Retrospective Cohort Analysis of Liposomal Amphotericin B Nephrotoxicity in Patients with Hematological Malignancies

ABSTRACT We retrospectively examined the incidence, onset, risk factors, and outcomes of renal injury during 103 treatment courses of liposomal amphotericin B (L-AMB) in 97 adult patients with hematological malignancies. All the patients were analyzed before, during, and after the administration of L-AMB, and renal injury was graded according to the RIFLE criteria (risk, injury, failure, loss of function, end-stage renal disease). Most patients (87.3%) received L-AMB at 3 mg/kg of body weight/day. Nearly two-thirds (61.7%) of the treatment courses did not meet any RIFLE category for renal injury, while 19.4% of patients were classified at risk, 13.6% met an injury classification, and 5.8% were categorized as developing renal failure. However, 15% of the patients developed renal injury within 48 h of the onset of multiorgan failure associated with sepsis, bleeding, or progressing malignancy. When these patients were analyzed as a competing risk for L-AMB-associated renal injury (RIFLE category I or above) in a multivariate Cox regression model, receipt of cyclosporine (subhazard ratio SHR, 2.62; 95% confidence interval CI, 1.10 to 6.27; P = 0.03), cyclosporine plus furosemide at ≥40 mg/day (SHR, 5.46; 95% CI, 1.89 to 15.74; P = 0.002), or cyclosporine plus foscarnet (SHR, 9.03; 95% CI, 3.68 to 22.14; P < 0.0001) were the only comedications significantly associated with increased rates of renal injury. The cumulative incidence of L-AMB renal injury during the first 10 days of therapy was 7% overall but only 3% in patients who were not receiving cyclosporine. Hence, the renal risk of L-AMB therapy may be lessened if patients are switched to alternative agents after 7 to 10 days or if aggressive diuresis and/or foscarnet is avoided, especially among patients receiving calcineurin inhibitors.