Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure

Background - Renal function is an important prognostic factor for patients with acutely decompensated heart failure (ADHF). We investigated the renal effects of nesiritide as treatment for ADHF. Methods and Results - Randomized clinical trials comparing nesiritide with either placebo or active control for ADHF were identified by electronic and manual searches and thorough review of US Food and Drug Administration files available via the website. Worsening renal function was defined as an increase in serum creatinine > 0.5 mg/dL. Relative risk across all studies was determined by meta- analysis with Mantel-Haenszel fixed-effects models (RRMH). Risk of dialysis and medical intervention for worsening renal function were compared between therapies. Frequency of worsening renal function was determined from 5 randomized studies that included 1269 patients. Use of Food and Drug Administration - approved doses of nesiritide ( <= 0.03 mu g center dot kg(-1) center dot min(-1)) significantly increased the risk of worsening renal function compared with non - inotrope-based control (RRMH, 1.52; 95% CI, 1.16 to 2.00; P = 0.003) or any control therapy, including non - inotrope- and inotrope-based therapies (RRMH, 1.54; 95% CI, 1.19 to 1.98; P = 0.001). Even low-dose nesiritide ( <= 0.015 mu g center dot kg(-1) center dot min(-1)) significantly increased risk ( P = 0.012 and P = 0.006 compared with non - inotrope- and inotrope- based controls, respectively), as did nesiritide administered at any dose up to 0.06 mu g center dot kg(-1) center dot min(-1) ( P = 0.002 and P = 0.001, respectively). There was no difference in the need for dialysis between therapies. Conclusions - Nesiritide significantly increases the risk of worsening renal function in patients with ADHF. Whether worsening renal function reflects hemodynamic effect or renal injury is unknown, but the prognostic importance of worsening renal function suggests the need for further investigation in appropriately powered clinical trials.