Bennett-Richards K, Kattenhorn M, Donald A, Oakley G, Varghese Z, Rees L, Deanfield J E
Department of Nephrology, Great Ormond Street Hospital for Children NHS Trust and Institute of Child Health, London, UK.
Circulation. 2002 Apr 16;105(15):1810-5. doi: 10.1161/01.cir.0000014417.95833.1d.
Accelerated vascular disease is common in chronic renal failure (CRF) and accounts for significant mortality and morbidity. Elevated homocysteine levels may contribute by an effect on endothelial function.
We performed a double-blind placebo-controlled randomized crossover trial of folic acid at 5 mg/m2 in 25 normotensive children 12+/-3 (7 to 17) years of age with CRF (glomerular filtration rate 26.8+/-13.2 mL/min per 1.73 m2) of noninflammatory etiology. Each subject underwent two 8-week periods of folic acid and placebo separated by an 8-week washout period. The effect of folic acid on homocysteine levels, LDL oxidation, and both endothelial-dependent and -independent vascular function were measured. After oral folic acid, serum folate levels rose from 11.7+/-4.25 to 635+/-519 microg/L (P=0.001), red cell folate levels rose from 364+/-195 to 2891+/-2623 microg/L (P<0.001), and total homocysteine levels fell from 10.28+/-4.16 to 8.62+/-2.32 micromol/L (P=0.03). In addition, there was a significant improvement in flow-mediated dilatation (FMD) (endothelial-dependent dilatation) from 7.21+/-2.8% to 8.47+/-3.01% (P=0.036) with no change in response to glyceryl trinitrate (endothelial-independent dilatation). There was no significant change in FMD or glyceryl trinitrate during the placebo phase. There was, however, no significant difference in final FMD after placebo or folic acid. Lag times for LDL oxidation were prolonged during the treatment phase (58.4+/-18.7 to 68.1+/-25.9 minutes, P=0.01).
Folic acid supplementation in children with CRF may improve endothelial function with an increased resistance of LDL to oxidation.
加速性血管疾病在慢性肾衰竭（CRF）中很常见，是导致显著死亡率和发病率的原因。同型半胱氨酸水平升高可能通过影响内皮功能而发挥作用。
我们对25名12±3（7至17）岁、患有非炎性病因的CRF（肾小球滤过率为每1.73平方米26.8±13.2毫升/分钟）的血压正常儿童进行了一项双盲、安慰剂对照的随机交叉试验，给予5毫克/平方米的叶酸。每位受试者经历两个为期8周的叶酸期和安慰剂期，中间间隔8周的洗脱期。测量了叶酸对同型半胱氨酸水平、低密度脂蛋白氧化以及内皮依赖性和非内皮依赖性血管功能的影响。口服叶酸后，血清叶酸水平从11.7±4.25微克/升升至635±519微克/升（P = 0.001），红细胞叶酸水平从364±195微克/升升至2891±2623微克/升（P < 0.001），总同型半胱氨酸水平从10.28±4.16微摩尔/升降至8.62±2.32微摩尔/升（P = 0.03）。此外，血流介导的血管舒张（FMD，内皮依赖性舒张）从7.21±2.8%显著改善至8.47±3.01%（P = 0.036），而对硝酸甘油的反应（非内皮依赖性舒张）无变化。在安慰剂期，FMD或硝酸甘油均无显著变化。然而，安慰剂或叶酸治疗后的最终FMD无显著差异。在治疗期，低密度脂蛋白氧化的延迟时间延长（从58.4±18.7分钟至68.1±25.9分钟，P = 0.01）。
补充叶酸可能改善CRF儿童的内皮功能，并增加低密度脂蛋白的抗氧化能力。
