Inhibition of tobramycin reabsorption in nephron segments by metabolic alkalosis.

Abstract

Chronic metabolic acidosis appears to potentiate aminoglycoside induced nephrotoxicity and renal cortical accumulation while some, but not all, studies show that bicarbonate loading reduces nephrotoxicity. The purpose of the present study was to determine if reabsorption of tobramycin in proximal and distal nephron segments in vivo is altered by systemic pH. To test this possibility on the single nephron level, 24 nl samples of [3H] tobramycin were micro-injected into proximal and distal nephron segments, and its recovery was compared to that of [14C] inulin in rats undergoing osmotic diuresis with NaHCO3 or Na2SO4 containing HCl. Results were obtained in 66 tubules in 20 rats. Although plasma and urine pH were altered as anticipated in bicarbonate-infused and acid-infused animals, urine and late proximal tubule flow rates were similar. When animals were acid infused, 24.8 +/- 1.90% of [3H] tobramycin injected into proximal nephrons was reabsorbed compared to 7.5 +/- 1.56% (P less than 0.001) when the animals were bicarbonate-infused. When [3H] tobramycin was injected into distal tubules, 5.9 +/- 0.75% was reabsorbed in acid-infused rats while virtually none of the injected tobramycin, 0.43 +/- 1.59%, was reabsorbed by the distal nephron of bicarbonate-loaded animals. Our results provide evidence that tobramycin reabsorption by both proximal and distal nephron segments is substantially reduced by bicarbonate-infusion.