Risk factors for amphotericin B-induced nephrotoxicity

The association of amphotericin B with nephrotoxicity is well known, but risk factors for this complication are not well characterized. One hundred and seventy-eight patients who received > 3 days of intravenous amphotericin B and a minimal total cumulative dose > 100 mg were reviewed retrospectively. The mean age, average cumulative dose of amphotericin B and duration of therapy were 46 +/- 22 years, 536 +/- 547 mg and 16.6 +/- 8.2 days, respectively. Eighty-six percent of patients received amphotericin B for empirical therapy of febrile neutropenia. Various definitions of nephrotoxicity were used; these were as follows (the incidence of nephrotoxicity as determined by the given definition is given in parentheses): definition 1, a change in creatinine of > 46 mumol/L over baseline (50%); definition 2, a doubling of creatinine over baseline (49%); definition 3, a change in creatinine of > 92 mumol/L (29%); definition 4, a doubling and/or a change in creatinine of > 92 mumol/L (49%); definition 5, an increase in creatinine to > 230 mumol/L (8%). Multivariate analysis showed that nephrotoxicity was associated with a greater cumulative dose of amphotericin B and receipt of concomitant nephrotoxic drugs for all definitions (P < 0.05). In those patients who experienced severe nephrotoxicity (creatinine increased to > 230 mumol/L), cyclosporin therapy was the most significant risk factor (odds ratio 18.8, P = 0.022). Haemodialysis was necessary in one patient, but multiple concomitant risk factors for renal dysfunction were present. No patient experienced irreversible nephrotoxicity. These findings allow for stratification of patients at risk for amphotericin B-induced nephrotoxicity and rational use of alternative agents.