-positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Global and local processing in adult humans (Homo sapiens), 5-year-old children (Homo sapiens), and adult cotton-top tamarins (Saguinus oedipus).

    PubMed

    Neiworth, Julie J; Gleichman, Amy J; Olinick, Anne S; Lamp, Kristen E

    2006-11-01

    This study compared adults (Homo sapiens), young children (Homo sapiens), and adult tamarins (Saguinus oedipus) while they discriminated global and local properties of stimuli. Subjects were trained to discriminate a circle made of circle elements from a square made of square elements and were tested with circles made of squares and squares made of circles. Adult humans showed a global bias in testing that was unaffected by the density of the elements in the stimuli. Children showed a global bias with dense displays but discriminated by both local and global properties with sparse displays. Adult tamarins' biases matched those of the children. The striking similarity between the perceptual processing of adult monkeys and humans diagnosed with autism and the difference between this and normatively developing human perception is discussed.

  19. Older Adults and Chronic Kidney Disease Decision Making by Primary Care Physicians: A Scholarly Review and Research Agenda

    PubMed Central

    Dale, William; Stankus, Nicole; Sachs, Greg A.

    2008-01-01

    Background Chronic kidney disease (CKD) is a growing public health concern that overwhelmingly affects older adults. National guidelines have called for earlier referral of CKD patients, but it is unclear how these should apply to older adults. Objective This scholarly review aims to explore the current literature about upstream referral decisions for CKD within the context of decisions about initiation of dialysis and general referral decisions. The authors propose a model for understanding the referral process and discuss future directions for research to guide decision making for older patients with CKD. Results While age has been shown to be influential in decisions to refer patients for dialysis and other medical therapies, the role of other patient factors such as competing medical co-morbidities, functional loss, or cognitive impairment in the decision making of physicians has been less well elucidated, particularly for CKD. Conclusions More information is needed on the decision-making behavior of physicians for upstream referral decisions like those being advocated for CKD. Exploring the role of geriatric factors like cognitive and functional status may help facilitate more appropriate use of resources and improve patient outcomes. PMID:18175190

  20. Targeted Therapies for Autosomal Dominant Polycystic Kidney Disease.

    PubMed

    Stayner, Cherie; Brooke, Darby G; Bates, Michael; Eccles, Michael R

    2018-05-07

    Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease in humans, affecting approximately 1 in 500 people. ADPKD is characterized by cyst growth in the kidney leading to progressive parenchymal damage and is the underlying pathology in approximately 10% of patients requiring hemodialysis or transplantation for end-stage kidney disease. The two proteins that are mutated in ADPKD, polycystin-1 and polycystin-2, form a complex located on the primary cilium and the plasma membrane to facilitate calcium ion release in the cell. There is currently no Food and Drug Administration (FDA)-approved therapy to cure or slow the progression of the disease. Rodent ADPKD models do not completely mimic the human disease, and therefore preclinical results have not always successfully translated to the clinic. Moreover, the toxicity of many of these potential therapies has led to patient withdrawals from clinical trials. Here, we review compounds in a clinical trial for treating ADPKD, and we examine the feasibility of using a kidney-targeted approach, with potential for broadening the therapeutic window, decreasing treatment-associated toxicity and increasing the efficacy of agents that have demonstrated activity in animal models. We make recommendations for integrating kidney-targeted therapies with current treatment regimes, to achieve a combined approach to treating ADPKD. Many compounds are currently in clinical trial for ADPKD, yet to date, none are FDA-approved for treating this disease. Patients could benefit from efficacious pharmacotherapy, especially if it can be kidney-targeted, and intensive efforts continue to be focused on this goal. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Interventions for chronic kidney disease in people with sickle cell disease

    PubMed Central

    Roy, Noemi BA; Fortin, Patricia M; Bull, Katherine R; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Estcourt, Lise J

    2017-01-01

    . One trial was published in 2011 and included 193 children aged 9 months to 18 months, and compared treatment with hydroxyurea to placebo. The second trial was published in 1998 and included 22 adults with normal blood pressure and microalbuminuria and compared ACEI to placebo. We rated the quality of evidence as low to very low across different outcomes according to GRADE methodology. This was due to trials having: a high or unclear risk of bias including attrition and detection bias; indirectness (the available evidence was for children aged 9 months to 18 months in one trial and a small and select adult sample size in a second trial); and imprecise outcome effect estimates of significant benefit or harm. Hydroxyurea versus placebo We are very uncertain if hydroxyurea reduces or prevents progression of kidney disease (assessed by change in glomerular filtration rate), or reduces hyperfiltration in children aged 9 to 18 months, mean difference (MD) 0.58 (95% confidence interval (CI) -14.60 to 15.76 (mL/min per 1.73 m2)) (one study; 142 participants; very low-quality evidence). In children aged 9 to 18 months, hydroxyurea may improve the ability to concentrate urine, MD 42.23 (95% CI 12.14 to 72.32 (mOsm/kg)) (one study; 178 participants; low-quality evidence). Hydroxyurea may make little or no difference to SCD-related serious adverse events including: incidence of acute chest syndrome, risk ratio (RR) 0.39 (99% CI 0.13 to 1.16); painful crisis, RR 0.68 (99% CI 0.45 to 1.02); and hospitalisations, RR 0.83 (99% CI 0.68 to 1.01) (one study, 193 participants; low-quality evidence). No deaths occurred in the trial. Quality of life was not reported. ACEI versus placebo We are very uncertain if ACEI reduces proteinuria in adults with SCD who have normal blood pressure and microalbuminuria, MD - 49.00 (95% CI -124.10 to 26.10 (mg per day)) (one study; 22 participants; very low-quality evidence). We are very uncertain if ACEI reduce or prevent kidney disease as measured by

  2. Renal cell carcinoma in a cat with polycystic kidney disease undergoing renal transplantation.

    PubMed

    Adams, Daniel J; Demchur, Jolie A; Aronson, Lillian R

    2018-01-01

    A 10-year-old spayed female American Shorthair cat underwent renal transplantation due to worsening chronic kidney disease secondary to polycystic kidney disease. During transplantation, the right kidney grossly appeared to be more diseased than the left and was firmly adhered to the surrounding tissues. An intraoperative fine-needle aspirate of the right native kidney revealed inflammatory cells but no evidence of neoplasia. To create space for the allograft, a right nephrectomy was performed. Following nephrectomy, the right native kidney was submitted for biopsy. Biopsy results revealed a renal cell carcinoma. Although the cat initially recovered well from surgery, delayed graft function was a concern in the early postoperative period. Significant azotemia persisted and the cat began to have diarrhea. Erythematous skin lesions developed in the perineal and inguinal regions, which were suspected to be secondary to thromboembolic disease based on histopathology. The cat's clinical status continued to decline with development of signs of sepsis, followed by marked obtundation with uncontrollable seizures. Given the postoperative diagnosis of renal cell carcinoma and the cat's progressively declining clinical status, humane euthanasia was elected. This case is the first to document renal cell carcinoma in a cat with polycystic kidney disease. An association of the two diseases has been reported in the human literature, but such a link has yet to be described in veterinary medicine. Given the association reported in the human literature, a plausible relationship between polycystic kidney disease and renal cell carcinoma in cats merits further investigation.

  3. Kidney pain (image)

    MedlinePlus

    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 ...

  4. Fibroblast Growth Factor 23: A Biomarker of Kidney Function Decline.

    PubMed

    Drew, David A; Katz, Ronit; Kritchevsky, Stephen; Ix, Joachim H; Shlipak, Michael G; Newman, Anne B; Hoofnagle, Andy; Fried, Linda; Sarnak, Mark J; Gutierrez, Orlando M

    2018-01-01

    Fibroblast growth factor 23 (FGF-23) is a hormone that regulates phosphorus levels and vitamin D metabolism. Previous studies have shown FGF-23 to be a risk factor for incident end-stage renal disease; however, there are less data on the association of FGF-23 with earlier kidney-related outcomes. Serum FGF-23 was assayed using an intact ELISA assay in 2,496 participants of the Healthy Aging and Body Composition Study, a cohort of well-functioning older adults. Kidney function was estimated by assaying cystatin C at baseline and years 3 and 10. The associations between FGF-23 and decline in kidney function (defined by estimated glomerular filtration rate (eGFR) decline ≥30% or ≥3 mL/min/year) and incident chronic kidney disease (CKD; incident eGFR <60 mL/min/1.73 m2 and ≥1 mL/min/year decline) were evaluated. Models were adjusted for demographics, baseline eGFR, urine albumin/creatinine ratio, comorbidity, and serum calcium, phosphorus, 25(OH) vitamin D and parathyroid hormone. The mean (SD) age was 75 (3) years, with 52% female and 38% black. There were 405 persons with 30% decline, 702 with >3 mL/min/year decline, and 536 with incident CKD. In fully adjusted continuous models, doubling of FGF-23 concentrations was not associated with kidney function decline (OR [95% CI] = 0.98 [0.82-1.19] for ≥30% decline and OR 1.17 [95% CI 1.00-1.37] for ≥3 mL/min/year decline), or incident CKD (incident rate ratio [IRR] 1.05 [95% CI 0.91-1.22]). In adjusted quartile analysis, the highest quartile of FGF-23 was significantly associated with incident CKD (IRR 1.27 [95% CI 1.02-1.58] for highest vs. lowest quartile). Higher FGF-23 concentrations were not consistently associated with decline in kidney function or incident CKD in community-dwelling older adults. © 2018 S. Karger AG, Basel.

  5. Kidney Failure and ESRD in the Atherosclerosis Risk in Communities (ARIC) Study: Comparing Ascertainment of Treated and Untreated Kidney Failure in a Cohort Study.

    PubMed

    Rebholz, Casey M; Coresh, Josef; Ballew, Shoshana H; McMahon, Blaithin; Whelton, Seamus P; Selvin, Elizabeth; Grams, Morgan E

    2015-08-01

    including treated and untreated disease identifies more cases than linkage to the USRDS registry alone, particularly among older adults. Future studies might consider reporting both USRDS-identified ESRD and a more inclusive kidney failure definition. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  6. Understanding Older Adult's Perceptions of Factors that Support Trust in Human and Robot Care Providers.

    PubMed

    Stuck, Rachel E; Rogers, Wendy A

    2017-06-01

    As the population of older adults increase so will the need for care providers, both human and robot. Trust is a key aspect to establish and maintain a successful older adult-care provider relationship. However, due to trust volatility it is essential to understand it within specific contexts. This proposed mixed methods study will explore what dimensions of trust emerge as important within the human-human and human-robot dyads in older adults and care providers. First, this study will help identify key qualities that support trust in a care provider relationship. By understanding what older adults perceive as needing to trust humans and robots for various care tasks, we can begin to provide recommendations based on user expectations for design to support trust.

  7. Health and Nutrition Literacy and Adherence to Treatment in Children, Adolescents, and Young Adults With Chronic Kidney Disease and Hypertension, North Carolina, 2015

    PubMed Central

    Ferris, Maria; Rak, Eniko

    2016-01-01

    Introduction Adherence to treatment and dietary restrictions is important for health outcomes of patients with chronic/end-stage kidney disease and hypertension. The relationship of adherence with nutritional and health literacy in children, adolescents, and young adults is not well understood. The current study examined the relationship of health literacy, nutrition knowledge, nutrition knowledge–behavior concordance, and medication adherence in a sample of children and young people with chronic/end-stage kidney disease and hypertension. Methods We enrolled 74 patients (aged 7–29 y) with a diagnosis of chronic/end-stage kidney disease and hypertension from the University of North Carolina Kidney Center. Participants completed instruments of nutrition literacy (Disease-Specific Nutrition Knowledge Test), health literacy (Newest Vital Sign), nutrition behavior (Nutrition Knowledge–Behavior Concordance Scale), and medication adherence (Morisky Medication Adherence Scale). Linear and binary logistic regressions were used to test the associations. Results In univariate comparisons, nutrition knowledge was significantly higher in people with adequate health literacy. Medication adherence was related to nutrition knowledge and nutrition knowledge–behavior concordance. Multivariate regression models demonstrated that knowledge of disease-specific nutrition restrictions did not significantly predict nutrition knowledge–behavior concordance scores. In logistic regression, knowledge of nutrition restrictions did not significantly predict medication adherence. Lastly, health literacy and nutrition knowledge–behavior concordance were significant predictors of medication adherence. Conclusion Nutrition knowledge and health literacy skills are positively associated. Nutrition knowledge, health literacy, and nutrition knowledge–behavior concordance are positively related to medication adherence. Future research should focus on additional factors that may predict

  8. Hispanic/Latino concerns about living kidney donation: a focus group study.

    PubMed

    Gordon, Elisa J; Mullee, Jack O; Ramirez, Daney I; MacLean, Jessica; Olivero, Maria; Feinglass, Joseph; Carney, Paula; O'Connor, Kate; Caicedo, Juan Carlos

    2014-06-01

    Given the shortage of kidneys for transplant, living kidney donation (LKD) is increasingly used to expand the organ donor pool. Although Hispanics/Latinos need disproportionately more kidney transplants, they receive a smaller proportion of living donor kidney transplants than other ethnic/racial groups. To assess Hispanics' awareness, perceptions, misconceptions, cultural beliefs, and values about and barriers to LKD. Nine focus groups were conducted with 76 adult Hispanics in Chicago, Illinois, between January and March 2012. Focus groups included kidney transplant recipients, living kidney donors, dialysis patients, and the general Hispanic public. Several themes emerged as perceived barriers to LKD. Many participants identified knowledge deficits about LKD, expressing uncertainty about the differences between LKD and deceased donation, and whether kidney disease simultaneously afflicts both kidneys. Many believed that donors experience dramatically shorter life expectancies, are unable to have children, and are more susceptible to kidney disease after donating. Recipients and donors reported that family members were involved in discussions about the donor's decision to donate, with some family members discouraging donation. Financial barriers cited included fear of becoming unable to work, losing one's job, or being unable to pay household bills while recovering. Participants also identified logistic barriers for undocumented immigrants (eg, the inability to obtain government insurance for transplant candidates and uncertainty about their eligibility to donate). Donors desired information about optimizing self-care to promote their remaining kidney's health. Culturally competent interventions are needed to redress Hispanics' knowledge deficits and misconceptions and reduce LKD disparities among Hispanics.

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

    PubMed

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

    2016-04-01

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

  10. What We Do and Do Not Know About Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman’s Day

    PubMed Central

    Piccoli, Giorgina B.; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

    2018-01-01

    Background: Chronic kidney disease affects approximately 10% of the world’s adult population: It is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus giving an occasion to reflect on open questions on the importance of kidney health in women for the present and the future generations. Objectives: In this review, we summarize some aspects that are unique to women’s kidney health, offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Findings: Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is not only a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for childbearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. Conclusion: Improving knowledge on women, kidney health, and kidney disease, may be a way to improve outcomes of kidney diseases worldwide. PMID:29552348

  11. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    PubMed

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Protective Role for Antioxidants in Acute Kidney Disease

    PubMed Central

    Dennis, Joanne M.; Witting, Paul K.

    2017-01-01

    Acute kidney injury causes significant morbidity and mortality in the community and clinic. Various pathologies, including renal and cardiovascular disease, traumatic injury/rhabdomyolysis, sepsis, and nephrotoxicity, that cause acute kidney injury (AKI), induce general or regional decreases in renal blood flow. The ensuing renal hypoxia and ischemia promotes the formation of reactive oxygen species (ROS) such as superoxide radical anions, peroxides, and hydroxyl radicals, that can oxidatively damage biomolecules and membranes, and affect organelle function and induce renal tubule cell injury, inflammation, and vascular dysfunction. Acute kidney injury is associated with increased oxidative damage, and various endogenous and synthetic antioxidants that mitigate source and derived oxidants are beneficial in cell-based and animal studies. However, the benefit of synthetic antioxidant supplementation in human acute kidney injury and renal disease remains to be realized. The endogenous low-molecular weight, non-proteinaceous antioxidant, ascorbate (vitamin C), is a promising therapeutic in human renal injury in critical illness and nephrotoxicity. Ascorbate may exert significant protection by reducing reactive oxygen species and renal oxidative damage via its antioxidant activity, and/or by its non-antioxidant functions in maintaining hydroxylase and monooxygenase enzymes, and endothelium and vascular function. Ascorbate supplementation may be particularly important in renal injury patients with low vitamin C status. PMID:28686196

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

    PubMed

    Weinberg, Kerstin; Ortiz, Michael

    2009-08-01

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

  14. Evaluation of Allelic Expression of Imprinted Genes in Adult Human Blood

    PubMed Central

    Frost, Jennifer M.; Monk, Dave; Stojilkovic-Mikic, Taita; Woodfine, Kathryn; Chitty, Lyn S.; Murrell, Adele; Stanier, Philip; Moore, Gudrun E.

    2010-01-01

    Background Imprinted genes are expressed from only one allele in a parent-of-origin dependent manner. Loss of imprinted (LOI) expression can result in a variety of human disorders and is frequently reported in cancer. Biallelic expression of imprinted genes in adult blood has been suggested as a useful biomarker and is currently being investigated in colorectal cancer. In general, the expression profiles of imprinted genes are well characterised during human and mouse fetal development, but not in human adults. Methodology/Principal Findings We investigated quantitative expression of 36 imprinted genes in adult human peripheral blood leukocytes obtained from healthy individuals. Allelic expression was also investigated in B and T lymphocytes and myeloid cells. We found that 21 genes were essentially undetectable in adult blood. Only six genes were demonstrably monoallelic, and most importantly, we found that nine genes were either biallelic or showed variable expression in different individuals. Separated leukocyte populations showed the same expression patterns as whole blood. Differential methylation at each of the imprinting control loci analysed was maintained, including regions that contained biallelically expressed genes. This suggests in some cases methylation has become uncoupled from its role in regulating gene expression. Conclusions/Significance We conclude that only a limited set of imprinted genes, including IGF2 and SNRPN, may be useful for LOI cancer biomarker studies. In addition, blood is not a good tissue to use for the discovery of new imprinted genes. Finally, lymphocyte DNA methylation status in the adult may not always be a reliable indicator of monoallelic gene expression. PMID:21042416

  15. Lithium Use, but Not Valproate Use, Is Associated With a Higher Risk of Chronic Kidney Disease in Older Adults With Mental Illness.

    PubMed

    Rej, Soham; Herrmann, Nathan; Shulman, Kenneth; Fischer, Hadas D; Fung, Kinwah; Harel, Ziv; Gruneir, Andrea

    Lithium is an essential mood disorder treatment; however, it remains unclear whether lithium increases chronic kidney disease (CKD) risk. There are few data on this in the elderly, even though older adults may be particularly susceptible to CKD. We wished to determine whether lithium is associated with increased CKD risk relative to valproate in older adults. This nested case-control study analyzed province-wide administrative health data from mental health service users aged ≥ 66 years in Ontario, Canada, from 2003 to 2014. Five-year incident CKD risk was compared in lithium users, valproate users, and patients who used neither medication. ICD-10 was used to assign CKD diagnosis. We used conditional logistic regression to control for hypertension, diabetes mellitus, acute kidney injury, medications associated with lithium toxicity, and other potential confounders. 21,741 cases and 86,930 age- and sex-matched controls were identified, including 529 lithium users and 498 valproate users. After controlling for confounders, we found that lithium use was associated with increased risk of incident CKD (adjusted odds ratio [OR] = 1.76 [95% CI, 1.41-2.19]), while valproate use was not (adjusted OR = 1.03 [95% CI, 0.81-1.29]). Lithium is independently associated with an almost 2-fold increase in CKD risk in this community sample of older mental health service users. In the absence of clear information about certain contributing factors, such as inadequate monitoring and acute and chronic lithium level elevations, causes for this increase will need to be determined in future research. © Copyright 2017 Physicians Postgraduate Press, Inc.

  16. Identification and quantification of human kidney atrial natriuretic peptide receptors.

    PubMed

    Kahana, L; Yechiely, H; Mecz, Y; Lurie, A

    1995-04-01

    The present study determined 125I-label atrial natriuretic peptide (ANP) binding sites in human kidney glomerular and papillary membranes. The membranes were prepared from non-malignant renal tissue obtained at nephrectomy of patients with renal carcinoma. To evaluate the proportion of ANP receptor classes ANP-R1 (ANPR-A, -B) versus ANP-R2 (ANPR-C), competitive binding studies were performed using [125I]-ANP in the presence of increasing concentrations of ANP or an internally ring-deleted analog, des(Gln116, Ser117, Gly118, Leu119, Gly120)ANP(102-121), called C-ANP, which binds selectively to ANPR-C receptors. Analysis of the competitive binding curve with ANP in glomerular membranes suggested the presence of one group of high-affinity receptors with dissociation constant Kd = 26 +/- 12 pmol/l and density Bmax = 101 +/- 47 nmol/kg protein. A decrease of 10-30% in Bmax with no change in Kd was obtained in the presence of excess (10(-6) mol/l) C-ANP, suggesting the existence of a small amount of a second class of receptors, the ANPR-C class. The densities of ANPR-A, -B versus ANPR-C receptors in human glomeruli, calculated from competitive inhibition experiments, were 75 +/- 42 and 22 +/- 16 nmol/kg protein (N = 8). Autoradiography of the sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions showed two bands: a highly labeled 130kD band and a weakly labeled 66 kD band, both displaced by ANP. Only the 66-kD band was displaced by the C-ANP analog. Human papilla membrane, as shown by competition binding studies and SDS gel electrophoresis, presented only one class of receptors with Kd = 40 +/- 23 pmol/l (mean +/- SD, N = 3) and Bmax = 17 +/- 6.3 nmol/kg protein.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

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

    2017-10-01

    Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction in measured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, age-related reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m 2 ) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria. Copyright © 2017 by the American Society of Nephrology.

  18. Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury

    PubMed Central

    Maicas, Nuria; van der Vlag, Johan; Bublitz, Janin; Florquin, Sandrine; Bakker-van Bebber, Marinka; Dinarello, Charles A.; Verweij, Vivienne; Masereeuw, Roos; Joosten, Leo A.

    2017-01-01

    Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery and vein for 20 min. hAAT (80 mg/kg, Prolastin®) was administered daily intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological and biochemical analysis. hAAT partially preserved renal function and tubular integrity after induction of bilateral kidney I/R injury, which was accompanied with reduced renal influx of macrophages and a significant decrease of neutrophil gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) protein levels in urine but showed no significant effect on renal fibrosis. Although the observed effect size of hAAT administration was limited and therefore the clinical relevance of our findings should be evaluated carefully, these data support the potential of this natural protein to ameliorate ischemic and inflammatory conditions. PMID:28235038

  19. Muc1 is protective during kidney ischemia-reperfusion injury

    PubMed Central

    Pastor-Soler, Núria M.; Sutton, Timothy A.; Mang, Henry E.; Kinlough, Carol L.; Gendler, Sandra J.; Madsen, Cathy S.; Bastacky, Sheldon I.; Ho, Jacqueline; Al-bataineh, Mohammad M.; Hallows, Kenneth R.; Singh, Sucha; Monga, Satdarshan P.; Kobayashi, Hanako; Haase, Volker H.

    2015-01-01

    Ischemia-reperfusion injury (IRI) due to hypotension is a common cause of human acute kidney injury (AKI). Hypoxia-inducible transcription factors (HIFs) orchestrate a protective response in renal endothelial and epithelial cells in AKI models. As human mucin 1 (MUC1) is induced by hypoxia and enhances HIF-1 activity in cultured epithelial cells, we asked whether mouse mucin 1 (Muc1) regulates HIF-1 activity in kidney tissue during IRI. Whereas Muc1 was localized on the apical surface of the thick ascending limb, distal convoluted tubule, and collecting duct in the kidneys of sham-treated mice, Muc1 appeared in the cytoplasm and nucleus of all tubular epithelia during IRI. Muc1 was induced during IRI, and Muc1 transcripts and protein were also present in recovering proximal tubule cells. Kidney damage was worse and recovery was blocked during IRI in Muc1 knockout mice compared with congenic control mice. Muc1 knockout mice had reduced levels of HIF-1α, reduced or aberrant induction of HIF-1 target genes involved in the shift of glucose metabolism to glycolysis, and prolonged activation of AMP-activated protein kinase, indicating metabolic stress. Muc1 clearly plays a significant role in enhancing the HIF protective pathway during ischemic insult and recovery in kidney epithelia, providing a new target for developing therapies to treat AKI. Moreover, our data support a role specifically for HIF-1 in epithelial protection of the kidney during IRI as Muc1 is present only in tubule epithelial cells. PMID:25925251

  20. Kidney (Renal) Failure

    MedlinePlus

    ... News Physician Resources Professions Site Index A-Z Kidney Failure Kidney failure, also known as renal failure, ... evaluated? How is kidney failure treated? What is kidney (renal) failure? The kidneys are designed to maintain ...

  1. Influence of Cold Ischemia Time in Combination with Donor Acute Kidney Injury on Kidney Transplantation Outcomes.

    PubMed

    Xia, Yu; Friedmann, Patricia; Cortes, Carlos M; Lubetzky, Michelle L; Kayler, Liise K

    2015-08-01

    Deceased-donor kidneys are often exposed to ischemic events from donor instability, as evidenced by acute kidney injury (AKI). Clinicians may be reluctant to transplant kidneys with AKI that also have prolonged cold ischemia time (CIT) for fear of an additional deleterious effect. We evaluated national data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys from donors with AKI (terminal serum creatinine ≥ 2 mg/dL), in which the CIT difference between recipients was ≥1, 5, 10, or 15 hours. On multivariate analysis of AKI kidney recipients, overall death-censored graft survival (DCGS) was comparable between recipients with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was at least 1 hour (adjusted hazard ratio [aHR] 0.98, 95% CI 0.85 to 1.13, n = 4,458), 5 hours (aHR 0.97, 95% CI 0.79 to 1.18, n = 2,412), 10 hours (aHR 0.82, 95% CI 0.59 to 1.15, n = 922), or 15 hours (aHR 0.94, 95% CI 0.57 to 1.58, n = 442). Overall patient survival of the longer CIT groups was comparable or protective with delta CIT of ≥1 (aHR 0.94, 95% CI 0.83 to 1.06), 5 (aHR 0.80, 95% CI 0.68 to 0.94), 10 (aHR 0.70, 95% CI 0.53 to 0.91), and 15 (aHR 0.64, 95%CI 0.43 to 0.95) hours. Between each of the 4 delta-CIT levels of shorter and longer CIT, there were no statistically significant differences in the proportion of acute rejection at delta ≥1, 5, 10, or 15 hours. These results suggest that in the setting of a previous ischemic donor event, prolonged CIT has limited bearing on long-term outcomes. This may be important evidence that despite the occurrence of other ischemic events, kidneys with prolonged CIT offer acceptable outcomes to recipients and are a potential source to expand the donor pool. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Kidney Failure and ESRD in the Atherosclerosis Risk in Communities (ARIC) Study: Comparing Ascertainment of Treated and Untreated Kidney Failure in a Cohort Study

    PubMed Central

    Rebholz, Casey M.; Coresh, Josef; Ballew, Shoshana H.; McMahon, Blaithin; Whelton, Seamus P.; Selvin, Elizabeth; Grams, Morgan E.

    2015-01-01

    . Conclusions A kidney failure definition including treated and untreated disease identifies more cases than linkage to the USRDS registry alone, particularly among older adults. Future studies might consider reporting both USRDS-identified ESRD and a more inclusive kidney failure definition. PMID:25773483

  3. Chronic Kidney Diseases

    MedlinePlus

    ... Safe Videos for Educators Search English Español Chronic Kidney Diseases KidsHealth / For Kids / Chronic Kidney Diseases What's ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  4. Human stones.

    PubMed

    Lonsdale, K

    1968-03-15

    X-ray diffraction studies have shown that there are several different kinds of human urinary calculi, with different age, sex, period, and geographical distributions. Juvenile bladder stones are typically urate and oxalate in small boys in certain stone belts. They have disappeared in some areas, particularly in Britain, but are still common in Thailand. India. and Turkey. Their cause is unknown. Adult bladder stones, formerly common in elderly men, were largely of uric acid and were due to a faulty diet. Juvenile kidney stones are rare, except in Turkey where they are similar to juvenile bladder stones. Adult kidney stones are by far the most universally common, especially in technically developed communities. They are found in both sexes (equally at postmortem), and in the United States and in Czechoslovakia the average number of hospital entries for stones, relative to the whole population, is about 1 per 1000 per annum (increasing) although the incidence in different districts varies by 4 to 1 or more. Such stones are mainly calcium oxalates and calcium and MgNH(4) phosphates. The incidence among the administrative class is at least 20 times that among agricultural workers, relative to their numbers. Stones are reported also to be an occupational hazard for air pilots. It is probably that much more exercise and the drinking of more water to prevent kidney dehydration (spirits and coffee are not effective for this purpose) would lower the high rate of incidence. Moderate acidification would prevent phosphate supersaturation of the urine, but is not effective for oxalates. It seems certain that, once a suitable seed is formed, epitaxy is largely responsible for deposition from urines that would otherwise remain supersaturated until voided. This would explain the curioLls radial and layered texture of many stones. Laboratory experiments might suggest ways of preventing orientated overgrowth.

  5. Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients.

    PubMed

    Zittema, Debbie; van den Berg, Else; Meijer, Esther; Boertien, Wendy E; Muller Kobold, Anneke C; Franssen, Casper F M; de Jong, Paul E; Bakker, Stephan J L; Navis, Gerjan; Gansevoort, Ron T

    2014-09-05

    Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney. Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging. Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0

  6. Cell type-specific glycoconjugates of collecting duct cells during maturation of the rat kidney.

    PubMed

    Holthöfer, H

    1988-08-01

    The ontogeny of lectin-positive epithelial cell types and the maturation of polarized expression of the glycocalyx of the collecting ducts (CD) of the rat kidney were studied from samples of 18th-day fetal and neonatal kidneys of various ages. Lectins from Dolichos biflorus (DBA) and Vicia villosa (VVA), with preferential affinity to principal cells, stained virtually all CD cells of the fetal kidneys. However, within two days postnatally, the number of cells positive for DBA and VVA decreased to amounts found in the adult kidneys. Moreover, a characteristic change occurred rapidly after birth in the intracellular polarization of the reactive glycoconjugates, from a uniform plasmalemmal to a preferentially apical staining. In contrast, lectins from Arachis hypogaea (PNA), Maclura pomifera (MPA) and Lotus tetragonolobus (LTA), reacting indiscriminatively with principal and intercalated cells of adult kidneys, stained most CD cells in the fetal kidneys, and failed to show any postnatal change in the amount of positive cells or in the intracellular polarization. The immunocytochemical tests for (Na + K)-ATPase and carbonic anhydrase (CA II) revealed the characteristic postnatal decrease in the amount of principal cells and simultaneous increase in the amount of CA II rich intercalated cells. DBA and VVA reactive cells also decreased postnatally, paralleling the changes observed in the (Na + K)-ATPase positive principal cells. The present results suggest that the expression of the cell type-specific glycocalyx of principal and intercalated cells is developmentally regulated, undergoes profound changes during maturation, and is most likely associated with electrolyte transport phenomena.

  7. KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease): design and methods.

    PubMed

    Oh, Kook-Hwan; Park, Sue Kyung; Park, Hayne Cho; Chin, Ho Jun; Chae, Dong Wan; Choi, Kyu Hun; Han, Seung Hyeok; Yoo, Tae Hyun; Lee, Kyubeck; Kim, Yong-Soo; Chung, Wookyung; Hwang, Young-Hwan; Kim, Soo Wan; Kim, Yeong Hoon; Kang, Sun Woo; Park, Byung-Joo; Lee, Joongyub; Ahn, Curie

    2014-05-19

    The progression and complications of chronic kidney disease should differ depending on the cause (C), glomerular filtration rate category (G), and albuminuria (A). The KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease), which is a prospective cohort study, enrolls subjects with chronic kidney disease stages 1 to 5 (predialysis). Nine nephrology centers in major university hospitals throughout Korea will enroll approximately 2,450 adults with chronic kidney disease over a 5-year period from 2011 to 2015. The participating individuals will be monitored for approximately 10 years until death or until end-stage renal disease occurs. The subjects will be classified into subgroups based on the following specific causes of chronic kidney disease: glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, polycystic kidney disease, and others. The eligible subjects will be evaluated at baseline for socio-demographic information, detailed personal/family history, office BP, quality of life, and health behaviors. After enrollment in the study, thorough assessments, including laboratory tests, cardiac evaluation and radiologic imaging, will be performed according to the standardized protocol. The biospecimen samples will be collected regularly. A renal event is defined by >50% decrease in estimated GFR (eGFR) from the baseline values, doubling of serum creatinine, or end-stage renal disease. The primary composite outcome consists of renal events, cardiovascular events, and death. As of September 2013, 1,470 adult chronic kidney disease subjects were enrolled in the study, including 543 subjects with glomerulonephritis, 317 with diabetic nephropathy, 294 with hypertensive nephropathy and 249 with polycystic kidney disease. As the first large-scale chronic kidney disease cohort study to be established and maintained longitudinally for up to 10 years, the KNOW-CKD will help to clarify the natural course, complication profiles, and risk

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

    PubMed Central

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

    2016-01-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID:26886165

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

    PubMed

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

    2016-03-01

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

  10. Kidney Tests

    MedlinePlus

    ... taking out waste products and making urine. Kidney tests check to see how well your kidneys are working. They include blood, urine, and imaging tests. Early kidney disease usually does not have signs ...

  11. Kidney School

    MedlinePlus

    ... 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 ...

  12. Kidney stones

    MedlinePlus Videos and Cool Tools

    ... kidneys, ureters, bladder and urethra. Within each kidney, urine flows from the outer cortex to the inner ... The renal pelvis is the funnel through which urine exits the kidney and enters the ureter. As ...

  13. Kidney Diseases

    MedlinePlus

    ... 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 ...

  14. COGNITIVE-HD study: protocol of an observational study of neurocognitive functioning and association with clinical outcomes in adults with end-stage kidney disease treated with haemodialysis.

    PubMed

    Palmer, Suetonia C; Ruospo, Marinella; Barulli, Maria Rosaria; Iurillo, Annalisa; Saglimbene, Valeria; Natale, Patrizia; Gargano, Letizia; Murgo, Angelo M; Loy, Clement; van Zwieten, Anita; Wong, Germaine; Tortelli, Rosanna; Craig, Jonathan C; Johnson, David W; Tonelli, Marcello; Hegbrant, Jörgen; Wollheim, Charlotta; Logroscino, Giancarlo; Strippoli, G F M

    2015-12-09

    The prevalence of cognitive impairment may be increased in adults with end-stage kidney disease compared with the general population. However, the specific patterns of cognitive impairment and association of cognitive dysfunction with activities of daily living and clinical outcomes (including withdrawal from treatment) among haemodialysis patients remain incompletely understood. The COGNITIVE impairment in adults with end-stage kidney disease treated with HemoDialysis (COGNITIVE-HD) study aims to characterise the age-adjusted and education-adjusted patterns of cognitive impairment (using comprehensive testing for executive function, perceptual-motor function, language, learning and memory, and complex attention) in patients on haemodialysis and association with clinical outcomes. A prospective, longitudinal, cohort study of 750 adults with end-stage kidney disease treated with long-term haemodialysis has been recruited within haemodialysis centres in Italy (July 2013 to April 2014). Testing for neurocognitive function was carried out by a trained psychologist at baseline to assess cognitive functioning. The primary study factor is cognitive impairment and secondary study factors will be specific domains of cognitive function. The primary outcome will be total mortality. Secondary outcomes will be cause-specific mortality, major cardiovascular events, fatal and non-fatal myocardial infarction and stroke, institutionalisation, and withdrawal from treatment at 12 months. This protocol was approved before study conduct by the following responsible ethics committees: Catania (approval reference 186/BE; 26/09/2013), Agrigento (protocol numbers 61-62; 28/6/2013), USL Roma C (CE 39217; 24/6/2013), USL Roma F (protocol number 0041708; 23/7/2013), USL Latina (protocol number 20090/A001/2011; 12/7/2013), Trapani (protocol number 3413; 16/7/2013) and Brindisi (protocol number 40259; 6/6/2013). All participants have provided written and informed consent and can withdraw from

  15. Kidney Cell Electrophoresis

    NASA Technical Reports Server (NTRS)

    Todd, P.

    1985-01-01

    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.

  16. Kidney function estimating equations in patients with chronic kidney disease.

    PubMed

    Hojs, R; Bevc, S; Ekart, R; Gorenjak, M; Puklavec, L

    2011-04-01

    The current guidelines emphasise the need to assess kidney function using predictive equations rather than just serum creatinine. The present study compares serum cystatin C-based equations and serum creatinine-based equations in patients with chronic kidney disease (CKD). Seven hundred and sixty-four adult patients with CKD were enrolled. In each patient serum creatinine and serum cystatin C were determined. Their glomerular filtration rate (GFR) was estimated using three serum creatinine-based equations [Cockcroft-Gault (C&G), modification of diet in renal disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)] and two serum cystatin C-based equations [our own cystatin C formula (GFR=90.63 × cystatin C(-1.192) ) and simple cystatin C formula (GFR=100/cystatin C)]. The GFR was measured using (51) CrEDTA clearance. Statistically significant correlation between (51) CrEDTA clearance with serum creatinine, serum cystatin C and all observed formulas was found. The receiver operating characteristic curve analysis (cut-off for GFR 60 ml/min/1.73m(2)) showed that serum cystatin C and both cystatin C formulas had a higher diagnostic accuracy than C&G formula. Bland and Altman analysis for the same cut-off value showed that all formulas except simple cystatin C formula underestimated measured GFR. The accuracy within 30% of estimated (51) CrEDTA clearance values differs according to stages of CKD. Analysis of ability to correctly predict patient's GFR below or above 60 ml/min/1.73m(2) showed statistically significant higher ability for both cystatin C formulas compared to MDRD formula. Our results indicate that serum cystatin C-based equations are reliable markers of GFR comparable with creatinine-based formulas. © 2011 Blackwell Publishing Ltd.

  17. BARTERING FOR A COMPATIBLE KIDNEY USING YOUR INCOMPATIBLE, LIVE KIDNEY DONOR: LEGAL AND ETHICAL ISSUES RELATED TO KIDNEY CHAINS.

    PubMed

    Tenenbaum, Evelyn M

    2016-01-01

    Kidney chains are a recent and novel method of increasing the number of available kidneys for transplantation and have the potential to save thousands of lives. However, because they are novel, kidney chains do not fit neatly within existing legal and ethicalframeworks, raising potential barriers to their full implementation. Kidney chains are an extension of paired kidney donation, which began in the United States in 2000. Paired kidney donations allow kidney patients with willing, but incompatible, donors to swap donors to increase the number of donor/recipient pairs and consequently, the number of transplants. More recently, transplant centers have been using non-simultaneous, extended, altruistic donor ("NEAD") kidney chains--which consist of a sequence of donations by incompatible donors--to further expand the number of donations. This Article fully explains paired kidney donation and kidney chains and focuses on whether NEAD chains are more coercive than traditional kidney donation to a family member or close friend and whether NEAD chains violate the National Organ Transplant Act's prohibition on the transfer of organs for valuable consideration.

  18. Gestational low-protein intake enhances whole-kidney miR-192 and miR-200 family expression and epithelial-to-mesenchymal transition in rat adult male offspring.

    PubMed

    Sene, Letícia B; Rizzi, Victor Hugo Gonçalves; Gontijo, José A R; Boer, Patricia A

    2018-05-22

    Studies have shown that adult offspring of mothers fed a protein-restricted diet during pregnancy present a pronounced reduction of nephron number associated with decreased fractional urinary sodium excretion and arterial hypertension. Additionally, recent advances in our understanding of the molecular pathways that govern the association of gestational nutritional restriction, intrauterine growth retardation and inflammation with impaired nephrogenesis, nephron underdosing and kidney fibrosis point to the epithelial to mesenchymal transition (EMT) as a common factor. In the current study, protein and sodium urinary excretion rates were evaluated in rats, and immunohistochemistry and western blot techniques were used to characterize kidney structure changes in 16 week old male offspring of mothers fed a low-protein diet during pregnancy (LP group) compared with age-matched (NP) controls. We also verified the expression of miRNA, mRNA and protein markers of fibrosis and the EMT in whole kidney prepared from LP offspring. We found, surprisingly, that arterial hypertension and long-term hyperfiltration, manifest by proteinuria, were associated with increased renal miR-192 and miR-200 family expression in 16 week old LP relative to age-matched NP rats. Measurement of kidney fibrosis and EMT-related protein markers, by histochemistry and immunoblot techniques, showed a significant rise of TGF-β1 and type-I collagen content in glomeruli and tubulointerstitial areas, accompanied by enhanced fibronectin and ZEB1 and decreased E-cadherin immunoreactivity in 16 week old LP offspring. The results were partially confirmed by increased gene (mRNA) expression of collagen 1α1, collagen 1α2 and ZEB1 in LP whole kidneys compared with those of age-matched NP offspring. In view of the presumed functional overload in the remaining nephrons, we suggest that hypertension and proteinuria development following maternal protein restriction may be a preponderant factor for EMT and

  19. Kidney Cancer

    MedlinePlus

    ... common cancers in the United States. Cancer Home Kidney Cancer Language: English (US) Español (Spanish) Recommend on ... work with the chemical trichloroethylene. What Are the Kidneys? The body has two kidneys, one on each ...

  20. Kidney disease - resources

    MedlinePlus

    Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Institute of Diabetes and Digestive and Kidney Disease -- www.niddk.nih.gov/health-information/kidney- ...

  1. Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis.

    PubMed

    Lemos, Dario R; McMurdo, Michael; Karaca, Gamze; Wilflingseder, Julia; Leaf, Irina A; Gupta, Navin; Miyoshi, Tomoya; Susa, Koichiro; Johnson, Bryce G; Soliman, Kirolous; Wang, Guanghai; Morizane, Ryuji; Bonventre, Joseph V; Duffield, Jeremy S

    2018-06-01

    Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined. Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1 α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo , in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids. Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro , stimulation of purified human kidney SCs and human kidney organoids with IL-1 β recapitulated the molecular events observed in vivo , inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1 β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury. Conclusions Our findings define a connection between IL-1 β and metabolic switch in fibrosis initiation and progression and highlight IL-1 β and MYC as potential therapeutic targets in tubulointerstitial diseases. Copyright © 2018 by the American Society of Nephrology.

  2. The role of the body in end-stage kidney disease in young adults: Gender, peer and intimate relationships.

    PubMed

    Lewis, Helen; Arber, Sara

    2015-09-01

    To understand how the physical body, and changes in the physical body, influence peer and intimate relationships and parenting in young adults on renal replacement therapies (RRT). Qualitative interview data from 40 young adults aged 16-30 years with end-stage kidney disease (ESKD), first diagnosed aged 0-19 years, were analysed using modified grounded theory. Alternating modalities of RRT had a 'yo-yo' effect on the bodies of interviewees, repeatedly reconstructing them as either 'transplanted' bodies, often initially obese, or as 'dialysis' bodies', often underweight. Invisible somatic changes had a major impact on gendered social identity, making intimate social relationships and parenthood problematic. Prepubertal onset interviewees were generally less successful in forming partnerships than those with postpubertal onset; and interviewees on dialysis were likely to postpone partnering until they were transplanted. Social networks were essential for finding a partner, but male interviewees had fewer networks than females. Parenthood was particularly challenging for female interviewees. In ESKD, life-saving RRT brings major changes to the body. These adversely affect social relationships and family formation during the crucial period of early adulthood. Effects vary according to age of onset, RRT modality, and gender, with those who were ill before puberty and those on dialysis worst affected. © The Author(s) 2015.

  3. Baseline kidney function as predictor of mortality and kidney disease progression in HIV-positive patients.

    PubMed

    Ibrahim, Fowzia; Hamzah, Lisa; Jones, Rachael; Nitsch, Dorothea; Sabin, Caroline; Post, Frank A

    2012-10-01

    Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Observational cohort study. 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Baseline estimated glomerular filtration rate (eGFR). Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m(2) for >3 months) in Cox proportional hazards and competing-risk regression models. Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m(2). Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m(2) remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m(2) was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m(2) and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m(2). The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Localization of PPAR isotypes in the adult mouse and human brain

    PubMed Central

    Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron

    2016-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430

  5. Localization of PPAR isotypes in the adult mouse and human brain.

    PubMed

    Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B; Mayfield, R Dayne; Harris, R Adron

    2016-06-10

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain.

  6. Association of kidney stones with atherosclerotic cardiovascular disease among adults in the United States: Considerations by race-ethnicity.

    PubMed

    Glover, LaShaunta M; Bass, Martha Ann; Carithers, Teresa; Loprinzi, Paul D

    2016-04-01

    There is a paucity of research examining the relationship between kidney stones and risk of cardiovascular disease while considering individuals of different race-ethnicities. The purpose of this study was to examine the association between history of kidney stones and increased odds of atherosclerotic cardiovascular disease (via the Pooled Cohort Equations) across race-ethnicity groups. 5571 participants aged 40-79 from the 2007-2012 cycles of the NHANES were used for this study. A history of kidney stones was collected from survey data. Predicted odds of having a 10-year atherosclerotic cardiovascular disease (ASCVD) event was assessed from the Pooled Cohort Equations. After adjustments, having kidney stones was not associated with an increase odds of having an ASCVD event within the next 10-years (OR 1.03; 95% CI: 0.58-1.82, P=0.91). However, among non-Hispanic blacks, those with kidney stones had a 2.24 increased odds (OR 2.24; 95% CI: 1.08-4.66; P=0.03) of having an ASCVD event within the next 10-years when compared to non-Hispanic blacks with no history of a kidney stone. Kidney stones were associated with 10-year risk of a future ASCVD event among non-Hispanic blacks. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Readiness of Wait-Listed Black Patients to Pursue Live Donor Kidney Transplantation

    PubMed Central

    Rodrigue, James R.; Paek, Matthew J.; Egbuna, Ogo; Waterman, Amy D.; Schold, Jesse D.; Pavlakis, Martha; Mandelbrot, Didier A.

    2015-01-01

    Context For adults with end-stage kidney disease, live donor kidney transplantation (LDKT) yields superior outcomes over long-term dialysis and deceased donor kidney transplantation. However, blacks receive LDKT at a much lower rate than adults of any other race or ethnicity. Objective To examine the LDKT readiness stage of blacks on the transplant waiting list and its association with LDKT knowledge, concerns, and willingness. Design Cross-sectional analysis of baseline data from a randomized controlled trial to improve knowledge and reduce concerns about LDKT. Patients and Setting One hundred fifty-two black patients on the kidney transplant waiting list at a single transplant center in the northeastern United States. Main Outcomes LDKT readiness stage, knowledge, concerns, and willingness to talk to others about living donation. Results Sixty percent of patients were not considering or not yet ready to pursue LDKT, while only 11% had taken action to talk to family members or friends about the possibility of living kidney donation. Patients in later stages of LDKT readiness (i.e., had talked to others about donation or were preparing to do so) had significantly more knowledge (p<0.001), fewer concerns (p=0.002), and more willingness (p=0.001) to talk to others about living donation than those in earlier readiness stages. Conclusions The large percentage of blacks who are in the earlier stages of LDKT readiness may account for the low rate of LDKT in this patient population at our transplant center. Innovative and tailored LDKT educational strategies for black patients are needed to help reduce racial disparities in LDKT. PMID:25488559

  8. Ex-vivo machine perfusion for kidney preservation.

    PubMed

    Hamar, Matyas; Selzner, Markus

    2018-06-01

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

  9. Kidney organogenesis in the zebrafish: insights into vertebrate nephrogenesis and regeneration

    PubMed Central

    Gerlach, Gary F.; Wingert, Rebecca A.

    2012-01-01

    Vertebrates form a progressive series of up to three kidney organs during development—the pronephros, mesonephros, and metanephros. Each kidney derives from the intermediate mesoderm and is comprised of conserved excretory units called nephrons. The zebrafish is a powerful model for vertebrate developmental genetics, and recent studies have illustrated that zebrafish and mammals share numerous similarities in nephron composition and physiology. The zebrafish embryo forms an architecturally simple pronephros that has two nephrons, and these eventually become a scaffold onto which a mesonephros of several hundred nephrons is constructed during larval stages. In adult zebrafish, the mesonephros exhibits ongoing nephrogenesis, generating new nephrons from a local pool of renal progenitors during periods of growth or following kidney injury. The characteristics of the zebrafish pronephros and mesonephros make them genetically tractable kidney systems in which to study the functions of renal genes and address outstanding questions about the mechanisms of nephrogenesis. Here, we provide an overview of the formation and composition of these zebrafish kidney organs, and discuss how various zebrafish mutants, gene knockdowns, and transgenic models have created frameworks in which to further delineate nephrogenesis pathways. PMID:24014448

  10. 76 FR 11501 - National Institute of Diabetes and Digestive and Kidney Diseases

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

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

  11. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

    PubMed

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

    2016-01-21

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

  12. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

    PubMed Central

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar; Ganesh, Santhi K.; Garcia, Melissa; Gaunt, Tom R.; Glazer, Nicole L.; Go, Min Jin; Goel, Anuj; Grässler, Jürgen; Grobbee, Diederick E.; Groop, Leif; Guarrera, Simonetta; Guo, Xiuqing; Hadley, David; Hamsten, Anders; Han, Bok-Ghee; Hardy, Rebecca; Hartikainen, Anna-Liisa; Heath, Simon; Heckbert, Susan R.; Hedblad, Bo; Hercberg, Serge; Hernandez, Dena; Hicks, Andrew A.; Hilton, Gina; Hingorani, Aroon D.; Bolton, Judith A Hoffman; Hopewell, Jemma C.; Howard, Philip; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Ikram, M. Arfan; Islam, Muhammad; Iwai, Naoharu; Jarvelin, Marjo-Riitta; Jackson, Anne U.; Jafar, Tazeen H.; Janipalli, Charles S.; Johnson, Toby; Kathiresan, Sekar; Khaw, Kay-Tee; Kim, Hyung-Lae; Kinra, Sanjay; Kita, Yoshikuni; Kivimaki, Mika; Kooner, Jaspal S.; Kumar, M. J. Kranthi; Kuh, Diana; Kulkarni, Smita R.; Kumari, Meena; Kuusisto, Johanna; Kuznetsova, Tatiana; Laakso, Markku; Laan, Maris; Laitinen, Jaana; Lakatta, Edward G.; Langefeld, Carl D.; Larson, Martin G.; Lathrop, Mark; Lawlor, Debbie A.; Lawrence, Robert W.; Lee, Jong-Young; Lee, Nanette R.; Levy, Daniel; Li, Yali; Longstreth, Will T.; Luan, Jian'an; Lucas, Gavin; Ludwig, Barbara; Mangino, Massimo; Mani, K. Radha; Marmot, Michael G.; Mattace-Raso, Francesco U. S.; Matullo, Giuseppe; McArdle, Wendy L.; McKenzie, Colin A.; Meitinger, Thomas; Melander, Olle; Meneton, Pierre; Meschia, James F.; Miki, Tetsuro; Milaneschi, Yuri; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Morris, Richard W.; Mosley, Thomas H.; Najjar, Samer; Narisu, Narisu; Newton-Cheh, Christopher; Nguyen, Khanh-Dung Hoang; Nilsson, Peter; Nyberg, Fredrik; O'Donnell, Christopher J.; Ogihara, Toshio; Ohkubo, Takayoshi; Okamura, Tomonori; Ong, RickTwee-Hee; Ongen, Halit; Onland-Moret, N. Charlotte; O'Reilly, Paul F.; Org, Elin; Orru, Marco; Palmas, Walter; Palmen, Jutta; Palmer, Lyle J.; Palmer, Nicholette D.; Parker, Alex N.; Peden, John F.; Peltonen, Leena; Perola, Markus; Pihur, Vasyl; Platou, Carl G. P.; Plump, Andrew; Prabhakaran, Dorairajan; Psaty, Bruce M.; Raffel, Leslie J.; Rao, Dabeeru C.; Rasheed, Asif; Ricceri, Fulvio; Rice, Kenneth M.; Rosengren, Annika; Rotter, Jerome I.; Rudock, Megan E.; Sõber, Siim; Salako, Tunde; Saleheen, Danish; Salomaa, Veikko; Samani, Nilesh J.; Schwartz, Steven M.; Schwarz, Peter E. H.; Scott, Laura J.; Scott, James; Scuteri, Angelo; Sehmi, Joban S.; Seielstad, Mark; Seshadri, Sudha; Sharma, Pankaj; Shaw-Hawkins, Sue; Shi, Gang; Shrine, Nick R. G.; Sijbrands, Eric J. G.; Sim, Xueling; Singleton, Andrew; Sjögren, Marketa; Smith, Nicholas L.; Artigas, Maria Soler; Spector, Tim D.; Staessen, Jan A.; Stancakova, Alena; Steinle, Nanette I.; Strachan, David P.; Stringham, Heather M.; Sun, Yan V.; Swift, Amy J.; Tabara, Yasuharu; Tai, E-Shyong; Talmud, Philippa J.; Taylor, Andrew; Terzic, Janos; Thelle, Dag S.; Tobin, Martin D.; Tomaszewski, Maciej; Tripathy, Vikal; Tuomilehto, Jaakko; Tzoulaki, Ioanna; Uda, Manuela; Ueshima, Hirotsugu; Uiterwaal, Cuno S. P. M.; Umemura, Satoshi; van der Harst, Pim; van der Schouw, Yvonne T.; van Gilst, Wiek H.; Vartiainen, Erkki; Vasan, Ramachandran S.; Veldre, Gudrun; Verwoert, Germaine C.; Viigimaa, Margus; Vinay, D. G.; Vineis, Paolo; Voight, Benjamin F.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wain, Louise V.; Wang, Xiaoling; Wang, Thomas J.; Wareham, Nicholas J.; Watkins, Hugh; Weder, Alan B.; Whincup, Peter H.; Wiggins, Kerri L.; Witteman, Jacqueline C. M.; Wong, Andrew; Wu, Ying; Yajnik, Chittaranjan S.; Yao, Jie; Young, J. H.; Zelenika, Diana; Zhai, Guangju; Zhang, Weihua; Zhang, Feng; Zhao, Jing Hua; Zhu, Haidong; Zhu, Xiaofeng; Zitting, Paavo; Zukowska-Szczechowska, Ewa; Okada, Yukinori; Wu, Jer-Yuarn; Gu, Dongfeng; Takeuchi, Fumihiko; Takahashi, Atsushi; Maeda, Shiro; Tsunoda, Tatsuhiko; Chen, Peng; Lim, Su-Chi; Wong, Tien-Yin; Liu, Jianjun; Young, Terri L.; Aung, Tin; Teo, Yik-Ying; Kim, Young Jin; Kang, Daehee; Chen, Chien-Hsiun; Tsai, Fuu-Jen; Chang, Li-Ching; Fann, S. -J. Cathy; Mei, Hao; Hixson, James E.; Chen, Shufeng; Katsuya, Tomohiro; Isono, Masato; Albrecht, Eva; Yamamoto, Kazuhiko; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki; Kato, Norihiro; He, Jiang; Chen, Yuan-Tsong; Tanaka, Toshihiro; Reilly, Muredach P; Schunkert, Heribert; Assimes, Themistocles L.; Hall, Alistair; Hengstenberg, Christian; König, Inke R.; Laaksonen, Reijo; McPherson, Ruth; Thompson, John R.; Thorsteinsdottir, Unnur; Ziegler, Andreas; Absher, Devin; Chen, Li; Cupples13, L. Adrienne; Halperin, Eran; Li, Mingyao; Musunuru, Kiran; Preuss, Michael; Schillert, Arne; Thorleifsson, Gudmar; Wells, George A.; Holm, Hilma; Roberts, Robert; Stewart, Alexandre F. R.; Fortmann, Stephen; Go, Alan; Hlatky, Mark; Iribarren, Carlos; Knowles, Joshua; Myers, Richard; Quertermous, Thomas; Sidney, Steven; Risch, Neil; Tang, Hua; Blankenberg, Stefan; Schnabel, Renate; Sinning, Christoph; Lackner, Karl J.; Tiret, Laurence; Nicaud, Viviane; Cambien, Francois; Bickel, Christoph; Rupprecht, Hans J.; Perret, Claire; Proust, Carole; Münzel, Thomas F.; Barbalic, Maja; Chen, Ida Yii-Der; Demissie-Banjaw, Serkalem; Folsom, Aaron; Lumley, Thomas; Marciante, Kristin; Taylor, Kent D.; Volcik, Kelly; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Stefansson, Kari; Thorgeirsson, Gudmundur; Andersen, Karl; Fischer, Marcus; Grosshennig, Anika; Linsel-Nitschke, Patrick; Stark, Klaus; Schreiber, Stefan; Aherrahrou, Zouhair; Bruse, Petra; Doering, Angela; Klopp, Norman; Diemert, Patrick; Loley, Christina; Medack, Anja; Nahrstedt, Janja; Peters, Annette; Wagner, Arnika K.; Willenborg, Christina; Böhm, Bernhard O.; Dobnig, Harald; Grammer, Tanja B.; Hoffmann, Michael M.; Meinitzer, Andreas; Winkelmann, Bernhard R.; Pilz, Stefan; Renner, Wilfried; Scharnagl, Hubert; Stojakovic, Tatjana; Tomaschitz, Andreas; Winkler, Karl; Guiducci, Candace; Burtt, Noel; Gabriel, Stacey B.; Dandona, Sonny; Jarinova, Olga; Qu, Liming; Wilensky, Robert; Matthai, William; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Epstein, Stephen E.; Rader, Daniel J.; Nelson, Christopher P.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Loehr, Laura R.; Rosamond, Wayne D.; Benjamin, Emelia; Haritunians, Talin; Couper, David; Murabito, Joanne; Wang, Ying A.; Stricker, Bruno H.; Chang, Patricia P.; Willerson, James T.; Felix, Stephan B.; Watzinger, Norbert; Aragam, Jayashri; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J.; Greiser, Karin Halina; Deckers, Jaap W.; Stritzke, Jan; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; Reffelmann, Thorsten; Redfield, Margaret M.; Werdan, Karl; Mitchell, Gary F.; Arnett, Donna K.; Gottdiener, John S.; Blettner, Maria; Friedrich, Nele; Kovacs, Peter; Wild, Philipp S.; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P. S.; Carroll, Robert J.; Penninx, Brenda W.; Scott, Rodney J.; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H.; Kardia, Sharon L. R.; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J.; Turner, Stephen T.; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J. F.; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P.; Parsa, Afshin; O'Connell, Jeffrey R.; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H.; Böger, Carsten A.; Goessling, Wolfram; Chasman, Daniel I.; Köttgen, Anna; Kao, W. H. Linda; Fox, Caroline S.

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  13. Association of the TG/HDL-C and Non-HDL-C/HDL-C Ratios with Chronic Kidney Disease in an Adult Chinese Population.

    PubMed

    Wen, Jia; Chen, Yiyin; Huang, Yun; Lu, Yao; Liu, Xing; Zhou, Honghao; Yuan, Hong

    2017-01-01

    Evidence indicates a role for dyslipidemia in the development of chronic kidney disease (CKD). However, the association of lipid abnormalities and their ratios with kidney disease using the new CKD Epidemiology Collaboration (CKD-EPI) equation is not well understood. This cross-sectional study included 48,054 adult subjects. CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2 or dipstick-positive proteinuria. Logistic regression models were used to examine the relationship between lipid variables and CKD. The prevalence of CKD in this study was 3.7%. When the participants exhibited higher serum triglyceride (TG), a higher TG/high-density lipoprotein cholesterol (TG/HDL-c) ratio or a higher non-HDL-c/HDL-c ratio or HDL-c in a lower quartile, the prevalence of CKD tended to be higher. The multivariate adjusted odds ratios for CKD per 1 standard deviation increase in lipid level were 1.17 (1.10-1.23) for TG, 0.86 (0.79-0.93) for HDL-c, 1.21 (1.13-1.31) for the TG/HDL-c ratio, and 1.14 (1.06-1.22) for the non-HDL-c/HDL-c ratio. No significant association was detected between CKD and total cholesterol (TC), non-HDL-c or the low-density lipoprotein cholesterol/HDL-c (LDL-c/HDL-c) ratio. In this relatively healthy adult Chinese population, the CKD-EPI equation determined that the TG/HDL-c and non-HDL-c/HDL-c ratios as well as TG and HDL-c correlate with the prevalence of CKD. © 2017 The Author(s). Published by S. Karger AG, Basel.

  14. The potential pitfalls of studying adult sex ratios at aggregate levels in humans.

    PubMed

    Pollet, Thomas V; Stoevenbelt, Andrea H; Kuppens, Toon

    2017-09-19

    Human adult sex ratios have been studied extensively across the biological and social sciences. While several studies have examined adult sex ratio effects in a multilevel perspective, many studies have focused on effects at an aggregated level only. In this paper, we review some key issues relating to such analyses. We address not only nation-level analyses, but also aggregation at lower levels, to investigate whether these issues extend to lower levels of aggregation. We illustrate these issues with novel databases covering a broad range of variables. Specifically, we discuss distributional issues with aggregated measures of adult sex ratio, significance testing, and statistical non-independence when using aggregate data. Firstly, we show that there are severe distributional issues with national adult sex ratio, such as extreme cases. Secondly, we demonstrate that many 'meaningless' variables are significantly correlated with adult sex ratio (e.g. the max. elevation level correlates with sex ratio at US state level). Finally, we re-examine associations between adult sex ratios and teenage fertility and find no robust evidence for an association at the aggregate level. Our review highlights the potential issues of using aggregate data on adult sex ratios to test hypotheses from an evolutionary perspective in humans.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

  15. Chronic Kidney Disease and Risk of Presenting with Acute Myocardial Infarction versus Stable Exertional Angina in Adults with Coronary Heart Disease

    PubMed Central

    Go, Alan S.; Bansal, Nisha; Chandra, Malini; Lathon, Phenius V.; Fortmann, Stephen P.; Iribarren, Carlos; Hsu, Chi-yuan; Hlatky, Mark A.

    2011-01-01

    Objective To examine whether kidney dysfunction is associated with the type of clinical presentation of coronary heart disease (CHD). Background Reduced kidney function increases risk of developing CHD, but it is not known whether it also influences the acuity of clinical presentation, which has important prognostic implications. Methods We conducted a case-control study of subjects whose first clinical presentation of CHD was either acute myocardial infarction or stable exertional angina between October 2001-December 2003. Glomerular filtration rate (eGFR) before the incident event was estimated using calibrated serum creatinine and the abbreviated MDRD equation. Patient characteristics and use of medications were ascertained from self-report and health plan databases. We used multivariable logistic regression to examine the association of reduced eGFR and CHD presentation. Results We studied 803 adults with incident acute myocardial infarction and 419 adults with incident stable exertional angina who had a baseline eGFR ≤130 ml/min/1.73 m2. Mean eGFR was lower among subjects with acute myocardial infarction compared with stable angina. Compared with eGFR 90–130 ml/min/1.73 m2, we found a strong, graded independent association between reduced eGFR and presenting with acute myocardial infarction: adjusted odds ratio (OR) 1.36 (95% CI: 0.99 to 1.86) for eGFR 60–89 ml/min/1.73 m2, OR 1.55 (0.92 to 2.62) for eGFR 45–59 ml/min/1.73 m2 and OR 3.82 (1.55 to 9.46) for eGFR <45 ml/min/1.73 m2 (P<0.001 for trend). Conclusion eGFR less than 45 ml/min/1.73 m2 is a strong, independent predictor of presenting with acute myocardial infarction versus stable angina as the initial manifestation of CHD. PMID:21958887

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

    PubMed

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

    2015-07-01

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

  17. Nephrectomy (Kidney Removal)

    MedlinePlus

    ... nephrectomy is needed because of other kidney diseases. Kidney function Most people have two kidneys — fist-sized ... and the disease that prompted the surgery? Monitoring kidney function Most people can function well with only ...

  18. Predicting kidney disease progression in patients with acute kidney injury after cardiac surgery.

    PubMed

    Mizuguchi, K Annette; Huang, Chuan-Chin; Shempp, Ian; Wang, Justin; Shekar, Prem; Frendl, Gyorgy

    2018-06-01

    The study objective was to identify patients who are likely to develop progressive kidney dysfunction (acute kidney disease) before their hospital discharge after cardiac surgery, allowing targeted monitoring of kidney function in this at-risk group with periodic serum creatinine measurements. Risks of progression to acute kidney disease (a state in between acute kidney injury and chronic kidney disease) were modeled from acute kidney injury stages (Kidney Disease: Improving Global Outcomes) in patients undergoing cardiac surgery. A modified Poisson regression with robust error variance was used to evaluate the association between acute kidney injury stages and the development of acute kidney disease (defined as doubling of creatinine 2-4 weeks after surgery) in this observational study. Acute kidney disease occurred in 4.4% of patients with no preexisting kidney disease and 4.8% of patients with preexisting chronic kidney disease. Acute kidney injury predicted development of acute kidney disease in a graded manner in which higher stages of acute kidney injury predicted higher relative risk of progressive kidney disease (area under the receiver operator characteristic curve = 0.82). This correlation persisted regardless of baseline kidney function (P < .001). Of note, development of acute kidney disease was associated with higher mortality and need for renal replacement therapy. The degree of acute kidney injury can identify patients who will have a higher risk of progression to acute kidney disease. These patients may benefit from close follow-up of renal function because they are at risk of progressing to chronic kidney disease or end-stage renal disease. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  19. Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

    PubMed

    Zhang, Shiwei; Zhang, Qing; Ji, Changwei; Zhao, Xiaozhi; Liu, Guangxiang; Zhang, Shun; Li, Xiaogong; Lian, Huibo; Zhang, Gutian; Guo, Hongqian

    2015-01-01

    We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  20. Delayed Consequences of Acute Kidney Injury

    PubMed Central

    Parr, Sharidan K; Siew, Edward D

    2016-01-01

    Acute kidney injury (AKI) is an increasingly common complication of hospitalization and acute illness. Experimental data indicate that AKI may cause permanent kidney damage through tubulointerstitial fibrosis and progressive nephron loss, while also lowering the threshold for subsequent injury. Furthermore, preclinical data suggest that AKI may also cause distant organ dysfunction. The extension of these findings to human studies suggests long-term consequences of AKI including, but not limited to recurrent AKI, progressive kidney disease, elevated blood pressure, cardiovascular events, and mortality. As the number of AKI survivors increases, the need to better understand the mechanisms driving these processes becomes paramount. Optimizing care for AKI survivors will require understanding the short- and long-term risks associated with AKI, identifying patients at highest risk for poor outcomes, and testing interventions that target modifiable risk factors. In this review, we examine the literature describing the association between AKI and long-term outcomes and highlight opportunities for further research and potential intervention. PMID:27113695

  1. Vasopressin and Diabetic Kidney Disease.

    PubMed

    El Boustany, Ray

    2018-01-01

    Diabetic nephropathy has become the most common cause of chronic kidney disease (CKD). Despite the progress accomplished in therapy, the prevalence of renal disorders remains high. Some modifiable factors driving the increase in incidence of CKD, in diabetes and other settings, might have been overlooked. Consistent evidence supports a role for vasopressin, hydration state, and urine concentration in kidney health. Plasma vasopressin is elevated in diabetes, even if metabolic control is good. Several epidemiological studies have pointed to a positive association between markers of vasopressin secretion (24-h fluid intake, urine volume, plasma copeptin concentration) and renal function decline in both the community and populations at high risk of CKD, namely, diabetic patients. Research involving animal models also supports a critical causal role of the V2 receptor antidiuretic effects of vasopressin in the early signs of kidney disease associated with type 1 or type 2 diabetes. Key Messages: Data supporting the detrimental effects of chronic vasopressin action on the kidney is consistent in animal models and human observational studies. Since vasopressin secretion can be modulated by water intake, and its actions by selective receptor antagonists, the vasopressin-hydration system could be a potential therapeutic target for the prevention and treatment of diabetic nephropathy. Intervention studies are needed to examine the relevance of lifestyle or pharmacological interventions. © 2018 The Author(s) Published by S. Karger AG, Basel.

  2. Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

    PubMed

    Orlando, Giuseppe; Khan, Muhammad A; El-Hennawy, Hany; Farney, Alan C; Rogers, Jeffrey; Reeves-Daniel, Amber; Gautreaux, Michael D; Doares, William; Kaczmorski, Scott; Stratta, Robert J

    2018-03-01

    To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) <20 hours, 27 patients; (ii) 20-30 hours, 52 patients; (iii) 30-40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow-up of 48 months, overall patient and graft survival rates were 91% and 81%. Death-censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT <20 hours compared to 85% with CIT >20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Translational value of animal models of kidney failure.

    PubMed

    Ortiz, Alberto; Sanchez-Niño, Maria D; Izquierdo, Maria C; Martin-Cleary, Catalina; Garcia-Bermejo, Laura; Moreno, Juan A; Ruiz-Ortega, Marta; Draibe, Juliana; Cruzado, Josep M; Garcia-Gonzalez, Miguel A; Lopez-Novoa, Jose M; Soler, Maria J; Sanz, Ana B

    2015-07-15

    Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with decreased renal function and increased mortality risk, while the therapeutic armamentarium is unsatisfactory. The availability of adequate animal models may speed up the discovery of biomarkers for disease staging and therapy individualization as well as design and testing of novel therapeutic strategies. Some longstanding animal models have failed to result in therapeutic advances in the clinical setting, such as kidney ischemia-reperfusion injury and diabetic nephropathy models. In this regard, most models for diabetic nephropathy are unsatisfactory in that they do not evolve to renal failure. Satisfactory models for additional nephropathies are needed. These include anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, IgA nephropathy, anti-phospholipase-A2-receptor (PLA2R) membranous nephropathy and Fabry nephropathy. However, recent novel models hold promise for clinical translation. Thus, the AKI to CKD translation has been modeled, in some cases with toxins of interest for human CKD such as aristolochic acid. Genetically modified mice provide models for Alport syndrome evolving to renal failure that have resulted in clinical recommendations, polycystic kidney disease models that have provided clues for the development of tolvaptan, that was recently approved for the human disease in Japan; and animal models also contributed to target C5 with eculizumab in hemolytic uremic syndrome. Some ongoing trials explore novel concepts derived from models, such TWEAK targeting as tissue protection for lupus nephritis. We now review animal models reproducing diverse, genetic and acquired, causes of AKI and CKD evolving to kidney failure and discuss the contribution to clinical translation and prospects for the future. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Fibroblast growth factor receptor signaling in kidney and lower urinary tract development.

    PubMed

    Walker, Kenneth A; Sims-Lucas, Sunder; Bates, Carlton M

    2016-06-01

    Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.

  5. Health Literacy and Access to Kidney Transplantation

    PubMed Central

    Grubbs, Vanessa; Gregorich, Steven E.; Perez-Stable, Eliseo J.; Hsu, Chi-yuan

    2009-01-01

    Background and objectives: Few studies have examined health literacy in patients with end stage kidney disease. We hypothesized that inadequate health literacy in a hemodialysis population is common and is associated with poorer access to kidney transplant wait-lists. Design, setting, participants, & measurements: We enrolled 62 Black and White maintenance hemodialysis patients aged 18 to 75. We measured health literacy using the short form Test of Functional Health Literacy in Adults. Our primary outcomes were (1) time from dialysis start date to referral date for kidney transplant evaluation and (2) time from referral date to date placed on kidney transplant wait-list. We used Cox proportional hazard models to examine the association between health literacy (adequate versus inadequate) and our outcomes after controlling for demographics and co-morbid conditions. Results: Roughly one third (32.3%) of participants had inadequate health literacy. Forty-seven (75.8%) of participants were referred for transplant evaluation. Among those referred, 40 (85.1%) were wait-listed. Participants with inadequate health literacy had 78% lower hazard of referral for transplant evaluation than those with adequate health literacy (adjusted hazard ratio [AHR] 0.22; 95% confidence interval 0.08, 0.60; P = 0.003). The hazard ratio of being wait-listed by health literacy was not statistically different (AHR 0.80, 95% CI, 0.39, 1.61), P = 0.5). Conclusions: Inadequate health literacy is common in our hemodialysis patient population and is associated with a lower hazard of referral for transplant evaluation. Strategies to reduce the impact of health literacy on the kidney transplant process should be explored. PMID:19056617

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

    PubMed

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

    2018-01-01

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

  7. Providers' assessment of transition readiness among adolescent and young adult kidney transplant recipients.

    PubMed

    Marchak, Jordan Gilleland; Reed-Knight, Bonney; Amaral, Sandra; Mee, Laura; Blount, Ronald L

    2015-12-01

    The Readiness for Transition Questionnaire- provider version (RTQ-Provider) was developed to evaluate adolescent patients' transition readiness and healthcare behaviors from the perspective of the healthcare provider. The RTQ-Provider is a parallel version of the RTQ-Teen and RTQ-Parent completed by patients and parents. This study seeks to evaluate the psychometric properties of the RTQ-Provider and its utility as a clinical transition planning tool. Participants consisted of 49 kidney transplant recipients between the ages of 15 and 21. The RTQ-Provider was completed by the pediatric nephrologist and psychologist from the multidisciplinary healthcare team and compared to RTQ data from teens and parents. The RTQ-Provider demonstrated good-to-excellent internal consistency and interrater reliability. Construct validity was supported through significant predictive relationships between providers' perceptions of transition readiness and older patient age, increased patient healthcare responsibility, and decreased parent involvement in health care. By providing parallel teen, parent, and provider forms, the RTQ has the potential to foster open communication between patients, families, and healthcare team members regarding transition readiness. The study provides initial support for the RTQ-Provider as a clinical tool to assess providers' perceptions of transition readiness; however, future longitudinal research is needed to evaluate predictive validity following patients' transfer to adult care. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Adult dual kidney transplantations obtained from marginal donors: two case reports.

    PubMed

    Kim, Y H; Jung, J H; Song, K B; Chung, Y S; Park, J B; Cho, Y M; Jang, H J; Kim, S-C; Han, D J

    2012-01-01

    Organ shortage has led us to use grafts from expanded criteria donors (ECD). Dual kidney transplantation (DKT) using organs from an ECD, which are not acceptable for single kidney transplantation (KT), may overcome the insufficient functioning nephron mass. We performed DKTs in two recipients, the first DKT to be reported from Korea. In case 1, the donor was a 36-year-old man with hypertension. The cause of his brain death was intracranial hemorrhage. He had no known underlying renal disease; his serum creatinine level was 4.2 mg/dL. Despite the relatively young age of the donor, a biopsy revealed mild interstitial fibrosis and tubular atrophy with moderate arteriolar narrowing. The recipient's postoperative course was uneventful over the 69-month follow-up; her last serum creatinine was 1.3 mg/dL. In case 2, the 80-year-old male donor with a history of hypertension had a normal creatinine. The donor biopsy revealed mild glomerular sclerosis, tubular atrophy, and interstitial fibrosis with moderate arteriolar narrowing. The recipient had undergone a previous KT 14 years previously on the right side of the abdomen, but had resumed dialysis 2 years previously due to chronic allograft nephropathy. There was no delayed graft function. At month 4 posttransplantation, lymphoceles were treated by fenestration. At 6-month follow-up, her creatinine was 1.0 mg/dL. In our experience with these two cases, DKT with ECD kidney grafts seemed to be a successful strategy to avoid poor graft outcomes and overcome the donor organ shortage. Further studies including histological criteria for DKT, should be performed to determine the safest means to utilize ECD grafts. Copyright © 2012. Published by Elsevier Inc.

  9. The impact of gut microbiota on kidney function and pathogenesis.

    PubMed

    Mahmoodpoor, Fariba; Rahbar Saadat, Yalda; Barzegari, Abolfazl; Ardalan, Mohammadreza; Zununi Vahed, Sepideh

    2017-09-01

    Chronic kidney diseases (CKDs) are a global health problem. Besides diverse leading reasons in initiation and progression of CKDs, it is evident that they might largely originate from changes in the gut microbial community (microbiota). Mounting evidence indicates that a bidirectional relationship exists between host and microbiome in humans and animals with CKDs. Changes in the microbiota composition and structure (dysbiosis) produce excessive amounts of uremic toxins (e.g. indoxyl sulfate, p-cresyl sulfate and trimethylamine-N-oxide) but less reno-protective metabolites that are implicated in oxidative stress, uremia, inflammation, deterioration of kidney function, kidney diseases progression, a higher prevalence of cardiovascular risk, and mortality in patients with CKD. The present review focuses on the pathogenic association between gut microbiota and kidney diseases like CKD, IgA nephropathy, and kidney stone disease. Certainly, novel insights into the impact of the gut microbiota in kidney diseases can be helpful to develop therapeutic strategies in order to avoid and/or treat aforementioned conditions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Formula Feeding Is Independently Associated With Acute Kidney Injury in Very Low Birth Weight Infants.

    PubMed

    Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

    2016-11-01

    Successful strategies to prevent neonatal acute kidney injury are lacking. Nevertheless, it is well known that in breastfed babies the excretory needs of the kidney are low because the intake of most nutrients is just above the nutritional requirement. This study aimed to determine whether feeding type predicts acute kidney injury in the very low birth weight infant. One hundred and eighty-six infants were enrolled in this pre-post cohort study (114 infants were included in the only human milk-fed group and 72 in the formula-fed group). Routine biological markers of acute kidney injury were collected in both groups from birth to discharge. Compared with formula feeding, human milk feeding was associated with almost 80% lower odds of acute kidney injury (odds ratio [OR] = 0.2; 95% confidence interval [CI], 0.05-0.77). After confounding variables had been controlled for, formula feeding was independently associated with acute kidney injury in very low birth weight infants. The study showed that, at our institution, acute kidney injury in the neonatal period is frequently associated with the avoidable procedure of formula feeding. Further prospective multicenter studies are needed to determine the generality of this association.

  11. Monocular Advantage for Face Perception Implicates Subcortical Mechanisms in Adult Humans

    PubMed Central

    Gabay, Shai; Nestor, Adrian; Dundas, Eva; Behrmann, Marlene

    2014-01-01

    The ability to recognize faces accurately and rapidly is an evolutionarily adaptive process. Most studies examining the neural correlates of face perception in adult humans have focused on a distributed cortical network of face-selective regions. There is, however, robust evidence from phylogenetic and ontogenetic studies that implicates subcortical structures, and recently, some investigations in adult humans indicate subcortical correlates of face perception as well. The questions addressed here are whether low-level subcortical mechanisms for face perception (in the absence of changes in expression) are conserved in human adults, and if so, what is the nature of these subcortical representations. In a series of four experiments, we presented pairs of images to the same or different eyes. Participants’ performance demonstrated that subcortical mechanisms, indexed by monocular portions of the visual system, play a functional role in face perception. These mechanisms are sensitive to face-like configurations and afford a coarse representation of a face, comprised of primarily low spatial frequency information, which suffices for matching faces but not for more complex aspects of face perception such as sex differentiation. Importantly, these subcortical mechanisms are not implicated in the perception of other visual stimuli, such as cars or letter strings. These findings suggest a conservation of phylogenetically and ontogenetically lower-order systems in adult human face perception. The involvement of subcortical structures in face recognition provokes a reconsideration of current theories of face perception, which are reliant on cortical level processing, inasmuch as it bolsters the cross-species continuity of the biological system for face recognition. PMID:24236767

  12. Simultaneous Liver-Kidney Allocation Policy: A Proposal to Optimize Appropriate Utilization of Scarce Resources.

    PubMed

    Formica, R N; Aeder, M; Boyle, G; Kucheryavaya, A; Stewart, D; Hirose, R; Mulligan, D

    2016-03-01

    The introduction of the Mayo End-Stage Liver Disease score into the Organ Procurement and Transplantation Network (OPTN) deceased donor liver allocation policy in 2002 has led to a significant increase in the number of simultaneous liver-kidney transplants in the United States. Despite multiple attempts, clinical science has not been able to reliably predict which liver candidates with renal insufficiency will recover renal function or need a concurrent kidney transplant. The problem facing the transplant community is that currently there are almost no medical criteria for candidacy for simultaneous liver-kidney allocation in the United States, and this lack of standardized rules and medical eligibility criteria for kidney allocation with a liver is counter to OPTN's Final Rule. Moreover, almost 50% of simultaneous liver-kidney organs come from a donor with a kidney donor profile index of ≤0.35. The kidneys from these donors could otherwise be allocated to pediatric recipients, young adults or prior organ donors. This paper presents the new OPTN and United Network of Organ Sharing simultaneous liver-kidney allocation policy, provides the supporting evidence and explains the rationale on which the policy was based. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. From arterial stiffness to kidney graft microvasculature: Mortality and graft survival within a cohort of 220 kidney transplant recipients.

    PubMed

    Cheddani, Lynda; Radulescu, Camélia; Chaignon, Michel; Karras, Alexandre; Neuzillet, Yann; Duong, Jean-Paul; Tabibzadeh, Nahid; Letavernier, Emmanuel; Delahousse, Michel; Haymann, Jean-Philippe

    2018-01-01

    Aortic stiffness assessed by carotid-femoral pulse wave velocity (CF-PWV) is a predictor of mortality in several populations. However, little is known in kidney transplant recipients. Our objectives were to evaluate the ability of CF-PWV measured 3 months following transplantation to predict mortality, graft loss and its potential links to measured Glomerular Filtration Rate (mGFR) or kidney graft microvasculature parameters. The study is based on a monocentric retrospective cohort including 220 adult kidney graft recipients evaluated three months after transplantation. CF-PWV measures, clinical, laboratory and histological data performed at 3 (M3) and 12 months (M12) following transplantation were retrospectively collected. The two primary endpoints were all-cause mortality and occurrence of end stage renal disease (ESRD) defined by initiation of dialysis. After a median follow up of 5.5 years [1.9; 8.8], death and graft loss occurred in 10 and 12 patients respectively. M3 CF-PWV was an independent mortality risk factor (HR = 1.29 [1.03; 1.61]; p = 0.03), despite no aortic stiffness variation during the first year of transplantation. Of notice, M3 CF-PWV was not associated with M12 mGFR or ESRD outcome. Graft microcirculation assessed by Banff vascular fibrous intimal thickening score (cv) worsened between M3 and M12 (p = 0.01), but no link was found with CF-PWV, mGFR or ESRD outcome. Surprisingly, acute rejections at M3 were associated after adjustment with mortality (p = 0.03) but not ESRD. Aortic stiffness measured 3 months after kidney transplantation is a strong predictor of mortality with no obvious influence on kidney graft microvasculature or graft loss.

  14. Perinatal lead (Pb) exposure results in sex and tissue-dependent adult DNA methylation alterations in murine IAP transposons.

    PubMed

    Montrose, L; Faulk, C; Francis, J; Dolinoy, D C

    2017-10-01

    Epidemiological and animal data suggest that adult chronic disease is influenced by early-life exposure-induced changes to the epigenome. Previously, we observed that perinatal lead (Pb) exposure results in persistent murine metabolic- and activity-related effects. Using phylogenetic and DNA methylation analysis, we have also identified novel intracisternal A particle (IAP) retrotransposons exhibiting regions of variable methylation as candidate loci for environmental effects on the epigenome. Here, we now evaluate brain and kidney DNA methylation profiles of four representative IAPs in adult mice exposed to human physiologically relevant levels of Pb two weeks prior to mating through lactation. When IAPs across the genome were evaluated globally, average (sd) methylation levels were 92.84% (3.74) differing by tissue (P < 0.001), but not sex or dose. By contrast, the four individual IAPs displayed tissue-specific Pb and sex effects. Medium Pb-exposed mice had 3.86% less brain methylation at IAP 110 (P < 0.01), while high Pb-exposed mice had 2.83% less brain methylation at IAP 236 (P = 0.01) and 1.77% less at IAP 506 (P = 0.05). Individual IAP DNA methylation differed by sex for IAP 110 in the brain and kidney, IAP 236 in the kidney, and IAP 1259 in the kidney. Using Tomtom, we identified three binding motifs that matched to each of our novel IAPs impacted by Pb, one of which (HMGA2) has been linked to metabolic-related conditions in both mice and humans. Thus, these recently identified IAPs display tissue-specific environmental lability as well as sex-specific differences supporting an epigenetic link between early exposure to Pb and later-in-life health outcomes. Environ. Mol. Mutagen. 58:540-550, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

    PubMed

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

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

  16. Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

    PubMed Central

    Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

    2015-01-01

    Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

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

    PubMed

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

    1994-12-15

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

  18. Diversity of the midstream urine microbiome in adults with chronic kidney disease.

    PubMed

    Kramer, Holly; Kuffel, Gina; Thomas-White, Krystal; Wolfe, Alan J; Vellanki, Kavitha; Leehey, David J; Bansal, Vinod K; Brubaker, Linda; Flanigan, Robert; Koval, Julia; Wadhwa, Anuradha; Zilliox, Michael J

    2018-06-01

    To examine the characteristics of the midstream urine microbiome in adults with stage 3-5 non-dialysis-dependent chronic kidney disease (CKD). Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m 2 ) and diuretic use were recruited from outpatient nephrology clinics. Midstream voided urine specimens were collected using the clean-catch method. The bacterial composition was determined by sequencing the hypervariable (V4) region of the bacterial 16S ribosomal RNA gene. Extraction negative controls (no urine) were included to assess the contribution of extraneous DNA from possible sources of contamination. Midstream urine microbiome diversity was assessed with the inverse Simpson, Chao and Shannon indices. The diversity measures were further examined by demographic characteristics and by comorbidities. The cohort of 41 women and 36 men with detectable bacterial DNA in their urine samples had a mean age of 71.5 years (standard deviation [SD] 7.9) years (range 60-91 years). The majority were white (68.0%) and a substantial minority were African-American (29.3%) The mean eGFR was 27.2 (SD 13.6) ml/min/1.73 m 2 . Most men (72.2%) were circumcised and 16.6% reported a remote history of prostate cancer. Many midstream voided urine specimens were dominated (> 50% reads) by the genera Corynebacterium (n = 11), Staphylococcus (n = 9), Streptococcus (n = 7), Lactobacillus (n = 7), Gardnerella (n = 7), Prevotella (n = 4), Escherichia_Shigella (n = 3), and Enterobacteriaceae (n = 2); the rest lacked a dominant genus. The samples had high levels of diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)]. Diversity measures were generally higher in participants with urgency urinary incontinence and higher estimated glomerular filtration rate (eGFR). After controlling for demographics

  19. Epidemiologic insights into pediatric kidney stone disease.

    PubMed

    Matlaga, Brian R; Schaeffer, Anthony J; Novak, Thomas E; Trock, Bruce J

    2010-12-01

    The epidemiology of pediatric kidney stone has not yet been as rigorously defined as that of adult kidney stone disease. Herein, we review our recent epidemiologic works characterizing pediatric stone disease using the Kids' Inpatient Database (KID). Specifically we investigated the age and gender distribution of pediatric kidney stone disease, changes in disease prevalence over time, and medical comorbidities associated with this disorder. We identified patients by International Classification of Disease 9th Edition (ICD-9) codes for renal and ureteral calculi as the primary diagnosis. Medical comorbidities were identified using specific comorbidity software. Statistical comparisons between children with and without stone disease were performed. In the first decade of life, stone disease was more prevalent among males than females; however, in the second decade of life females were more commonly affected. Of note, there was a significant increase in treated stone disease across both genders between 1997 and 2003. We also found that the risk of kidney stone diagnosis in children younger than 6 years of age was significantly associated with hypertension and diabetes mellitus. The gender distribution among pediatric stone formers varies significantly by age, although overall females have a greater prevalence than males. There is also a strong association of stone disease and both diabetes and hypertension, although this was only observed in children less than 6 years of age. Taken all together, these findings suggest that urolithiasis in the young child is a complex systemic disease process.

  20. Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

    PubMed

    Rees, M A; Dunn, T B; Kuhr, C S; Marsh, C L; Rogers, J; Rees, S E; Cicero, A; Reece, L J; Roth, A E; Ekwenna, O; Fumo, D E; Krawiec, K D; Kopke, J E; Jain, S; Tan, M; Paloyo, S R

    2017-03-01

    Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Dietary sodium in chronic kidney disease: a comprehensive approach.

    PubMed

    Wright, Julie A; Cavanaugh, Kerri L

    2010-01-01

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

  2. Dietary Sodium in Chronic Kidney Disease: A Comprehensive Approach

    PubMed Central

    Wright, Julie A.; Cavanaugh, Kerri L.

    2010-01-01

    Despite existing guidelines, dietary sodium intake among people worldwide often exceeds recommended limits. Research evidence is growing in both animal and human studies showing indirect and direct adverse consequences of high dietary sodium on the kidney. In patients with kidney disease, dietary sodium may have important effects on proteinuria, efficacy of antiproteinuric pharmacologic therapy, hypertension control, maintaining an optimal volume status, and immunosuppressant therapy. Dietary sodium intake is an important consideration in patients with all stages of chronic kidney disease, including those receiving dialysis therapy or those who have received a kidney transplant. We review in detail the dietary sodium recommendations suggested by various organizations for patients with kidney disease. Potential barriers to successfully translating current sodium intake guidelines into practice include poor knowledge about the sodium content of food among both patients and providers, complex labeling information, patient preferences related to taste, and limited support for modifications in public policy. Finally, we offer existing and potential solutions that may assist providers in educating and empowering patients to effectively manage their dietary sodium intake. PMID:20557489

  3. The response of the anterior striatum during adult human vocal learning

    PubMed Central

    Leech, Robert; Iverson, Paul; Wise, Richard J. S.

    2014-01-01

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia “loops,” which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts. PMID:24805076

  4. Urine biomarkers of kidney injury among adolescents in Nicaragua, a region affected by an epidemic of chronic kidney disease of unknown aetiology

    PubMed Central

    Ramírez-Rubio, Oriana; Amador, Juan José; Kaufman, James S.; Weiner, Daniel E.; Parikh, Chirag R.; Khan, Usman; McClean, Michael D.; Laws, Rebecca L.; López-Pilarte, Damaris; Friedman, David J.; Kupferman, Joseph; Brooks, Daniel R.

    2016-01-01

    Background An epidemic of chronic kidney disease (CKD) of non-traditional aetiology has been recently recognized by health authorities as a public health priority in Central America. Previous studies have identified strenuous manual work, agricultural activities and residence at low altitude as potential risk factors; however, the aetiology remains unknown. Because individuals are frequently diagnosed with CKD in early adulthood, we measured biomarkers of kidney injury among adolescents in different regions of Nicaragua to assess whether kidney damage might be initiated during childhood. Methods Participants include 200 adolescents aged 12–18 years with no prior work history from four different schools in Nicaragua. The location of the school served as a proxy for environmental exposures and geographic locations were selected to represent a range of factors that have been associated with CKD in adults (e.g. altitude, primary industry and CKD mortality rates). Questionnaires, urine dipsticks and kidney injury biomarkers [interleukin-18, N-acetyl-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL) and albumin–creatinine ratio] were assessed. Biomarker concentrations were compared by school using linear regression models. Results Protein (3.5%) and glucose (1%) in urine measured by dipstick were rare and did not differ by school. Urine biomarkers of tubular kidney damage, particularly NGAL and NAG, showed higher concentrations in those schools and regions within Nicaragua that were defined a priori as having increased CKD risk. Painful urination was a frequent self-reported symptom. Conclusions Although interpretation of these urine biomarkers is limited because of the lack of population reference values, results suggest the possibility of early kidney damage prior to occupational exposures in these adolescents. PMID:26311057

  5. Preemptive Deceased Donor Kidney Transplantation: Considerations of Equity and Utility

    PubMed Central

    Chen, B. Po-Han; Coresh, Josef; Segev, Dorry L.

    2013-01-01

    Summary Background and objectives There exists gross disparity in national deceased donor kidney transplant availability and practice: waiting times exceed 6 years in some regions, but some patients receive kidneys before they require dialysis. This study aimed to quantify and characterize preemptive deceased donor kidney transplant recipients and compare their outcomes with patients transplanted shortly after dialysis initiation. Design, setting, participants, & measurements Using the Scientific Registry of Transplant Recipients database, first-time adult deceased donor kidney transplant recipients between 1995 and 2011 were classified as preemptive, early (on dialysis≤1 year), or late recipients. Random effects logistic regression and multivariate Cox proportional hazards regression were used to identify characteristics of preemptive deceased donor kidney transplant and evaluate survival in preemptive and early recipients, respectively. Results Preemptive recipients were 9.0% of the total recipient population. Patients with private insurance (adjusted odds ratio=3.15, 95% confidence interval=3.01–3.29, P<0.001), previous (nonkidney) transplant (adjusted odds ratio=1.94, 95% confidence interval=1.67–2.26, P<0.001), and zero-antigen mismatch (adjusted odds ratio=1.45, 95% confidence interval=1.37–1.54, P<0.001; Caucasians only) were more likely to receive preemptive deceased donor kidney transplant, even after accounting for center-level clustering. African Americans were less likely to receive preemptive deceased donor kidney transplant (adjusted odds ratio=0.44, 95% confidence interval=0.41–0.47, P<0.001). Overall, patients transplanted preemptively had similar survival compared with patients transplanted within 1 year after initiating dialysis (adjusted hazard ratio=1.06, 95% confidence interval=0.99–1.12, P=0.07). Conclusions Preemptive deceased donor kidney transplant occurs most often among Caucasians with private insurance, and survival is fairly

  6. Racial disparities in paediatric kidney transplantation.

    PubMed

    Grace, Blair S; Kennedy, Sean E; Clayton, Philip A; McDonald, Stephen P

    2014-01-01

    Transplantation is the preferred treatment for children with end-stage kidney disease (ESKD). Pre-emptive transplants, those from live donors and with few human leukocyte antigen (HLA) mismatches provide the best outcomes. Studies into disparities in paediatric transplantation to date have not adequately disentangled different transplant types. We studied a retrospective cohort of 823 patients aged <18 years who started renal replacement therapy (RRT) in Australia 1990-2011, using the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). The primary outcomes were time to first kidney transplant and kidney donor type (deceased or living), analysed using competing risk regression. Caucasian patients were most likely to receive any transplant, due largely to disparities in live donor transplantation. No Indigenous patients received a pre-emptive transplant. Indigenous patients were least likely to receive a transplant from a live donor (sub-hazard ratio 0.41, 95 % confidence interval 0.20-0.82, compared to Caucasians). Caucasian recipients had fewer HLA mismatches, were less sensitised and were more likely to have kidney diseases that could be diagnosed early or progress slowly. Caucasian paediatric patients are more likely to receive optimum treatment--a transplant from a living donor and fewer HLA mismatches. Further work is required to identify and address barriers to live donor transplantation among minority racial groups.

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

    PubMed

    Musso, Carlos G; Oreopoulos, Dimitrios G

    2011-01-01

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

  8. [Geomagnetic field variations in the human prenatal period and cancer in adults].

    PubMed

    Iamshanov, V A

    2007-01-01

    Our earlier evidence pointed to a relationship between geomagnetic field (GMF) variations in pre- and early postnatal periods and appearance in the future of oncopathology in these patients. It appears to contribute to risk for such malignancies in adults as breast, lung, liver, bladder, kidney, prostate, hypophysis cancer, ovarian carcinoma, skin melanoma, Hodgkin's disease, lymphoma, and probably stomach cancer. No link was detected between esophageal, thyroid, colorectal cancer or cervical carcinoma, on the one hand, and GMF variations in prenatal period, on the other. It is suggested that low intensity of GMF is associated with increased death of macrophages and other granulocytes as well as nitric oxide formation both in fetal and maternal organism. The latter factor induces genes responsible for detoxication. In adults, under normal or disturbed GMF conditions, detoxication processes take care of excessive blood-nitric oxide. Both in fetus and mother, due to high GMF intensity, granulocyte decay is inhibited thus causing nitric oxide levels to fall. As a consequence, detoxication fails. That accounts for excessive blood-nitric oxide formation at adult stage when GMF intensity is low or normal. Nitric oxide causes certain nitrosamines to form, which are tissue-specific carcinogens. Therefore, the lower level of GMF oscillations was in pre- and early postnatal periods than in more late terms tumors appeared (for example, the negative correlation for breast cancer took place).

  9. Both high and low maternal salt intake in pregnancy alter kidney development in the offspring.

    PubMed

    Koleganova, Nadezda; Piecha, Grzegorz; Ritz, Eberhard; Becker, Luis Eduardo; Müller, Annett; Weckbach, Monika; Nyengaard, Jens Randel; Schirmacher, Peter; Gross-Weissmann, Marie-Luise

    2011-08-01

    In humans, low glomerular numbers are related to hypertension, cardiovascular, and renal disease in adult life. The present study was designed 1) to explore whether above- or below-normal dietary salt intake during pregnancy influences nephron number and blood pressure in the offspring and 2) to identify potential mechanisms in kidney development modified by maternal sodium intake. Sprague-Dawley rats were fed low (0.07%)-, intermediate (0.51%)-, or high (3.0%)-sodium diets during pregnancy and lactation. The offspring were weaned at 4 wk and subsequently kept on a 0.51% sodium diet. The kidney structure was assessed at postnatal weeks 1 and 12 and the expression of proteins of interest at term and at week 1. Blood pressure was measured in male offspring by telemetry from postnatal month 2 to postnatal month 9. The numbers of glomeruli at weeks 1 and 12 were significantly lower and, in males, telemetrically measured mean arterial blood pressure after month 5 was higher in offspring of dams on a high- or low- compared with intermediate-sodium diet. A high-salt diet was paralleled by higher concentrations of marinobufagenin in the amniotic fluid and an increase in the expression of both sprouty-1 and glial cell-derived neutrophic factor in the offspring's kidney. The expression of FGF-10 was lower in offspring of dams on a low-sodium diet, and the expression of Pax-2 and FGF-2 was lower in offspring of dams on a high-sodium diet. Both excessively high and excessively low sodium intakes during pregnancy modify protein expression in offspring kidneys and reduce the final number of glomeruli, predisposing the risk of hypertension later in life.

  10. Identification of human drug-metabolizing enzymes involved in the metabolism of SNI-2011.

    PubMed

    Washio, T; Arisawa, H; Kohsaka, K; Yasuda, H

    2001-11-01

    In vitro studies were conducted to identify human drug-metabolizing enzymes involved in the metabolism of SNI-2011 ((+/-)-cis-2-methylspiro [1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline hydrochloride hydrate). When 14C-SNI-2011 was incubated with human liver microsomes, SNI-2011 trans-sulfoxide and cis-sulfoxide were detected as major metabolites. These oxidations required NADPH, and were markedly inhibited by SKF-525A, indicating that cytochrome P450 (CYP) was involved. In a chemical inhibition study, metabolism of SNI-2011 in liver microsomes was inhibited (35-65%) by CYP3A4 inhibitors (ketoconazole and troleandomycin) and CYP2D6 inhibitors (quinidine and chlorpromazine). Furthermore, using microsomes containing cDNA-expressed CYPs, it was found that high rates of sulfoxidation activities were observed with CYP2D6 and CYP3A4. On the other hand, when 14C-SNI-2011 was incubated with human kidney microsomes, SNI-2011 N-oxide was identified as a major metabolite. This N-oxidation required NADPH, and was completely inhibited by thiourea, indicating that flavin-containing monooxygenase (FMO) was involved. In addition, microsomes containing cDNA-expressed FMO1, a major isoform in human kidney, mainly catalyzed N-oxidation of SNI-2011, but microsomes containing FMO3, a major isoform in adult human liver, did not. These results suggest that SNI-2011 is mainly catalyzed to sulfoxides and N-oxide by CYP2D6/3A4 in liver and FMOI in kidney, respectively.

  11. Human serum albumin hydropersulfide is a potent reactive oxygen species scavenger in oxidative stress conditions such as chronic kidney disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shibata, Akitomo; Ishima, Yu; Ikeda, Mayumi

    Recently, hydropersulfide (RSSH) was found to exist in mammalian tissues and fluids. Cysteine hydropersulfide can be found in free cysteine residues as well as in proteins, and it has potent antioxidative activity. Human serum albumin (HSA) is the most abundant protein in mammalian serum. HSA possesses a free thiol group in Cys-34 that could be a site for hydropersulfide formation. HSA hydropersulfide of high purity as a positive control was prepared by treatment of HSA with Na{sub 2}S. The presence of HSA hydropersulfide was confirmed by spectroscopy and ESI-TOFMS analysis where molecular weights of HSA hydropersulfide by increments of approximatelymore » 32 Da (Sulfur atom) were detected. The fluorescent probe results showed that Alexa Fluor 680 conjugated maleimide (Red-Mal) was a suitable assay and bromotrimethylammoniumbimane bromide appeared to be a selective reagent for hydropersulfide. The effect of oxidative stress related disease on the existence of albumin hydropersulfides was examined in rat 5/6 nephrectomy model of chronic kidney disease (CKD). Interestingly, the level of hydropersulfides in rat 5/6 nephrectomy model serum was decreased by a uremic toxin that increases oxidative stress in rat 5/6 nephrectomy model. Furthermore, we demonstrated that the levels of HSA hydropersulfide in human subjects were reduced in CKD but restored by hemodialysis using Red-Mal assay. We conclude that HSA hydropersulfide could potentially play an important role in biological anti-oxidative defense, and it is a promising diagnostic and therapeutic marker of oxidative diseases. - Highlights: • Hydropersulfide can behave as potent antioxidants. • We firstly detected human serum albumin hydropersulfide in healthy subjects. • Human serum albumin hydropersulfide in human subjects were reduced in chronic kidney disease but restored by hemodialysis.« less

  12. Incidence of kidney stones in kidney transplant recipients: A systematic review and meta-analysis

    PubMed Central

    Cheungpasitporn, Wisit; Thongprayoon, Charat; Mao, Michael A; Kittanamongkolchai, Wonngarm; Jaffer Sathick, Insara J; Dhondup, Tsering; Erickson, Stephen B

    2016-01-01

    AIM To evaluate the incidence and characteristics of kidney stones in kidney transplant recipients. METHODS A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the inception of the databases through March 2016. Studies assessing the incidence of kidney stones in kidney transplant recipients were included. We applied a random-effects model to estimate the incidence of kidney stones. RESULTS Twenty one studies with 64416 kidney transplant patients were included in the analyses to assess the incidence of kidney stones after kidney transplantation. The estimated incidence of kidney stones was 1.0% (95%CI: 0.6%-1.4%). The mean duration to diagnosis of kidney stones after kidney transplantation was 28 ± 22 mo. The mean age of patients with kidney stones was 42 ± 7 years. Within reported studies, approximately 50% of kidney transplant recipients with kidney stones were males. 67% of kidney stones were calcium-based stones (30% mixed CaOx/CaP, 27%CaOx and 10%CaP), followed by struvite stones (20%) and uric acid stones (13%). CONCLUSION The estimated incidence of kidney stones in patients after kidney transplantation is 1.0%. Although calcium based stones are the most common kidney stones after transplantation, struvite stones (also known as “infection stones”) are not uncommon in kidney transplant recipients. These findings may impact the prevention and clinical management of kidney stones after kidney transplantation. PMID:28058231

  13. Amyloidosis and Kidney Disease

    MedlinePlus

    ... Solitary Kidney Your Kidneys & How They Work Amyloidosis & Kidney Disease What is amyloidosis? Amyloidosis is a rare ... the organs and tissues affected. What are the kidneys and what do they do? The kidneys are ...

  14. Association between water intake, chronic kidney disease, and cardiovascular disease: a cross-sectional analysis of NHANES data.

    PubMed

    Sontrop, Jessica M; Dixon, Stephanie N; Garg, Amit X; Buendia-Jimenez, Inmaculada; Dohein, Oriane; Huang, Shih-Han S; Clark, William F

    2013-01-01

    Evidence from animal and human studies suggests a protective effect of higher water intake on kidney function and cardiovascular disease (CVD). Here the associations between water intake, chronic kidney disease (CKD) and CVD were examined in the general population. We conducted a cross-sectional analysis of the 2005-2006 National Health and Nutrition Examination Survey. Non-pregnant adults with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m(2) who were not taking diuretics were included. Total water intake from foods and beverages was categorized as low (<2.0 l/day), moderate (2.0-4.3 l/day) and high (>4.3 l/day). We examined associations between low total water intake and CKD (eGFR 30-60 ml/min/1.73 m(2)) and self-reported CVD. Of 3,427 adults (mean age 46 (range 20-84); mean eGFR 95 ml/min/1.73 m(2) (range 30-161)), 13% had CKD and 18% had CVD. CKD was higher among those with the lowest (<2.0 l/day) vs. highest total water intake (>4.3 l/day) (adjusted odds ratio (OR) 2.52; 95% confidence interval (CI) 0.91-6.96). When stratified by intake of (1) plain water and (2) other beverages, CKD was associated with low intake of plain water: adjusted OR 2.36 (95% CI 1.10-5.06), but not other beverages: adjusted OR 0.87 (95% CI 0.30-2.50). There was no association between low water intake and CVD (adjusted OR 0.76; 95% CI 0.37-1.59). Our results provide additional evidence suggesting a potentially protective effect of higher total water intake, particularly plain water, on the kidney. Copyright © 2013 S. Karger AG, Basel.

  15. Long noncoding RNA Hoxb3os is dysregulated in autosomal dominant polycystic kidney disease and regulates mTOR signaling.

    PubMed

    Aboudehen, Karam; Farahani, Shayan; Kanchwala, Mohammed; Chan, Siu Chiu; Avdulov, Svetlana; Mickelson, Alan; Lee, Dayeon; Gearhart, Micah D; Patel, Vishal; Xing, Chao; Igarashi, Peter

    2018-06-15

    Autosomal dominant polycystic kidney disease (ADPKD) is a debilitating disease that is characterized by the accumulation of numerous fluid-filled cysts in the kidney. ADPKD is primarily caused by mutations in two genes, PKD1 and PKD2 Long noncoding RNAs (lncRNA), defined by a length >200 nucleotides and absence of a long ORF, have recently emerged as epigenetic regulators of development and disease; however, their involvement in PKD has not been explored previously. Here, we performed deep RNA-Seq to identify lncRNAs that are dysregulated in two orthologous mouse models of ADPKD (kidney-specific Pkd1 and Pkd2 mutant mice). We identified a kidney-specific, evolutionarily conserved lncRNA called Hoxb3os that was down-regulated in cystic kidneys from Pkd1 and Pkd2 mutant mice. The human ortholog HOXB3-AS1 was down-regulated in cystic kidneys from ADPKD patients. Hoxb3os was highly expressed in renal tubules in adult WT mice, whereas its expression was lost in the cyst epithelium of mutant mice. To investigate the function of Hoxb3os , we utilized CRISPR/Cas9 to knock out its expression in mIMCD3 cells. Deletion of Hoxb3os resulted in increased phosphorylation of mTOR and its downstream targets, including p70 S6 kinase, ribosomal protein S6, and the translation repressor 4E-BP1. Consistent with activation of mTORC1 signaling, Hoxb3os mutant cells displayed increased mitochondrial respiration. The Hoxb3os mutant phenotype was partially rescued upon re-expression of Hoxb3os in knockout cells. These findings identify Hoxb3os as a novel lncRNA that is down-regulated in ADPKD and regulates mTOR signaling and mitochondrial respiration. © 2018 Aboudehen et al.

  16. Quantifying the medication burden of kidney transplant recipients in the first year post-transplantation.

    PubMed

    Low, Jac Kee; Crawford, Kimberley; Manias, Elizabeth; Williams, Allison

    2018-06-28

    Background Kidney transplantation is an effective treatment, but it is not a cure. Since the risk of graft rejection and the presence of comorbid conditions remain for a lifetime, medications are necessary. Objective To examine the prescription medication burden of adult kidney transplant recipients from 3- to 12-months post-transplantation. Setting All five adult kidney transplant units in Victoria, Australia. Method As part of a larger intervention study, we conducet a retrospective review of prescription refill records and medical records containing the history of medication changes of 64 participants who completed the study was undertaken. The complexity of the medication management was studied, and we looked at the burden of maintaining the medications supply. Outcome measures Pill burden, administration frequency, dose changes frequency, immunosuppressive medication changes, the estimated out-of-pocket costs of medications and frequency of pharmacy visits. Results At 3 months, the average daily pill burden was 22 (SD = 9) whilst at 12 months, it was 23 (SD = 10). Some participants required long-term prophylaxis of fungal infections up to 4 times a day whilst those with diabetes had to manage up to 4 insulin doses a day. The average out-of-pocket cost per person and the frequency of pharmacy visits at 6, 9 and 12 months post-transplantation remained relatively unchanged. Conclusion The medication regimen prescribed for kidney transplant recipients is complex and for most patients, it did not simplify over time post transplantation. Strategies are needed to support patients in managing the complexity of their medication regimen following kidney transplantation.

  17. Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

    ERIC Educational Resources Information Center

    Smith, Douglas H.

    2006-01-01

    Adult Continuing Education (ACE) and Human Resource Development (HRD) have grown tremendously in the last quarter century. ACE experienced tremendous growth in the 60s and 70s, with over 17 million attending colleges and universities, and local school and community adult education programs by the end of the 1970s. More ACE programs were started…

  18. Generation of a KLF15 homozygous knockout human embryonic stem cell line using paired CRISPR/Cas9n, and human cardiomyocytes derivation.

    PubMed

    Noack, Claudia; Haupt, Luis Peter; Zimmermann, Wolfram-Hubertus; Streckfuss-Bömeke, Katrin; Zelarayán, Laura Cecilia

    2017-08-01

    Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. A simplified donor risk index for predicting outcome after deceased donor kidney transplantation.

    PubMed

    Watson, Christopher J E; Johnson, Rachel J; Birch, Rhiannon; Collett, Dave; Bradley, J Andrew

    2012-02-15

    We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, P<0.001). A history of donor hypertension was also associated with increased risk (hazard ratio 1.30, P=0.001), and increased donor body weight, longer hospital stay before death, and use of adrenaline were also significantly associated with poorer outcomes up to 3 years posttransplant. Other donor factors including donation after circulatory death, history of cardiothoracic disease, diabetes history, and terminal creatinine were not significant. A donor risk index based on the five significant donor factors was derived and confirmed to be prognostic of outcome in a validation cohort (concordance statistic 0.62). An index developed in the United States by Rao et al., Transplantation 2009; 88: 231-236, included 15 factors and gave a concordance statistic of 0.63 in the UK context, suggesting that our much simpler model has equivalent predictive ability. A Kidney Donor Risk Index based on five donor variables provides a clinically useful tool that may help with organ allocation and informed consent.

  20. Women and Kidney Disease: Reflections on World Kidney Day 2018.

    PubMed

    Piccoli, Giorgina B; Alrukhaimi, Mona; Liu, Zhi-Hong; Zakharova, Elena; Levin, Adeera

    2018-01-01

    World Kidney Day and International Women's Day 2018 are commemorated on the same day (March 8), an opportunity to highlight the importance of women's health, and particularly, their kidney health. On its 13th anniversary, World Kidney Day promotes affordable and equitable access to health education, health care, and prevention for all women and girls in the world. In this article, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide. Copyright© by the American Nephrology Nurses Association.

  1. The association of serum angiogenic growth factors with renal structure and function in patients with adult autosomal dominant polycystic kidney disease.

    PubMed

    Coban, Melahat; Inci, Ayca

    2018-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a common congenital chronic kidney disease (CKD). We report here the relationship of serum angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) with total kidney volume (TKV), total cyst volume (TCV), and renal failure in adult ADPKD patients at various stages of CKD. This cross-sectional study was conducted with 50 patients diagnosed with ADPKD and a control group of 45 age-matched healthy volunteers. In patient group, TKV and TCV were determined with upper abdominal magnetic resonance imaging, whereas in controls, TKV was determined with ultrasonography according to ellipsoid formula. Renal function was assessed with serum creatinine, estimated glomerular filtration rate (eGFR), and spot urinary protein/creatinine ratio (UPCR). Ang-1, Ang-2, and VEGF were measured using enzyme-linked immunosorbent assay. Patients with ADPKD had significantly higher TKV (p < 0.001) and UPCR (p < 0.001), and lower eGFR (p ≤ 0.001) compared to the controls. Log 10 Ang-2 was found to be higher in ADPKD patients at all CKD stages. Multiple linear regression analysis showed that there was no association between log 10 Ang-1, log 10 Ang-2, or log 10 VEGF and creatinine, eGFR, UPCR, log 10 TKV (p > 0.05). There was no association of serum angiogenic growth factors with TKV or renal failure in ADPKD patients. Increased serum Ang-2 observed in stages 1-2 CKD suggests that angiogenesis plays a role in the progression of early stage ADPKD, but not at later stages of the disease. This may be explained by possible cessation of angiogenesis in advanced stages of CKD due to the increased number of sclerotic glomeruli.

  2. Baseline Kidney Function as Predictor of Mortality and Kidney Disease Progression in HIV-Positive Patients

    PubMed Central

    Ibrahim, Fowzia; Hamzah, Lisa; Jones, Rachael; Nitsch, Dorothea; Sabin, Caroline; Post, Frank A.

    2012-01-01

    Background Chronic kidney disease (CKD) is associated with increased all-cause mortality and kidney disease progression. Decreased kidney function at baseline may identify human immunodeficiency virus (HIV)-positive patients at increased risk of death and kidney disease progression. Study Design Observational cohort study. Setting & Participants 7 large HIV cohorts in the United Kingdom with kidney function data available for 20,132 patients. Predictor Baseline estimated glomerular filtration rate (eGFR). Outcomes Death and progression to stages 4-5 CKD (eGFR <30 mL/min/1.73 m2 for >3 months) in Cox proportional hazards and competing-risk regression models. Results Median age at baseline was 34 (25th-75th percentile, 30-40) years, median CD4 cell count was 350 (25th-75th percentile, 208-520) cells/μL, and median eGFR was 100 (25th-75th percentile, 87-112) mL/min/1.73 m2. Patients were followed up for a median of 5.3 (25th-75th percentile, 2.0-8.9) years, during which 1,820 died and 56 progressed to stages 4-5 CKD. A U-shaped relationship between baseline eGFR and mortality was observed. After adjustment for potential confounders, eGFRs <45 and >105 mL/min/1.73 m2 remained associated significantly with increased risk of death. Baseline eGFR <90 mL/min/1.73 m2 was associated with increased risk of kidney disease progression, with the highest incidence rates of stages 4-5 CKD (>3 events/100 person-years) observed in black patients with eGFR of 30-59 mL/min/1.73 m2 and those of white/other ethnicity with eGFR of 30-44 mL/min/1.73 m2. Limitations The relatively small numbers of patients with decreased eGFR at baseline and low rates of progression to stages 4-5 CKD and lack of data for diabetes, hypertension, and proteinuria. Conclusions Although stages 4-5 CKD were uncommon in this cohort, baseline eGFR allowed the identification of patients at increased risk of death and at greatest risk of kidney disease progression. PMID:22521282

  3. Decline of kidney function during the pre-dialysis period in chronic kidney disease patients: a systematic review and meta-analysis.

    PubMed

    Janmaat, Cynthia J; van Diepen, Merel; van Hagen, Cheyenne Ce; Rotmans, Joris I; Dekker, Friedo W; Dekkers, Olaf M

    2018-01-01

    Substantial heterogeneity exists in reported kidney function decline in pre-dialysis chronic kidney disease (CKD). By design, kidney function decline can be studied in CKD 3-5 cohorts or dialysis-based studies. In the latter, patients are selected based on the fact that they initiated dialysis, possibly leading to an overestimation of the true underlying kidney function decline in the pre-dialysis period. We performed a systematic review and meta-analysis to compare the kidney function decline during pre-dialysis in CKD stage 3-5 patients, in these two different study types. We searched PubMed, EMBASE, Web of Science and Cochrane to identify eligible studies reporting an estimated glomerular filtration rate (eGFR) decline (mL/min/1.73 m 2 ) in adult pre-dialysis CKD patients. Random-effects meta-analysis was performed to obtain weighted mean annual eGFR decline. We included 60 studies (43 CKD 3-5 cohorts and 17 dialysis-based studies). The meta-analysis yielded a weighted annual mean (95% CI) eGFR decline during pre-dialysis of 2.4 (95% CI: 2.2, 2.6) mL/min/1.73 m 2 in CKD 3-5 cohorts compared to 8.5 (95% CI: 6.8, 10.1) in dialysis-based studies (difference 6.0 [95% CI: 4.8, 7.2]). To conclude, dialysis-based studies report faster mean annual eGFR decline during pre-dialysis than CKD 3-5 cohorts. Thus, eGFR decline data from CKD 3-5 cohorts should be used to guide clinical decision making in CKD patients and for power calculations in randomized controlled trials with CKD progression during pre-dialysis as the outcome.

  4. Model systems for the study of kidney development: use of the pronephros in the analysis of organ induction and patterning.

    PubMed

    Vize, P D; Seufert, D W; Carroll, T J; Wallingford, J B

    1997-08-15

    Most vertebrate organs, once formed, continue to perform the function for which they were generated until the death of the organism. The kidney is a notable exception to this rule. Vertebrates, even those that do not undergo metamorphosis, utilize a progression of more complex kidneys as they grow and develop. This is presumably due to the changing conditions to which the organism must respond to retain what Homer Smith referred to as our physiological freedom. To quote, "Recognizing that we have the kind of blood we have because we have the kind of kidneys we have, we must acknowledge that our kidneys constitute the major foundation of our physiological freedom. Only because they work the way they do has it become possible for us to have bones, muscles, glands, and brains. Superficially, it might be said that the function of the kidneys is to make urine; but in a more considered view one can say that the kidneys make the stuff of philosophy itself" ("From Fish to Philosopher," Little, Brown and Co., Boston, 1953). Different kidneys are used to make the stuff of philosophy at different stages of development depending on the age and needs of the organism, rather than the usual approach of simply making embryonic organs larger as the animal grows. Although evolution has provided the higher vertebrates with complex adult kidneys, they continue to utilize simple kidneys in embryogenesis. In lower vertebrates with simple adult kidneys, even more simple versions are used during early developmental stages. In this review the anatomy, development, and gene expression patterns of the embryonic kidney, the pronephros, will be described and compared to the more complex kidney forms. Despite some differences in anatomy, similar developmental pathways seem to be responsible for the induction and the response to induction in both evanescent and permanent kidney forms. Gene expression patterns can, therefore, be added to the morphological and functional data indicating that all

  5. Fibroblast growth factor receptor signaling in kidney and lower urinary tract development

    PubMed Central

    Walker, Kenneth A; Sims-Lucas, Sunder; Bates, Carlton M.

    2015-01-01

    Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans. PMID:26293980

  6. War on Carcinogens: industry disputes human relevance of chemicals causing cancer in laboratory animals based on unproven hypotheses, using kidney tumors as an example.

    PubMed

    Melnick, Ronald L; Ward, Jerrold M; Huff, James

    2013-01-01

    Evidence from studies in animals is essential for identifying chemicals likely to cause or contribute to many diseases in humans, including cancers. Yet, to avoid or delay the implementation of protective public health standards, the chemical industry typically denies cancer causation by agents they produce. The spurious arguments put forward to discount human relevance are often based on inadequately tested hypotheses or modes of action that fail to meet Bradford Hill criteria for causation. We term the industry attacks on the relevance of animal cancer findings as the "War on Carcinogens." Unfortunately, this tactic has been effective in preventing timely and appropriate health protective actions on many economically important yet carcinogenic chemicals, including: arsenic, asbestos, benzene, 1,3-butadiene, formaldehyde, methylene chloride, phthalates, tobacco usage, trichloroethylene [TCE], and others. Recent examples of the "War on Carcinogens" are chemicals causing kidney cancer in animals. Industry consultants argue that kidney tumor findings in rats with exacerbated chronic progressive nephropathy (CPN) are not relevant to humans exposed to these chemicals. We dispute and dismiss this unsubstantiated claim with data and facts, and divulge unprofessional actions from a leading toxicology journal.

  7. Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

    PubMed

    Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

    2015-07-01

    Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

  8. Reciprocal Risk of Acute Kidney Injury and Acute Respiratory Distress Syndrome in Critically Ill Burn Patients.

    PubMed

    Clemens, Michael S; Stewart, Ian J; Sosnov, Jonathan A; Howard, Jeffrey T; Belenkiy, Slava M; Sine, Christy R; Henderson, Jonathan L; Buel, Allison R; Batchinsky, Andriy I; Cancio, Leopoldo C; Chung, Kevin K

    2016-10-01

    To evaluate the association between acute respiratory distress syndrome and acute kidney injury with respect to their contributions to mortality in critically ill patients. Retrospective analysis of consecutive adult burn patients requiring mechanical ventilation. A 16-bed burn ICU at tertiary military teaching hospital. Adult patients more than 18 years old requiring mechanical ventilation during their initial admission to our burn ICU from January 1, 2003, to December 31, 2011. None. A total 830 patients were included, of whom 48.2% had acute kidney injury (n = 400). These patients had a 73% increased risk of developing acute respiratory distress syndrome after controlling for age, gender, total body surface area burned, and inhalation injury (hazard ratio, 1.73; 95% CI, 1.18-2.54; p = 0.005). In a reciprocal multivariate analysis, acute respiratory distress syndrome (n = 299; 36%) demonstrated a strong trend toward developing acute kidney injury (hazard ratio, 1.39; 95% CI, 0.99-1.95; p = 0.05). There was a 24% overall in-hospital mortality (n = 198). After adjusting for the aforementioned confounders, both acute kidney injury (hazard ratio, 3.73; 95% CI, 2.39-5.82; p < 0.001) and acute respiratory distress syndrome (hazard ratio, 2.16; 95% CI, 1.58-2.94; p < 0.001) significantly contributed to mortality. Age, total body surface area burned, and inhalation injury were also significantly associated with increased mortality. Acute kidney injury increases the risk of acute respiratory distress syndrome in mechanically ventilated burn patients, whereas acute respiratory distress syndrome similarly demonstrates a strong trend toward the development of acute kidney injury. Acute kidney injury and acute respiratory distress syndrome are both independent risks for subsequent death. Future research should look at this interplay for possible early interventions.

  9. Successful Posttransplant Treatment of Hepatitis C With Ledipasvir-Sofosbuvir in HIV+ Kidney Transplant Recipients.

    PubMed

    Sawinski, Deirdre; Lee, Dong H; Doyle, Alden M; Blumberg, Emily A

    2017-05-01

    Ledipasvir-sofosbuvir is effective at eradicating hepatitis C virus (HCV) infection in the general population and in HCV-monoinfected kidney transplant recipients, but there are no data to guide its use in human immunodeficiency virus/HCV coinfected kidney transplant patients. We treated 6 human immunodeficiency virus/HCV coinfected kidney transplant recipients with ledipasvir-sofosbuvir at our 2 centers. All were infected with genotype 1 and 66% had received kidneys from HCV+ donors. All patients cleared the virus while on therapy and 100% have achieved a sustained virologic response at 12 weeks after completion of ledipasvir-sofosbuvir. Tacrolimus dosing required adjustment during and after ledipasvir-sofosbuvir therapy but antiretroviral regimens did not. Ledipasvir-sofosbuvir was well tolerated. Although all patients in our series were treated posttransplant, the ideal timing of HCV therapy in this population is unknown, and the impact of HCV clearance on posttransplant outcomes is yet to be determined.

  10. An interactive, bilingual, culturally targeted website about living kidney donation and transplantation for hispanics: development and formative evaluation.

    PubMed

    Gordon, Elisa J; Feinglass, Joe; Carney, Paula; Ramirez, Daney; Olivero, Maria; O'Connor, Kate; MacLean, Jessica; Brucker, James; Caicedo, Juan Carlos

    2015-04-20

    As the kidney shortage continues to grow, patients on the waitlist are increasingly turning to live kidney donors for transplantation. Despite having a disproportionately higher prevalence of end-stage kidney disease (ESKD), fewer waitlisted Hispanic patients received living donor kidney transplants (LDKTs) than non-Hispanic whites in 2014. Although lack of knowledge has been identified as a barrier to living kidney donation (LKD) among Hispanics, little is known about information needs, and few bilingual educational resources provide transplant-related information addressing Hispanics' specific concerns. This paper describes the process of developing a bilingual website targeted to the Hispanic community. The website was designed to increase knowledge about LKD among Hispanic patients with ESKD, their families, and the public, and was inspired by educational sessions targeted to Hispanic transplant patients provided by Northwestern University's Hispanic Kidney Transplant Program. Northwestern faculty partnered with the National Kidney Foundation of Illinois for expertise in ESKD and Hispanic community partners across the Chicago area. We established a Community Advisory Board (CAB) of 10 Chicago-area Hispanic community leaders to provide insight into cultural concerns and community and patients' needs. Website content development was informed by 9 focus groups with 76 adult Hispanic kidney transplant recipients, living kidney donors, dialysis patients, and the general Hispanic public. The website development effort was guided by community input on images, telenovela scripts, and messages. After initial development, formal usability testing was conducted with 18 adult Hispanic kidney transplant recipients, dialysis patients, and living kidney donors to identify ways to improve navigability, design, content, comprehension, and cultural sensitivity. Usability testing revealed consistently high ratings as "easy to navigate", "informative", and "culturally appropriate

  11. Grouper tshβ Promoter-Driven Transgenic Zebrafish Marks Proximal Kidney Tubule Development

    PubMed Central

    Wang, Yang; Sun, Zhi-Hui; Zhou, Li; Li, Zhi; Gui, Jian-Fang

    2014-01-01

    Kidney tubule plays a critical role in recovering or secreting solutes, but the detailed morphogenesis remains unclear. Our previous studies have found that grouper tshβ (gtshβ) is also expressed in kidney, however, the distribution significance is still unknown. To understand the gtshβ role and kidney tubule morphogenesis, here, we have generated a transgenic zebrafish line Tg(gtshβ:GFP) with green fluorescent protein driven by the gtshβ promoter. Similar to the endogenous tshβ in zebrafish or in grouper, the gtshβ promoter-driven GFP is expressed in pituitary and kidney, and the developing details of proximal kidney tubule are marked in the transgenic zebrafish line. The gfp initially transcribes at 16 hours post fertilization (hpf) above the dorsal mesentery, and partially co-localizes with pronephric tubular markers slc20a1a and cdh17. Significantly, the GFP specifically localizes in proximal pronephric segments during embryogenesis and resides at kidney duct epithelium in adult fish. To test whether the gtshβ promoter-driven GFP may serve as a readout signal of the tubular development, we have treated the embryos with retinoic acid signaing (RA) reagents, in which exogenous RA addition results in a distal extension of the proximal segments, while RA inhibition induces a weakness and shortness of the proximal segments. Therefore, this transgenic line provides a useful tool for genetic or chemical analysis of kidney tubule. PMID:24905828

  12. Acute kidney failure

    MedlinePlus

    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. Endothelin Blockade in Diabetic Kidney Disease.

    PubMed

    Anguiano, Lidia; Riera, Marta; Pascual, Julio; Soler, María José

    2015-05-25

    Diabetic kidney disease (DKD) remains the most common cause of chronic kidney disease and multiple therapeutic agents, primarily targeted at the renin-angiotensin system, have been assessed. Their only partial effectiveness in slowing down progression to end-stage renal disease, points out an evident need for additional effective therapies. In the context of diabetes, endothelin-1 (ET-1) has been implicated in vasoconstriction, renal injury, mesangial proliferation, glomerulosclerosis, fibrosis and inflammation, largely through activation of its endothelin A (ETA) receptor. Therefore, endothelin receptor antagonists have been proposed as potential drug targets. In experimental models of DKD, endothelin receptor antagonists have been described to improve renal injury and fibrosis, whereas clinical trials in DKD patients have shown an antiproteinuric effect. Currently, its renoprotective effect in a long-time clinical trial is being tested. This review focuses on the localization of endothelin receptors (ETA and ETB) within the kidney, as well as the ET-1 functions through them. In addition, we summarize the therapeutic benefit of endothelin receptor antagonists in experimental and human studies and the adverse effects that have been described.

  14. Kidney cell electrophoresis in space flight: Rationale, methods, results and flow cytometry applications

    NASA Technical Reports Server (NTRS)

    Todd, P.; Morrison, Dennis R.; Barlow, Grant H.; Lewis, Marian L.; Lanham, J. W.; Cleveland, C.; Williams, K.; Kunze, M. E.; Goolsby, C. L.

    1988-01-01

    Cultures of human embryonic kidney cells consistently contain an electrophoretically separable subpopulation of cells that produce high levels of urokinase and have an electrophoretic mobility about 85 percent as high as that of the most mobile human embryonic kidney cells. This subpopulation is rich in large epithelioid cells that have relatively little internal structure. When resolution and throughput are adequate, free fluid electrophoresis can be used to isolate a broad band of low mobility cells which also produces high levels of plasminogen activators (PAs). In the course of performing this, it was discovered that all electrophoretic subpopulations of cultured human embryonic kidney cells produce some PAs and that separate subpopulations produce high quantities of different types of PA's. This information and the development of sensitive assays for this project have provided new insights into cell secretion mechanisms related to fibrinolysis. These advances would probably not have been made without the NASA program to explore fundamental questions of free fluid electrophoresis in space.

  15. Decision aids to increase living donor kidney transplantation

    PubMed Central

    Gander, Jennifer C.; Gordon, Elisa J.; Patzer, Rachel E.

    2017-01-01

    Purpose of review For the more than 636,000 adults with end-stage renal disease (ESRD) in the U.S., kidney transplantation is the preferred treatment compared to dialysis. Living donor kidney transplantation (LDKT) comprised 31% of kidney transplantations in 2015, an 8% decrease since 2004. We aimed to summarize the current literature on decision aids that could be used to improve LDKT rates. Recent findings Decision aids are evidence-based tools designed to help patients and their families make difficult treatment decisions. LDKT decision aids can help ESRD patients, patients’ family and friends, and healthcare providers engage in treatment decisions and thereby overcome multifactorial LDKT barriers. Summary We identified 12 LDKT decision aids designed to provide information about LDKT, and/or to help ESRD patients identify potential living donors, and/or to help healthcare providers make decisions about treatment for ESRD or living donation. Of these, 4 were shown to be effective in increasing LDKT, donor inquiries, LDKT knowledge, and willingness to discuss LDKT. Although each LDKT decision aid has limitations, adherence to decision aid development guidelines may improve decision aid utilization and access to LDKT. PMID:29034143

  16. Kidney lesions in baboons infected with Schistosoma mansoni.

    PubMed Central

    Houba, V; Sturrock, R F; Butterworth, A E

    1977-01-01

    Glomerular lesions in baboons (Papio anubis) infected with different dosage regimes of Schistosoma mansoni were studied by immunofluorescence and light microscopy on kidney sections and by countercurrent immunoelectrophoresis on kidney homogenates and tissue eluates. Mild lesions, characterized by focal and segmental deposits of immune complexes, developed in sixty-two out of 103 baboons, irrespective of the intensity and duration of the infection. Severe, diffuse lesions developed in six baboons after prolonged and heavy infections. Adult worm and soluble egg antigens, together with IgM, IgG and C3, were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in most of the severe lesions and in some of the mild lesions. In some animals, antigens were detected in acid homogenates and eluates of kidneys which showed no deposits of immunoglobulins or complement. These observations indicate that renal lesions in S. mansoni infections may be attributable to the deposition of immune complexes pre-formed in the circulation. However, the demonstration of antigens alone in some animals may suggest an alternative possibility, namely that antigens are deposited first with a subsequent binding of antibody and complement. PMID:414868

  17. Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

    PubMed Central

    Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

    2015-01-01

    Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

  18. Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

    PubMed

    Tomlinson, James A P; Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C; Khadayate, Sanjay; Mas, Valeria R; Nitsch, Dorothea D; Wang, Zhen; Norman, Jill T; Wilcox, Christopher S; Wheeler, David C; Leiper, James

    2015-12-01

    Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. Copyright © 2015 by the American Society of Nephrology.

  19. Autophagy and kidney inflammation.

    PubMed

    Kimura, Tomonori; Isaka, Yoshitaka; Yoshimori, Tamotsu

    2017-06-03

    Inflammation plays a pivotal role in pathophysiological processes of kidney diseases. Macroautophagy/autophagy plays multiple roles in inflammatory responses, and the regulation of inflammation by autophagy has great potential as a treatment for damaged kidneys. A growing body of evidence suggests autophagy protects kidney from versatile kidney inflammatory insults, including those that are acute, chronic, metabolic, and aging-related. It is noteworthy that, in kidney, mitophagy is active, and damaged lysosomes are removed by autophagy. In this mode, autophagy suppresses inflammation to protect the kidney. Systemic inflammation also affects the kidney via pro-inflammatory cytokines and infiltration of inflammatory cells, and autophagy also has a regulatory role in systemic inflammation. This review focuses on the roles of autophagy in kidney diseases and aging through inflammation, and discusses the potential usage of autophagy as an inflammatory modulator for the treatment of kidney diseases.

  20. Risk of kidney stones with surgical intervention in living kidney donors.

    PubMed

    Thomas, S M; Lam, N N; Welk, B K; Nguan, C; Huang, A; Nash, D M; Prasad, G V R; Knoll, G A; Koval, J J; Lentine, K L; Kim, S J; Lok, C E; Garg, A X

    2013-11-01

    A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.