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      Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis

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          Abstract

          Background/Aims: Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury. Methods: To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays. Results: Deemed to be mainly exosomes based on their size distribution, the EVs in urine contained FSP1, and a portion of the FSP1-positive vesicles was also positive for podocalyxin. FSP1 levels in urinary EVs were (1) positively correlated with rates of biopsy-proven cellular crescent formation ( r = 0.562, p < 0.001) and total crescent formation ( r = 0.448, p = 0.005) among total glomeruli; (2) significantly higher in patients with cellular crescents affecting 20% or more of their glomeruli than in those with fewer affected glomeruli ( p = 0.003); and (3) significantly decreased after glucocorticoid and immunosuppressant therapy ( p < 0.05). A positive correlation between FSP1 levels in urinary EVs and urinary soluble CD163 levels was confirmed ( r = 0.367, p < 0.05). Conclusion: These data suggest that a portion of urinary FSP1 is secreted as EVs originating from podocytes, and that FSP1 levels reflect active and ongoing glomerular injury and disease activity, such as cellular crescent formation.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          2019
          March 2019
          12 December 2018
          : 141
          : 3
          : 177-187
          Affiliations
          aDepartment of Nephrology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
          bDS Pharma Biomedical Co., Ltd., Suita, Japan
          cDepartment of Molecular Pathology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
          dIwamuro Health Promotion Center, Niigata, Japan
          Author notes
          *Dr. Naoki Takahashi, Department of Nephrology, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193 (Japan), E-Mail ntakahas@u-fukui.ac.jp,
          Article
          495217 Nephron 2019;141:177–187
          10.1159/000495217
          30540988
          © 2018 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: 6, Tables: 1, Pages: 11
          Categories
          Clinical Practice: Original Paper

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