Atrial Natriuretic Factor in Oliguric Acute Renal Failure Julia Lewis, MD, Mahmoud M. Salem, MD, Glenn M. Chertow, MD, Lawrence S. Weisberg, MD, Frank McGrew, MD, Thomas C. Marbury, MD, and Robin L. Allgren, MD, PhD, for the Anaritide Acute Renal Failure Study Group ● Atrial natriuretic peptide (ANP), an endogenous hormone synthesized by the cardiac atria, has been shown to improve renal function in multiple animal models of acute renal failure. In a recent multicenter clinical trial of 504 patients with acute tubular necrosis (oliguric and nonoliguric), ANP decreased the need for dialysis only in the oliguric patients. In the present study, 222 patients with oliguric acute renal failure were enrolled into a multicenter, randomized, double-blind, placebo-controlled trial designed to assess prospectively the safety and efficacy of ANP compared with placebo. Subjects were randomized to treatment with a 24-hour infusion of ANP (anaritide, 0.2 g/kg/min; synthetic form of human ANP) or placebo. Dialysis and mortality status were followed up for 60 days. The primary efficacy end point was dialysis-free survival through day 21. Dialysis-free survival rates were 21% in the ANP group and 15% in the placebo group (P  0.22). By day 14 of the study, 64% and 77% of the ANP and placebo groups had undergone dialysis, respectively (P  0.054), and 9 additional patients (7 patients, ANP group; 2 patients, placebo group) needed dialysis but did not receive it. Although a trend was present, there was no statistically significant beneficial effect of ANP in dialysis-free survival or reduction in dialysis in these subjects with oliguric acute renal failure. Mortality rates through day 60 were 60% versus 56% in the ANP and placebo groups, respectively (P  0.541). One hundred two of 108 (95%) versus 63 of 114 (55%) patients in the ANP and placebo groups had systolic blood pressures less than 90 mm Hg during the study-drug infusion (P < 0.001). The maximal absolute decrease in systolic blood pressure was significantly greater in the anaritide group than placebo group (33.6 versus 23.9 mm Hg; P < 0.001). This well-characterized population with oliguric acute renal failure had an overall high morbidity and mortality. © 2000 by the National Kidney Foundation, Inc. INDEX WORDS: Atrial natriuretic factor; acute renal failure (ARF); atrial natriuretic peptide (ANP). A CUTE TUBULAR necrosis (ATN) is a com- mon and clinically severe form of acute renal failure resulting from either decreased re- nal blood flow caused by hypotension, sepsis, or trauma or from toxic renal injury. Examples of toxic insults include exposure to intravenous (IV) radiographic contrast agents or certain anti- biotic classes. Patients with acute renal failure experience high morbidity and mortality. 1 Cur- rently, there are no specific treatments to prevent or accelerate recovery from acute renal failure. Atrial natriuretic peptide (ANP) is an endoge- nous hormone synthesized by the cardiac atria 2 shown to improve renal function in multiple animal models of ATN. 3,4 ANP is known to preferentially dilate afferent and efferent arte- rioles of the renal microcirculation, augmenting filtration fraction and increasing glomerular filtra- tion rate. 5 Anaritide (Auriculin anaritide; Scios, Sunnyvale, CA) is a 25–amino acid synthetic form of human ANP. In a recent multicenter, randomized, double-blinded, placebo-controlled study, 504 subjects withATN were administered a 24-hour IV infusion of either placebo or anari- tide. 6 In that study, treatment with anaritide had no beneficial effect on dialysis requirements or mortality in a heterogeneous general ATN study population or in subjects with nonoliguric ATN. 6 However, in subjects with oliguric ATN, anari- tide administration was associated with an im- provement in 21-day dialysis-free survival rates from 8% in the placebo group to 27% in the anaritide group (P = 0.008). To prospectively examine the effect of anari- tide in oliguricATN, we conducted a multicenter, randomized, double-blind, placebo-controlled study of anaritide in patients with oliguric ATN. From the Division of Nephrology, Vanderbilt University Medical Center, Nashville; Baptist Clinical Research Ser- vice, Memphis, TN; University Medical Center, Jackson, MS; Brigham and Women’s Hospital, Boston, MA; Cooper Hospital, University Medical Center, Camden, NJ; Orlando Clinical Research Center for Internal Medical Specialists, Orlando, FL; and Scios, Inc, Sunnyvale, CA. Additional institutions and investigators participating in the clinical trial are listed in the Appendix. Received February 7, 2000; accepted in revised form May 12, 2000. Supported by Scios, Inc. Address reprint requests to Julia Lewis, MD, Vanderbilt University Medical Center, Division of Nephrology, S-3223 Medical Center North, Nashville, TN 37232-2372. E-mail: julia.lewis@mcmail.vanderbilt.edu © 2000 by the National Kidney Foundation, Inc. 0272-6386/00/3604-0013$3.00/0 doi:10.1053/ajkd.2000.17659 American Journal of Kidney Diseases, Vol 36, No 4 (October), 2000: pp 767-774 767