Effect of amiloride on experimental gentamicin nephrotoxicity

Potassium and magnesium deficiency have been reported as risk factors for experimental gentamicin nephrotoxicity. Amiloride, a potassium-sparing diuretic, also leads to increased renal magnesium reabsorption. Amiloride, 2 mg/kg/day, was given to groups of 8-12 Fischer 344 rats receiving gentamicin, 20 mg/kg b.i.d., for 3, 7, 10 and 14 days. Control animals received the vehicle for gentamicin, amiloride alone or gentamicin alone. The degree of renal failure and weight loss were similar in gentamicin and gentamicin + amiloride groups at all time points despite increases in serum potassium and magnesium in the amiloride-treated animals. Tubular dysfunction as assessed by depression of renal cortical slice uptake of p-aminohippurate and N-methylnicotinamide was not improved by the addition of amiloride. In addition, a comparable degree of tubular necrosis and regeneration was observed in all gentamicin-treated groups. Maximum gentamicin concentrations in the renal cortex did not differ. Thus, despite reduction of urinary losses of potassium and magnesium with resultant increased serum values, amiloride did not protect against experimental gentamicin nephrotoxicity. The tubular electrolyte wasting noted clinically is likely to be a result, rather than a cause of proximal tubular cell damage.