Avosentan lower doses for Overt Diabetic Nephropathy ?

Avosentan (see structure) is a potent, selective endothelin A  receptor blocker and there is convincing evidence that the endothelin system contributes to diabetic nephropathy and cardiovascular disease. Many groups are working with this drug.  Now researchers from Schwabing General Hospital and KfH Kidney Centre, in Munchen, Germany have come out with interesting results, as per claim by the lead researcher, Dr.Johannes Mann, the drug avosentan substantially reduces urinary protein loss in people with type 2 diabetes and kidney disease, but the drug causes serious side effects.

Avosentan at either dose (25 & 50 mg) lowered patients' urinary protein excretion by 40%-50% (compared with less than 10% in patients taking placebo), individuals taking the drug experienced a high incidence of serious, sometimes life-threatening side effects. These included complications of fluid overload such as pulmonary edema, as well as congestive heart failure. In addition, there were more deaths in the groups taking avosentan (21 and 17) than in the group taking placebo. 

Dr. Mann noted that the findings from the ASCEND trial highlight the risks and potential benefits of endothelin antagonists in kidney disease patients with proteinuria and will help investigators design future studies to test the drugs' potential. Specifically, lower doses of avosentan may generate more positive results....

Ref : Mann J.F., et. al., J Am Soc Nephrol. 2010 Feb 18.