Salamon Kristin, Linn-Peirano Sarah, Simoni Aaron, de Dios Ruiz-Rosado Juan, Becknell Brian, John Preeti, Schwartz Laura, Spencer John David
The Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's, Columbus, Ohio, USA.
The Ohio State University College of Veterinary Medicine, Columbus, Ohio, USA.
Diabetes Obes Metab. 2025 Jan;27(1):40-53. doi: 10.1111/dom.15981. Epub 2024 Sep 30.
Sodium-glucose co-transporter-2 (SGLT2) inhibitors have revolutionized clinical medicine, but their association with urinary tract infection (UTI) risk remains debated. This study investigates the influence of dapagliflozin on UTI outcomes, focusing on kidney injury.
Female non-diabetic C57BL/6J and C3H/HeOuJ mice, along with diabetic db/db mice, were orally administered dapagliflozin (1 mg/kg or 10 mg/kg) for 7 days before transurethral uropathogenic Escherichia coli (UPEC) infection. Mice were killed either 24 h after UTI or after six additional days of dapagliflozin treatment. UPEC titers were enumerated, and kidney histopathology, injury, fibrosis and function were assessed.
Vehicle- and dapagliflozin-treated C57BL/6J mice exhibited similar urine and bladder UPEC titers, with minimal kidney burden 24 h after UTI. In C3H/HeOuJ mice, UPEC burden was comparable in vehicle- and 1 mg/kg dapagliflozin-treated groups both 24 h and 7 days after UTI. However, C3H/HeOuJ mice receiving 10 mg/kg dapagliflozin had increased UPEC titers in the urine, bladder and kidneys at both endpoints. Kidney injury and fibrosis markers, as well as kidney function, were similar in vehicle and dapagliflozin groups. In diabetic db/db mice receiving dapagliflozin, UPEC strain UTI89 titers were reduced 7 days after UTI compared to vehicle-treated mice, but no difference in UPEC titers was observed when mice were infected with UPEC strain CFT073. Kidney injury and fibrosis markers and kidney function remained similar across treatment groups.
Dapagliflozin does not consistently influence UTI susceptibility and shows limited impact on kidney injury or fibrosis, suggesting SGLT2 inhibitors have minimal effects on UTI-related kidney complications.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂彻底改变了临床医学，但它们与尿路感染（UTI）风险的关联仍存在争议。本研究调查达格列净对UTI结局的影响，重点关注肾损伤。
雌性非糖尿病C57BL/6J和C3H/HeOuJ小鼠，以及糖尿病db/db小鼠，在经尿道感染尿路致病性大肠杆菌（UPEC）前7天口服给予达格列净（1mg/kg或10mg/kg）。在UTI后24小时或达格列净治疗额外6天后处死小鼠。对UPEC滴度进行计数，并评估肾脏组织病理学、损伤、纤维化和功能。
给予赋形剂和达格列净治疗的C57BL/6J小鼠尿液和膀胱中的UPEC滴度相似，UTI后24小时肾脏负担最小。在C3H/HeOuJ小鼠中，给予赋形剂和1mg/kg达格列净治疗的组在UTI后24小时和7天时UPEC负担相当。然而，接受10mg/kg达格列净的C3H/HeOuJ小鼠在两个时间点尿液、膀胱和肾脏中的UPEC滴度均升高。给予赋形剂组和达格列净组的肾脏损伤和纤维化标志物以及肾功能相似。在接受达格列净治疗的糖尿病db/db小鼠中，与给予赋形剂治疗的小鼠相比，UTI后7天UPEC菌株UTI89滴度降低，但当小鼠感染UPEC菌株CFT073时，未观察到UPEC滴度有差异。各治疗组之间的肾脏损伤和纤维化标志物以及肾功能仍相似。
达格列净并不始终影响UTI易感性，对肾损伤或纤维化的影响有限，提示SGLT2抑制剂对UTI相关肾脏并发症的影响最小。
