Canagliflozin prevents acute kidney injury in euglycemic rats.

Abstract

The aim of this study was to investigate the impact of canagliflozin (CANA) on acute kidney injury (AKI) caused by ischemia-reperfusion injury (IRI) in nondiabetic rats. Male Wistar rats weighing 250-300 g were randomized into four groups: SHAM (rats subjected to sham renal ischemia-reperfusion surgery); CANA (canagliflozin by gavage, 200 mg/kg, once, daily, 5 days); ischemia-reperfusion (I/R): rats subjected to I/R-AKI (bilateral renal hilum clamping, 30 min); CANA + I/R: I/R rats that received canagliflozin 5 days before I/R. Evaluated parameters include renal function [serum creatinine (CrS), inulin clearance (inCl)]; renal hemodynamics [mean arterial pressure (MAP), renal blood flow (RBF), renal vascular resistance (RVR)]; redox profile [urinary peroxides, lipid peroxidation, urinary nitrate, renal tissue thiols, and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression], and Western blot for identification of sodium-glucose cotransporter 2 (SGLT2) in the kidneys and renal histology. Western blot essays confirmed the presence of SGLT2 in the kidneys. Regarding renal function in the animals subjected to IRI, an increase in CrS and a reduction in inCl were observed, whereas the group treated with CANA showed a reduction in CrS and an increase in inCl, demonstrating improved renal function after CANA treatment. Besides, canagliflozin pretreatment induced an improvement in renal hemodynamics and redox profile. Renal histology showed an increase in the tubular injury score in the IRI group, whereas canagliflozin was able to reduce tubular injury and inflammation in treated animals. Canagliflozin treatment prevented IRI-AKI, considering the methods used in this study.NEW & NOTEWORTHY Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a class of medications that act as glucose reducers in patients with type 2 diabetes mellitus. Recent studies have shown that SGLT2i also prevent acute kidney injury (AKI). The aim of this study was to investigate the impact of canagliflozin on ischemia-reperfusion (I/R)-induced AKI in nondiabetic rats.