Uremic Toxins Adsorbed by AST-120 Promote Tubular Hypertrophy and Interstitial Fibrosis in Nephrectomized Rats

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Abstract

Background: Uremic toxins have been shown to promote glomerular hypertrophy. The present study was performed to elucidate the relation between uremic toxins and tubulointerstitial changes. Methods: Sixty male Sprague-Dawley rats underwent 2/3 nephrectomy (Nx; n = 30) and 4/5 Nx (n = 30). Experiments were initiated 2 weeks after surgery, and were performed over an 8-week period. Half of each group (Nx-A) was administered 1 g/day of an oral carbonaceous adsorbent, AST-120, with pair-feeding, and the other half (Nx-C) served as controls. All rats were sacrificed at week 8 after a clearance study. Results: The shortest diameter of proximal tubules (PTD) and interstitial fibrosis area (IFA) at week 8 in 2/3 Nx-A rats was significantly decreased compared to that in 2/3 Nx-C rats (similar body weights, systolic blood pressures, glomerular filtration rates, and urinary protein excretion levels). The values of PTD and IFA, glomerular filtration rate and urinary protein excretion level at week 8 in 4/5 Nx-A rats were significantly decreased compared to those in 4/5 Nx-C rats (similar body weights and systolic blood pressures). Conclusion: Administration of AST-120 minimized the appearance of proximal tubular hypertrophy and interstitial fibrosis, and subsequently prevented the occurrence of proteinuria and decreased renal function. The present study indicates that uremic toxins adsorbed by AST-120 promote tubular hypertrophy and interstitial fibrosis in nephrectomized rats.

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Author and article information

Journal

Journal ID (publisher-id): KBR

Journal ID (nlm-ta): Kidney Blood Press Res

Journal ID (doi): 10.1159/issn.1420-4096

Title: Kidney and Blood Pressure Research

Publisher: S. Karger AG

ISSN (Print): 1420-4096

ISSN (Electronic): 1423-0143

Publication date Subscription-year: 2005

Publication date (Print): December 2004

Publication date (Electronic): 11 January 2005

Volume: 28

Issue: 1

Pages: 8-13

Affiliations

^aSecond Department of Internal Medicine, Nihon University School of Medicine, and ^bNihon University Graduate School, Tokyo, Japan

Article

Publisher ID: 80935 Other ID: Kidney Blood Press Res 2005;28:8–13

DOI: 10.1159/000080935

PubMed ID: 15377820

SO-VID: a7433d2f-8e46-45e1-bffa-bcb688da8cdf

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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 : 30 October 2003

Page count

Figures: 2, Tables: 2, References: 21, Pages: 6

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