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      Effect of Demeclocycline on Renal Function and Urinary Prostaglandin E 2 and Kallikrein in Hyponatremic Cirrhotics

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          Abstract

          8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E<sub>2</sub> and kallikrein. In 7 patients DMC induced an increase of free water clearance (from – 0.36 ± 0.06 to 0.13 ± 0.06 ml/min) and serum sodium concentration (from 125.4 ± 0.09 to 131.1 ± 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 ± 6.2 to 31,2 ± 4.7 ml/min) and renal plasma flow (from468 ± 98 to 195 ± 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of β<sub>2</sub>-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E<sub>2</sub> (from 0.82 ± 0.27 to 6.16 ± 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 ± 4.4 to 4.2 ± 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 µg/ml in all patients who responded to DMC, greater than 8 µg/ml in all cases who developed renal insufficiency and of 3 µg/ml in the case not responding to DMC. These findings indicate that: (1) DMC is an effective therapy for water retention and dilutional hyponatremia in cirrhosis but it produces renal insufficiency associated with an impairment of renal perfusion and with a reduced urinary kallikrein activity in a high proportion of patients. (2) The inhibitory effect of DMC on water reabsorption in these patients may be due, at least in part, to an increased renal synthesis of prostaglandin E<sub>2</sub> induced by the drug. (3) A closed relationship exists between the renal effects and the serum levels of DMC in cirrhosis.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1984
          1984
          03 December 2008
          : 36
          : 1
          : 30-37
          Affiliations
          Liver Unit and Hormonal Laboratory, Hospital Clínico y Provincial, University of Barcelona, Spain
          Article
          183112 Nephron 1984;36:30–37
          10.1159/000183112
          6419136
          © 1984 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

          Cardiovascular Medicine, Nephrology

          Prostaglandin E2 , Demeclocycline, Hyponatremia, Cirrhosis, Kallikrein

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