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


METHODS
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.
Urquhart
Bradley L
BL
Department of Physiology and Pharmacology, University of Western Ontario, London Health Sciences Centre, London, Ontario, Canada.
Freeman
David J
DJ
Cutler
Murray J
MJ
Mainra
Rahul
R
Spence
J David
JD
House
Andrew A
AA
D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D015080:Mesna / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006435:Renal Dialysis; D016896:Treatment Outcome
D006710:Homocysteine; D015080:Mesna