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| |  ASN: Fenoldopam Buffers Kidney in Acute Tubular Necrosis By Roberta Friedman, PhD SAN DIEGO, CA -- November 21, 2003 -- Fenoldopam mesylate can interrupt acute tubular necrosis by providing blood flow to the part of the kidney placed at risk after bypass surgery. This finding from a 3-centre, randomised, blinded trial of the dopamine agent was presented here November 17th at the 36th Annual Meeting of the American Society of Nephrology. Patients randomised to take fenoldopam had an 8% absolute reduction in rate of death or need for dialysis in the trial. For non-diabetics, the difference in this primary study outcome reached statistical significance (P < .0042). The results are "not enough to change practice," said study investigator James Tumlin, MD, associate professor, Emory University Medical School, Atlanta, Georgia, United States. But the results do indicate that nephrologists should be brought into the treatment process earlier in the course of the decline in kidney function that can follow open-heart surgery, said Dr. Tumlin in an interview. When creatinine bumps up 50% from baseline at hospital entry, Dr. Tumlin said, a third of patients will either die or have to go on dialysis by day 21. "That's the bottom line," he stated. Diabetics may be put at risk of further damage to the kidney by the drug, which acts selectively at dopamine 1 receptors to dilate the renal vasculature. Dr. Tumlin speculated that the outermost medulla is already vasodilated in diabetics to compensate for the damage they are experiencing. When given a vasodilator, the other parts of the kidney vasculature will dilate more and capture the blood flow, exacerbating tubular necrosis. Diabetics in the study showed a trend towards higher mortality or need for dialysis. The 3 study centres enrolled 155 patients who met criteria of a 50% rise in creatinine from days 1 and 2 of hospitalisation. If patients couldn't maintain a mean arterial pressure of 60 mm Hg, they were pulled from the study. Investigators ran into problems finding appropriate patients, as the thoracic surgeons began to use the drug. "We were victims of our own salesmanship," Dr. Tumlin said. Patients randomised to receive fenoldopam began at a 0.05 mcg/kg/min infusion that was titrated up to 0.2 mcg/kg/min and continued for 72 hours. The mean age of the study subjects was 56. Low blood pressure in the period surrounding surgery was the most common cause of acute tubular necrosis (75%). A third of the participants in this study were diabetic. Thirteen percent of the patients died, with 82% mortality among those who required dialysis. "Most of our patients were not oliguric," Dr. Tumlin noted. Only 21% of placebo patients had oliguria (19% of all study patients produced less than 500 ml of urine daily). Dialysis was required if creatinine was above 6 mg/dl, or if acidosis or pulmonary oedema proved intractable. The mean creatinine at enrollment was 1.21 mg/dl. Serum creatinine separated by day 2 of the treatment, but not significantly. Still, Dr. Tumlin said, "We think this is an encouraging finding." Ten patients had a blood pressure crash -- enough to require stopping fenoldopam -- but were retitrated, said Dr. Tumlin in response to audience query. "We successfully gave the drug to a very sick population." Dr. Tumlin receives research support from Abbott, but this study was funded by the National Heart, Blood, and Lung Institute.
[Study Title: Dopamine receptor 1 agonists in early acute tubular necrosis: A prospective, randomized, double blind, placebo-controlled trial of fenoldopam mesylate. Abstract PUB001]
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