Abstract: TH-OR96
SGLT2 Inhibitor Protects from Repeated Low-Dose Cisplatin-Induced Chronic Kidney Damage
Session Information
- Onconephrology and Precision Pharmacology
November 02, 2023 | Location: Room 107, Pennsylvania Convention Center
Abstract Time: 05:15 PM - 05:24 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Sanchez Vega, Dianet, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Siskind, Leah J., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Orwick, Andrew, University of Louisville School of Medicine, Louisville, Kentucky, United States
- Garimella, Pranav S., University of California San Diego, La Jolla, California, United States
- Vallon, Volker, University of California San Diego, La Jolla, California, United States
- Weis, Theresa A., University of Louisville School of Medicine, Louisville, Kentucky, United States
- Hammouri, Dana, University of Louisville School of Medicine, Louisville, Kentucky, United States
Background
Cisplatin is a commonly used chemotherapeutic agent that causes a dose dependent acute kidney injury (AKI) in nearly a third of treated patients, which subsequently leads to chronic kidney disease (CKD). There are no current FDA approved medications to prevent cisplatin induced kidney damage. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce risk of AKI and CKD in humans, and have shown renoprotection in a single high dose experimental model of cisplatin-induced AKI. We hypothesized that SGLT2i could protect the kidney in a mouse model of repeated low dose cisplatin and cancer to better mimic the clinical scenario.
Methods
B6:129 mice with and without lung adenocarcinoma were treated with daily SGLT2i (empagliflozin or dapagliflozin) or vehicle control for 28 days beginning 1 week prior to the first dose of weekly cisplatin (7mg/kg) or vehicle control. Following the third cisplatin injection, biomarkers for kidney function, injury, fibrosis, inflammation, kidney histology and tumor growth were assessed and compared between SGLT2i and vehicle control.
Results
SGLT2i treatment attenuated cisplatin-induced alterations in kidney function and injury. Markers of kidney fibrosis including TGF-b, a-SMA, fibronectin and collagen were lower in mice co-administered SGLT2i and cisplatin as compared to mice given vehicle control and cisplatin. SGLTi did not alter tumor growth or response to cisplatin.
Conclusion
SGLTi demonstrate a beneficial effect against kidney damage in a model of repeated low dose cisplatin and lung cancer. Future studies are needed to determine if they can be used post cisplatin treatment to improve and/or prevent progression of kidney injury to fibrosis and CKD.
Funding
- NIDDK Support