Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease - A randomized controlled trial
Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease - A randomized controlled trial
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DOI：
10.1001/jama.298.10.1163
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发表时间：
2007-09-12
影响因子：
120.7
通讯作者：
Gaziano, J. Michael
中科院分区：
文献类型：
--
作者：
Jamison, Rex L.;Hartigan, Pamela;Gaziano, J. Michael
在慢性肾脏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危险因素。叶酸和B族维生素降低同型半胱氨酸水平在这个population，但他们是否降低mortality is unknown.Objective To determine whether high-dose of folic acid and B vitamin 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.对2056名年龄在21岁或以上的晚期慢性肾脏病患者（估计肌酐清除率= 15 μ mol/L）进行中位随访3.2年。干预参与者每天接受一粒胶囊，其中含有40 mg叶酸、100 mg盐酸吡哆醇（维生素B-6）和2 mg氰钴胺（维生素B-12）或安慰剂。主要结局指标主要结局为全因死亡率。次要结果包括心肌梗死（MI），中风，截肢的全部或部分下肢，这3个加上全因死亡率的复合，时间开始透析，血栓形成的动静脉通路在血液透析patients.Results平均基线同型半胱氨酸水平为24.0 μ mol/L的维生素组和24.2 μ mol/L的安慰剂组。降低6.3 μ mol/L 3个月时，维生素组为0.4 μ mol/L（25.8%; P <0.001），安慰剂组为0.4 μ mol/L（1.7%; P = 0.14），但对死亡率无显著影响（维生素组448例死亡vs安慰剂组436例死亡）（风险比[HR]，1.04; 95%CI，0.91-1.18）。对于次要结果或不良事件没有显着影响：维生素组有129例MI，安慰剂组有150例MI（HR，0.86; 95% CI，0.67-1.08），维生素组37例卒中，安慰剂组41例（HR，0.90; 95%CI，0.58-1.40），维生素组截肢60例，安慰剂组截肢53例（HR，1.14; 95%CI，0.79-1.64）。此外，MI、卒中和截肢加上死亡率的复合指标（P = .85），透析时间（P = .38），血液透析患者血栓形成时间（P = .97）结论：高剂量叶酸和B族维生素治疗不能提高晚期慢性肾脏病患者的生存率或降低血管疾病的发生率疾病或终末期肾病。
Context 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.Objective 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 = 15 mu mol/L).Intervention Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B-6), and 2 mg of cyanocobalamin (vitamin B-12) or a placebo. Main Outcome Measures 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.Results Mean baseline homocysteine level was 24.0 mu mol/L in the vitamin group and 24.2 mu mol/L in the placebo group. It was lowered 6.3 mu mol/L (25.8%; P < .001) in the vitamin group and 0.4 mu mol/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.Conclusion 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.