For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
13
views
34
references
 Top references
cited by
5
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
1 collections
    0
    shares
      597
      similar
       All similar

      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before July 31, 2024

      About Blood Purification: 3.0 Impact Factor I 5.6 CiteScore I 0.83 Scimago Journal & Country Rank (SJR)

      • Record: found
      • Abstract: found
      • Article: found

      The Contribution of Podocytes to Chronic Allograft Nephropathy

      research-article

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: Progressive proteinuria and glomerulosclerosis characterize chronic allograft nephropathy. However, the causes are not fully elucidated. Podocytes function to prevent proteinuria; injury to this glomerular cell leads to glomerulosclerosis. The potential role of podocytes in the failing transplanted kidney is unknown. A rat model of kidney transplantation, characterized by proteinuria and glomerulosclerosis, was utilized to examine the potential role of podocytes. Methods: Archival tissue was examined from allografts (Dark Agouti kidneys transplanted into operationally tolerant Albino Surgery rats), isografts (Dark Agouti) and controls (Dark Agouti: age-matched or after unilateral nephrectomy). The number of podocytes (by WT-1 staining) as well as the podocyte proteins podocin, nephrin and synaptopodin (by immunostaining) were measured at days 0, 2, 6 and at 6 months after transplantation. Changes in these parameters were compared between groups and correlated with urinary protein excretion. Results: At 6 months, podocyte number was reduced in allografted kidneys, accompanied by a decrease in nephrin and synaptopodin, but not podocin staining. Remnant kidneys in the uninephrectomized rats also showed a decreased podocyte number but no change in podocyte protein staining. Podocyte loss in allografts was established on day 6, whereas a decrease in nephrin and synaptopodin was not evident until 6 months. In contrast, podocyte number and protein staining was decreased but not significantly so in remnant and isografted kidneys. Conclusion: A decrease in the slit diaphragm proteins, nephrin and synaptopodin, is a component of chronic allograft pathology.

          Related collections

          Most cited references34

          • Record: found
          • Abstract: found
          • Article: not found

          The natural history of chronic allograft nephropathy.

          Brian Nankivell, Richard J Borrows, Caroline L S Fung … (2003)
          With improved immunosuppression and early allograft survival, chronic allograft nephropathy has become the dominant cause of kidney-transplant failure. We evaluated the natural history of chronic allograft nephropathy in a prospective study of 120 recipients with type 1 diabetes, all but 1 of whom had received kidney-pancreas transplants. We obtained 961 kidney-transplant-biopsy specimens taken regularly from the time of transplantation to 10 years thereafter. Two distinctive phases of injury were evident as chronic allograft nephropathy evolved. An initial phase of early tubulointerstitial damage from ischemic injury (P<0.05), prior severe rejection (P<0.01), and subclinical rejection (P<0.01) predicted mild disease by one year, which was present in 94.2 percent of patients. Early subclinical rejection was common (affecting 45.7 percent of biopsy specimens at three months), and the risk was increased by the occurrence of a prior episode of severe rejection and reduced by tacrolimus and mycophenolate therapy (both P<0.05) and gradually abated after one year. Both subclinical rejection and chronic rejection were associated with increased tubulointerstitial damage (P<0.01). Beyond one year, a later phase of chronic allograft nephropathy was characterized by microvascular and glomerular injury. Chronic rejection (defined as persistent subclinical rejection for two years or longer) was uncommon (5.8 percent). Progressive high-grade arteriolar hyalinosis with luminal narrowing, increasing glomerulosclerosis, and additional tubulointerstitial damage was accompanied by the use of calcineurin inhibitors. Nephrotoxicity, implicated in late ongoing injury, was almost universal at 10 years, even in grafts with excellent early histologic findings. By 10 years, severe chronic allograft nephropathy was present in 58.4 percent of patients, with sclerosis in 37.3 percent of glomeruli. Tubulointerstitial and glomerular damage, once established, was irreversible, resulting in declining renal function and graft failure. Chronic allograft nephropathy represents cumulative and incremental damage to nephrons from time-dependent immunologic and nonimmunologic causes. Copyright 2003 Massachusetts Medical Society
          Article 0 comments Cited 300 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Podocyte biology and response to injury.

            Stuart Shankland, Peter Mundel (2002)
            Article 0 comments Cited 164 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Delayed graft function: risk factors and implications for renal allograft survival.

              A. Ojo, R Wolfe, P J Held … (1997)
              Delayed graft function (DGF) may be associated with diminished kidney allograft survival. We studied the risk factors that lead to nonimmediate function of a renal allograft and the consequences of DGF on short- and long-term renal transplant survival. Data from the U.S. Renal Data System were used to measure the relationships among cold ischemia time, delayed graft function, acute rejection, and graft survival in 37,216 primary cadaveric renal transplants (1985-1992). These relationships were investigated using the unconditional logistic and Cox multivariate regression methods. Cold ischemia time was strongly associated with DGF, with a 23% increase in the risk of DGF for every 6 hr of cold ischemia (P<0.001). Acute transplant rejection occurred more frequently in grafts with delayed function (37% vs. 20%; odds ratio=2.25, P=0.001). DGF was independently predictive of 5-year graft loss (relative risk=1.53, P<0.001). The presence of both early acute rejection and DGF portended a dismal 5-year graft survival rate of 35%. Zero-HLA mismatch conferred a 10-15% improvement in 1- and 5-year graft survival regardless of early functional status of the allograft. However, the 5-year graft survival rate in HLA-mismatched kidneys without DGF was significantly higher than that of zero-mismatched kidneys with DGF (63% vs. 51%; P<0.001). DGF independently portends a significant reduction in short- and long-term graft survival. Delayed function and early rejection episodes exerted an additive adverse effect on allograft survival. The deleterious impact of delayed function is comparatively more severe than that of poor HLA matching.
              Article 0 comments Cited 146 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (publisher-id): NEE
                Journal ID (nlm-ta): Nephron Exp Nephrol
                Journal ID (doi): 10.1159/issn.1660-2129
                Title: Cardiorenal Medicine
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2129
                Publication date Subscription-year: 2009
                Publication date (Print): January 2009
                Publication date (Electronic): 02 December 2008
                Volume: 111
                Issue: 1
                Pages: e1-e10
                Affiliations
                aNephrology, University of Washington, Seattle, Wash., USA; bMonash University, Department of Medicine, Central and Eastern Clinical School, Alfred Hospital, Prahran, Vic., Australia
                Article
                Publisher ID: 178762 Other ID: Nephron Exp Nephrol 2009;111:e1
                DOI: 10.1159/000178762
                PubMed ID: 19052472
                SO-VID: dd557354-4d43-464a-94aa-a80e5fe3231c
                Copyright © © 2009 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 16 April 2008
                Date accepted : 24 September 2008
                Page count
                Figures: 4, References: 47, Pages: 1
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Podocyte,Kidney transplant,Chronic allograft nephropathy
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Podocyte, Kidney transplant, Chronic allograft nephropathy

                Comments

                Comment on this article

                scite_

                Similar content597

                See all similar

                Cited by5

                See all cited by

                Most referenced authors479

                See all reference authors