Diuretic strategies in patients with renal failure.

A thorough understanding of the clinical pharmacology of diuretic agents, particularly loop diuretics, is crucial in patients with abnormal (and those with normal) renal function. Renal insufficiency represents a pathophysiological state characterised by diuretic resistance. Diuretic resistance is defined as a diminished pharmacological response, or diminished natriuresis, to a given dose of a diuretic. The phenomenon of diuretic resistance is demonstrated by a shift in the dose-response curve relating urinary diuretic excretion rates (dose) with sodium excretion (response). Pharmacokinetic factors underlie the diuretic resistance observed in patients with renal failure. Diminished renal blood flow and sodium filtration, accumulation of organic acids that inhibit tubular secretion of the diuretic, and inadequate cumulative sodium excretion to meet patients' needs contribute to the diuretic-resistant state. In contrast, the pharmacological response of remnant (i.e. remaining) nephrons to diuretic agents remains intact. The time course of delivery of diuretics to their intraluminal site of action is an independent determinant of natriuretic response. An administration regimen that continuously maintains effective rates of excretion of diuretics into the urine would be expected to cause a greater overall natriuretic effect than the same amount of diuretic administered in intermittent doses. Thus, diuretic administration strategies that take account of the altered pharmacological responses in patients with renal failure are necessary to provide effective and safe treatment. Additionally, such strategies warrant revision by the prescribing physician as renal function changes over time.