Amphotericin B (AmB) is a crucial agent in the management of serious systemic fungal
infections. In spite of its proven track record, its well-known side effects and toxicity
will sometimes require discontinuation of therapy despite a life-threatening systemic
fungal infection. The mechanism of action of AmB is based on the binding of the AmB
molecule to the fungal cell membrane ergosterol, producing an aggregate that creates
a transmembrane channel, allowing the cytoplasmic contents to leak out, leading to
cell death. Most of the efforts at improving AmB have been focused on the preparation
of AmB with a lipid conjugate. AmB administration is limited by infusion-related toxicity,
an effect postulated to result from proinflammatory cytokine production. The principal
acute toxicity of AmB deoxycholate includes nausea, vomiting, rigors, fever, hypertension
or hypotension, and hypoxia. Its principal chronic adverse effect is nephrotoxicity.
AmB probably produces renal injury by a variety of mechanisms. Risk factors for AmB
nephrotoxicity include male gender, higher average daily dose of AmB (> or = 35 mg/day),
diuretic use, body weight > or = 90 kg, concomitant use of nephrotoxic drugs, and
abnormal baseline renal function. Clinical manifestations of AmB nephrotoxicity include
renal insufficiency, hypokalemia, hypomagnesemia, metabolic academia, and polyuria
due to nephrogenic diabetes insipidus. Human studies show convincingly that sodium
loading in excess of the usual dietary intake notably reduces the incidence and severity
of AmB-induced nephrotoxicity.