[Acute nephrotoxicity caused by amphotericin B in the dog]

Abstract

Amphotericin-B is the drug of choice for the treatment of serious systemic fungal infections. The major limitation for the use of this drug is its potential nephrotoxicity. The chronic and acute administration causes both a reduction of renal blood flow and glomerular filtration rate, determining a fall of renal concentrating ability. Our study was designed to determine the acute effects of Amphotericin-B on dogs renal function, during hydropenia and water diuresis. In addition a hemodynamic study, with the measurement of intrarenal blood flow by the microsphere method was performed. The hydropenic dogs received the drug directly into the left renal artery. There was a significant decrease in creatinine clearance, urinary osmolality, and urinary solute excretion, in the left kidney only. Amphotericin-B was infused into the aorta above the renal arteries in the group in which the water diuresis was induced. This acute infusion produced intense fall in creatinine clearance and in the free water formation, as well as in absolute excretion of sodium. The hemodynamic study showed that the reduction of creatinine clearance may be due to the decrease in renal blood flow, and the alterations in the urinary excretion of water and sodium could not be correlated with the distribution of cortical blood flow to the deep nephrons. These findings suggest that the effects of Amphotericin-B may be attributed, at least in part, to its ischemic action.