Metabolomic Markers of Dietary Factors Associated with Kidney Health

与肾脏健康相关的饮食因素的代谢组学标志物

基本信息

批准号：
10333394
负责人：
Casey Marie Rebholz
金额：
$ 12.28万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10333394
关键词：
Acids Adherence African American Animal Sources Animals Applications Grants Atherosclerosis Risk in Communities Biological Markers Biomarker of Dietary Intake Chronic Kidney Failure Clinical Clinical Trials Communities Dairy Products Data Data Reporting Diet Diet Modification Dietary Assessment Dietary Factors Dietary Intervention Dietary Practices Dietary Proteins Dietary intake Disease Outcome Edible Plants Equilibrium Fabaceae Fatty acid glycerol esters Food Funding General Population Goals Grant Guidelines Health Human Resources Hypertension Incidence Intake Intervention Intervention Trial Kidney Kidney Diseases Mediating Mediation Mediator of activation protein Metabolic Metabolic Marker Metabolic Pathway Morbidity - disease rate National Institute of Diabetes and Digestive and Kidney Diseases Nutrient Nuts Onset of illness Outcome Patient Self-Report Patients Physiological Plants Population Prevention strategy Processed Meats Proteins Public Health Randomized Clinical Trials Reporting Research Research Design Research Personnel Research Proposals Risk Risk Factors Source Testing Training Vegetable Proteins Vegetables Woman base biomarker discovery candidate marker career clinically relevant cohort cost effective design dietary dietary guidelines disorder prevention disorder risk effective therapy evidence base follow-up fruits and vegetables high risk high throughput technology improved men metabolomics middle age modifiable risk mortality novel novel marker nutritional epidemiology protein biomarkers protein metabolite small molecule study population

项目摘要

PROJECT SUMMARY / ABSTRACT Chronic kidney disease is associated with high rates of the morbidity and mortality, but few effective therapies exist. Diet is central to kidney disease and its management, and is a modifiable risk factor for kidney disease onset and its progression. Metabolomics can now quantify hundreds of small molecules in an unbiased approach providing an opportunity to assess the proximal physiologic effect of diet and to identify diet-modifiable metabolic pathways leading to kidney disease. The specific aims of the research proposal are: 1) to assess metabolomic markers of protein sources in a general population and evaluate mediation of protein and CKD risk by metabolites; 2) to externally validate purported metabolic markers of dietary acid load in an independent study population and to examine metabolomic mediators of CKD risk; and 3) to identify biomarkers of plant-based diets and determine which biomarkers explain the association between plant-based diets and CKD. Whereas previous clinical guidelines for kidney disease patients have recommended restriction of overall protein and other nutrients, we will focus on novel dietary factors, including specific protein sources, dietary acid load, and plant-based diets, which have been recently shown to be related to kidney disease risk. The analyses to be conducted will strengthen the evidence for clinically-relevant aspects of the diet that mediate kidney disease risk to be pursued in a diet intervention trial. The proposed research leverages existing metabolomics, dietary, and kidney disease outcome data in the Atherosclerosis Risk in Communities (ARIC) study, a well-characterized cohort of middle-aged black and white men and women from four U.S. communities. The successful completion of the project is assured given the existing approval from the ARIC study, access to data, and personnel with the necessary training and expertise. The proposed research, if funded, will greatly advance dietary assessment and will elucidate compounds and their metabolic pathways implicated in the diet-kidney disease relationship. The anticipated results of this project will lend support for a subsequent R01 grant application by refining the essential components of an improved renal diet and identify mediators that could be assessed as intermediate outcomes in a diet intervention trial. In summary, this grant will catalyze the next career stage for a NIDDK K01-funded investigator and has the potential to reduce the public health burden of 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，但有效很少存在疗法。饮食是肾脏疾病及其管理的核心，是肾脏的可修改风险因素疾病发作及其进展。代谢组学现在可以量化数百个小分子公正的方法提供了评估饮食近端生理效果的机会并确定饮食调整的代谢途径导致肾脏疾病。研究建议的具体目的是：1）评估A中蛋白质源的代谢标记一般人群并评估代谢产物蛋白质和CKD风险的介导； 2）外部验证在独立研究人群中据称是饮食酸负荷的代谢标记，并检查 CKD风险的代谢组介质； 3）确定植物性饮食的生物标志物，并确定哪个生物标志物解释了植物性饮食与CKD之间的关联。虽然先前关于肾脏疾病患者的临床指南建议限制整体蛋白质和其他营养素，我们将重点关注新的饮食因素，包括特定的蛋白质来源，饮食酸负荷和植物性饮食，最近已证明与肾脏疾病风险有关。这进行的分析将加强饮食中临床相关方面的证据在饮食干预试验中，肾脏疾病的风险被追求。拟议的研究利用了现有的代谢组学，饮食和肾脏疾病结果数据社区（ARIC）研究中的动脉粥样硬化风险，这是一项良好的中年黑白的群体来自美国四个社区的男人和女人。鉴于该项目的成功完成。 ARIC研究的现有批准，访问数据以及必须接受必要培训的人员专业知识。拟议的研究（如果资助）将大大提高饮食评估，并将阐明化合物他们的代谢途径涉及饮食 - 凯尼疾病的关系。预期结果项目将通过完善随后的R01赠款申请的支持，通过完善改善肾脏饮食并确定可以评估为饮食中的中级结果的介体干预试验。总而言之，该赠款将催化NIDDK K01资助的下一个职业阶段研究人员有可能减轻肾脏疾病的公共卫生负担。