AMPHOTERICIN-B NEPHROTOXICITY - THE ADVERSE CONSEQUENCES OF ALTERED MEMBRANE-PROPERTIES

Amphotericin B (AmB) has been in clinical use for more than 30 yr but has remained the most effective drug for treatment of serious fungal i nfections. Its use has increased in recent years, as the result of inc reases in aggressive intensive care support and increased numbers of i mmunocompromised patients. Nephrotoxic manifestations are common, and this is the major factor limiting the clinical use of the drug. A numb er of recent studies have contributed to a better understanding of the mechanism by which AmB exerts its nephrotoxic effect, AmB alters cell membrane permeability and probably as a consequence alters tubular an d vascular smooth muscle cell function, leading to various tubular tra nsport defects and vasoconstriction. Decreased RBF appears to play a m ajor role in AmB-induced reduction GFR, and recurrent ischemia may be the basis of permanent structural nephrotoxic effects. Salt loading is the only measure proven by controlled prospective study to ameliorate AmB nephrotoxicity in humans, Liposomal AmB and the formulation of an emulsion of AmB in lipid may provide a protective effect based on alt ering the affinity of AmB for mammalian cell membranes, while preservi ng high efficacy against fungal cells. However, further studies are ne eded to evaluate the efficacy and safety of these new AmB formulations .