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Previous Volume 336:828-834 March 20, 1997 Number 12 Next

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ABSTRACT

Background Atrial natriuretic peptide, a hormone synthesized by the cardiac atria, increases the glomerular filtration rate by dilating afferent arterioles while constricting efferent arterioles. It has been shown to improve glomerular filtration, urinary output, and renal histopathology in laboratory animals with acute renal dysfunction. Anaritide is a 25-amino-acid synthetic form of atrial natriuretic peptide.

Methods We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial of anaritide in 504 critically ill patients with acute tubular necrosis. The patients received a 24-hour intravenous infusion of either anaritide (0.2 µg per kilogram of body weight per minute) or placebo. The primary end point was dialysis-free survival for 21 days after treatment. Other end points included the need for dialysis, changes in the serum creatinine concentration, and mortality.

Results The rate of dialysis-free survival was 47 percent in the placebo group and 43 percent in the anaritide group (P = 0.35). In the prospectively defined subgroup of 120 patients with oliguria (urinary output, <400 ml per day), dialysis-free survival was 8 percent in the placebo group (5 of 60 patients) and 27 percent in the anaritide group (16 of 60 patients, P = 0.008). Anaritide-treated patients with oliguria who no longer had oliguria after treatment benefited the most. Conversely, among the 378 patients without oliguria, dialysis-free survival was 59 percent in the placebo group (116 of 195 patients) and 48 percent in the anaritide group (88 of 183 patients, P = 0.03).

Conclusions The administration of anaritide did not improve the overall rate of dialysis-free survival in critically ill patients with acute tubular necrosis. However, anaritide may improve dialysis-free survival in patients with oliguria and may worsen it in patients without oliguria who have acute tubular necrosis.

Source Information

From the Clinical Research Division, Scios, Inc., Mountain View, Calif. (R.L.A., F.C.G.); Orlando Clinical Research Center, Orlando, Fla. (T.C.M.); University of Texas Health Science Center, Houston (S.N.R.); Cooper Hospital, Camden, N.J. (L.S.W., B.R.C.K.); Baylor University Medical Center, Dallas (A.Z.F.); New England Medical Center, Boston (R.A.L.); Kidney Disease and Critical Care Associates, Minneapolis (R.M.S.); Denver Veterans Affairs Medical Center, Denver (J.D.C.); and Brigham and Women's Hospital, Boston (M.H.S.). Presented as an abstract at the 28th Annual Meeting of the American Society of Nephrology, San Diego, Calif., Nov. 5–8, 1995, and the 13th International Congress of Nephrology, Madrid, Spain, July 2–6, 1995.

Address reprint requests to Dr. Sayegh at the Renal Division, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.

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