mesna and Proteinuria

Topics: Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bowman Capsule; Dacarbazine; Deoxycytidine; Disease Progression; Docetaxel; Doxorubicin; Endothelium, Vascular; Fibrosarcoma; Gemcitabine; Glomerulonephritis, Membranoproliferative; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Muscle Neoplasms; Podocytes; Proteinuria; Taxoids; Vascular Endothelial Growth Factor A

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.

Topics: Adolescent; Adult; Child; Child, Preschool; Creatinine; Female; Humans; Ifosfamide; Kidney Diseases; Male; Mercaptoethanol; Mesna; Neoplasms; Proteinuria

The nephrotoxic effects of ifosfamide were assessed in 18 children and adolescents given cumulative doses of 32-112 g/m2 (1.6 g/m2 per day in sequential 5-day courses) with the uroprotectant mesna (1.2 g/m2 per day). Tubular nephrotoxicity was evaluated by measuring the urinary concentrations of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and total protein before and during sequential courses of therapy. Of 15 patients who had normal levels of tubular markers before ifosfamide therapy, only 1 developed a persistent increase in baseline values of the three tubular markers with the sixth course of ifosfamide. Although transient increases in the excretion of these markers were observed during each 5-day course of ifosfamide, the magnitude did not increase over sequential courses in these 15 patients. Of the remaining three patients who had increased NAG levels before ifosfamide therapy, two showed a progressive increase in enzymuria and proteinuria, and serum creatinine concentrations increased in a single patient who had obstructive uropathy. Our data suggest that children with normal renal function can be given large cumulative amounts of ifosfamide in fractionated doses with little risk of progressive clinical nephrotoxicity.

Topics: Acetylglucosaminidase; Aminopeptidases; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; CD13 Antigens; Creatinine; Dose-Response Relationship, Drug; Drug Evaluation; Humans; Ifosfamide; Infusions, Intravenous; Injections, Intravenous; Kidney Tubules; Mesna; Proteinuria; Time Factors

We monitored acute tubular damage in 16 patients who received a 5-day course of ifosfamide (1.6 g/m2/day) and mesna (1.2 g/m2/day) therapy. Urinary concentrations of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein increased in every patient, but the extent of tubular toxicity varied widely among patients. Evidence of toxicity was greatest in patients whose tumors involved the kidneys. The time course of enzymuria and proteinuria indicated tubular cell necrosis. We observed this acute toxic effect despite the administration of sufficient mesna to prevent hemorrhagic cystitis. Urinary marker concentrations returned towards pre-dose levels, and there were no increases in serum creatinine concentrations measured 3 weeks after treatment.

Topics: Acetylglucosaminidase; Adolescent; Adult; Aminopeptidases; CD13 Antigens; Child; Child, Preschool; Creatinine; Drug Evaluation; Female; Humans; Ifosfamide; Kidney Diseases; Kidney Tubules; Male; Mercaptoethanol; Mesna; Proteinuria