George Institute for Global Health, PO Box M201, Camperdown, NSW 2050, Australia.
BMJ. 2012 Jun 13;344:e3533. doi: 10.1136/bmj.e3533.
To systematically review the effect of folic acid based homocysteine lowering on cardiovascular outcomes in people with kidney disease.
Systematic review and meta-analysis.
Medline, Embase, the Cochrane Library, and ClinicalTrials.gov to June 2011.
Randomised trials in people with non-dialysis dependent chronic kidney disease or end stage kidney disease or with a functioning kidney transplant reporting at least 100 patient years of follow-up and assessing the effect of folic acid based homocysteine lowering therapy. No language restrictions were applied.
Two reviewers independently extracted data on study setting, design, and outcomes using a standardised form. The primary endpoint was cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality, or as defined by study author). Secondary endpoints included the individual composite components, all cause mortality, access thrombosis, requirement for renal replacement therapy, and reported adverse events, including haematological and neurological events. The effect of folic acid based homocysteine lowering on outcomes was assessed with meta-analysis using random effects models.
11 trials were identified that reported on 4389 people with chronic kidney disease, 2452 with end stage kidney disease, and 4110 with functioning kidney transplants (10,951 participants in total). Folic acid based homocysteine therapy did not prevent cardiovascular events (relative risk 0.97, 95% confidence interval 0.92 to 1.03, P = 0.326) or any of the secondary outcomes. There was no evidence of heterogeneity in subgroup analyses, including those of kidney disease category, background fortification, rates of pre-existing disease, or baseline homocysteine level. The definitions of chronic kidney disease varied widely between the studies. Non-cardiovascular events could not be analysed as few studies reported these outcomes.
Folic acid based homocysteine lowering does not reduce cardiovascular events in people with kidney disease. Folic acid based regimens should not be used for the prevention of cardiovascular events in people with kidney disease.
系统评价叶酸降低同型半胱氨酸对肾病患者心血管结局的影响。
系统评价和荟萃分析。
Medline、Embase、Cochrane 图书馆和 ClinicalTrials.gov 至 2011 年 6 月。
入选非透析依赖的慢性肾脏病或终末期肾脏病或有功能的肾移植患者的随机试验，随访至少 100 患者年，并评估叶酸降低同型半胱氨酸治疗的效果。未应用语言限制。
两名评价者使用标准表格独立提取研究背景、设计和结局的数据。主要终点是心血管事件（心肌梗死、卒中和心血管死亡率，或由研究作者定义）。次要终点包括各复合成分、全因死亡率、通路血栓形成、需要肾脏替代治疗以及报告的不良事件，包括血液学和神经学事件。使用随机效应模型荟萃分析评估叶酸降低同型半胱氨酸对结局的影响。
共确定了 11 项试验，报道了 4389 例慢性肾脏病患者、2452 例终末期肾脏病患者和 4110 例有功能的肾移植患者（共 10951 例患者）。叶酸降低同型半胱氨酸治疗并未预防心血管事件（相对危险度 0.97，95%可信区间 0.92 至 1.03，P=0.326）或任何次要结局。在亚组分析中，包括肾脏病类别、背景强化、现有疾病发生率或基线同型半胱氨酸水平，均无异质性证据。研究之间慢性肾脏病的定义差异很大。由于很少有研究报告这些结局，因此无法分析非心血管事件。
叶酸降低同型半胱氨酸不能减少肾脏病患者的心血管事件。叶酸方案不应用于预防肾脏病患者的心血管事件。
