Dopamine, Nesiritide Do Not Improve Kidney Function in Acute HF
Adding low-dose dopamine or low-dose nesiritide to diuretic therapy did not preserve renal function or enhance urine output in patients with acute heart failure and renal dysfunction, despite previous evidence suggesting otherwise.
The clinical trial yielding those results was conducted by cardiologist Horng H. Chen, MBBCh, of the Mayo Clinic in Rochester, Minn., and fellow investigators. As the team explained in the Journal of the American Medical Association, dopamine, an endogenous catecholamine, may promote renal vasodilatation at doses no higher than 3 µg/kg/min. Nesiritide is human recombinant B-type natriuretic peptide approved for the management of acute heart failure: The recommended dose of 2 µg/kg bolus followed by infusion at 0.01 µg/kg/min reduces blood pressure and atrial pressures and produces modest improvement in dyspnea, but does not improve clinical outcomes or renal function, Dr. Chen and colleagues noted.
The group's project—the Renal Optimization Strategies Evaluation (ROSE)—involved 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate 15–60 mL/min/1.73m2). Participants were randomized within 24 hours of admission to active treatment with dopamine or with nesiritide, or to placebo.
The 122 dopamine patients received 2 µg/kg/min for 72 hours, infused via vascular access. The 119 nesiritide recipients were given 0.005 µg/kg/min for 72 hours via peripheral intravenous access without initial bolus. These groups were then compared with the pooled group of 119 placebo recipients on the primary decongestion endpoint of 72-hour cumulative urine volume and on the primary renal function end point of serum cystatin C from enrollment to 72 hours. All patients received open-label, intravenous loop diuretics; the recommended total daily dose was equal to 2.5 times the total daily oral outpatient furosemide (or equivalent) dose at 7 days before admission, up to a maximum of 600 mg per day.
Compared with placebo, neither low-dose dopamine nor low-dose nesiritide had any significant effect on 72-hour cumulative urine volume (dopamine, 8,524 mL; nesiritide, 8,574 mL; placebo, 8,296 mL) or on the change in cystatin C level (dopamine, 0.12 mg/L; nesiritide, 0.07 mg/L; placebo, 0.11 mg/L). Compared with placebo, the agents also had no effect on other urine measure, weight change, renal function, or clinical outcomes.
According to the authors, the current findings differ from those of previous small studies that suggested benefits of these treatments because most of those studies did not target persons with renal dysfunction, included only patients with ejection fraction less than 40%, used higher dopamine doses, and used variable durations of dopamine infusion.