The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy

• Published in: The American journal of medicine Vol. 111; no. 7; pp. 528 - 534
• Main Authors: Harbarth, Stephan, Pestotnik, Stanley L, Lloyd, James F, Burke, John P, Samore, Matthew H
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2001; Elsevier; Elsevier Sequoia S.A
• Subjects: Adult; Aged; Amphotericin B - adverse effects; Amphotericin B - therapeutic use; Biological and medical sciences; Dose-Response Relationship, Drug; Drug therapy; Drug toxicity and drugs side effects treatment; Epidemiology; Female; Health risk assessment; Humans; Kidney - drug effects; Kidneys; Male; Medical sciences; Pharmacology. Drug treatments; Proportional Hazards Models; Retrospective Studies; Risk Factors; Toxicity; Toxicity: urogenital system; Kidney disease; Human; Antifungal agent; Urinary system disease; Amphotericin B; Polyenic compound; Toxicity; Risk factor; Epidemiology; Kidney; Incidence
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/S0002-9343(01)00928-7

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. We performed a 9-year retrospective analysis of amphotericin B-associated nephrotoxicity in 494 adult inpatients who received ≥2 doses of amphotericin B. Nephrotoxicity was classified according to two nonmutually exclusive severity categories (50% increase or doubling in the baseline creatinine level). 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. For each 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 ≥35 mg, male sex, weight ≥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 1 risk factor, 18% (21 of 117) in those with 2 risk factors, and 29% (17 of 59) in patients with ≥3 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 ≥0.5 mg/dL above baseline. Amphotericin B-related nephrotoxicity is an 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.