Sunder-Plassmann Gere, Födinger Manuela, Buchmayer Heidi, Papagiannopoulos Menelaos, Wojcik Jadwiga, Kletzmayr Josef, Enzenberger Brigitte, Janata Oskar, Winkelmayer Wolfgang C, Paul Gernot, Auinger Martin, Barnas Ursula, Hörl Walter H
Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Vienna, Austria.
Klinisches Institut für Medizinische und Chemische Labordiagnostik, University of Vienna, Vienna, Austria.
J Am Soc Nephrol. 2000 Jun;11(6):1106-1116. doi: 10.1681/ASN.V1161106.
Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29. 9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P = 0.0001), whereas the 5, 10-methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C --> T and 1298A --> C) had no influence. Nevertheless, patients with the MTHFR 677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P = 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P = 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with the MTHFR 677TT genotype, which even exceeded baseline values in several patients (P = 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with the MTHFR 677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.
同型半胱氨酸与动脉粥样硬化及心血管疾病风险增加相关。在以往研究中，高达15mg/d的叶酸治疗未能纠正大多数终末期肾病患者的高同型半胱氨酸血症。为使150名血液透析患者的高同型半胱氨酸血症正常化，将每日30mg或60mg叶酸剂量与15mg/d的剂量进行了比较。在一项随机、双盲、多中心研究中，144名患者完成了4周治疗期，121名患者完成了6个月随访。三个治疗组间血浆总同型半胱氨酸水平分别降低了32.1%（15mg/d）、29.9%（30mg/d）或37.8%（60mg/d），差异无统计学意义。基线血浆总同型半胱氨酸浓度是叶酸治疗反应的独立预测因素（P = 0.0001），而5,10 - 亚甲基四氢叶酸还原酶多态性（MTHFR 677C→T和1298A→C）无影响。然而，与CC或CT基因型患者相比，MTHFR 677TT基因型患者更常达到血浆总同型半胱氨酸水平正常（P = 0.025）。每日服用60mg叶酸时，TT基因型患者的血浆叶酸水平低于CC或CT基因型患者（P = 0.016）。在每日服用30mg或60mg叶酸完成4周治疗期后，MTHFR 677TT基因型患者在随访结束时血浆总同型半胱氨酸水平出现明显反弹，部分患者甚至超过基线值（P = 0.0001）。本研究清楚表明，每日30mg或60mg叶酸剂量在降低常规血液透析患者高同型半胱氨酸血症方面并不比15mg/d更有效。MTHFR 677TT基因型患者更有可能实现血浆总同型半胱氨酸水平正常。当治疗停止时，30mg/d或60mg/d而非15mg/d的叶酸会导致血浆总同型半胱氨酸浓度反弹。
