Metabolomic Markers of Dietary Factors Associated with Kidney Health

项目总结/摘要 慢性肾脏病的发病率和死亡率高，但有效的治疗方法少 治疗是存在的。饮食是肾脏疾病及其管理的核心，也是肾脏疾病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数百个小分子， 无偏倚的方法提供了一个机会，以评估近端生理效应的饮食，并确定 导致肾脏疾病的饮食可改变的代谢途径。 研究建议的具体目标是：1）评估蛋白质来源的代谢组学标志物， 一般人群，并评价代谢产物对蛋白质和CKD风险的介导作用; 2）外部验证 在一项独立的研究人群中， CKD风险的代谢组学介质;和3）识别植物性饮食的生物标志物，并确定 生物标志物解释了植物性饮食与CKD之间的关联。 尽管先前的肾病患者临床指南建议限制总体 蛋白质和其他营养素，我们将集中在新的饮食因素，包括特定的蛋白质来源，饮食 酸负荷和植物性饮食，最近已被证明与肾脏疾病风险有关。的 将要进行的分析将加强饮食的临床相关方面的证据， 肾脏疾病风险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，饮食和肾脏疾病的结果数据， 社区动脉粥样硬化风险（ARIC）研究，一项中年黑人和白色人的良好特征队列研究 来自美国四个社区的男女鉴于该项目的成功完成是有保证的， ARIC研究的现有批准、数据访问和经过必要培训的人员， 专业知识 这项拟议中的研究，如果得到资助，将大大推进饮食评估，并将阐明化合物 以及与饮食和肾脏疾病关系有关的代谢途径。预期的结果是， 该项目将通过完善一个R 01赠款申请的基本组成部分， 改善肾脏饮食，并确定可作为饮食中中间结果评估的介质 干预试验。总之，这笔赠款将促进下一个职业阶段的NIDDK K 01资助 研究者，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.