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      Xanthopterin-lnduced Renal Dysfunction: A Reversible Model of Crystal Nephropathy

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          Abstract

          Xanthopterin (XPT), an unconjugated pteridine compound, affects cell growth and differentiation. When injected into rats, XPT has caused changes that have been interpreted as renal growth and hypertrophy. In the present study, we investigated the effect of intraperitoneal administration of XPT on the renal function in the rat. XPT administration was associated with polyuria and a reversible form of nonoliguric acute renal failure (ARF), with renal function declining maximally after 2 days and returning to normal after 7 days. The polyuria was due, at least in part, to a concentrating defect that was vasopressin resistant. The ability of XPT to induce ARF was modulated by dietary salt intake, being enhanced by a low-sodium diet and prevented by a high sodium intake. Histological examination of the kidneys showed intratubular crystal deposition and acute tubule necrosis, suggesting that XPT induces crystal nephropathy. There was an increase in wet and dry weights of the kidney and an increased DNA/protein ratio, compatible with a hyperplastic response. Because the severity of other crystal nephropathies may be modulated by urine flow rate and pH, we studied the ability of water diuresis or alkaline diuresis to protect against XPT-induced ARF. Both water diuresis and HCO<sub>3</sub> loading blunted the ability of XPT to decrease renal function. The change in renal function induced by XPT in the various groups was paralleled by corresponding changes in the levels of XPT-like substances in the kidney and by the amount of crystal deposition. Thus, XPT injection induces crystal nephropathy, the severity of which can be modulated by dietary salt intake, urine pH, and urine flow rate.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1995
          1995
          17 December 2008
          : 69
          : 1
          : 71-78
          Affiliations
          Sections of Nephrology of the Cook County Hospital, of the Hektoen Institute for Medical Research, WSVAMC, and of the University of Illinois, Chicago, Ill., USA
          Article
          188363 Nephron 1995;69:71–78
          10.1159/000188363
          7891801
          © 1995 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: 8
          Categories
          Original Paper

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