Metabolomics for Identifying Biomarkers of Dietary Intake & Kidney Disease Progression

项目摘要/摘要 慢性肾脏疾病的发病率和死亡率很高，但很少有效。 治疗方法是存在的。饮食是肾脏疾病及其治疗的核心，也是可改变的风险因素 肾脏疾病的进展。代谢组学现在可以无偏地对800多个小分子进行量化 为评估饮食的近端生理效应提供了一个机会。 研究方案的具体目的是：1)研究各组成部分之间的关系 饮食摄入量与肾脏疾病进展；2)量化饮食摄入量的代谢表达；以及 3)研究反映膳食摄入量的代谢物与肾脏疾病进展的关系。 这项拟议的研究利用了三项慢性肾脏疾病的研究：1)肾脏饮食的改变 疾病(MDRD)研究，限制饮食蛋白质的随机临床试验(N=840)；2)慢性肾脏 不充分性队列研究(CRIC)，一项前瞻性队列研究(N=3939)；3)德国慢性肾脏 疾病(GCKD)研究，前瞻性队列研究(N=5,217)。与这些领域的领导者进行广泛合作 研究性研究将促进拟议的研究。资金是通过家长研究和其他 资助赠款(由Andrew Levey博士和Josef Coresh博士领导的NIDDK R01，慢性肾脏疾病Biomarkers 财团)进行全球代谢组谱分析。 Casey M.Rebholz，博士、硕士、公共卫生硕士，约翰霍普金斯大学彭博社终身教职助理教授 公共卫生学院。她寻求获得导师研究科学家发展奖，以获得 基本技能和有指导的研究经验，为未来的独立职业生涯做准备 营养学和慢性肾脏疾病领域的研究人员。研究和职业发展建议 详细介绍了一个由代谢组学和慢性肾脏疾病方面的深入培训组成的五年计划；高级 营养学、肾脏疾病和代谢组学课程(实验室方法和分析技术)；初级 由约瑟夫·科雷什博士、医学博士、博士指导；由劳伦斯·J·阿佩尔博士、医学博士、公共卫生硕士、摩根·E博士共同指导。 Grams医学博士、博士和David R.Graham博士，以及肾脏疾病风险的流行病学研究 与饮食摄入量有关。近期的职业目标包括掌握以下统计技术 通过与研究相结合的学术课程进行代谢组学数据分析和营养科学 计划。从长远来看，Rebholz博士的目标是领导独立的研究计划，调查老年人的最佳饮食 防治慢性肾脏疾病。 拟议的研究将推动饮食评估方法的发展，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，将在未来的拨款中进行测试 Rebholz博士为约13%患有慢性肾脏疾病的美国人口提出的建议。

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.