The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy

PURPOSE: We sought to quantify the incidence of, define risk factors for, and examine the relation between renal functional impairment and treatment with conventional amphotericin B. SUBJECTS AND METHODS: We performed a 9-year retrospective analysis of amphotericin B-associated nephrotoxicity in 494 adult inpatients who received greater than or equal to2 doses of amphotericin B. Nephrotoxicity was classified according to two nonmutually exclusive severity categories (50% increase or doubling in the baseline creatinine level). RESULTS: The median cumulative dosage of amphotericin B was 240 mg (interquartile range, 113 to 500 mg), with the majority of patients (n = 361) receiving it for empiric treatment. Overall, 139 (28%) patients experienced renal toxicity, including 58 (12%) with moderate-to-severe nephrotoxicity. The rate of nephrotoxicity was relatively constant during amphotericin B treatment. Foreach 10-mg increase in the mean daily amphotericin B dose, the adjusted rate of renal toxicity increased by a factor of 1.13 (95% confidence interval: 1.02 to 1.25). We defined 5 categorical risk factors: mean daily amphotericin B dose greater than or equal to 35 mg, male sex, weight greater than or equal to 90 kg, chronic renal disease, and use of amikacin or cyclosporine, The incidence of moderate-to-severe nephrotoxicity was 4% (6 of 137) in patients with none of these risk factors, 8% (14 of 181) in those with I risk factor, 18% (21 of 117) in those with 2 risk factors, and 29% (17 of 59) in patients with greater than or equal to3 risk factors. Nephrotoxicity rarely led to hemodialysis (n = 3); however, at the time of discharge or death, 70% of patients with moderate-to-severe nephrotoxicity had a serum creatinine level that was greater than or equal to0.5 mg/dL above baseline. CONCLUSION: Amphotericin B-related nephrotoxicity is ail important dose-dependent and duration-dependent toxicity that is accentuated by certain nephrotoxic drugs and patient characteristics. Patients with more than two risk factors for nephrotoxicity are potential candidates for alternative antifungal therapy. (C) 2001 by Exerpta Medica, Inc.