Authors: Bove T et al., JAMA 2014 Sep 29;
No difference between placebo and this renal vasodilator was seen, except for fenoldopam-associated hypotension.
Acute kidney injury (AKI) commonly occurs after cardiac surgery and can increase costs, morbidity, and mortality. Effective strategies to prevent AKI have been elusive. Small, single-center trials and meta-analyses have suggested that fenoldopam — a selective agonist of the dopamine D1 receptor, with renal vasodilatory and natriuretic effects — effectively reduces AKI. These researchers designed a randomized, double-blind, multicenter study to more definitively assess fenoldopam’s effect on AKI after cardiac surgery (NCT00621790).
Among 9235 cardiac-surgery patients who agreed to participate, 667 developed early AKI (creatinine increases of greater than 50% over baseline, or oliguria) and were randomized in intensive care units (ICUs) to infusion of fenoldopam or placebo (mean age, 70; 64% men; 43% undergoing coronary artery bypass grafting). Infusions lasted 96 hours or until ICU discharge or death. The groups did not differ on the primary endpoint, renal replacement therapy instituted at the treating clinician’s discretion (fenoldopam group, 20%; placebo group, 18%). No group differences were seen in death rate (in the ICU or at 30 days), time requiring mechanical ventilation, length of ICU and hospital stays, or worsening AKI. Significantly more patients receiving fenoldopam than placebo developed hypotension (26% vs. 15%). The study was terminated early due to futility.
In this rigorous trial, fenoldopam did not benefit patients, but did cause more hypotension. Despite the enthusiasm of earlier studies and the theoretical appeal of a renal vasodilator to prevent progressive AKI after high-risk events, this study should put the brakes on fenoldopam for this use. The investigators note that the elevated hypotension risk may signal that fenoldopam dosing was too high. However, the burden of proof falls upon the agent; until evidence of benefit is forthcoming, fenoldopam should not be considered for this purpose — and one might also question its utility in broader clinical situations involving high AKI risk.