Amphotericin B is the treatment of choice for severe systemic
fungal infections. Nephrotoxicity is the most clinically significant adverse effect, but studies examining nephrotoxicity in children are scarce. Nephrotoxicity includes decreased glomerular filtration rate and distal tubulopathy with urinary loss of
potassium and
magnesium,
renal tubular acidosis, loss of urine concentrating ability, and sometimes Fanconi's syndrome. The mechanisms involved in nephrotoxicity include the use of
deoxycholate, the vehicle for
amphotericin, reduction in renal blood flow and glomerular filtration rate, increased
salt concentrations at the macula densa, interaction of
amphotericin with
ergosterol in the cell membrane, and apoptosis in proximal tubular cells and medullary interstitial cells. Some risk factors for
amphotericin nephrotoxicity have been determined over the years. Cumulative dosage,
treatment duration, and dosing schedule as well as the combination of
amphotericin with other nephrotoxic drugs, such as
diuretics and
cyclosporine, are important risk factors. Mechanisms to prevent nephrotoxicity include the use of
lipid formulations such as
amphotericin B lipid complex,
amphotericin B colloidal dispersion, and
liposomal amphotericin B and the concurrent use of volume repletion.
Amiloride can be considered in serious
potassium loss.