Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial.
BACKGROUND
Elevated total homocysteine (tHcy) levels may represent a potentially modifiable risk factor for cardiovascular disease in hemodialysis patients. Current therapies, including multivitamins, have been ineffective at normalizing homocysteine levels in this population; hence, new therapies are needed. There is increasing interest in the use of thiol pharmaceutical agents to displace homocysteine from albumin and improve its dialyzability. We designed a randomized, double-blind, placebo-controlled trial to determine the effect of prolonged administration of oral dimercaptosuccinic acid (DMSA) on plasma tHcy levels in vitamin-replete hemodialysis patients.


METHODS
Forty-four long-term stable dialysis patients were treated for a minimum of 4 weeks with a standard multivitamin, ensuring a vitamin-replete state, then matched on the basis of tHcy levels and randomly assigned as pairs to the administration of DMSA, 2.5 mg/kg/d, or identical placebo for 8 weeks. Multivitamins were continued for the duration of the trial.


RESULTS
Thirty-eight subjects (including 16 pairs) completed the trial. All important determinants of homocysteine level were balanced, and the only significant baseline difference was weight (P = 0.02). At 8 weeks, by paired analysis, there was no statistically significant difference in tHcy levels between the placebo and DMSA groups, at 21.2 micromol/L (2.87 mg/L) and 22.6 micromol/L (3.06 mg/L), respectively (mean difference, -1.4; 95% confidence interval, -5.3 to 2.5; P = 0.45). The same was true for unpaired and multivariable analyses.


CONCLUSIONS
This randomized placebo-controlled trial found that prolonged oral administration of the thiol DMSA had no impact on tHcy levels in hemodialysis patients. Additional strategies to test the homocysteine hypothesis in this population require investigation.
House
Andrew A
AA
Department of Medicine, University of Western Ontario, London, Ontario, Canada. andrew.house@lhsc.on.ca
Eliasziw
Michael
M
Urquhart
Bradley L
BL
Freeman
David J
DJ
Spence
J David
JD
D000284:Administration, Oral; D002318:Cardiovascular Diseases; D002614:Chelating Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012307:Risk Factors; D004113:Succimer / Q000008:administration & dosage / Q000627:therapeutic use*; D014815:Vitamins / Q000008:administration & dosage / Q000378:metabolism
D002614:Chelating Agents; D014815:Vitamins; D006710:Homocysteine; D004113:Succimer