Metabolomic Markers of Dietary Factors Associated with Kidney Health

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，也是肾脏的一个可改变的风险因素。 疾病的发生和发展。代谢组学现在可以量化成百上千个小分子 不偏不倚的方法提供了一个机会来评估饮食的近端生理效应并确定 饮食可改变的代谢途径导致肾脏疾病。 该研究计划的具体目标是：1)评估蛋白质来源的代谢标记。 一般人群和评价代谢物对蛋白质和CKD风险的中介作用；2)外部验证 一项独立研究人群中膳食酸负荷的据称代谢标记物 CKD风险的代谢介体；以及3)确定植物性饮食的生物标记物并确定哪些 生物标记物解释了植物性饮食和慢性肾脏病之间的联系。 鉴于此前针对肾病患者的临床指南建议限制总体 蛋白质和其他营养素，我们将专注于新的饮食因素，包括特定的蛋白质来源，饮食 酸负荷和植物性饮食，最近被证明与肾脏疾病风险有关。这个 将要进行的分析将加强与临床相关的饮食方面的证据 肾脏疾病风险将在饮食干预试验中进行追踪。 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 社区动脉粥样硬化风险(ARIC)研究，一项具有良好特征的中年黑人和白人队列 来自美国四个社区的男性和女性。这项工程的顺利完成是有保证的，因为 ARIC研究的现有批准、对数据的访问以及具有必要培训和 专业知识。 这项拟议的研究，如果得到资助，将极大地促进饮食评估，并将阐明化合物 他们的代谢途径与饮食和肾脏疾病的关系有关。这样做的预期结果是什么 项目将通过细化基本组件来支持后续R01赠款申请 改善肾脏饮食，并确定可被评估为饮食中间结果的介质 干预试验。总之，这笔赠款将催化NIDDK K01资助的下一个职业阶段 研究人员，并有可能减少肾脏疾病的公共卫生负担。

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.