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

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 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.

• Authors: Bradley L Urquhart, David J Freeman, Murray J Cutler, Rahul Mainra, J David Spence, Andrew A House
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 3 Issue 4 Pg. 1041-7 (Jul 2008) ISSN: 1555-905X [Electronic] United States
• PMID: 18337551 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Homocysteine
• Mesna

Topics

• Aged
• Double-Blind Method
• Drug Administration Schedule
• Female
• Homocysteine (blood)
• Humans
• Hyperhomocysteinemia (blood, complications, drug therapy)
• Injections, Intravenous
• Kidney Failure, Chronic (blood, complications, therapy)
• Male
• Mesna (administration & dosage, adverse effects, pharmacokinetics)
• Renal Dialysis
• Treatment Outcome