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Clinical Chemistry 51: 196-201, 2005. First published November 4, 2004; 10.1373/clinchem.2004.041210
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(Clinical Chemistry. 2005;51:196-201.)
© 2005 American Association for Clinical Chemistry, Inc.

General Clinical Chemistry

Response of Homocysteine, Cystathionine, and Methylmalonic Acid to Vitamin Treatment in Dialysis Patients

Rima Obeid1, Martin K. Kuhlmann2,3, Hans Köhler2 and Wolfgang Herrmann1,a

1 Department of Clinical Chemistry, Central Laboratory, and 2 Department of Nephrology and Hypertension, Saarland University Hospital, Homburg, Germany.
3 Renal Research Institute, New York, NY.

aAddress correspondence to this author at: Zentrallabor der Universitätskliniken des Saarlandes, Kirrberger Strasse, Gebäude 40, 66421 Homburg, Germany. Fax 49-6841-1623109; 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.




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