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 NH4Cl-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)Pco2 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)Pco2 gradient during administration of the HCO3 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)Pco2. The normal (U-B)Pco2 was interpreted as the result of normal H+ secretion during alkalinization of the urine. The low (U-B)Pco2 in the second group was attributed to the low urinary HCO3 concentration.

3. In order to investigate the effect of large concentrations of amphotericin on distal H+ secretion, amphotericin was administered acutely to HCO3-loaded rats. Acute intravenous administration of amphotericin resulted in a significant decrease in (U-B)Pco2 and urine HCO3 concentration; the decrease in urinary Pco2 was of greater magnitude than the decrease in urine HCO3 concentration, leading to a rise in urine pH. The maximum urine pH achieved during HCO3 loading (maximal urine HCO3 was the same in both groups) was significantly higher in the animals infused acutely with amphotericin than in controls, thus indicating that amphotericin-treated animals have a distal acidification defect. These data are compatible with the hypothesis that amphotericin induces an acidification defect by increasing H+ back-diffusion in the form of carbonic acid or dissolved CO2 when the urine is highly alkaline and in the form of weak acid or proton when the urine is acid.

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