Uncoupling glucosuria from infection: SGLT2 inhibition modulates kidney immune response during pyelonephritis.

Abstract

Sodium-glucose cotransporter 2 inhibitors increase urinary glucose excretion, theoretically predisposing to urinary tract infection, yet clinical trials have not shown higher rates of severe infection. In this issue of Kidney International, Sendtner et al. provide a plausible mechanistic framework for this paradox. Combining human cohort data with experimental pyelonephritis, they demonstrate that sodium-glucose cotransporter 2 inhibition with empagliflozin is associated with reduced C1q expression, preserved antibacterial defenses, and altered inflammatory signaling. These findings suggest that sodium-glucose cotransporter 2 inhibition with empagliflozin may influence kidney antibacterial defenses without increasing infection risk.