There is continuing debate as to the merits of vasoactive agents and diuretics in the amelioration and prevention of ARF. Of these perhaps the most widely used is dopamine. Two dopamine-specific receptors have been identified. Dopamine-1 (D1) receptors are located on vascular smooth muscle cells. Dopamine-2 (D2) receptors are found predominantly on presynaptic terminals of post-ganglionic sympathetic nerves. Stimulation of D2 receptors results in decreased noradrenaline release and passive vasodilation. Both receptors are found in the kidney. Dopamine can also stimulate peripheral a and cardiac b1 adrenoreceptors. The benefits to renal function have been attributed to use of dopamine at relatively low dosage. Doses of 0.5 - 1.0 microg/kg/min primarily activates D1 and D2 receptors resulting in vasodilation while doses of 2 - 3 microg/kg/min causes stimulation of b1 receptors, increasing cardiac output. These two actions will support renal blood flow and GFR. Higher doses lead to stimulation of a1 and a2 receptors and a predominantly vasoconstrictor action.
There is little good controlled data on the efficacy of dopamine in ARF, particularly in children. However evidence suggests that dopamine does not have a significant effect on the outcome of ARF. A number of studies have combined dopamine with furosemide and shown an improvement in azotaemia and shortening of the duration of ARF.
Furosemide inhibits metabolically demanding chloride-pumps in the thick ascending limb of the loop of Henle. It may therefore reduce oxygen requirements in the renal medulla, where oxygen delivery is precarious. Experience suggests that it is helpful to give furosemide when intravascular volume is replete and urine is still being produced, although there is no conclusive evidence of benefit. The furosemide should be administered as an infusion rather than boluses, as toxicity is reduced and the dose response improved. The dose can be 0.1 - 4 mg/kg/hr, higher doses being needed in renal failure. Once anuria is established, further furosemide is of no benefit.
Calcium-channel blockers are now widely used to improve renal function post-transplantation and a possible benefit in ARF has been proposed. The effect in transplant patients is likely to be related to its ability to counter the renal vasoconstrictor effect of cyclosporine. A beneficial effect of verapamil plus frusemide was noted in a study of 6 patients with established ARF secondary to malaria or leptospirosis comparing them with 6 patients given iv frusemide alone. Recovery of GFR was faster in the verapamil group. The same workers have also shown a benefit of another calcium-channel blocker, gallopamil in a mixed group of ARF patients.
Atrial natruretic peptides (ANP) have given promising results in experimental models of ARF and may be of value in improving renal function and decreasing the need for dialysis in established ARF. However a recent multicentre study involving 504 critically ill adults with ARF failed to improve the overall rate of dialysis-free survival. It did improve dialysis-free survival in patients with oliguria, but appeared to worsen it in patients without oliguria who had acute tubular necrosis.