Preventing contrast-induced nephropathy with fenoldopam.
Fenoldopam is an interesting orphan drug that is a variant of dopamine. It differs significantly from dopamine in that it is a specific agonist for the type I (DA-1) receptor. The DA-1 receptors are particularly prominent in the renal vasculature, renal tubules, mesenteric vasculature, and peripheral vessels. The DA-1 receptor stimulation vasodilates renal and peripheral vessels, causing a decrease in blood pressure and an increase in renal blood flow (RBF). Stimulation of the DA-1 receptors in the tubules causes an increase in sodium excretion, which gives rise to an increase in urine volume on the basis of a sodium natriuresis. Animal testing with fenoldopam has indicated that it is 6 times more potent than dopamine in its ability to decrease renal vascular resistance and increase RBF; this suggests that it could be a much more selective and potent renal protective agent against any toxin or stimulus that causes renal dysfunction by reducing RBF or increasing renal ischemia. The clinical activity of fenoldopam, which is administered intravenously, begins almost immediately and is clearly noticeable after 5 minutes. The drug has no rebound effect, and its use can be stopped at any time. The protocol for the use of fenoldopam as a renal protective agent (performed at the University of Minnesota) involves starting an intravenous fenoldopam infusion 2 hours before the procedure at a rate of 0.1 microg/kg/min and increasing the dose in increments of 0.1 microg/kg/min every 20 minutes, until a rate of 0.5 microg/kg/min is reached or the systolic blood pressure falls more than 40 mm Hg (or below 110 mm Hg). Any infusion level at or above 0.1 microg/kg/min is considered acceptable because the response in individual patients varies so widely. The fenoldopam infusion is maintained at the maximum rate throughout the procedure and for up to 4 hours after the end of the contrast administration. At the University of Minnesota, we have had anecdotal experience using the drug in 29 patients. The drug was used for patients who were thought to be at the highest risk for contrast-induced nephropathy, ie, patients who have both diabetes and pre-existing renal failure. In this small group of patients in whom hydration and other variables were not controlled, there was a startling lack of contrast-induced creatinine increase at any point during the 24 to 48 hours after the administration of contrast in all but 1 patient. Our experience suggests that fenoldopam may be of distinct benefit to high-risk patients who need intravascular contrast, especially those who may receive a large contrast dose, such as patients undergoing peripheral or coronary angiography and intervention and/or computed tomography. Although it is impossible on the basis of simple anecdotal case reports to determine whether or not the drug was the primary reason that such a marked protective effect was seen, the results are promising enough to indicate that a careful, prospective, randomized trial of fenoldopam versus hydration is warranted.
Hunter
D W
DW
Department of Radiology, MMC 292, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Chamsuddin
A
A
Bjarnason
H
H
Kowalik
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects* / Q000592:standards; D018491:Dopamine Agonists / Q000592:standards / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D018818:Fenoldopam / Q000592:standards / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D012039:Regional Blood Flow / Q000187:drug effects; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use
D003287:Contrast Media; D018491:Dopamine Agonists; D014665:Vasodilator Agents; D018818:Fenoldopam