+1 Recommend
1 collections
      Call for Papers in Kidney and Blood Pressure ResearchKidney Function and Omics Science

      Submission Deadline: December 20, 2023

      Submit now

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

      Kidney Regeneration in Mammals

      , , *
      Cardiorenal Medicine
      S. Karger AG
      Regeneration, Nephron, Mammals

      Read this article at

          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.


          Background: Several organs such as the skin and liver have a great capacity for regeneration. However, many approaches only delay the progression of end-stage kidney disease and do not achieve efficient long-term stabilization, let alone regeneration. Summary: In mammals, the kidney has an innate but limited capacity for regeneration which can only modify the nephron structure and function but not increase the nephron number. Several clinical and animal studies have indicated that functional improvements and/or structural regression can occur in chronic kidney disease. Cell reconstitution, matrix remodeling, and tissue reorganization are major mechanisms for kidney regeneration. Current approaches achieve only partial kidney regeneration, but this does not occur in all animals and is not sustained in the long term. Multipronged and early interventions are future choices for the induction of kidney regeneration. Key Messages: Kidney regeneration in mammals is feasible but limited and may be enhanced by multitargeting key mechanisms.

          Related collections

          Most cited references23

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

          Reversal of lesions of diabetic nephropathy after pancreas transplantation.

          In patients with type I diabetes mellitus who do not have uremia and have not received a kidney transplant, pancreas transplantation does not ameliorate established lesions of diabetic nephropathy within five years after transplantation, but the effects of longer periods of normoglycemia are unknown. We studied kidney function and performed renal biopsies before pancreas transplantation and 5 and 10 years thereafter in eight patients with type I diabetes but without uremia who had mild to advanced lesions of diabetic nephropathy at the time of transplantation. The biopsy samples were analyzed morphometrically. All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P=0.07 for the comparison of values at base line and at 5 years; P=0.11 for the comparison between base line and 10 years). The mean (+/-SD) creatinine clearance rate declined from 108+/-20 ml per minute per 1.73 m2 of body-surface area at base line to 74+/-16 ml per minute per 1.73 m2 at 5 years (P<0.001) and 74+/-14 ml per minute per 1.73 m2 at 10 years (P<0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570+/-64 and 928+/-173 nm, respectively) and at base line (594+/-81 and 911+/-133 nm, respectively) but had decreased by 10 years (to 404+/-38 and 690+/-111 nm, respectively; P<0.001 and P=0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33+/-0.07) to 5 years (0.39+/-0.10, P=0.02) but had decreased at 10 years (0.27+/-0.02, P=0.05 for the comparison with the baseline value and P=0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix. Pancreas transplantation can reverse the lesions of diabetic nephropathy, but reversal requires more than five years of normoglycemia.
            • Record: found
            • Abstract: found
            • Article: not found

            Reversibility of structural and functional damage in a model of advanced diabetic nephropathy.

            The reversibility of diabetic nephropathy remains controversial. Here, we tested whether replacing leptin could reverse the advanced diabetic nephropathy modeled by the leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition of the renin-angiotensin-aldosterone system (RAAS), resulted in near-complete reversal of both structural (mesangial matrix expansion, mesangiolysis, basement membrane thickening, podocyte loss) and functional (proteinuria, accumulation of reactive oxygen species) measures of advanced diabetic nephropathy. Immunohistochemical labeling with the podocyte markers Wilms tumor 1 and p57 identified parietal epithelial cells as a possible source of regenerating podocytes. Thus, the leptin-deficient BTBR ob/ob mouse provides a model of advanced but reversible diabetic nephropathy for further study. These results also suggest that restoration of lost podocytes is possible but is not induced by RAAS inhibition, possibly explaining the limited efficacy of RAAS inhibitors in promoting repair of diabetic nephropathy.
              • Record: found
              • Abstract: found
              • Article: not found
              Is Open Access

              Cells of renin lineage are progenitors of podocytes and parietal epithelial cells in experimental glomerular disease.

              Glomerular injury leads to podocyte loss, a process directly underlying progressive glomerular scarring and decline of kidney function. The inherent repair process is limited by the inability of podocytes to regenerate. Cells of renin lineage residing alongside glomerular capillaries are reported to have progenitor capacity. We investigated whether cells of renin lineage can repopulate the glomerulus after podocyte injury and serve as glomerular epithelial cell progenitors. Kidney cells expressing renin were genetically fate-mapped in adult Ren1cCreER×Rs-tdTomato-R, Ren1cCre×Rs-ZsGreen-R, and Ren1dCre×Z/EG reporter mice. Podocyte depletion was induced in all three cell-specific reporter mice by cytotoxic anti-podocyte antibodies. After a decrease in podocyte number, a significant increase in the number of labeled cells of renin lineage was observed in glomeruli in a focal distribution along Bowman's capsule, within the glomerular tuft, or in both locations. A subset of cells lining Bowman's capsule activated expression of the glomerular parietal epithelial cell markers paired box protein PAX2 and claudin-1. A subset of labeled cells within the glomerular tuft expressed the podocyte markers Wilms tumor protein 1, nephrin, podocin, and synaptopodin. Neither renin mRNA nor renin protein was detected de novo in diseased glomeruli. These findings provide initial evidence that cells of renin lineage may enhance glomerular regeneration by serving as progenitors for glomerular epithelial cells in glomerular disease characterized by podocyte depletion. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                May 2014
                19 May 2014
                : 126
                : 2
                : 50-53
                Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn., USA
                Author notes
                *Agnes B. Fogo, MD, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, MCN C3310, 1161 21st Ave S., Nashville, TN 37232 (USA), E-Mail agnes.fogo@vanderbilt.edu
                360661 Nephron Exp Nephrol 2014;126:50-53
                © 2014 S. Karger AG, Basel

                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.

                Page count
                Pages: 4
                Further Section

                Cardiovascular Medicine,Nephrology
                Cardiovascular Medicine, Nephrology
                Mammals, Nephron, Regeneration


                Comment on this article