Journal Article

Reduced renal Na<sup>+</sup>–K<sup>+</sup>–Cl<sup>−</sup> co-transporter activity and inhibited <i>NKCC2</i> mRNA expression by <i>Leptospira shermani</i>: from bed-side to bench

Mai-Szu Wu, Chih-Wei Yang, Ming-Jen Pan, Chiz-Tzung Chang and Yung-Chih Chen

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 10, pages 2472-2479
Published in print October 2004 | ISSN: 0931-0509
Published online October 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh452
Reduced renal Na+–K+–Cl− co-transporter activity and inhibited NKCC2 mRNA expression by Leptospira shermani: from bed-side to bench

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Background. Renal involvement is common in leptospirosis. Interstitial nephritis with interstitial oedema and mononuclear cellular infiltration are the usual findings. Clinically, non-oligouric acute renal failure, hypokalaemia and sodium wasting appear frequently in leptospirosis. The outer membrane protein from leptospira has been thought to be responsible for the disorder. However, the exact mechanisms of renal involvement are still unclear.

Methods. To address these questions, we first performed detailed in vivo clearance tests in three patients with leptospirosis (Leptospira shermani) and hypokalaemia to define the tubular lesion. These tests indicated a defective Na+–K+–Cl co-transporter and a poor response to furosemide infusion. We performed further in vitro studies in a model of medullary thick ascending limb (mTAL) cultured cells derived from normal mouse.

Results. Outer membrane protein extract from L.shermani (0.3 μg/ml) inhibited Na+–K+–Cl co-transporter activity in mTAL cells (control, 10.15±0.52; L.shermani, 6.47±0.47 nmol/min/mg protein). The basolateral Na+–K+ ATPase remained intact. Reverse transcription–polymerase chain reaction (RT–PCR) further revealed that the outer membrane protein extract from L.shermani downregulated Na+–K+–Cl co-transporter (mNKCC2) mRNA expression. These changes were dose dependent and could be reversed by the antibody against outer membrane protein extract from L.shermani. Experiments with a less pathogenic strain of leptospira (L.bratislava) and Escherichia coli did not affect Na+–K+–Cl co-transporter activity.

Conclusions. We conclude that L.shermani leptospirosis downregulates mNKCC2 mRNA expression and inhibits Na+–K+–Cl co-transporter activity in TAL cells. These alterations may explain the observed electrolyte disorders in leptospirosis.

Keywords: kidney; leptospirosis; Na+–K+ ATPase; Na+–K+–Cl− co-transporter; thick ascending limb

Journal Article.  4824 words.  Illustrated.

Subjects: Nephrology

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