Magnesium- and potassium-sparing effects of amiloride. Review and recent findings

One of the most common and most serious side-effects of diuretic therapy is an increased urinary loss of potassium. Another, although less well publicized, side-effect of diuretic therapy is excessive loss of urinary magnesium. Loop-blocking diuretics, especially, cause major losses of urinary magnesium, and this is consistent with micropuncture studies in laboratory animals which indicate that the loop of Henle is a major site of magnesium reabsorption. Potassium-sparing diuretics such as amiloride can be administered concomitantly with more potent diuretics to counteract diuretic-induced potassium depletion. Amiloride may also exert magnesium-sparing actions. Our experimental investigations and clinical studies with congestive heart failure patients, providing evidence for both potassium- and magnesium-sparing actions of amiloride, will be discussed. In saline-loaded rats, the magnesium-sparing effect of amiloride was demonstrated when amiloride was administered either alone or in combination with furosemide. Renal clearance studies in rats indicated that the magnesium-sparing effect of amiloride was a direct renal action and not secondary to possible extra-renal actions. A dose-response relationship has been established for the actions of amiloride in reducing fractional excretion of magnesium and potassium during furosemide diuresis in rats. Congestive heart failure patients being treated with furosemide were found to be both potassium and magnesium deficient as indicated by reduced lymphocyte potassium and magnesium. In these patients, amiloride reduced urinary magnesium and potassium, increased plasma magnesium and potassium and also increased lymphocyte magnesium and potassium. The magnesium-sparing actions of amiloride may have important therapeutic implications in that many experimental and clinical studies from our laboratory and from other investigators have shown that magnesium plays an important role in the maintenance and restoration of cellular potassium.