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Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial.
Am J Kidney Dis 2004; 44(4):689-94AJ

Abstract

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.

CONCLUSION

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.

Authors+Show Affiliations

Department of Medicine, University of Western Ontario, London, Ontario, Canada. andrew.house@lhsc.on.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15384020

Citation

House, Andrew A., et al. "Dimercaptosuccinic Acid for the Treatment of Hyperhomocysteinemia in Hemodialysis Patients: a Placebo-controlled, Double-blind, Randomized Trial." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 44, no. 4, 2004, pp. 689-94.
House AA, Eliasziw M, Urquhart BL, et al. Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial. Am J Kidney Dis. 2004;44(4):689-94.
House, A. A., Eliasziw, M., Urquhart, B. L., Freeman, D. J., & Spence, J. D. (2004). Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 44(4), pp. 689-94.
House AA, et al. Dimercaptosuccinic Acid for the Treatment of Hyperhomocysteinemia in Hemodialysis Patients: a Placebo-controlled, Double-blind, Randomized Trial. Am J Kidney Dis. 2004;44(4):689-94. PubMed PMID: 15384020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial. AU - House,Andrew A, AU - Eliasziw,Michael, AU - Urquhart,Bradley L, AU - Freeman,David J, AU - Spence,J David, PY - 2004/9/24/pubmed PY - 2005/3/2/medline PY - 2004/9/24/entrez SP - 689 EP - 94 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am. J. Kidney Dis. VL - 44 IS - 4 N2 - 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. CONCLUSION: 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/15384020/Dimercaptosuccinic_acid_for_the_treatment_of_hyperhomocysteinemia_in_hemodialysis_patients:_a_placebo_controlled_double_blind_randomized_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272638604009382 DB - PRIME DP - Unbound Medicine ER -