The mechanism of amphotericin-induced distal acidification defect in rats.

1. The effect of chronic and acute administration of amphotericin B on renal function, especially urinary acidification, was studied in rats. Chronic intraperitoneal administration of amphotericin B resulted in blood concentrations similar to or higher than those seen in patients treated with the antibiotic, but failed to produce hyperchloraemic acidosis. The minimum urine pH achieved during NH,Cl-induced acidosis was significantly higher in amphotericin-treated rats than in controls; net acid excretion, however, was not significantly different from that of controls. These data were interpreted as indicating the presence of an incomplete distal acidification defect. 2. The ability to raise urine-blood (U-B)Pco, during alkalinization of the urine was examined in another group of amphotericin-treated rats. The data on amphotericin-treated rats could be artificially divided into two groups. One group had a normal glomerular filtration rate (GFR) and was able to raise the (U-B)Pco, gradient during administration of the HCO, to the same as that seen in control rats infused with the vehicle for amphotericin, sodium deoxycholate. The second group, which comprised only 15% of the total, had a decreased glomerular filtration rate and an abnormally low (U-B)Pco,. The normal (UB)Pco, was interpreted as the result of normal H+ secretion during alkalinization of the urine. The low (U-B)Pco, in the second group was attributed to the low urinary HCO; concentration.