THE INFLUENCE OF SODIUM STATUS AND FUROSEMIDE ON CANINE ACUTE AMPHOTERICIN-B NEPHROTOXICITY

Abstract

The influence of Na balance and furosemide administration on acute amphotericin B[antifungal agent]-induced nephrotoxicity was investigated in the anesthetized dog. In Na-depleted dogs, amphotericin B (1 mg/kg i.v.) reduced renal blood flow by 32% and glomerular filtration rate by 90% 40 min after the infusion and 32 and 65%, respectively, 140 min after infusion. Filtration fraction was reduced, fractional Na excretion increased 13-fold. Renal renin secretion rate decreased by 64%. Prior Na loading abolished the acute response to amphotericin B. Pretreatment of Na-depleted dogs with furosemide (5 mg/kg bolus followed by 260 .mu.g/kg per min i.v.) attenuated the reduction in renal blood flow and glomerular filtration rate produced by amphotericin B. Acute reductions in renal blood flow and glomerular filtration rate in response to amphotericin B infusion are not direct but related to Na status. The changes do not seem to be mediated by the renin-angiotensin system and can be inhibited by Na loading and attenuated by concurrent furosemide administration. These observations are consistent with the hypothesis that the acute response is mediated by tubulo-glomerular feedback.