Must we really fear toxicity of conventional amphotericin B in oncological patients?

Abstract

Fungal infections are an important cause of morbidity and mortality in patients with malignancies. Therefore, the use of amphotericin B (AmB) is essential for these patients. Results from the literature to date show that renal toxicity is the most serious adverse effect of AmB. Renal impairment manifests as a decrease in glomerular filtration and damage to tubular function. Currently, there is no reliable method of preventing nephrotoxicity. We have observed that sodium supplementation alone may not prevent nephrotoxicity. We noted that a large decrease in serum potassium and magnesium was followed 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 damage. We decided to test our hypothesis in 32 cancer patients. During AmB therapy, serum electrolyte concentrations and biochemical parameters of renal function and fluid balance were monitored frequently. The daily ion supplementation corresponded to the amount lost through the kidneys. The total duration 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/kg). The average diuresis was 3863 ml/day, and the median 4000 ml/day. The daily 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. magnesium was 9.0 mmol. The frequency of infusion-related side-effects was only 10.0%. These reactions were treated with hydrocortisone. We observed a significant increase in potassium and magnesium lost through the kidneys, and a significant increase in fractional sodium and potassium excretion through the renal tubuli. We did not observe a significant increase in serum creatinine and ion imbalances. Interestingly, the average creatinine clearance did not decrease, but actually increased slightly, though to a statistically insignificant degree, from 1.425 ml/s at the beginning of treatment to 1.589 ml/s on the 20th day of AmB use. Sufficient hydration of patients and ion supplementation corresponding to the amount lost by the kidneys is an effective prophylaxis for prevention of AmB-induced decrease in renal function and for countering imbalances of serum electrolyte concentrations during use of AmB. The frequency of infusion-related side-effects is minimal relative to other reports.