THERAPY IN DIALYSIS HYPOALBUMINEMIA AND HOMOCYSTEINEMIA

说明(改编自应用程序) 终末期肾病与几种复杂的营养相关 有问题。低蛋白血症是透析死亡率的最强预测因素， 与营养、炎症和共病因素的组合有关，但 这些因素的相对重要性尚未进行前瞻性评估。 相对的维生素缺乏，特别是B6、B12和叶酸的缺乏 发生。高同型半胱氨酸血症--一种新的心血管和血栓形成 风险因素，至少可以用叶酸、维生素B6和B12部分纠正 补充，但这种疗法的临床益处还没有确定。 本申请中概述的项目将允许尤斯塔斯博士继续 他对这两个主要营养问题的指导研究， 低蛋白血症和高同型半胱氨酸。 PI将：(1A)对以下项目的风险因素进行纵向分析 以蛋白质摄入和炎症为重点的透析相关性低蛋白血症 (C-反应蛋白)，使用在选择队列研究中收集的数据。这是 全国代表性的5月份925例透析患者队列 一年的后续行动，由鲍威博士、克拉格博士和科雷什博士领导。(1B)建立在 临床试验，他最近完成了，通过进行一个双中心，2x2 280例新入院血液透析患者血清因素试验 小于4.0g/dl的白蛋白，在试验的一只手臂上检查疗效 口服必需氨基酸补充剂与安慰剂在改善血清方面的比较 白蛋白水平和降低住院率和(1C)使用决定 比较口服的成本-效果、效用和结果的分析模型 补充剂与替代管理策略的对比，包括非肠道治疗 营养、鼻胃喂养和合成代谢剂。(2A)比较在 以上第二臂临床试验，疗效高对标准 补充叶酸、B6和B12可减少心血管疾病 终点和血管通路血栓。(2B)对以下项目进行元分析 已发表的维生素疗法对患者实际存活率的益处的试验。 这种观测和实验研究的结合是在 Coresh博士和Klag博士的指导，结合教学课程工作，在 韦尔奇中心的支持背景将使尤斯塔斯博士能够在他的基础上 目前的理论知识，使之过渡到独立的临床 科学家并为他的职业生涯做好准备，研究营养在 肾脏疾病。

DESCRIPTION (Adapted from the application) End stage renal disease is associated with several complex nutritional problems. Hypoalbuminemia, the strongest predictor of mortality on dialysis, is related to a combination of nutritional, inflammatory and comorbid factors, but the relative importance of these factors has not been prospectively evaluated. Relative vitamin deficiencies, especially that of B6, B12 and folate, also occur. Hyperhomocysteinemia (hyperHcy), a novel cardio-vascular and thrombotic risk factor, is at least partly correctable with folate and vitamin B6 and B12 supplementation but the clinical benefits of this therapy is not established. The projects outlined in this application will allow Dr. Eustace to continue his mentored research into these two major nutritional problems, hypoalbuminemia and hyperHcy. The PI will: (1A) Conduct a longitudinal analysis of risk factors for dialysis-associated hypoalbuminemia focusing on protein intake and inflammation (C-Reactive Protein), using data collected in the CHOICE cohort study. This is a nationally representative cohort of 925 incident dialysis patients in its 5th year of follow-up, headed by Drs. Powe, Klag and Coresh. (1B) Build on a clinical trial, he recently completed, by conducting a two-center, 2 x 2 factorial trial of 280 recently hospitalized hemodialysis patients, with serum albumins of less then 4.0 g/dl, examining in one arm of the trial the efficacy of oral essential amino acids supplements versus placebo at improving serum albumin levels and reducing hospitalization rates and (1C) Use a decision analysis model to compare the cost-effectiveness, utility and outcomes of oral supplements versus alternative management strategies, including parenteral nutrition, naso-gastric feeding and anabolic agents. (2A) Compare, in the second arm of the above clinical trial, the efficacy of high versus standard dose folate, B6 & B12 supplementation at reducing all cause cardiovascular endpoints and vascular access thromboses. (2B) Perform a meta-analysis of published trials of the benefit of vitamin therapy on actual patient survival. This combination of observational and experimental research under the mentorship of Drs. Coresh and Klag, combined with didactic course work, in the supportive context of the Welch Center will allow Dr. Eustace to build on his current theoretical knowledge, make the transition into an independent clinical scientist and prepare him for a career investigating the role of nutrition in renal disease.