Effect of Spironolactone on Progression of Nephropathy in Type 2 Diabetic Rat Model

Han, Kum Hyun; Kang, Young Sun; Cha, Dae Ryong; Kim, Hyoung Kyu

Abstract

BACKGROUND
Aldosterone induces renal fibrosis and administration of spironolactone showed beneficial effect in various animal models of renal injury such as unilateral ureteral obstruction model and hypertensive renal injury models. The aim of this study is to demonstrate that inhibition of aldosterone may have additional beneficial effect independent of angiotensin blockade in diabetic nephropathy. METHODS: We investigated the effect of aldosterone blockade on renal function in animal model of type II diabetic nephropathy. Diabetic rats were treated with spironolactone (20 mg/kg/day), starting at 20 weeks of age. RESULTS: In diabetic rats, proteinuria was increased since 24 weeks, and presented five-fold increment at 52 weeks comparing to that at 24 weeks. Aldosterone blockade significantly reduced proteinuria without affecting blood glucose concentration and blood pressure. In the diabetic kidney, profibrogenic molecules such as CTGF and type I collagen expression was enhanced and spironolactone treatment decreased their expression. It is of interest that plasma aldosterone level showed a weak but significant relationship with blood glucose levels. CONCLUSION: Aldosterone blockade prevents fibrotic process in the kidney associated with decrement in profibrotic molecule such as CTGF and type I collagen. Furthermore, aldosterone blockade resulted in decrease in urinary protein excretion and glomerulosclerosis. These results suggest that aldosterone blockade may be a new therapeutic target for retarding the progression of diabetic nephropathy.