Amphotericin B deoxycholate versus liposomal amphotericin B: effects on kidney function

Juan Pablo Botero Aguirre, Alejandra Maria Restrepo Hamid

The incidence of invasive fungal infections has increased globally as a result of several factors. Conventional amphotericin B (sodium deoxycholate) has been used as standard therapy for the treatment of invasive fungal infections; however, it is associated with adverse drug reactions, including acute kidney injury (AKI). New formulations of amphotericin B have aimed to improve the safety profile of the conventional formulation. This review aimed to assess the effects of amphotericin B deoxycholate versus liposomal amphotericin B on kidney function. We searched Cochrane Kidney and Transplant's Specialised Register to 10 March 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. We included randomised controlled trials (RCTs) that compared amphotericin B sodium deoxycholate with liposomal amphotericin B. Two authors independently assessed studies for eligibility and conducted risk of bias evaluation. We included 12 studies (2298 participants) in this review. Of these, 10 were meta-analysed (2172 participants). Liposomal amphotericin B was found to be significantly safer than conventional amphotericin B in terms of serum creatinine increase (RR 0.49, 95% CI 0.40 to 0.59). There was significant decrease in all infusion-related reactions in the liposomal group compared with the conventional group: fever (4 studies, 1092 participants): RR 0.39, 95% CI 0.28 to 0.55; I(2) = 32%); chills and/or rigours (5 studies, 1081 participants): RR 0.27, 95% CI 0.15 to 0.48; I(2) = 75%); fever and/or rigours (2 studies, 720 participants): RR 0.68, 95% CI 0.52 to 0.90; I(2) = 58%); nausea (6 studies, 1187 participants): RR 0.50, 95% CI 0.35 to 0.72; I(2) = 0%); and vomiting (3 studies, 1019 participants): RR 0.51, 95% CI 0.27 to 0.95; I(2) = 61%). Overall, risk of bias in included studies was low or unclear for most domains. However, blinding of participants and personnel, blinding of outcome assessment and other bias (funding) tended to have a high risk of bias. The sensitivity analysis performed did not change the significance of difference in favour of the liposomal formulation. Assessment for publication bias found that review results were robust. Current evidence suggests that liposomal amphotericin B is less nephrotoxic than conventional amphotericin B (when the effect on kidney function is measured as an increase in serum creatinine level equal to or greater than two-fold from the baseline level). We also found that there were fewer infusion-related reactions associated with the liposomal formulation.