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

Acidosis is associated with E. coli induced pyelonephritis but whether bacterial cell wall constituents inhibit HCO(3) transport in the outer medullary collecting duct from the inner stripe (OMCDi) is not known. We examined the effect of lipopolysaccharide (LPS), on HCO(3) absorption in isolated perfused rabbit OMCDi. LPS caused a ~ 40% decrease in HCO(3) absorption, providing a mechanism for E. coli pyelonephritis-induced acidosis. Monophosphoryl lipid A (MPLA), a detoxified TLR4 agonist, and Wortmannin, a phosphoinositide 3-kinase inhibitor, prevented the LPS-mediated decrease, demonstrating the role of TLR4-PI3-kinase signaling and providing proof-of-concept for therapeutic interventions aimed at ameliorating OMCDi dysfunction and pyelonephritis-induced acidosis.