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      Fenofibrate Increases Creatininemia by Increasing Metabolic Production of Creatinine

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          Abstract

          Fenofibrate is a potent hypolipemic agent, widely used in patients with renal insufficiency in whom dyslipidemia is frequent. A moderate reversible increase in creatinine plasma levels is an established side effect of fenofibrate therapy, which mechanism remains unknown. We have previously reported that in 13 patients with normal renal function or moderate renal insufficiency, two weeks of fenofibrate therapy increased creatininemia without any changes in renal plasma flow and glomerular filtration rate [<citeref rid="ref001">1</citeref>]. In 13 additional patients, muscular enzymes (AST, GPT, CPK, LDH) and myoglobin were measured before and after 2 weeks on fenofibrate, and the values of creatininemia obtained by the Jaffé technique and HPLC were compared. CPK and AST activity and plasma myoglobin increased in 2 patients with fenofibrate, but muscular enzymes remained unchanged in the population as a whole, and were not correlated to the changes in creatininemia. The changes in creatininemia induced by fenofibrate measured by the Jaffé technique were strongly correlated to those measured by HPLC (r<sup>2</sup> = 0.675, p = 0.0006). Analysis of the pooled data of the two arms of the study showed in 26 patients that two weeks of fenofibrate therapy efficiently reduced total cholesterol and triglycerides plasma levels, and raised creatininemia from 139 ± 8 to 160 ± 10 µmol/l (p < 0.0001), but confirmed that creatininuria also increased to the extent that creatinine clearance remained unchanged (68 ± 6 vs. 67 ± 6 ml/min, n.s.). It is concluded that the increase in creatininemia induced by fenofibrate in renal patients does not reflect an impairment of renal function, nor an alteration of tubular creatinine secretion, and is not falsely increased by a dosage interference. Fenofibrate-induced increase of daily creatinine production is neither readily explained by accelerated muscular cell lysis. It is proposed that fenofibrate increases the metabolic production rate of creatinine.

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          Peroxisome Proliferator-activated Receptor α Activators Improve Insulin Sensitivity and Reduce Adiposity

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            New molecular aspects of regulation of mitochondrial activity by fenofibrate and fasting

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              Author and article information

              Journal
              NEF
              Nephron
              10.1159/issn.1660-8151
              Nephron
              S. Karger AG
              1660-8151
              2235-3186
              2002
              September 2002
              26 September 2002
              : 92
              : 3
              : 536-541
              Affiliations
              Departments of aNephrology and bBiochemistry, CHU Amiens, France
              Article
              64083 Nephron 2002;92:536–541
              10.1159/000064083
              12372935
              © 2002 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: 1, Tables: 2, References: 23, Pages: 6
              Product
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/64083
              Categories
              Original Paper

              Cardiovascular Medicine, Nephrology

              Fibrates, Glomerular filtration rate, Creatininemia

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