Limitation on the use of amiloride in early renal failure

Summary

The effect of a single oral dose of 10 mg amiloride was studied on urinary excretion of Na⁺, K⁺, Ca⁺⁺ and Mg⁺⁺ in healthy subjects and in patients with varying degrees of renal impairment. Amiloride produced a moderate diuresis and sodium excretion, and a slight calciuresis. Urinary excretion of potassium was significantly reduced as compared to the controls. Despite its diuretic and natriuretic effects, amiloride did not change the excretion of Mg⁺⁺ as compared to the pretreatment period. When the creatinine clearance was below 50 ml/min, the net excretion of Na⁺ and Ca⁺⁺ was drastically reduced. However, K⁺ retention and neutrality of Mg⁺⁺ excretion were maintained down to end-stage renal disease. In the healthy volunteers the mean elimination half-life of amiloride was 20 h, and it rose to about 100 h in end-stage renal disease. This was because about 3/4 of native amiloride was eliminated through the kidney. Nonrenal elimination of amiloride was calculated to amount to only 1/4 of the total elimination. Therefore, the antikaliuretic amiloride is a valuable comedication in subjects with normal kidney function to prevent K⁺ and Mg⁺⁺ loss. However, its use is hazardous if plasma creatinine is raised.