Amphotericin B Nephrotoxicity in Children

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.