Obeid Rima, Kuhlmann Martin K, Köhler Hans, Herrmann Wolfgang
Department of Clinical Chemistry, Central Laboratory, Saarland University Hospital, 66421 Homburg, Germany.
Clin Chem. 2005 Jan;51(1):196-201. doi: 10.1373/clinchem.2004.041210. Epub 2004 Nov 4.
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.
We administered folic acid (5 mg) plus vitamin B(6) (50 mg) and B(12) (0.7 mg) intravenously to 38 hyperhomocysteinemic patients (tHcy >18 micromol/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.
The median serum tHcy concentration decreased significantly, from 26.1 micromol/L at baseline to 13.2 micromol/L at week 4. The median change in tHcy after 4 weeks was 13.4 micromol/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 micromol/L).
The combination of folic acid, vitamin B(12), and vitamin B(6) 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.
超过80%的血液透析患者存在高同型半胱氨酸血症，其被认为是心血管疾病的一个危险因素。维生素治疗可降低血浆中总同型半胱氨酸（tHcy）浓度，因此可能降低相关风险。目前的治疗策略未能使大多数透析患者的tHcy恢复正常。
我们在每次透析治疗后，对38例高同型半胱氨酸血症患者（tHcy>18μmol/L）静脉给予叶酸（5mg）加维生素B6（50mg）和维生素B12（0.7mg）。治疗阶段持续1个月，并在第0、2、4、6、8和24周测量tHcy、甲基丙二酸（MMA）和胱硫醚的血清浓度。
血清tHcy浓度中位数显著下降，从基线时的26.1μmol/L降至第4周时的13.2μmol/L。与基线相比，4周后tHcy的中位数变化为13.4μmol/L（-51%）。血清MMA和胱硫醚浓度分别降低了28%和26%，但在4周时均未恢复正常。向后逐步回归分析显示，基线时较高的tHcy、MMA和胱硫醚浓度以及较低的叶酸水平可预测治疗后tHcy的变化。停用维生素20周后，tHcy浓度恢复至与基线相当的值（中位数，24.8μmol/L）。
本研究中使用的叶酸、维生素B12和维生素B6联合应用使几乎所有高同型半胱氨酸血症透析患者的血清tHcy浓度恢复正常。该方案可用于研究同型半胱氨酸正常化对血液透析患者心血管结局的影响。
