Abstract: PO0939
Effects of Dapagliflozin-Induced Glucosuria on Urinary Tract Infection Susceptibility
Session Information
- Diabetic Kidney Disease: New Pathways and Therapies
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Bender, Kristin, Nationwide Children's Hospital, Columbus, Ohio, United States
- Schwartz, Laura, Nationwide Children's Hospital, Columbus, Ohio, United States
- Spencer, John David, Nationwide Children's Hospital, Columbus, Ohio, United States
Background
Individuals with diabetes mellitus (DM) have a higher risk for urinary tract infection (UTI). The infection is more likely to cause acute kidney injury leading to an increased risk for chronic and end-stage kidney disease. Glucosuria is one of the proposed mechanisms by which people with DM have increased UTI risk, but this association is understudied and uncertain. In order to study the relationship between glucosuria and UTI susceptibly in vivo, mice were treated with an SGLT-2 inhibitor Dapagliflozin (Dapa) and subjected to experimental UTI.
Methods
Non-diabetic C57BL/6 female mice were treated via oral gavage with vehicle or Dapa at 0.1, 1, or 10 mg/kg/dose. One group received a 2-dose regimen: 6 hours before and 3 hours post infection. Another group was treated daily for 7 days. Mice were transurethrally infected with uropathogenic E. coli (UPEC). 24 hours post infection (hpi) bacterial burden was enumerated in the urine and bladder. Serum glucose, urine glucose, and urinary output was monitored over the course of treatment.
Results
Compared to controls, Dapa-treated mice developed glucosuria while maintaining normoglycemia and comparable weights. After UTI with the 2-dose regimen, control and Dapa-treated mice had comparable bladder and urine UPEC titers. Mice treated over a longer time course had no significant differences in CFUs in the bladder and urine at 24 hpi – suggesting that glucosuria may not be a primary UTI risk factor. Urine output was increased in mice treated with Dapa which could impact infection susceptibility.
Conclusion
These data suggest that there is no direct relationship between glucosuria, SGLT2 inhibitors, and UTI susceptibility. Also, glucosuria alone doesn’t explain the increase in DM-associated UTI risk. More studies are needed to understand the mechanisms that increase UTI susceptibility in individuals with DM.
Funding
- NIDDK Support