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

Authors

Bradley L. Urquhart, Western University
David J. Freeman, Western University
Murray J. Cutler, Western University
Rahul Mainra, Western University
J. David Spence, Western UniversityFollow
Andrew A. House, Western University

Document Type

Article

Publication Date

7-1-2008

Journal

Clinical Journal of the American Society of Nephrology

Volume

3

Issue

4

First Page

1041

Last Page

1047

URL with Digital Object Identifier

10.2215/CJN.04771107

Abstract

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. Copyright © 2008 by the American Society of Nephrology.