Metabolomic Markers of Dietary Factors Associated with Kidney Health

项目摘要/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.