Adenosine A1 receptor antagonist rolofylline – renoprotection could not be demonstrated

Adenosine A1 receptor antagonist rolofylline

Adenosine A1 receptor antagonist rolofylline was noted to enhance diuresis and produce improvement in renal function in those with heart failure in small scale studies. Hence Voors AA and associates [1] checked out on this in a study with over two thousand patients. The subjects had acute heart failure with volume overload, lowered creatinine clearance and elevated natriuretic peptide levels. They were randomized within a day of hospital admission to either rolofylline 30 mg/day or an intravenous placebo for the initial three days. The study was named PROTECT, may be because it aimed at protecting the kidneys with rolofylline (Placebo-controlled randomized study of the selective A1 adenosine receptor antagonist rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function). But contrary to the expectation, rolofylline did not prevent persistent worsening of renal function in patients with acute heart failure, volume overload and renal dysfunction. Changes in serum creatinine levels and estimated creatinine clearance were similar in both rolofylline and placebo groups. Persistent worsening of renal function occurred in 13.7% of the placebo group and 15.0% of the rolofylline group (p=0.44).

Reference

1. Adriaan A Voors, Howard C Dittrich, Barry M Massie, Paul DeLucca, George A Mansoor, Marco Metra, Gad Cotter, Beth D Weatherley, Piotr Ponikowski, John R Teerlink, John G F Cleland, Christopher M O’Connor, Michael M Givertz. J Am Coll Cardiol, 2011; 57:1899-1907.