Potential of dopamine A-1 agonists in the management of acute renal failure

Abstract

Many therapeutic approaches have been undertaken both to prevent acute ischemic or nephrotoxic renal injury and, once acute renal failure (ARF) has developed, to improve renal function and reduce mortality. To date, most therapeutic studies have investigated the effects of diuretics (eg, mannitol, furosemide), vasoactive agents (calcium channel blockers, atrial natriuretic peptide), or dopamine (a nonselective dopaminergic agent [DAA]) in one or more phases of ARF. Unfortunately, studies of the use of DAA in ARF are complicated by the existence of at least two different DAA receptors (DA-1 and DA-2), and by the stimulation of alpha- and/or beta-adrenergic receptors by high doses of DAA. The undesirable side effects of high doses of dopamine and the inconclusive results using low doses (ie, "renal doses") of dopamine (a nonselective DAA) have prompted consideration of the use of more selective dopaminergic agonists for the prophylaxis and treatment of ARF. Selective DA-1 agonists exhibit many desirable renal effects that theoretically support their use for the prophylaxis and/or treatment of ARF, including decreases in renal vascular resistance accompanied by increases in renal blood flow and glomerular filtration rate, and increases in sodium excretion and urine volume. Even at high doses, some selective DA-1 agonists, such as fenoldopam, do not stimulate DA-2 receptors, or adrenergic alpha- or beta-receptors, and thus are free of unwanted side effects (eg, arrhythmias). Results of several studies in normal and hypertensive humans, and a few studies in animal models, are consistent with the notion that DA-1 agonists may be useful in preventing or treating ARF. Careful randomized prospective clinical trials of DA-1 agonists in human ARF are needed to test this hypothesis.