Protection from pyelonephritis during glucosuria

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Glucose promotes bacterial growth. Under normal conditions, it is effectively removed from the primary urine by active transport, chiefly by the SGLT2 transporter. Clinical indications for SGLT2 inhibitor use have markedly expanded in the recent past. Beyond diabetes, they now are recommended for heart failure and chronic kidney disease. However, overall upper urinary tract infection rates were unaltered in the sizeable number of randomized controlled trials. The aim of this project is to define antibacterial mechanisms in renal glucosuria. The planned experiments will address tubular epithelial and innate immune defense mechanisms and regulation of bacterial virulence factors by glucose and pharmacologic SGTL2 inhibitors in human cell and bacterial culture and in a murine pyelonephritis model in vivo. Human renal biopsy and urine analyses will serve to validate individual factors. Resulting mechanisms could provide new angles to protect the urinary tract against bacterial infection.