Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial.
Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial.
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DOI：
10.1161/circulationaha.110.000588
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发表时间：
2011-04-26
期刊：
影响因子：
37.8
通讯作者：
Weir M
中科院分区：
文献类型：
--
作者：
Bostom AG;Carpenter MA;Kusek JW;Levey AS;Hunsicker L;Pfeffer MA;Selhub J;Jacques PF;Cole E;Gravens-Mueller L;House AA;Kew C;McKenney JL;Pacheco-Silva A;Pesavento T;Pirsch J;Smith S;Solomon S;Weir M
肾移植受者和其他慢性肾脏疾病(CKD)患者一样，经历了心血管疾病(CVD)的额外风险和总同型半胱氨酸(THcy)浓度的升高。对CKD患者的观察研究表明，同型半胱氨酸增加是CVD的危险因素。降低肾移植受者总同型半胱氨酸(THcy)水平的影响尚不清楚。在一项双盲对照试验中，我们将4110名稳定的肾移植受者随机分为高剂量(n=2056)或低剂量(n=2054)叶酸、维生素B6和维生素B12，以确定降低tHcy浓度是否降低了原发性复合性动脉硬化性心血管疾病(心肌梗死、中风、心血管死亡、复苏性猝死、冠状动脉或肾动脉血运重建术、下肢动脉疾病、颈动脉内膜切除术或血管成形术或腹主动脉瘤修补术)的发生率。平均随访时间为4.0年。与低剂量复合维生素相比，大剂量复合维生素治疗降低了同型半胱氨酸水平，但并未降低主要结果(n=547个总事件；危险比[95%可信区间]=0.99[0.84-1.17])或全因死亡(n=431例死亡；1.04[0.86-1.26])或依赖透析的肾功能衰竭(n=343个事件；1.15[0.93-1.43])的次要结果。肾移植受者接受大剂量叶酸、B6和B12复合维生素治疗后，尽管同型半胱氨酸水平显著降低，但并未降低综合心血管疾病结局、全因死亡率或透析依赖性肾功能衰竭。
Kidney transplant recipients, like other patients with chronic kidney disease (CKD), experience excess risk of cardiovascular disease (CVD) and elevated total homocysteine (tHcy) concentrations. Observational studies of patients with CKD suggest increased homocysteine is a risk factor for CVD. The impact of lowering total homocysteine (tHcy) levels in kidney transplant recipients is unknown. In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing tHcy concentrations reduced the rate of the primary composite arteriosclerotic CVD outcome (myocardial infarction, stroke, CVD death, resuscitated sudden death, coronary artery or renal artery revascularization, lower extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n= 547 total events; hazards ratio [95% confidence interval] = 0.99 [0.84–1.17]), or secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86–1.26]) or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93–1.43]) compared to the low dose multivitamin. Treatment with a high dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.