Amphotericin B nephrotoxicity

Abstract

Abstract The use of amphotericin B limited by dose-dependent nephrotoxicity. Elevated creatinine associated with amphotericin B is not only a marker for renal dysfunction, but is also linked to an increase in hospital costs and a substantial risk for the use of haemodialysis and a higher mortality rate. Therefore, amphotericin B nephrotoxicity is not a benign complication and its prevention is essential. Several manipulations have been proposed to minimize amphotericin B-induced nephrotoxicity. Mannitol and frusemide administration are reported to be protective based on anecdotal observational reports. Small prospective and randomized trials do not suggest a protective effect. Three new formulations have been developed in attempts to improve both efficacy and tolerability: amphotericin B in a lipid complex (ABLC; Abelcet); amphotericin B colloidal dispersion; and liposomal amphotericin B (AmBisome). Three prospective randomized studies have clearly shown that AmBisome is less nephrotoxic than amphotericin B. In a double-blind randomized trial significantly fewer patients receiving AmBisome had nephrotoxic effects. This significant reduction in azotaemia was also observed among subgroups of patients receiving concomitant therapy with nephrotoxic agents. Moreover, there were fewer patients with hypokalaemia in the group receiving AmBisome. A recent multicentre double-blind study has shown that AmBisome (3 or 5 mg/kg/day) has a better safety profile than Abelcet (5 mg/kg). Patients in both AmBisome treatment groups experienced less chills/rigors, less nephrotoxicity based on a doubling of serum creatinine, and fewer toxic reactions resulting in discontinuation of therapy. In conclusion, amphotericin B nephrotoxicity is observed frequently. It clearly increases patient mortality. Nephrotoxicity must be recognized early, based on tubular abnormalities and a mild increase in serum creatinine. Its prevention relies on the detection and suppression of risk factors and the use of AmBisome.