Metabolomics for Identifying Biomarkers of Dietary Intake & Kidney Disease Progression

项目总结/摘要 慢性肾脏病的发病率和死亡率高，但有效的治疗方法少 治疗是存在的。饮食是肾脏疾病及其管理的核心，也是一个可改变的风险因素， 肾脏疾病进展。代谢组学现在可以以无偏的方式定量800多种小分子。 方法提供了一个机会来评估饮食的近端生理效应。 研究建议的具体目标是：1）研究成分之间的关系， 饮食摄入和肾脏疾病进展; 2）量化饮食摄入的代谢组学表达;以及 3)研究反映饮食摄入的代谢物与肾脏疾病进展之间的关系。 这项拟议的研究利用了三项慢性肾脏疾病研究：1）肾脏疾病患者饮食的改变 疾病（MDRD）研究，一项饮食蛋白质限制的随机临床试验（N=840）; 2）慢性肾功能衰竭患者 肾功能不全队列（CRIC）研究，一项前瞻性队列研究（N= 3，939）;以及3）德国慢性肾脏病研究 疾病（GCKD）研究，一项前瞻性队列研究（N= 5，217）。与这些领域的领导者开展广泛合作 研究将促进拟议的研究。资金是通过家长研究和其他 由Andrew Levey和Josef Coresh博士领导的NIDDK R 01，慢性肾脏病生物标志物 Consortium）进行总体代谢组学分析。 凯西M. Rebholz博士，硕士，公共卫生硕士是约翰霍普金斯彭博社的终身助理教授 公共卫生学院。她寻求一个指导研究科学家发展奖，以获得 基本技能和指导研究经验，为未来的职业生涯做好准备，作为一个独立的 营养和慢性肾病领域的研究者。研究和职业发展建议 详细介绍了一个五年计划，包括在代谢组学和慢性肾脏疾病的深入培训;先进的 营养学、肾脏疾病和代谢组学（实验室方法和分析技术）课程;初级 导师：Josef Coresh博士，医学博士，哲学博士;共同导师：Lawrence J.阿佩尔博士，医学博士，公共卫生硕士，Morgan E. Grams，MD，PhD和Dr.大卫R.格雷厄姆博士;以及关于肾脏疾病风险的流行病学研究 与饮食摄入有关。近期的职业目标包括掌握统计技术， 代谢组学数据分析和营养科学通过与研究整合的学术课程 计划从长远来看，Rebholz博士的目标是领导独立的研究项目，调查最佳饮食， 慢性肾脏病的预防和治疗。 拟议的研究将推进饮食评估方法，并为肾脏提供新的见解 疾病发病机制，目标是通过饮食干预指导治疗，将在未来的赠款中进行测试 Rebholz博士的建议，为约13%的美国慢性肾病患者提供治疗。

PROJECT SUMMARY / ABSTRACT Chronic kidney disease is associated with high rates of the morbidity and mortality, but few effective treatments exist. Diet is central to kidney disease and its management, and is a modifiable risk factor for kidney disease progression. Metabolomics can now quantify over 800 small molecules in an unbiased approach providing an opportunity to assess the proximal physiologic effect of diet. The specific aims of the research proposal are: 1) to study the relationship between components of dietary intake and kidney disease progression; 2) to quantify the metabolomic expression of dietary intake; and 3) to examine the relationship between metabolites that reflect dietary intake and kidney disease progression. The proposed research leverages three chronic kidney disease studies: 1) the Modification of Diet in Renal Disease (MDRD) study, a randomized clinical trial of dietary protein restriction (N=840); 2) the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective cohort study (N=3,939); and 3) the German Chronic Kidney Disease (GCKD) study, a prospective cohort study (N=5,217). Extensive collaboration with leaders in these research studies will catalyze the proposed research. Funding is provided through the parent studies and other funded grants (NIDDK R01 led by Drs. Andrew Levey and Josef Coresh, Chronic Kidney Disease Biomarkers Consortium) to perform global metabolomic profiling. Casey M. Rebholz, PhD, MS, MPH is a tenure-track Assistant Professor at Johns Hopkins Bloomberg School of Public Health. She seeks a Mentored Research Scientist Development Award in order to obtain essential skills and mentored research experience to prepare for a future career as an independent investigator in the field of nutrition and chronic kidney disease. The research and career development proposal details a five-year plan consisting of in-depth training in metabolomics and chronic kidney disease; advanced coursework in nutrition, kidney disease, and metabolomics (lab methods and analytic techniques); primary mentorship by Dr. Josef Coresh, MD, PhD; co-mentorship by Dr. Lawrence J. Appel, MD, MPH, Dr. Morgan E. Grams, MD, PhD, and Dr. David R. Graham, PhD; and epidemiologic research on the risk of kidney disease associated with dietary intake. Immediate career goals include the mastery of statistical techniques for metabolomics data analysis and nutrition science through an academic curriculum integrated with the research plan. Long term, Dr. Rebholz aims to lead independent research programs investigating optimal diets for the prevention and treatment of chronic kidney disease. Proposed research will advance dietary assessment methodology and provide novel insights into kidney disease pathogenesis with the goal of guiding therapy through dietary interventions, to be tested in future grant proposals by Dr. Rebholz, for the ~13% of the U.S. population with chronic kidney disease.