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Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct

Shuichi Tsuruoka1, Jeffrey M Purkerson2, George J Schwartz3

  • 1Department of Medicine, Tajirigaoka Hospital, Hitachi, Ibaraki, Japan.

Scientific Reports
|November 26, 2020
PubMed

Insights

Bacterial lipopolysaccharide (LPS) reduces kidney bicarbonate transport, contributing to E. coli pyelonephritis-induced acidosis. Targeting Toll-like receptor 4 (TLR4) signaling may prevent this dysfunction.

Area of Science:

  • Nephrology
  • Microbiology
  • Cellular Physiology

Background:

  • Acidosis is linked to E. coli pyelonephritis.
  • The effect of bacterial components on kidney bicarbonate transport is unclear.

Purpose of the Study:

  • To investigate if lipopolysaccharide (LPS), a bacterial cell wall component, inhibits bicarbonate (HCO3) absorption in the outer medullary collecting duct inner stripe (OMCDi).
  • To explore the underlying signaling pathways and potential therapeutic targets.

Main Methods:

  • Isolated perfused rabbit OMCDi were used to measure HCO3 absorption.
  • The effects of LPS, Monophosphoryl lipid A (MPLA), and Wortmannin were examined.

Main Results:

  • LPS significantly decreased HCO3 absorption by approximately 40% in OMCDi.
  • MPLA and Wortmannin prevented the LPS-induced reduction in HCO3 absorption.
  • These findings implicate TLR4-PI3-kinase signaling in LPS-mediated inhibition.

Conclusions:

  • Bacterial LPS inhibits HCO3 transport in the OMCDi, offering a mechanism for E. coli pyelonephritis-induced acidosis.
  • The Toll-like receptor 4 (TLR4)-phosphoinositide 3-kinase (PI3K) pathway mediates this effect.
  • Targeting this pathway presents a potential therapeutic strategy for pyelonephritis-associated acidosis.

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