Avosentan reduced urinary albumin excretion rate

Avosentan may slow progression of kidney disease, prevent ESRD.

In patients with macroalbuminuria and nephropathy, treatment with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers plus avosentan decreased urinary albumin excretion rate.

The researchers randomly assigned 286 patients with diabetic nephropathy, macroalbuminuria and blood pressure <180 mm Hg/110 mm Hg to 12 weeks of treatment with ACE inhibitors and/or angiotensin receptor blockers plus 5 mg, 10 mg, 25 mg or 50 mg of avosentan or placebo.

Improvement seen

Compared with placebo (35.5%; P<.01), the mean absolute change in urinary albumin excretion rate with avosentan treatment was –20.9% for 5 mg, –16.3% for 10 mg, –25.0% for 25 mg and –29.9% for 50 mg.

The median absolute change with avosentan treatment when compared with placebo (0.05 mg/minute) was –0.15 mg/minute for 5 mg and 10 mg and –0.21 mg/minute for 25 mg and 50 mg.

The median relative change in urinary albumin excretion rate with avosentan treatment was –28.7% (5 mg), –42.2% (10 mg), –44.8% (25 mg) and –40.2% (50 mg) compared with placebo (12.1%), according to the researchers.

Adverse events included peripheral edema (12%), and there was no change in creatinine clearance or BP, according to the researchers. The optimal dose may be ≤10 mg as there seemed to be no additional benefit with doses >25 mg, according to a press release.

“A large outcome trial is mandatory to confirm these findings and to determine whether avosentan’s anti-proteinuric effects can be translated into long-term benefits also with lower dosages of avosentan, which are likely to have an optimal tolerability,” they wrote. “Nevertheless, the marked and significant reduction in macroalbuminuria after 12 weeks of avosentan treatment suggests a clinically valuable and nephroprotective effect.” – by Christen Haigh

Wenzel RR. J Am Soc Nephrol. 2009;doi:10.1681/ASN.2008050482.