Endothelin antagonist Avosentan showed promising results in reduction of proteinuria and prevention of progressive renal disease in animal studies. Please see images above that showed improvement in renal histology after administration of endothelin antagonist in animal studies. ASCEND trial (Mann et al, JASN 2010) is a multicenter, multinational, double-blind, placebo-controlled trial of 1392 patients that evaluated addition of Avosentan to ACEi/ARB in diabetic nephropathy. Trial was terminated prematurely after a median follow-up of 4 months (maximum 16 months) because of an excess of cardiovascular events (esp.CHF) with avosentan. During this short follow-up, no difference was detected in the frequency of time to doubling of serum creatinine, ESRD or death between groups. However, Avosentan significantly reduced proteinuria by about 50%.
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