Dopamine & Renal Failure

What’s the story with low dose dopamine and dopamine receptors?

Stimulation of DA1 receptors causes renal vasodilation as well as inhibition of active sodium transport in the proximal tubule, leading to natriuresis and diuresis. Stimulation of presynaptic DA2 receptors inhibits norepinephrine release and promotes peripheral vasodilation but appears to attenuate the beneficial effects of DA1 effectors on renal blood flow. Dopamine is a nonselective DA1 and DA2 agonist, and this may explain why its effect on renal blood flow is less potent than fenoldopam, a selective DA1 agonist.

Dopamine has traditionally been used as a “reno-protective” agent in low dose. Many doubt whether it has this effect. Plasma dopamine levels vary markedly (up to 10-fold) in different individuals, and it is likely that in many cases dopamine benefits the kidney by its beta-adrenergic actions (increased cardiac output, renal blood flow, and perfusion pressure). The use of low-dose dopamine may be limited by tachycardia and supraventricular and ventricular arrhythmias

Fenoldopam, a selective DA1 receptor agonist, was originally licensed for treatment if accelerated hypertetsion – it’s effect is in increased urinary flow, sodium excretion and creatinine clearance. In lower dose it has a cleaner pharmacokinetic profile than dopamine, less tachycardia, and has minimal hypotensive effects.

The possible clinical indications for LDRD appear limited to (1) as a diuretic in oliguric patients resistant to other diuretics, and (2) to convert a patient from an oliguric to a nonoliguric state. Although an increase urine output may make the clinician feel better, results of clinical studies have not conclusively proven a benefit with routine or prophylactic use of dopamine therapy in preventing or improving ARF.
A meta-analysis by Kellum and an adequately powered randomized control trial by Bellomo and colleagues have failed to demonstrate any benefit from so-called "renal dose dopamine". The continued use of dopamine for this purpose is not advised.

I have heard that dopamine may actually harm the kidneys, is this true?

Many argue that the increased urine output is simply caused by the natriuretic and diuretic effects of the drug. Although medullary blood flow may increase, medullary PO2 was shown not to be altered significantly. If dopamine increases GFR, increased solute presentation to the mTAL, with resultant increased medullary oxygen demand may result. At a time of stress, dopamine may augment medullary ischemia, which may explain why many studies have found no outcome benefit from its use. There is, however, no objective evidence that dopamine actually harms patients. In the studies referenced above, there was no demonstrable increase in adverse outcomes in the dopamine group compared with placebo.

References

   (1)  Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. Low-dose dopamine in patients with early renal dysfunction: a placebo- controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356(9248):2139-2143.

   (2)  Kellum JA, Decker M. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001; 29(8):1526-1531.

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