Canagliflozin prevents acute kidney Injury in euglycemics rats.

Abstract

Introduction: The aim of this study was to investigate the impact of canagliflozin on AKI caused by ischemia-reperfusion injury (IRI) in non-diabetic rats. Methods: Male Wistar rats weighing 250-300g were randomized into four groups: SHAM (rats subjected to sham renal ischemia-reperfusion surgery); CANA (canagliflozin by gavage, 200mg/kg, once, daily, 5 days); I/R: rats subjected to I/R- AKI (bilateral renal hilum clamping, 30 minutes); CANA+I/R: I/R rats that received canagliflozin 5 days prior to I/R. Evaluated parameters: 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), western blot for identification of SGLT2 in the kidneys and renal histology. Results: 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, while 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, while canagliflozin was able to reduce tubular injury and inflammation in treated animals. Conclusion: Canagliflozin treatment prevented IRI-AKI, considering the methods employed in this study.