THERAPY IN DIALYSIS HYPOALBUMINEMIA AND HOMOCYSTEINEMIA

描述（改编自应用程序） 终末期肾病与几种复杂的营养相关。 问题低白蛋白血症是透析死亡率的最强预测因子， 与营养、炎症和共病因素的结合有关， 尚未对这些因素的相对重要性进行前瞻性评估。 相对的维生素缺乏，特别是B6，B12和叶酸， 发生.高同型半胱氨酸血症（Hyperhomocysteinemia，hyperHcy）是一种新的心血管和血栓性疾病， 叶酸、维生素B6和维生素B12至少可以部分纠正这种危险因素 补充，但这种疗法的临床效益尚未建立。 本申请中概述的项目将允许尤斯塔斯博士继续 他指导的这两个主要营养问题的研究， 低白蛋白血症和高Hcy血症。 PI将：（1A）对以下风险因素进行纵向分析 透析相关的低白蛋白血症，重点是蛋白质摄入和炎症 （C-反应蛋白），使用在CHOICE队列研究中收集的数据。这是 在第五届全国透析治疗研究中， 一年的后续行动，由博士领导。(1B)推进这样一种 临床试验，他最近完成，通过进行两个中心，2 × 2 280例近期住院血液透析患者的析因试验，血清 白蛋白低于4.0 g/dl，在试验的一个组中检查 口服必需氨基酸补充剂与安慰剂相比， 白蛋白水平和降低住院率，以及（1C）使用决策 分析模型，以比较口服避孕药的成本效益、效用和结局 补充剂与替代管理策略，包括胃肠外 营养、鼻饲和合成代谢剂。(2A)比较一下， 上述临床试验的第二组，高剂量与标准剂量的疗效比较 剂量叶酸，B6和B12补充剂在减少所有原因的心血管疾病 终点和血管通路血栓形成。(2B)进行荟萃分析， 发表的关于维生素治疗对实际患者生存的益处的试验。 这种观察和实验研究的结合， Coresh和Klag博士的指导，结合教学课程工作， 韦尔奇中心的支持性环境将使尤斯塔斯博士能够在他的基础上 目前的理论知识，使过渡到一个独立的临床 科学家，并准备他的职业生涯调查营养的作用， 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.