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      On the Mechanism of Toluene-Induced Renal Tubular Acidosis

      , ,

      Nephron

      S. Karger AG

      Renal tubular acidosis, Toluene, Potassium, Acid Base

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          Abstract

          This study was aimed to investigate the pathogenesis of toluene-induced renal tubular acidosis (RTA). In 5 individuals addicted to toluene sniffing we documented the occurrence of hypokalemia and hyperchloremic metabolic acidosis associated with inability to lower urine pH below 5.5 (6.06 ± 0.24). Overall kidney bicarbonate reabsorption was normal or enhanced, a feature characteristic of the distal form of RTA (DRTA). These findings resemble those found during the administration of amphotericin B, a drug felt to cause DRTA by increasing hydrogen ion (H<sup>+</sup>) back-diffusion in the collecting tubule. In toluene sniffers, the urine pCO<sub>2</sub> measured in a highly alkaline urine was reduced (47 ± 8.8 mm Hg), suggesting a decrease in the rate of collecting tubule H<sup>+</sup> secretion rather than H<sup>+</sup> back-diffusion. To investigate these two mechanisms of altered distal acidification more directly we studied the effect of toluene on acidification by the urinary turtle bladder, an epithelial analogue of the mammalian collecting tubule. In this preparation, toluene resulted in a decrease in the rate of H<sup>+</sup> secretion measured by either the pH stat technique or the reverse short circuit current. When mucosal pH was progressively lowered to examine H<sup>+</sup> secretion against an H<sup>+</sup> gradient, toluene-treated bladders displayed a significant decrease in proton conductance but the lowest mucosal pH required to nullify H<sup>+</sup> secretion, (MpH) JH = O, was not different from that of control bladders (4.05 ± 0.29 and 3.90 ± 0.13, respectively). In contrast, in amphotericin B-treated bladders (MpH) JH =·was 5.15 ± 0.39, a value more than 1 pH unit higher than that of control and toluene-treated bladders (p < 0.05). Thus, amphotericin B, but not toluene, reduced the pH gradient that could be generated across the turtle bladder. These findings suggest that toluene, unlike amphotericin B, does not cause H<sup>+</sup> back-diffusion. Decreased conductance of protons through the active transport pathway is the mechanism that best explains the toluene-induced defect in distal acidification.

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          Author and article information

          Journal
          NEF
          Nephron
          10.1159/issn.1660-8151
          Nephron
          S. Karger AG
          1660-8151
          2235-3186
          1988
          1988
          09 December 2008
          : 49
          : 3
          : 210-218
          Affiliations
          Departments of Medicine and Nephrology Sections, Northwestern University Medical School, and the Lake Side VA Medical Center, Chicago, Ill., USA; Texas Tech University Health Sciences Center, Lubbock, Tex., USA
          Article
          185057 Nephron 1988;49:210–218
          10.1159/000185057
          3135502
          © 1988 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: 9
          Categories
          Original Paper

          Cardiovascular Medicine, Nephrology

          Renal tubular acidosis, Potassium, Toluene, Acid Base

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