Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Effects of sodium-coupled glucose transporter inhibitor Canagliflozin on Cisplatin-induced nephrotoxicity in renal proximal tubular cells

Cisplatin is an effective chemotherapeutic, yet acute kidney injury is a significant dose-limiting factor in cisplatin-based therapies. Canagliflozin (INVOKANA®), a sodium-coupled glucose transporter 2 inhibitor, has demonstrated off-target protection from cisplatin nephrotoxicity, though the underlying mechanisms remain unclear. Our laboratory was the first to isolate CD133+CD24+ Human Renal Tubular Precursor TERT cells (HRTPT) from an immortalized proximal tubule cell line derived from renal cortical tissue (RPTEC/TERT1). These cells exhibit renal progenitor features, including multipotent differentiation and nephrosphere formation. The purpose of this study is to investigate off-target effects of canagliflozin in cisplatin nephrotoxicity. For this study, RPTEC/TERT1 cells were treated with clinically relevant canagliflozin in moderately toxic cisplatin conditions to determine cell viability. HRTPT cells were treated with clinically relevant canagliflozin while exposed to increasingly toxic cisplatin concentrations to observe changes in CD133 expression, and HRTPT cells were chronically passaged in cisplatin and canagliflozin-treated media to investigate cisplatin-induced cell cycle arrest. Results indicate canagliflozin improved RPTEC/TERT1 cell viability in a concentration-dependent manner, and canagliflozin-treated HRTPT cells either resisted a decrease or increased CD133 expression in moderately toxic cisplatin conditions. Canagliflozin also attenuated cisplatin-induced cell cycle arrest and retained normal morphology in HRTPT cells. Moving forward, we will investigate how canagliflozin affects cell viability and protein expression in cisplatin-treated HRTPT populations and what mechanisms modulate the attenuation of HRTPT cisplatin-induced cell cycle arrest.