Ducloux Didier, Aboubakr Abdelfatah, Motte Gérard, Toubin Gérard, Fournier Véronique, Chalopin Jean-Marc, Drüeke Tilman, Massy Ziad A
Division of Nephrology, Biochemistry B Laboratory, CHU St Jacques, Besançon, France.
Nephrol Dial Transplant. 2002 May;17(5):865-70. doi: 10.1093/ndt/17.5.865.
In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose, i.v. folinic acid combined with high-dose i.v. pyridoxine was highly effective in correcting plasma total homocysteine (tHcy) concentrations in haemodialysis patients. To confirm these findings, we conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid.
In a 6-month prospective, randomized, controlled trial, 60 chronic haemodialysis patients, matched for age, gender, dialysis duration, and average screening pre-treatment-fasting tHcy levels, were given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60 patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral vitamin B12.
Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3, respectively, P=NS). Mean percentage reduction at 6 months was also similar in the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively, P=NS).
These findings show that the tHcy-lowering effects of high-dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable, suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism. Furthermore, they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients.
在最近一份非对照回顾性报告中,我们指出长期静脉注射高剂量亚叶酸钙联合高剂量静脉注射维生素B6能有效纠正血液透析患者的血浆总同型半胱氨酸(tHcy)浓度。为证实这些发现,我们开展了一项随机对照试验,旨在评估静脉注射或口服亚叶酸钙与口服叶酸相比,在降低血液透析患者tHcy方面是否具有更高的疗效。
在一项为期6个月的前瞻性随机对照试验中,60名年龄、性别、透析时间和平均筛查预处理空腹tHcy水平相匹配的慢性血液透析患者,分别接受每周50mg静脉注射亚叶酸钙(第1组)、每周50mg口服亚叶酸钙(第2组)或每周45mg口服叶酸(第3组)治疗。所有60名患者还接受每周750mg静脉注射维生素B6和每周3mg口服维生素B12治疗。
治疗2个月后,三组患者的空腹tHcy均显著下降且下降程度相似,在4个月和6个月时保持稳定(第1组、第2组和第3组分别为16.6±3.5、18.3±4和19.1±3.1,P=无显著性差异)。三个治疗组在6个月时的平均降低百分比也相似(第1组、第2组和第3组分别为46%、43%和42%,P=无显著性差异)。
这些发现表明,高剂量静脉注射亚叶酸钙、口服亚叶酸钙或口服叶酸降低tHcy的效果相当,这表明血液透析患者中观察到的高同型半胱氨酸血症并非由于叶酸代谢异常。此外,这些结果与以下观点相符,即其他异常情况也参与了尿毒症患者同型半胱氨酸清除受损的过程。