title: Mesna excretion and ifosfamide nephrotoxicity in children.
abstract: To characterize the excretion of 2-mercaptoethanesulfonate sodium (mesna) administered by intermittent infusion, urinary concentrations of mesna and its corresponding inactive disulfide were measured during 50 courses of ifosfamide (1.6 g/m2 for 5 days) and mesna (400 mg/m2 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 mM by 1 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 within 4 h after infusion was lower (P less than 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 subtherapeutic renal tubular levels. However, ifosfamide nephrotoxicity was subclinical and is not necessarily linked to differences in mesna excretion.
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: M P
authors.initials: MP
authors.lastname: Goren
authors.forename: C B
authors.initials: CB
authors.lastname: Pratt
authors.forename: W H
authors.initials: WH
authors.lastname: Meyer
authors.forename: R K
authors.initials: RK
authors.lastname: Wright
authors.forename: R K
authors.initials: RK
authors.lastname: Dodge
authors.forename: M J
authors.initials: MJ
authors.lastname: Viar
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008623:Mercaptoethanol; D015080:Mesna / Q000652:urine*; D009369:Neoplasms / Q000188:drug therapy / Q000652:urine; D011507:Proteinuria / Q000139:chemically induced
chemical_list: D008623:Mercaptoethanol; D003404:Creatinine; D015080:Mesna; D007069:Ifosfamide