Liposomal Amphotericin B Nephrotoxicity in Patients with Hematological Malignancies: A Retrospective Cohort Analysis [PublishAheadOfPrint]

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 patients were analyzed before, during and after the administration of L-AMB, and renal injury was graded per the RIFLE criteria. Most patients (87.3%) received L-AMB at 3 mg/kg/day. Nearly two-thirds (61.7%) of 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 patients developed renal injury within 48 hours 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 2.62, 95% CI 1.10-6.27; P=0.03), cyclosporine plus furoseminde ≥ 40 mg/day (SHR 5.46,1.89-15.74;P=0.002) or cyclosporine plus foscarnet (SHR 9.03, 3.68-22.14; 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 risks of L-AMB therapy may be lessened if patients are switched to alternative agents after 7-10 days, or aggressive diuresis and/or foscarnet are avoided, especially among patients receiving calcineurin inhibitors.

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