AMPHOTERICIN B RENAL TOXICITY IN THE DOG

¹ Department of Health, Education and Welfare, Public Health Service, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Clinical Investigations, Bethesda, Maryland

The effect of solubilized amphotericin B on the clearance of inulin and of para-aminohippurate (PAH) was studied in dogs: (a) during intravenous or intrarenal arterial infusion of the drug (5.0 mg per kg), (b) before, during and after a 4-day course of the drug (0.5 mg per kg per day) and (c) after prolonged administration (range: 149 to 223 days) of the drug (range: 7 to 47.5 mg per kg total dose). In some studies, the maximal tubular secretion of RAH (PAH Tm) was determined.

Solubilized amphotericin B given either intravenously or into the renal artery consistently produced a profound fall in the clearances of inulin and PAH, and in the PAH Tm. Grossly, the kidney became pale and soft. However, there was gradual return of the renal function tests to control values within 4 to 6 hours after drug infusion.

In each of the two dogs given solubilized amphotericin B for 4 days, the clearances of inulin and PAH and the PAH Tm were depressed following drug administration. Two weeks later, in one of the dogs, the PAH clearance remained abnormal although the inulin clearance and PAH Tm had returned to normal. The other dog's renal function tests returned to control values simultaneously.

The four dogs studied after long-term administration of solubilized amphotericin B were markedly azotemic and showed a profound depression in the clearances of inulin and of PAH.

These results suggested that solubilized amphotericin B causes marked renal vasoconstriction, which in turn causes depression of renal blood flow, glomerular filtration rate and tubular transport of PAH.

The effect of crystalline amphotericin B on the clearance of inulin and of PAH was studied during and after 4 repeated doses of the drug (5 mg per kg per dose) over a 4-hour period, and during infusion of the drug into the renal artery. In contrast to solubilized amphotericin B, a single intravenous dose of crystalline amphotericin B caused only a mild decrease in the clearances of inulin and PAH. When repeated doses of crystalline drug were given intravenously, however, there was a gradual decline of renal blood flow. Crystalline amphotericin B caused ipsilateral anuria when given into the renal artery. This latter finding was interpreted as due to mechanical obstruction of the renal vasculature by particles of the drug.

This article has been cited by other articles:

				R. D. Goldman, M. Ong, J. Wolpin, J. Doyle, C. Parshuram, and G. Koren Pharmacological Risk Factors for Amphotericin B Nephrotoxicity in Children J. Clin. Pharmacol., August 1, 2007; 47(8): 1049 - 1054. [Full Text] [PDF]