Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebo-controlled clinical trial.
BACKGROUND
Acute tubular necrosis (ATN) occurs commonly in critically ill patients and is associated with increased morbidity and mortality. Fenoldopam is a dopamine receptor alpha1-specific agonist that increases renal blood flow in patients with kidney failure. We hypothesized that administration of low-dose fenoldopam during early ATN would decrease the need for dialysis therapy and/or incidence of death at 21 days.


METHODS
We conducted a prospective, randomized, double-blind, placebo-controlled, clinical trial in 155 patients with early ATN. Patients were considered eligible for enrollment if serum creatinine level increased to 50% greater than admission levels within 24 hours and mean arterial pressure was greater than 70 mm Hg. Patients were randomly assigned to the administration of placebo or fenoldopam for 72 hours.


RESULTS
Overall, 22 of 80 patients (27.5%) in the fenoldopam group reached the primary end point compared with 29 of 75 patients (38.7%) in the placebo group (P = 0.235). This 11% absolute reduction in the primary end point was not statistically significant (P = 0.23). Similarly, there was no difference in the incidence of dialysis therapy between patients randomly assigned to fenoldopam (13 of 80 patients; 16.25%) versus the placebo group (19 of 75 patients; 25.3%; P = 0.163). Moreover, there was no statistically significant difference in 21-day mortality rates between the 2 groups (fenoldopam, 13.8% versus placebo, 25.3%; P = 0.068). In secondary analyses, fenoldopam tended to reduce the primary end point in patients without diabetes and postoperative cardiothoracic surgery patients with early ATN (fenoldopam patients without diabetes, 14 of 54 patients [25.9%] versus placebo patients without diabetes, 23 of 52 patients [44.2%]; P = 0.048) and postoperative cardiothoracic patients (6 of 34 patients [17.6%] versus 14 of 36 patients [38.8%]; P = 0.049). Conversely, fenoldopam did not improve the primary end point in patients with diabetes or those with acute renal failure from other causes. A larger multicenter trial using separate randomizations for patients with and without diabetes will be needed to determine the efficacy of fenoldopam mesylate in specific subpopulations with ATN.


CONCLUSIONS
Fenoldopam does not reduce the incidence of death or dialysis therapy in intensive care unit patients with early ATN.
Emory University School of Medicine, Renal Division, Atlanta, GA 30322, USA. jtumlin@emory.edu
James A
JA
Tumlin
Kevin W
KW
Finkel
Patrick T
PT
Murray
Joshua
J
Samuels
George
G
Cotsonis
Andrew D
AD
Shaw
D003404:Creatinine / Q000097:blood; D048909:Diabetes Complications / Q000453:epidemiology; D018450:Disease Progression; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D042241:Early Diagnosis; D005260:Female; D018818:Fenoldopam / Q000009:adverse effects / Q000627:therapeutic use*; D005440:Fluid Therapy; D017052:Hospital Mortality; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000628:therapy; D007683:Kidney Tubular Necrosis, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000628:therapy; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy; D011446:Prospective Studies; D017447:Receptors, Dopamine D1 / Q000819:agonists; D006435:Renal Dialysis; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D014665:Vasodilator Agents; C098593:dopamine D1A receptor; D003404:Creatinine; D018818:Fenoldopam