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Received on August 5, 2004
Accepted on October 6, 2004
General Clinical Chemistry |
1 Department of Clinical Chemistry, Central Laboratory, Saarland University Hospital, Homburg, Germany
2 Department of Nephrology and Hypertension, Saarland University Hospital, Homburg, Germany, and Renal Research Institute, New York, NY
3 Department of Nephrology and Hypertension, Saarland University Hospital, Homburg, Germany
* To whom correspondence should be addressed. E-mail: kchwher{at}uniklinik-saarland.de.
Background: Hyperhomocysteinemia is observed in >80% of hemodialysis patients and is considered a risk factor for cardiovascular disease. Vitamin treatment lowers total homocysteine (tHcy) concentrations in plasma and may therefore reduce the associated risk. Current treatment strategies have not achieved normalization of tHcy in the majority of dialysis patients.
Methods: We administered folic acid (5 mg) plus vitamin B6 (50 mg) and B12 (0.7 mg) intravenously to 38 hyperhomocysteinemic patients (tHcy >18 µmol/L) after each dialysis treatment. The treatment phase lasted 1 month, and serum concentrations of tHcy, methylmalonic acid (MMA), and cystathionine were measured at weeks 0, 2, 4, 6, 8, and 24.
Results: The median serum tHcy concentration decreased significantly, from 26.1 µmol/L at baseline to 13.2 µmol/L at week 4. The median change in tHcy after 4 weeks was 13.4 µmol/L (-51%) compared with baseline. Serum MMA and cystathionine concentrations were reduced by 28% and 26%, respectively, but neither was normalized at 4 weeks. Backward-elimination stepwise regression analysis revealed that higher concentrations of tHcy, MMA, and cystathionine and lower folate at baseline predict changes of tHcy after treatment. Twenty weeks after vitamin withdrawal, tHcy concentrations returned to values comparable to baseline (median, 24.8 µmol/L).
Conclusions: The combination of folic acid, vitamin B12, and vitamin B6 used in this study normalized serum concentrations of tHcy in almost all of our hyperhomocysteinemic dialysis patients. This regimen may be used to investigate the effects of homocysteine normalization on cardiovascular outcomes in hemodialysis patients.
The following articles in journals at HighWire Press have cited this article:
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  B. L. Urquhart, D. J. Freeman, M. J. Cutler, R. Mainra, J. D. Spence, and A. A. House Mesna for Treatment of Hyperhomocysteinemia in Hemodialysis Patients: A Placebo-Controlled, Double-Blind, Randomized Trial Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 1041 - 1047. [Abstract] [Full Text] [PDF]
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 R. Obeid, M. Kasoha, J.-P. Knapp, P. Kostopoulos, G. Becker, K. Fassbender, and W. Herrmann Folate and Methylation Status in Relation to Phosphorylated Tau Protein(181P) and {beta}-Amyloid(1-42) in Cerebrospinal Fluid Clin. Chem., June 1, 2007; 53(6): 1129 - 1136. [Abstract] [Full Text] [PDF]
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R. Obeid, P. Kostopoulos, J.-P. Knapp, M. Kasoha, G. Becker, K. Fassbender, and W. Herrmann Biomarkers of Folate and Vitamin B12 Are Related in Blood and Cerebrospinal Fluid Clin. Chem., February 1, 2007; 53(2): 326 - 333. [Abstract] [Full Text] [PDF]
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A. Pastore, S. De Angelis, S. Casciani, R. Ruggia, G. Di Giovamberardino, A. Noce, G. Splendiani, C. Cortese, G. Federici, and M. Dessi' Effects of Folic Acid Before and After Vitamin B12 on Plasma Homocysteine Concentrations in Hemodialysis Patients with Known MTHFR Genotypes Clin. Chem., January 1, 2006; 52(1): 145 - 148. [Abstract] [Full Text] [PDF]
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W. Herrmann, H. Schorr, R. Obeid, J. Makowski, B. Fowler, and M. K. Kuhlmann Disturbed Homocysteine and Methionine Cycle Intermediates S-Adenosylhomocysteine and S-Adenosylmethionine Are Related to Degree of Renal Insufficiency in Type 2 Diabetes Clin. Chem., May 1, 2005; 51(5): 891 - 897. [Abstract] [Full Text] [PDF]
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