Blog entry by Meguid El Nahas
Kohan et al in JASN April 2011 present data suggesting that endothelin A receptor blockade reduces albuminuria in diabetic nephropathy over and above RAAS Blockade. The study was conducted in diabetic patients with GFR>20 ml/min and albuminuria between 100 and 3000 mg/g. Patients were randonised into placebo, atrasentan 0.25, 0.75 and 1.75mg/day groups. Follow-up was 8 weeks. Analysis was on intention to treat (ITT). Atrasentan at 0.75 and 1.75 mg/day reduced albuminuria significantly. Atrasentan also reduced systolic and diastolic BP, thus making difficult any conclusion regarding a albuminuria lowering effect independently of BP reduction!
Of note, fluid retention and oedema was a significant side effecst affecting up to 46% of those on the highest dose of Atrasentan.
This observation is consistent with that made recently with another ETA Receptor antagonist, namely avosenta; in this study avosentan also erduced albuminuria in diabetic nephropathy but the trial had to be discontinued on safety ground due to increased death related to fluid retention and heart failure.
Endothelin A antagonists may prove useful adjuncts to the current management of Diabetic nephropathy. Whether, it adds much to tighter BP control remains to be elucidated.