Peroxisome Proliferator-Activated Receptor-gamma Agonist Rosiglitazone Prevents Albuminuria but Not Glomerulosclerosis in Experimental Diabetes

Backgrounds/Aims: Renal inflammation and nephrin downregulation contribute to albuminuria in diabetes. We studied, in streptozotocin-induced diabetic rats, the effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-gamma agonist, on renal macrophage infiltration, MCP1, and nephrin expression in relation to albuminuria. Methods: We investigated control and diabetic rats treated or untreated with RSG. Animals were sacrificed at 1, 3, and 9 months. Renal MCP1 and nephrin expression were studied by immunoblotting, renal macrophage infiltration by immunohistochemistry, and albuminuria by ELISA. Electron microscopy was used to assess glomerular ultrastructural morphology. In vitro experiments were conducted in isolated cultured rat glomeruli. Results: Glycaemic control was similar in diabetic rats treated and untreated with RSG, and blood pressure was comparable in all groups. RSG prevented diabetes-induced albuminuria at 9 months, and renal macrophage infiltration and MCP1 upregulation at 3 and 9 months. Diabetes-mediated nephrin downregulation was abolished by RSG. Diabetes-induced glomerulosclerosis, glomerular basement membrane thickening, and foot process fusion were not affected by RSG. In isolated glomeruli, MCP1 directly induced nephrin downregulation and this was prevented by RSG. RSG had no effect on nephrin expression. Conclusion: RSG prevents albuminuria and nephrin downregulation in experimental diabetes independently of glycaemic and blood pressure control. This effect likely occurs via correction of diabetes-induced inflammatory processes. Copyright (C) 2010 S. Karger AG, Basel