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Mesna for Treatment of Hyperhomocysteinemia in Hemodialysis Patients: A Placebo-Controlled, Double-Blind, Randomized Trial

Bradley L. Urquhart^*, David J. Freeman^*,,, Murray J. Cutler^*, Rahul Mainra^,, J. David Spence^,||, and Andrew A. House^,,

Departments of ^* Physiology and Pharmacology and Medicine, University of Western Ontario, Lawson Health Research Institute, Division of Nephrology, London Health Sciences Centre, and ^|| Robarts Research Institute, London, Ontario, Canada

Correspondence: Dr. Andrew A. House, Department of Medicine, University of Western Ontario, Division of Nephrology, University Campus, London Health Sciences Centre, 339 Windermere Road, London, Ontario, Canada N6A 5A5. Phone: 519-663-3167; Fax: 519-663-8808; E-mail: andrew.house{at}lhsc.on.ca

Background and objectives: Increased plasma total homocysteine is a graded, independent risk factor for the development of atherosclerosis and thrombosis. More than 90% of patients with end-stage renal disease have hyperhomocysteinemia despite vitamin supplementation. It was shown in previous studies that a single intravenous dose of mesna 5 mg/kg caused a drop in plasma total homocysteine that was significantly lower than predialysis levels 2 d after dosing. It was hypothesized 5 mg/kg intravenous mesna administered thrice weekly, before dialysis, for 8 wk would cause a significant decrease in plasma total homocysteine compared with placebo.

Design, setting, participants, & measurements: Patients with end-stage renal disease were randomly assigned to receive either intravenous mesna 5 mg/kg or placebo thrice weekly before dialysis. Predialysis plasma total homocysteine concentrations at weeks 4 and 8 were compared between groups by paired t test.

Results: Mean total homocysteine at 8 wk in the placebo group was 24.9 µmol/L compared with 24.3 µmol/L in the mesna group (n = 22 [11 pairs]; mean difference 0.63). Interim analysis at 4 wk also showed no significant difference between mesna and placebo (n = 32 [16 pairs]; placebo 26.3 µmol/L, mesna 24.5 µmol/L; mean difference 1.88). Multivariable adjustments for baseline characteristics did not alter the analysis. Plasma mesna seemed to reach steady-state concentrations by 4 wk.

Conclusions: It is concluded that 5 mg/kg mesna does not lower plasma total homocysteine in hemodialysis patients and that larger dosages may be required.