Endothelin Antagonist Reduces Albuminuria in Diabetic Nephropathy

Treatment with the endothelin A-selective antagonist avosentan can reduce urinary albumin excretion in diabetic patients with macroalbuminuria, concludes a trial in the Journal of the American Society of Nephrology.

The Endothelin Antagonist Evaluation in Diabetic Nephropathy Study included 286 patients with diabetic nephropathy at 58 European centers. All had macroalbuminuria, with a urinary albumin excretion rate (UAER) of 0.2 to 5.6 mg/min, and blood pressure of less than 180/110 mm Hg. In addition to standard angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker therapy, patients were randomly assigned to 12 weeks of treatment with avosentan, 5 to 50 mg, or placebo.

All avosentan dosage groups had reductions in UAER: from 16 to 30 percent, compared with a 36 percent increase in the placebo group. Median relative reductions in UAER were 29 to 45 percent with avosentan, compared to a 12 percent increase with placebo. Creatinine clearance and blood pressure were unaffected. Peripheral edema occurred mainly at avosentan doses of 25 mg or higher; the rate of adverse events leading to treatment discontinuation was 7 percent.

Studies in rats suggest that endothelin antagonists can reduce inflammation, renal fibrosis, and albumin excretion. Adding avosentan to standard therapy can reduce albumin excretion in patients with advanced diabetic nephropathy, this industry-sponsored study reports. Larger confirmatory trials are needed, including data on the optimal avosentan dosage and long-term benefits of treatment [Wenzel RR, Littke T, Kuranoff S, Jürgens C, Bruck H, Ritz E, Philipp T, and Mitchell A, for the SPP301 (Avosentan) Endothelin Antagonist Evaluation in Diabetic Nephropathy Study investigators. Avosentan reduces albumin excretion in diabetics with macroalbuminuria. J Am Soc Nephrol 2009; 20:655–664].