Jamison Rex L, Hartigan Pamela, Kaufman James S, Goldfarb David S, Warren Stuart R, Guarino Peter D, Gaziano J Michael
Veterans Affairs Palo Alto Health Care Systems and Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94304, USA.
JAMA. 2007 Sep 12;298(10):1163-70. doi: 10.1001/jama.298.10.1163.
High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown.
To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L).
Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo.
The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients.
Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups.
Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease.
clinicaltrials.gov Identifier: NCT00032435.
在慢性肾病患者的观察性研究中，高血浆同型半胱氨酸水平是死亡率和血管疾病的一个风险因素。叶酸和B族维生素可降低该人群的同型半胱氨酸水平，但它们是否能降低死亡率尚不清楚。
确定每日服用高剂量叶酸和B族维生素是否能降低慢性肾病患者的死亡率。
设计、地点和参与者：在美国36个退伍军人事务部医疗中心进行的双盲随机对照试验（2001 - 2006年）。对2056名年龄在21岁及以上、患有晚期慢性肾病（估计肌酐清除率≤30 mL/分钟）（n = 1305）或终末期肾病（n = 751）且同型半胱氨酸水平较高（≥15 μmol/L）的参与者进行了中位随访3.2年。
参与者每日服用一粒胶囊，其中含有40毫克叶酸、100毫克盐酸吡哆醇（维生素B6）和2毫克氰钴胺素（维生素B12）或安慰剂。
主要结局是全因死亡率。次要结局包括心肌梗死（MI）、中风、下肢全部或部分截肢、这三者与全因死亡率的综合指标、开始透析的时间以及血液透析患者动静脉通路血栓形成的时间。
维生素组的平均基线同型半胱氨酸水平为24.0 μmol/L，安慰剂组为24.2 μmol/L。3个月时，维生素组降低了6.3 μmol/L（25.8%；P < 0.001），安慰剂组降低了0.4 μmol/L（1.7%；P = 0.14），但对死亡率没有显著影响（维生素组448例死亡，安慰剂组436例死亡）（风险比[HR]，1.04；95%可信区间，0.91 - 1.18）。对于次要结局或不良事件未显示出显著影响：维生素组有129例心肌梗死，安慰剂组有150例（HR，0.86；95%可信区间，0.67 - 1.08）；维生素组有37例中风，安慰剂组有41例（HR，0.90；95%可信区间，0.58 - 1.40）；维生素组有60例截肢，安慰剂组有53例（HR，1.14；95%可信区间，0.79 -
