Reduced Nephrotoxicity of Conventional Amphotericin B Therapy after Minimal Nephroprotective Measures: Animal Experiments and Clinical Study

Amphotericin B (AmB)-treated rats develop severe polyuria, polydypsia, impairment of renal concentrating ability, and morphologic signs of tubular damage. However, renal insufficiency develops quickly only in animals in which water intake is restricted to the median volume drunk by rats of the control group. Therefore, vigorous hydration seems crucial for prevention of AmB-induced nephrotoxicity. In a clinical study, 61 patients with hematologic malignancies receiving AmB therapy were massively hydrated to ensure urine output of > or =4000 mL/day. Urine sodium, potassium, and magnesium were also measured, and all losses were supplemented (potassium as a 7.45% solution via central venous catheter). AmB-treated patients developed signs of renal tubular damage (increased fractional excretion of sodium and potassium) and required large amounts of ion supplementation. The serum ion concentration and creatinine clearance remained stable. No clinically significant renal damage developed to force premature cessation of AmB treatment.