IntroductionDiabetic nephropathy is a major microvascular complication of diabetes, affecting 20 % to 40 % of diabetic patients [1]. It is an independent risk factor for cardiovascular disease and is associated with increased morbidity and mortality [2]. The glucose-induced oxidative stress and persistent inflammatory condition can cause deleterious renal changes contributing to the pathophysiology of diabetic nephropathy [3]. Increased reactive oxygen species production and reduced availability of antioxidant mechanisms can influence the renal function and structure by modulating cell growth, apoptosis, and inflammatory responses [4]. Also, early diabetic nephropathy is associated with glomerular hyperfiltration, cytokine release and tissue proliferation, processes that have been linked to progression of the kidney disease [5,6].Inhibitors of the renin-angiotensin system inhibitors are commonly used to decrease glomerular hyperfiltration, reduce proteinuria and delay progression of diabetic nephropathy [7]. Telmisartan, a selective angiotensin receptor blocker have shown to provide renal benefit at all stages of nephropathy in diabetic patients [8,9]. Some investigators have shown that telmisartan also possesses anti-inflammatory and antioxidant properties [10]. However, blockade of the renin-angiotensin system does not completely arrest kidney disease progression and many patients pass to end-stage renal disease [7].Recently, selective Sodium Glucose Cotransporter 2 (SGLT2) inhibitors have been developed for use in patients with type 2 diabetes [11,12]. Canagliflozin is a selective SGLT2 inhibitor, developed for treatment type 2 diabetes, showing improved glycemic control, both as monotherapy and in combination with other antidiabetics [13,14]. More recently, treatments with SGLT2 inhibitors have been reported to prevent the features of diabetic nephropathy including glomerular hyperfiltration and mesangial matrix expansion in diabetic animal models [15,16]. Beyond their antihyperglycemic properties, use of SGLT2 inhibitors was associated with additional non-glycemic benefits including reduction in blood pressure, plasma Abdel-Wahab AF, et al., J Nephrol Renal Ther 2016
AbstractCanagliflozin is a new antidiabetic, SGLT2 inhibitor, that interfere with renal glucose reabsorption but its effect on renal structure and function has not been elucidated. So, we investigated the renal protective effects of canagliflozin in comparison with the angiotensin blocker, telmisartan, in a rat model of diabetic nephropathy. Sixty male Wistar rats were randomly divided into six groups. Group 1; non-diabetic controls, given only vehicles. Group 2; non-treated diabetic rats injected with nicotinamide and streptozotocin. Group 3 and 4; diabetic rats treated for 8 weeks with canagliflozin 20 and 40 mg/kg/day. Group 5 and 6; diabetic rats treated with telmisartan 5 and 10 mg/kg/day, respectively. Biochemical analysis included plasma glucose, HbA1c, urinary albumin excretion, BUN, serum creatinine, creatinine clearance, TNF-α, TGF-β...