POTASSIUM-DEPLETION POTENTIATES AMPHOTERICIN-B-INDUCED TOXICITY TO RENAL TUBULES

Hypokalemia and potassium depletion are frequent complications of amph otericin B therapy. Both ischemic and gentamicin-induced renal failure is potentiated by potassium depletion; it is, therefore, possible tha t amphotericin B nephrotoxicity is similarly influenced. This study ev aluated whether the acute nephrotoxic response to amphotericin B is po tassium sensitive. Potassium-depleted and control rats were subjected to an acute intravenous infusion of either amphotericin B (AmB-K; AmB, n = 10 in each) or its vehicle (V-K, V; n = 6 in each). Potassium-dep leted rats had both lower urinary daily excretion and lower plasma lev els of potassium than control animals (0.1 +/- 0.0 vs. 2.1 +/- 0.2 mEq /day, p < 0.001, and 3.8 +/- 0.2 vs. 1.9 +/- 0.1 mEq/l, p < 0.001, res pectively). In AmB and AmB-K groups, there were equivalent falls in gl omerular filtration rate and renal blood flow, and a rise in renal vas cular resistance, compared with V and V-K. In contrast, the AmB-K grou p showed a higher urinary excretion of sodium (AmB-K vs. AmB: 2.9 +/- 0.7 vs. 1.1 +/- 0.3 mu Eq/min; p < 0.05) and fractional excretion of N a (AmB-K vs. AmB: 1.6 +/- 0.4 vs. 0.6 +/- 0.1%; p < 0.05) in compariso n to the AmB group. Neither of these parameters changed in either amph otericin B or vehicle-treated groups. These results suggest that potas sium depletion does not influence the acute renovascular effects of am photericin B but potentiates its tubular toxicity. This may have clini cal implications since hypokalemia and potassium depletion are frequen t complications of amphotericin B therapy.