Mesna Excretion and Ifosfamide Nephrotoxicity in Children1

To characterize the excretion of 2-mercaptoethanesulfonate sodium (mesna) administered by intermittent infusion, urinary concentrations of mesna and its corresponding inactive disulfide »eremeasured during 50 courses of ifosfamide (1.6 g/nr for 5 days) and mesna (400 mg/nr at 0.25, 4, and 6 h after each ifosfamide dose) administered i.v. to 19 patients. Some patients had previously received nephrotoxic therapy that might influence the excretion of mesna and its associated uroprotective effects. The median urinary free thiol concentration increased to 3 HIM by l h after mesna infusion, declining to background levels by 4 h. The rate of mesna excretion correlated with the creatinine clearance rate in a subset of six patients. The proportion of mesna recovered in urine »¡thin 4 h after infusion was lower (/' < 0.05) in children who had evidence of preexisting renal tubular damage. Ifosfamide-induced tubular proteinuria was associated with lower urinary mesna recovery. Low urinary mesna concentrations indicated potentially subthcrapeutic renal tubular levels. However, ifosfamide nephrotoxicity was subclinical and is not necessarily linked to differences in mesna excretion.