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.

Public Health Relevance

Diet is a modifiable risk factor for chronic kidney disease, a common and morbid condition with few effective therapies. The proposed research will identify novel biomarkers of dietary intake and kidney disease risk. This project will provide evidence for diet interventions to ultimately improve the treatment for and outcomes of chronic kidney disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
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Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
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Rankin, Tracy L
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Johns Hopkins University
Public Health & Prev Medicine
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United States
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Hu, Emily A; Selvin, Elizabeth; Grams, Morgan E et al. (2018) Coffee Consumption and Incident Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis 72:214-222
Hu, Jiun-Ruey; Coresh, Josef; Inker, Lesley A et al. (2018) Serum metabolites are associated with all-cause mortality in chronic kidney disease. Kidney Int 94:381-389
Mok, Yejin; Sang, Yingying; Ballew, Shoshana H et al. (2018) American Heart Association's Life's Simple 7 at Middle Age and Prognosis After Myocardial Infarction in Later Life. J Am Heart Assoc 7:
Rebholz, Casey M; Yu, Bing; Zheng, Zihe et al. (2018) Serum metabolomic profile of incident diabetes. Diabetologia 61:1046-1054
Fretz, Anna; McEvoy, John W; Rebholz, Casey M et al. (2018) Relation of Lifestyle Factors and Life's Simple 7 Score to Temporal Reduction in Troponin Levels Measured by a High-Sensitivity Assay (from the Atherosclerosis Risk in Communities Study). Am J Cardiol 121:430-436
Rebholz, Casey M; Selvin, Elizabeth; Liang, Menglu et al. (2018) Plasma galectin-3 levels are associated with the risk of incident chronic kidney disease. Kidney Int 93:252-259
Luo, Shengyuan; Coresh, Josef; Tin, Adrienne et al. (2018) Soluble Urokinase-Type Plasminogen Activator Receptor in Black Americans with CKD. Clin J Am Soc Nephrol 13:1013-1021
Jung, Molly; Warren, Bethany; Grams, Morgan et al. (2018) Performance of non-traditional hyperglycemia biomarkers by chronic kidney disease status in older adults with diabetes: Results from the Atherosclerosis Risk in Communities Study. J Diabetes 10:276-285
Hu, Emily A; Lazo, Mariana; Selvin, Elizabeth et al. (2018) Coffee consumption and liver-related hospitalizations and deaths in the ARIC study. Eur J Clin Nutr :
Warren, Bethany; Rebholz, Casey M; Sang, Yingying et al. (2018) Diabetes and Trajectories of Estimated Glomerular Filtration Rate: A Prospective Cohort Analysis of the Atherosclerosis Risk in Communities Study. Diabetes Care 41:1646-1653

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