Therapeutic use

The rationale for the use of loop diuretics in acute renal failure is as follows. The inhibition of tubular reabsorption in the thick ascending limb of the loop of Henle produces a cellular resting state and a decrease of oxygen consumption, thereby improving cell tolerance to hypoxia. A protective effect also occurs at the mitochondrial level and prevents the influx of calcium. Furthermore, following inhibition of salt reabsorption at the macula densa level, glomerular vasodilatation occurs secondary to a fall in afferent arteriolar resistance caused by inhibition of vasoconstrictive feedback of the tubular glomeruli. Another possibility is that the hydraulic pressure generated by the induced diuresis leads to dislodgement of obstructive tubular casts in the damaged nephrons. Finally, loop diuretics also increase the secretion of renal vasodilatory prostaglandins, thus counteracting the renal vascular constrictive feedback mechanism. Although loop diuretics are potent drugs, resistance may develop. The etiological factors responsible for the decreased efficacy of natriuretic medication are numerous and represent a mechanism of adaptation to chronic overload of Na+ at the distal part of the nephron. When this situation occurs, an association with other diuretics acting principally on another segment of the nephron is recommended; for example, metolazone is often used to circumvent this resistance (C..haQQ§L,e.t.,.al 1994).

Loop diuretics are prescribed to prevent oliguric acute renal failure or to render it non-oliguric. The rationale is that non-oliguric acute renal failure is easier to manage and may have a better prognosis than oliguric acute renal failure. Even if easier management is widely accepted, alteration of the course of acute renal failure with diuretics still needs to be proved. Indeed, spontaneously non-oliguric patients and those converting from oliguric to non-oliguric acute renal failure probably have less severe damage than oliguric patients, and thus a different outcome is expected. Other loop diuretics (e.g. ethacrynic acid, piretanide) have similar pharmacological effects, but are used less or not at all in the critically ill.

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