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Mesna excretion and ifosfamide nephrotoxicity in children
M P Goren1, C B Pratt, W H Meyer
1Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
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.
Insights
Urinary excretion of 2-mercaptoethanesulfonate sodium (mesna) was studied during ifosfamide treatment. Lower mesna recovery in children with renal damage suggests potentially subtherapeutic levels, though ifosfamide nephrotoxicity may be subclinical.
Area of Science:
- Pharmacokinetics
- Uro-oncology
- Nephrology
Background:
- Mesna (2-mercaptoethanesulfonate sodium) is a uroprotective agent co-administered with ifosfamide.
- Understanding mesna's urinary excretion is crucial for ensuring its efficacy in preventing ifosfamide-induced hemorrhagic cystitis.
- Preexisting renal conditions may impact mesna's pharmacokinetics and uroprotective potential.
Purpose of the Study:
- To characterize the urinary excretion profile of mesna when administered via intermittent infusion alongside ifosfamide.
- To investigate the correlation between mesna excretion and renal function, including creatinine clearance.
- To assess the impact of prior nephrotoxic therapy and ifosfamide-induced proteinuria on mesna recovery.
Main Methods:
- Urinary concentrations of mesna and its disulfide were measured in 19 patients receiving ifosfamide and mesna therapy.
- Mesna was administered intravenously at specific time points relative to ifosfamide infusion.
- Creatinine clearance was assessed, and patients with prior renal damage or ifosfamide-induced proteinuria were identified.
Main Results:
- Median urinary free thiol concentrations peaked at 3 mM within 1 hour post-infusion, returning to baseline by 4 hours.
- Mesna excretion rate correlated with creatinine clearance in a subset of patients.
- Lower mesna recovery was observed in children with pre-existing renal tubular damage and in patients with ifosfamide-induced tubular proteinuria.
Conclusions:
- Urinary mesna concentrations can indicate potentially subtherapeutic renal tubular levels.
- Reduced mesna recovery in specific patient groups may impact uroprotection.
- Subclinical ifosfamide nephrotoxicity is not definitively linked to altered mesna excretion patterns.