Protection from glucosuria

SP7: Protection from pyelonephritis during glucosuria

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.
This project addresses the renal antibacterial response in glucosuria. This clinical scenario rapidly grows in relevance as the indications for therapeutic SGLT2 inhibition expand and now include chronic kidney disease and heart failure. Definition of antibacterial mechanisms in glucosuria is needed to understand the infectious risk of the rapidly growing number of individuals treated with SGLT2 inhibitors. The experimental results will potentially define new approaches to pyelonephritis risk assessment during SGTL2 inhibition (SGLT2i) therapy and thereby stratify treatment decisions in common diseases. Beyond this, they may define novel resistance factors that could be employed for the benefit other patient groups with recurrent pyelonephritis