September 8, 1997

Cause of Acute Tubular Necrosis Affects Its Prognosis

Author Affiliations

for the Auriculin Anaritide Acute Renal Failure Study Group

From the Department of Medicine, Division of Nephrology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Cooper Hospital/University Medical Center, Camden, NJ (Drs Weisberg and Kurnik), and the Clinical Research Division, Scios Inc, Mountain View, Calif (Drs Genter and Allgren). Members of the Auriculin Anaritide Acute Renal Failure Study Group are listed on page 1835 of the article.

Arch Intern Med. 1997;157(16):1833-1838. doi:10.1001/archinte.1997.00440370073007

Background:  Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed.

Objective:  To test the hypothesis that the cause of ATN affects its clinical outcome.

Methods:  The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes.

Results:  Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysisfree survival improved significantly and mortality tended to decline with advancing age.

Conclusions:  Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious comorbidities in the ischemic ATN group. Advancing age was associated with improved dialysisfree survival and a tendency toward reduced mortality in patients with ischemic ATN.Arch Intern Med. 1997;157:1833-1838