An additive effect of eplerenone to ACE inhibitor on slowing the progression of diabetic nephropathy in the db/db mice.

An additive effect of eplerenone to ACE inhibitor on slowing the progression of diabetic nephropathy in the db/db mice. Am J Transl Res. 2016;8(3):1339-54 Authors: Zhou G, Johansson U, Peng XR, Bamberg K, Huang Y Abstract Although blockade of the renin-angiotensin-system (RAS) has become standard therapy for diabetic nephropathy (DN), decline in kidney function towards end-stage renal disease is seen in many patients. Elevated plasma aldosterone often accompanies RAS blockade by a phenomenon known as "aldosterone escape" and activates the mineralocorticoid receptor (MR). We therefore examined whether addition of the MR antagonist eplerenone to an ACEI would enhance the efficacy in slowing the progression of DN. Untreated uninephrectomized diabetic db/db mice developed progressive albuminuria and glomerulosclerosis between weeks 18 and 22, associated with decreased number of podocytes and increased renal expression of fibrotic markers. The therapeutic effect of eplerenone at 100 mg/kg BW/d on albuminuria, podocyte injury and renal fibrosis was similar to that of enalapril given alone at maximally effective doses. Adding eplerenone to enalapril resulted in further reduction in these measurements. Renal expressions of TNF-α, MCP-1, Nox2 and p47phox and renal TBARS levels, markers of inflammation and oxidative stress, were increased during disease progression in diabetic mice, which were reduced by eplerenone or enalapril given alone an...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research