SGLT2 inhibition decreases complement C1q, maintaining renal antibacterial response

SGLT2 inhibitors, which inhibit glucose reabsorption in the proximal tubule, are well established in the treatment of diabetes mellitus, chronic kidney disease, and heart failure. Although these agents induce glucosuria, clinical trials have consistently shown no increase in renal bacterial infection rates. To investigate the mechanisms that compensate for the increased risk of bacterial growth associated with glucosuria, we employed a pyelonephritis mouse model. In this model, approximately 40-day-old C57BL/6J mice were treated with or without empagliflozin and subsequently infected with the uropathogenic Escherichia coli strain 536. RNA-seq data were obtained from kidneys 16 hours post-infection. Overall design: Female C57BL/6J mice were treated with 20 mg/L empagliflozin or control for three days prior to urethral infection with uropathogenic E. coli strain 536, which was instilled into the bladder twice at a 3-hour interval. Kidneys were harvested 16 hours after the second infection.