Mesna for treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial.

Author(s): Urquhart BL, Freeman DJ, Cutler MJ, Mainra R, Spence JD, House AA

Affiliation(s): Department of Physiology and Pharmacology, University of Western Ontario, London Health Sciences Centre, London, Ontario, Canada.

Publication date & source: 2008-07, Clin J Am Soc Nephrol., 3(4):1041-7. Epub 2008 Mar 12.

Publication type: Research Support, Non-U.S. Gov't

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 micromol/L compared with 24.3 micromol/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 micromol/L, mesna 24.5 micromol/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.