The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy

PURPOSE: We sought to quantify the incidence of, define risk factors for, a nd examine the relation between renal functional impairment and treatment w ith conventional amphotericin B. SUBJECTS AND METHODS: We performed a 9-year retrospective analysis of ampho tericin B-associated nephrotoxicity in 494 adult inpatients who received gr eater than or equal to2 doses of amphotericin B. Nephrotoxicity was classif ied according to two nonmutually exclusive severity categories (50% increas e or doubling in the baseline creatinine level). RESULTS: The median cumulative dosage of amphotericin B was 240 mg (interqu artile range, 113 to 500 mg), with the majority of patients (n = 361) recei ving it for empiric treatment. Overall, 139 (28%) patients experienced rena l toxicity, including 58 (12%) with moderate-to-severe nephrotoxicity. The rate of nephrotoxicity was relatively constant during amphotericin B treatm ent. Foreach 10-mg increase in the mean daily amphotericin B dose, the adju sted rate of renal toxicity increased by a factor of 1.13 (95% confidence i nterval: 1.02 to 1.25). We defined 5 categorical risk factors: mean daily a mphotericin 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 cycl osporine, The incidence of moderate-to-severe nephrotoxicity was 4% (6 of 1 37) in patients with none of these risk factors, 8% (14 of 181) in those wi th 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. Nephrotoxi city rarely led to hemodialysis (n = 3); however, at the time of discharge or death, 70% of patients with moderate-to-severe nephrotoxicity had a seru m creatinine level that was greater than or equal to0.5 mg/dL above baselin e. CONCLUSION: Amphotericin B-related nephrotoxicity is ail important dose-dep endent and duration-dependent toxicity that is accentuated by certain nephr otoxic drugs and patient characteristics. Patients with more than two risk factors for nephrotoxicity are potential candidates for alternative antifun gal therapy. (C) 2001 by Exerpta Medica, Inc.