Metabolomics for Identifying Biomarkers of Dietary Intake & Kidney Disease Progression

用于识别膳食摄入生物标志物的代谢组学

基本信息

批准号：
9351513
负责人：
Casey Marie Rebholz
金额：
$ 15.49万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-12 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9351513
关键词：
Affect Animals Applications Grants Arginine Biological Biological Assay Biological Markers Biomarker of Dietary Intake Cell physiology Cessation of life Chronic Kidney Failure Chronic Kidney Insufficiency Clinical Clinical Nutrition Cohort Studies Collaborations Consumption Data Analyses Development Diet Diet Modification Diet Records Dietary Assessment Dietary Component Dietary Factors Dietary Intervention Dietary Proteins Dietary intake Disease Progression Doctor of Philosophy Educational Curriculum End stage renal failure Exposure to Five-Year Plans Food Frequencies Functional disorder Funding Future German population Goals Grant Health Health Benefit Hour Individual Intervention Kidney Kidney Diseases Laboratories Lead Letters Magnesium Mediating Mentored Research Scientist Development Award Mentors Mentorship Metabolism Methodology Methods Modeling Morbidity - disease rate National Institute of Diabetes and Digestive and Kidney Diseases Nitric Oxide Nutritional Science Outcome Parents Participant Pathogenesis Patient Self-Report Physiological Population Prevention Production Prospective cohort study Proteins Public Health Public Health Schools Questionnaires Randomized Randomized Clinical Trials Renal function Research Research Personnel Research Proposals Research Training Risk Risk Factors Senior Scientist Site Source Techniques Testing Training Treatment outcome Vegetables Visit adverse outcome career career development cohort design disorder risk effective therapy epidemiology study experience follow-up high risk improved insight metabolome metabolomics modifiable risk mortality novel novel marker nutrition professor programs protein intake randomized trial research and development research study skills small molecule soft drink tenure track trimethyloxamine

项目摘要

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.

项目概要/摘要慢性肾病与高发病率和死亡率相关，但有效的治疗方法很少治疗方法是存在的。饮食对于肾脏疾病及其治疗至关重要，并且是可改变的危险因素肾脏疾病进展。代谢组学现在可以公正地量化 800 多种小分子方法提供了评估饮食的近端生理效应的机会。该研究计划的具体目标是：1）研究各组成部分之间的关系。饮食摄入量和肾脏疾病进展； 2）量化饮食摄入的代谢组表达；和 3）检查反映饮食摄入量的代谢物与肾脏疾病进展之间的关系。拟议的研究利用了三项慢性肾脏疾病研究：1）肾脏饮食的改变疾病（MDRD）研究，饮食蛋白质限制的随机临床试验（N=840）； 2）慢性肾病不足队列（CRIC）研究，一项前瞻性队列研究（N=3,939）； 3) 德国慢性肾病疾病 (GCKD) 研究，一项前瞻性队列研究 (N=5,217)。与这些领域的领导者进行广泛的合作研究将促进拟议的研究。资金通过家长研究和其他方式提供资助的赠款（NIDDK R01 由 Drs. Andrew Levey 和 Josef Coresh 领导，慢性肾病生物标志物联盟）进行全球代谢组学分析。 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授助理教授公共卫生学院。她寻求指导研究科学家发展奖以获得为未来的独立职业生涯做好准备的基本技能和受指导的研究经验营养和慢性肾脏病领域的研究员。研究和职业发展建议详细介绍了一个五年计划，其中包括代谢组学和慢性肾脏病方面的深入培训；先进的营养、肾脏疾病和代谢组学课程（实验室方法和分析技术）；基本的由 Josef Coresh 博士（医学博士、哲学博士）指导；由 Lawrence J. Appel 博士（医学博士、公共卫生硕士）、Morgan E. 博士共同指导 Grams 医学博士、哲学博士和 David R. Graham 博士；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研究项目，调查人类的最佳饮食。预防和治疗慢性肾脏病。拟议的研究将推进饮食评估方法并提供对肾脏的新见解疾病发病机制，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 博士针对约 13% 的美国慢性肾病患者提出的建议。