Differential Gender Differences in Ischemic and Nephrotoxic Acute Renal Failure

Abstract

Background/Aims:Recent work has shown that female animals are more resistant to ischemic acute renal failure (ARF) than male animals. The mechanism underlying the gender difference is unclear. Moreover, whether the gender difference holds true for ARF induced by other insults is unknown. This study sought to determine the gender differences in ischemic and nephrotoxic ARF. Methods: Gender differences were tested in two experimental models of ARF. For ischemic ARF, bilateral clamping of renal pedicles was conducted in C57BL/6 and129/Sv mice followed by reperfusion. For nephrotoxic ARF, cisplatin was administered to the animals. Renal function, tissue damage, animal survival, and renal cell apoptosis were examined. Results: Ischemic ARF was significantly ameliorated in female mice, as shown by lower serum creatinine and blood urea nitrogen (BUN). Female mice also showed better renal histology, less apoptosis and caspase activation, and a much better survival rate than male mice following ischemic insult. On the contrary, female mice were more sensitive to cisplatin-induced ARF. In these animals, BUN increased at day 1 following cisplatin injection, while in males BUN increases were not shown until day 3. Higher levels of serum creatinine were also recorded in female mice. Renal histology showed severer necrotic tubular damage in females, although apoptosis and caspase activation appeared similar in both genders. Consistently, male mice survived better than females in the nephrotoxic model. Conclusion: While female mice were resistant to ischemic ARF, they appeared more sensitive to cisplatin-induced ARF. Investigation of the gender differences at the cellular and molecular levels might provide a new area for mechanistic study of ARF.

Journal

Journal ID (publisher-id): AJN

Journal ID (nlm-ta): Am J Nephrol

Journal ID (doi): 10.1159/issn.0250-8095

Title: American Journal of Nephrology

Publisher: S. Karger AG

ISSN (Print): 0250-8095

ISSN (Electronic): 1421-9670

Publication date Subscription-year: 2005

Publication date (Print): October 2005

Publication date (Electronic): 12 October 2005

Volume: 25

Issue: 5

Pages: 491-499

Affiliations

Departments of ^aCellular Biology and Anatomy, and ^bPhysiology, Medical College of Georgia, and ^cDepartment of Veterans Affairs Medical Center, Medical Research Service, Augusta, Ga., USA

Article

Publisher ID: 88171 Other ID: Am J Nephrol 2005;25:491–499

DOI: 10.1159/000088171

PubMed ID: 16155358

Copyright statement: © 2005 S. Karger AG, Basel

License:

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, References: 20, Pages: 9

Product

Self URI (application/pdf): https://www.karger.com/Article/Pdf/88171

Self URI (text/html): https://www.karger.com/Article/FullText/88171

Self URI (journal page): https://www.karger.com/SubjectArea/Nephrology

Categories

Subject: Original Report: Laboratory Investigation