Bernasconi Amelia R, Liste Andrés, Del Pino Noemí, Rosa Diez Guillermo J, Heguilén Ricardo M
Division of Nephrology, Hospital Juan A Fernandez, Buenos Aires, Argentina.
Nephrology (Carlton). 2006 Apr;11(2):137-41. doi: 10.1111/j.1440-1797.2006.00536.x.
Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease with a remarkable prevalence in patients with chronic renal failure (CRF). Low doses of folic acid (FA) with or without vitamin B6 and B12 has been shown to effectively reduce plasma homocysteine (Hcy). The aim of this study was to compare the short-term effects of two different oral doses of FA (5 vs 15 mg/d) on plasma Hcy levels in subjects suffering from moderate-severe CRF.
A double-blind, double-dummy, comparative, two-stage randomised study was performed. Seventeen patients aged 45-71 years, with glomerular filtration rates between 15.4-50 mL/min 1.73/m2 were randomly assigned to receive FA 5 mg/d (FA-5, n: 8) or FA 15 mg/d (FA-15, n: 9) for 30 days. At the end of this 30-day double-blind period, all the participants were placed on FA 5 mg/d (open period), for 5 additional months. Both groups were also supplemented with vitamins B1, B6 and B12 throughout the trial. Blood samples were drawn at 0, 15, 30, 90 and 180 days to assess Hcy, complete blood count (CBC) and sequential multichannel analysis (SMA). Chest X-ray and a 12-lead electrocardiogram (ECG) were also performed.
Plasma Hcy (mean +/- SEM) decreased from 27.9 +/- 1.4 (baseline) to 15.1 +/- 0.6, 13.3 +/- 0.9, 14.1 +/- 0.5 and 13.8 +/- 0.5 micromol/L (FA-5) and from 28.8 +/- 2.7 to 15.6 +/- 1.2, 14.4 +/- 1.3, 13.0 +/- 0.7 and 13.1 +/- 0.6 micromol/L (FA-15) at days 15, 30, 90 and 180, respectively. (P < 0.01 from day 15 to 180 vs baseline for both groups with no differences between them). Renal function remained stable throughout the entire period of the study in all but one patient in whom it deteriorated to pre-end stage disease. No adverse cardiovascular events developed during the trial.
Both folic acid doses induced a significant and similar decrease in plasma Hcy in subjects with moderate-severe chronic renal failure. The possible dose-related effect of this approach in reducing the risk of accelerated sclerotic vascular disease and cardiovascular events in this especially vulnerable population should be a matter of further investigation.
高同型半胱氨酸血症是心血管疾病的独立危险因素，在慢性肾衰竭（CRF）患者中具有较高的患病率。低剂量叶酸（FA）联合或不联合维生素B6和B12已被证明能有效降低血浆同型半胱氨酸（Hcy）水平。本研究的目的是比较两种不同口服剂量FA（5mg/d与15mg/d）对中重度CRF患者血浆Hcy水平的短期影响。
进行了一项双盲、双模拟、比较性、两阶段随机研究。17例年龄在45 - 71岁之间、肾小球滤过率在15.4 - 50mL/min/1.73/m²的患者被随机分配接受30天的5mg/d FA（FA - 5组，n = 8）或15mg/d FA（FA - 15组，n = 9）治疗。在这30天的双盲期结束后，所有参与者均接受5mg/d FA治疗（开放期），持续5个月。在整个试验过程中，两组均补充维生素B1、B6和B12。在第0、15、30、90和180天采集血样，以评估Hcy、全血细胞计数（CBC）和连续多通道分析（SMA）。还进行了胸部X线和12导联心电图（ECG）检查。
血浆Hcy（均值±标准误）在第15、30、90和180天，FA - 5组分别从27.9±1.4（基线）降至15.1±0.6、13.3±0.9、14.1±0.5和13.8±0.5μmol/L，FA - 15组分别从28.8±2.7降至15.6±1.2、14.4±1.3、13.0±0.7和13.1±0.6μmol/L。（两组从第15天到180天与基线相比P均<0.01，且两组之间无差异）。除一名患者肾功能恶化为终末期疾病前期外，所有患者在整个研究期间肾功能均保持稳定。试验期间未发生不良心血管事件。
两种叶酸剂量均能使中重度慢性肾衰竭患者血浆Hcy水平显著且相似地降低。这种方法在降低这一特别脆弱人群中加速硬化性血管疾病和心血管事件风险方面可能存在的剂量相关效应值得进一步研究。
