Atrial Natriuretic Peptide Helpful for Acute Ischemic Renal Failure

Laurie Barclay, MD

June 21, 2004

June 21, 2004 -- Human atrial natriuretic peptide (h-ANP) infusion is helpful for managing acute ischemic renal failure, according to the results of a randomized trial published in the June issue of Critical Care Medicine. The commentator suggests that these results are encouraging but need confirmation.

“Acute renal failure is associated with significant morbidity and mortality rates. Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery,” write Kristina Sward, MD, from Sahlgrenska University Hospital in Göteborg, Sweden, and colleagues. “H-ANP is a potent endogenous natriuretic and diuretic substance. Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure.”

In this prospective, double-blind study conducted at the cardiothoracic intensive care units of two tertiary care centers, 61 patients were randomized to receive a continuous infusion of either recombinant h-ANP (50 ng/kg/min) or placebo when serum creatinine increased by more than 50% from baseline. The treatment with h-ANP or placebo continued until serum creatinine decreased below the trigger value for inclusion, or until patients fulfilled predefined criteria for dialysis.

All patients had normal preoperative renal function and postcardiac surgical heart failure requiring significant inotropic and vasoactive support. The primary outcome was dialysis on or before day 21 after starting treatment, and secondary outcomes were dialysis-free survival at day 21 and creatinine clearance.

Dialysis before or at day 21 occurred in six (21%) of 29 patients in the h-ANP group and in 14 (47%) of 30 patients in the placebo group (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.10 - 0.73; P = .009).

The combined end point of dialysis or death before or at day 21 occurred in eight patients (28%) in the h-ANP group and in 17 patients (57%) in the placebo group (HR, 0.35; 95% CI, 0.14 - 0.82; P = .017). Compared with placebo, h-ANP improved creatinine clearance ( P = .040).

Study limitations were relatively small sample size and differing proportions of diabetics in the treatment groups.

“Infusion of h-ANP at a rate of 50 ng/kg/min enhances renal excretory function, decreases the probability of dialysis, and improves dialysis-free survival in early, ischemic acute renal dysfunction after complicated cardiac surgery,” the authors write.

In an accompanying commentary, Damien du Cheyron, MD, from Caen University Hospital in France, reviews the demographics, clinical characteristics, and treatment options for acute renal failure in all hospitalized patients as well as in the subgroup of cardiac surgery patients undergoing cardiopulmonary bypass. He describes the use of h-ANP as “a novel approach to prevent renal dysfunction that seems to be effective in ameliorating early postoperative nephropathy caused by complicated cardiac surgery.”

Dr. du Cheyron adds, “Overall, considering these results in a specific population of patients with early acute renal dysfunction following complicated cardiac surgery, prevention of [acute renal failure] with low-dose and long-term infusion of atrial natriuretic peptide is quite encouraging. The next step now should be to confirm the performance of this old new promising drug in a large multiple-center, randomized, placebo-controlled trial in reducing [acute renal failure]-related dialysis and mortality rate by using the same infusion rate of h-ANP.”

Crit Care Med. 2004;32:1310-1315, 1421-1422

Reviewed by Gary D. Vogin, MD