The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy.
OBJECTIVE
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.


METHODS
We performed a 9-year retrospective analysis of amphotericin B-associated nephrotoxicity in 494 adult inpatients who received > or = 2 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. 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 > or = 35 mg, male sex, weight > or = 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 > or = 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 > or = 0.5 mg/dL above baseline.


CONCLUSIONS
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.
Harbarth
S
S
Division of Infectious Diseases, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Pestotnik
S L
SL
Lloyd
J F
JF
Burke
J P
JP
Samore
M H
MH
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors
D000666:Amphotericin B