Protection from pyelonephritis during glucosuria

葡萄糖促进细菌生长。在正常情况下，它主要通过SGLT2转运蛋白从初级尿液中有效地被主动转运。SGLT2抑制剂的临床适应症在最近几年已显著扩大。除了糖尿病，它们现在还被推荐用于心力衰竭和慢性肾脏疾病。然而，在相当数量的随机对照试验中，总体上尿路感染率没有改变。该项目的目的是明确肾性葡萄糖尿症的抗菌机制。计划中的实验将研究肾小管上皮细胞和先天免疫防御机制，以及葡萄糖和药物SGTL2抑制剂在人类细胞和细菌培养中以及体内小鼠肾盂肾炎模型中对细菌毒力因子的调节。人类肾脏活检和尿液分析将用于验证个别因素。由此产生的机制可能为保护尿路免受细菌感染提供新的角度。

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.