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.