Antidiabetic Drugs May Prevent Kidney Damage

Abstract

IntroductionSodium-glucose cotransporter 2 inhibitors (SGLT2i) are a class of drugs that act as glucose reducers in patients with type 2 diabetes mellitus. Recent meta-analyses have shown that SGLT2i also prevent acute kidney injury (AKI) in diabetic patients. The aim of this study was to investigate the protective effect of canagliflozin an SGLT2i on AKI due to ischemia and reperfusion (I/R) in non-diabetic rats. MethodsMale Wistar rats weighing 250-300 g were divided into four groups: Control; SHAM (rats submitted to surgical simulation of renal ischemia); I/R: rats submitted to renal ischemia (bilateral clamping of the renal hilum for 30 minutes); CANA+I/R: I/R rats that received canagliflozin (30mg/kg, oral, gavage; 5 days before I/R). Renal function parameters were evaluated (serum creatinine [CrS], inulin clearance [Clin]; renal hemodynamics mean arterial pressure [MAP], renal blood flow [RBF], renal vascular resistance [RVR]); oxidative profile (urinary peroxides - FOX, lipid peroxidation - TBARS, urinary nitrate- NO) and thiols in renal tissue and expression of nuclear factor-erythroid 2 related factor 2 [Nrf2] protein. ResultsThe I/R group showed an increase in CrS and a reduction in inulin clearance, while the CANA+I/R group showed a reduction in serum creatinine and an increase in inulin clearance compared to the I/R group. In addition, the CANA+I/R group showed a decrease in oxidative metabolites (FOX and TBARS) and an increase in Nrf2 compared to the I/R group. ConclusionCanagliflozin treatment prevented the reduction in renal function induced by ischemia and reperfusion. In addition, there was a reduction in oxidative activity due to a decrease in oxidative metabolites and urinary peroxides and an increase in renal tissue thiols and Nrf-2, which is responsible for transcribing antioxidant activity. Therefore, the current study confirmed a relevant renoprotective effect of canagliflozin in the presence of renal ischemia.