Lovcić Vesna, Kes Petar, Zeljko Reiner, Kusec Vesna
Centar za dijalizu, Odjel za internu medicinu, Opća bolnica Bjelovar, Hrvatska.
Acta Med Croatica. 2006 Jun;60(3):201-8.
The aim of the study was to determine the effects of high-flow and low-flow hemodialysis (HD), with simultaneous treatment with folic acid and vitamin B12, on total homocysteine (tHcy) concentration in plasma of dialyzed patients.
The planned clinical observation included 46 patients of both sexes, aged 21-82, treated with bicarbonate dialysis for a mean of 4.7 years. The patients were divided into group A, subsequently dialyzed by use of high-flow polysulphonic membrane (AN 69ST, Nephral 300), and group B that continued to be dialyzed by use of low-flow diacetate membrane (Diacepal 14 and 16). The subjects in both groups received 30 mg of folic acid at the end of each dialysis (3 times a week), and 500 g of vitamin B12 at the end of every other dialysis. The method of stable isotopic dilution mass spectrometry was used to measure tHcy. Folic acid was determined by the test based on ion capture technology. Vitamin B12 was determined by MEIA.
An increase in the concentration of tHcy was observed in 39/46 (85%) patients with a mean concentration of 24.76 +/- 11.04 micromol/L. The mean concentration of folic acid and vitamin B12 was within the normal limits. In the group dialyzed by high-flow dialyzer, the values of tHcy and folic acid decreased (18.74 +/- 2.95 micromol/L and 13.90 +/- 6.78 pmol/L) after hemodialysis, which was significant compared to the initial value (p<0.01 and p<0.05, respectively). At four weeks of treatment, tHcy concentration before HD showed a significant decrease both in the group dialyzed by high-flow dialyzer (15.10 +/- 4.26 mmol/L, p<0.01) and in the group dialyzed by low-flow dialyzer (12.54 +/- 3.87 micromol/L, p<0.01) compared to the measure before HD and before the treatment. There was no statistically significant difference (z -0.40, p>0.68) in the percentage of tHcy change between the group treated by high-flow dialyzer and the group treated by low-flow dialyzer in the measurements before HD and before the treatment with folic acid and vitamin B12, and after the treatment.
There is a literature report on the concentration increase by 26 micromol/L, which is very similar to our result. The absence of long-term effect on predialysis concentration of tHcy in HD by high-flow membrane has also been described, because the decrease of tHcy is mantained until the uremic toxins, enzyme inhibitors that are necessary for the process of remethylation of Hcy, accumulated again. During high-flow HD, the folic acid concentration decreased by 23.05% on an average, consistent with other literature reports. Some reports support our observation that the dosage of folic acid required for tHcy decrease is 15-30 mg, and that the dosage higher than 60 mg does not significantly decrease tHcy concentration. Our study confirmed the reported observations that treatment with folic acid and vitamin B12 rather than high-flow dialyzer contributes to tHcy decrease.
The study confirmed the high prevalence of hyperhomocysteinemia in patients on dialysis. The treatment with folic acid and vitamin B12 results in a significant decrease of tHcy. After individual HD by high-flow dialyzer, there is a significant, but temporary decrease of tHcy concentration in plasma. There is no significant difference in the efficiency on pre-dialysis tHcy concentration between the high-flow and low-flow dialyzer membrane. Because of the atherogenic effect of hyperhomocysteinemia, the treatment with folic acid and vitamin B12 should be accepted as an options to lower the risk factors for the rapid atherosclerosis in patients on dialysis, thus reducing the occurrence and fatality of cardiovascular diseases.
本研究旨在确定高流量和低流量血液透析（HD）联合叶酸和维生素B12治疗对透析患者血浆总同型半胱氨酸（tHcy）浓度的影响。
计划进行的临床观察纳入了46例年龄在21 - 82岁之间的男女患者，他们接受碳酸氢盐透析平均4.7年。患者被分为A组，随后使用高流量聚砜膜（AN 69ST，Nephral 300）进行透析，以及B组，继续使用低流量双醋酸膜（Diacepal 14和16）进行透析。两组受试者在每次透析结束时（每周3次）接受30mg叶酸，每隔一次透析结束时接受500μg维生素B12。采用稳定同位素稀释质谱法测量tHcy。叶酸通过基于离子捕获技术的检测方法测定。维生素B12通过微粒子酶免疫分析（MEIA）测定。
在46例患者中有39例（85%）tHcy浓度升高，平均浓度为24.76±11.04μmol/L。叶酸和维生素B12的平均浓度在正常范围内。在使用高流量透析器透析的组中，血液透析后tHcy和叶酸的值下降（分别为18.74±2.95μmol/L和13.90±6.78pmol/L），与初始值相比有显著差异（分别为p<0.01和p<0.05）。在治疗四周时，与血液透析前及治疗前的测量值相比，使用高流量透析器透析的组和使用低流量透析器透析的组在血液透析前tHcy浓度均显著降低（分别为15.10±4.26mmol/L，p<0.01和12.54±3.87μmol/L，p<0.01）。在血液透析前、叶酸和维生素B12治疗前以及治疗后的测量中，使用高流量透析器治疗的组和使用低流量透析器治疗的组之间tHcy变化百分比无统计学显著差异（z = -0.40，p>0.68）。
有文献报道浓度升高26μmol/L，这与我们的结果非常相似。也有文献描述高流量膜血液透析对透析前tHcy浓度没有长期影响，因为tHcy的降低会持续到尿毒症毒素（同型半胱氨酸再甲基化过程所需的酶抑制剂）再次积累。在高流量血液透析期间，叶酸浓度平均下降23.05%，与其他文献报道一致。一些报告支持我们的观察结果，即降低tHcy所需的叶酸剂量为15 - 30mg，高于60mg的剂量不会显著降低tHcy浓度。我们的研究证实了已报道的观察结果，即叶酸和维生素B12治疗而非高流量透析器有助于降低tHcy。
该研究证实透析患者中高同型半胱氨酸血症的患病率很高。叶酸和维生素B12治疗可导致tHcy显著降低。在使用高流量透析器进行单次血液透析后，血浆中tHcy浓度有显著但暂时的降低。高流量和低流量透析器膜对透析前tHcy浓度的降低效果无显著差异。由于高同型半胱氨酸血症的致动脉粥样硬化作用，叶酸和维生素B12治疗应被视为降低透析患者快速动脉粥样硬化风险因素的一种选择，从而减少心血管疾病的发生和死亡率。
