Reduced renal Na+ -K+ -Cl- co-transporter activity and inhibited NKCC2 mRNA expression by Leptospira shermani: From bed-side to bench

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

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2472-2479
Number of pages8
JournalNephrology Dialysis Transplantation
Volume19
Issue number10
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

Keywords

  • Kidney
  • Leptospirosis
  • Na -KATPase
  • Na -K -Cl co-transporter
  • Thick ascending limb

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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