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.

项目摘要 /摘要慢性肾脏疾病与发病率和死亡率高有关，但有效很少存在治疗。饮食是肾脏疾病及其管理的核心，是可修改的风险因素肾脏疾病进展。代谢组学现在可以在公正的中量化超过800个小分子方法提供了评估饮食近端生理效应的机会。研究建议的具体目的是：1）研究组成部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；和 3）检查反映饮食摄入量和肾脏疾病进展的代谢产物之间的关系。拟议的研究利用了三项慢性肾脏疾病研究：1）肾脏饮食的修饰疾病（MDRD）研究，这是一项饮食蛋白限制的随机临床试验（n = 840）； 2）慢性肾脏一项前瞻性队列研究（n = 3,939）； 3）德国慢性肾脏疾病（GCKD）研究，一项前瞻性队列研究（n = 5,217）。与这些领导者的广泛合作研究将催化拟议的研究。通过父母研究和其他资助的赠款（NIDDK R01由Andrew Levey博士和Josef Coresh领导，慢性肾脏病生物标志物联盟）进行全球代谢组分析。 Casey M. Rebholz，博士，MPH，MPH是Johns Hopkins Bloomberg的终身助理教授公共卫生学院。她寻求指导的研究科学家发展奖，以获得基本技能和指导的研究经验，为作为独立的未来职业做准备营养和慢性肾脏疾病领域的研究者。研究和职业发展建议详细介绍了一个五年计划，包括代谢组学和慢性肾脏疾病的深入培训；先进的营养，肾脏疾病和代谢组学的课程（实验室方法和分析技术）；基本的医学博士Josef Coresh博士的指导；劳伦斯·J·阿佩尔（Lawrence J. Grams，MD，PhD和David R. Graham博士博士；以及关于肾脏疾病风险的流行病学研究与饮食摄入有关。直接的职业目标包括掌握统计技术通过与研究集成的学术课程，代谢组学数据分析和营养科学计划。长期，Rebholz博士旨在领导独立研究计划，调查针对该研究的最佳饮食预防和治疗慢性肾脏疾病。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理的目的是通过饮食干预措施指导治疗，将在未来的赠款中进行测试 Rebholz博士提出的建议，约有13％的美国患有慢性肾脏疾病的人群。