Must we really fear toxicity of conventional amphotericin B in oncologicalpatients?

Fungal infections are an important cause of morbidity and mortality in pati ents with malignancies. Therefore, the use of amphotericin B (AmB) is essen tial for these patients. Results from the literature to date show that rena l toxicity is the most serious adverse effect of AmB. Renal impairment mani fests as a decrease in glomerular filtration and damage to tubular function . Currently, there is no reliable method of preventing nephrotoxicity. We h ave observed that sodium supplementation alone may not prevent nephrotoxici ty. We noted that a large decrease in serum potassium and magnesium was fol lowed by a significant reduction in creatinine clearance and an increase in both serum urea and creatinine. Therefore, we surmised that potassium and magnesium supplements corresponding to the amounts lost by the kidneys, as well as sufficient hydration, are necessary to prevent renal function damag e. We decided to test our hypothesis in 32 cancer patients. During AmB ther apy, serum electrolyte concentrations and biochemical parameters of renal f unction and fluid balance were monitored frequently. The daily ion suppleme ntation corresponded to the amount lost through the kidneys. The total dura tion of administration ranged from 4 to 39 days, with a mean of 13.7 days ( median 11.0 days). The mean daily AmB dose was 0.89 mg/kg (median 0.88 mg/k g). The average diuresis was 3863 ml/day, and the median 4000 ml/day. The d aily mean i.v.-administered sodium dose was 195.9 mmol, the daily mean dose of i.v. potassium was 103.7 mmol, and the daily mean dose of i.v. magnesiu m was 9.0 mmol. The frequency of infusion-related side-effects was only 10. 0%. These reactions were treated with hydrocortisone. We observed a signifi cant increase in potassium and magnesium lost through the kidneys, and a si gnificant increase in fractional sodium and potassium excretion through the renal tubuli. We did not observe a significant increase in serum creatinin e and ion imbalances. Interestingly, the average creatinine clearance did n ot decrease, but actually increased slightly, though to a statistically ins ignificant degree, from 1.425 ml/s at the beginning of treatment to 1.589 m l/s on the 20th day of AmB use. Sufficient hydration of patients and ion su pplementation corresponding to the amount lost by the kidneys is an effecti ve prophylaxis for prevention of AmB-induced decrease in renal function and for countering imbalances of serum electrolyte concentrations during use o f AmB. The frequency of infusion-related side-effects is minimal relative t o other reports.