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      Endostatin Is an Independent Risk Factor of Graft Loss after Kidney Transplant

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          Abstract

          Background: Endostatin is a 20-kDa C-terminal fragment of collagen XVIII, known for its ability to inhibit the proliferation of capillary endothelial cells. Previous studies suggested that circulating endostatin independently predicts incident chronic kidney disease. However, the impact of endostatin on graft loss level in kidney transplant recipients (KTRs) remains unknown. Methods: We conducted a prospective observational cohort study in 574 maintenance KTRs. Patients were followed for kidney graft loss and all-cause mortality during a median follow-up of 48 months. Serum-, and urine-samples and clinical data were collected at baseline. Serum Endostatin concentration was analyzed by an ELISA. Results: Among 574 patients, 37 patients had graft loss and 62 patients died. For graft loss, the optimal cut-off value based on receiver operating characteristics analysis (area under the curve 0.79, 95% CI 0.71–0.86, p < 0.001) of endostatin was 147.3 pmol/L. Kaplan-Meier curves revealed that higher serum endostatin concentrations positively correlated with graft loss ( p < 0.001). Multivariable Cox regression analyses showed that baseline endostatin concentrations were significantly associated with graft loss after adjusting for graft loss risk factors (adjusted hazard ratio [HR] 8.34; 95% CI 2.19–31.72; p = 0.002). The adjusted HRs for classical graft loss risk factors such as baseline estimated glomerular filtration rate and urinary protein excretion were lower (1.91 and 5.44, respectively). In contrast to graft loss, baseline endostatin concentrations were not associated with all-cause mortality. Conclusion: Increased serum endostatin at baseline is independently associated with the risk of graft loss in KTRs.

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          Author and article information

          Journal
          AJN
          Am J Nephrol
          10.1159/issn.0250-8095
          American Journal of Nephrology
          S. Karger AG
          0250-8095
          1421-9670
          2020
          May 2020
          22 April 2020
          : 51
          : 5
          : 373-380
          Affiliations
          aDepartment of Nephrology, Charité, Universitätsmedizin Berlin, Berlin, Germany
          bFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany
          cInstitute of Nutritional Science, University of Potsdam, Potsdam, Germany
          dDepartment of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
          eFaculty of Veterinary Medicine, Benha University, Toukh, Egypt
          fDepartment of Nephrology and Endocrinology/Diabetology, Klinikum Ernst von Bergmann, Potsdam, Germany
          gKey Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China
          hInstitute of Medical Diagnostics, IMD Berlin, Berlin, Germany
          Author notes
          *Prof. Berthold Hocher, Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, DE–68167 Mannheim (Germany), E-Mail berthold.hocher@medma.uni-heidelberg.de
          Article
          507824 Am J Nephrol 2020;51:373–380
          10.1159/000507824
          32320989
          © 2020 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
          Figures: 3, Tables: 3, Pages: 8
          Categories
          Transplantation: Research Article

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