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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01DK107782-01A1
Application #
9179786
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK-D)
Program Officer
Rankin, Tracy L
Project Start
2016-09-12
Project End
2021-06-30
Budget Start
2016-09-12
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$156,536
Indirect Cost
$10,484
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Loomis, Stephanie J; Chen, Yuan; Sacks, David B et al. (2017) Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort. Clin Chem 63:980-989
Ishigami, Junichi; Jaar, Bernard G; Rebholz, Casey M et al. (2017) Biomarkers of Mineral and Bone Metabolism and 20-Year Risk of Hospitalization With Infection: The Atherosclerosis Risk in Communities Study. J Clin Endocrinol Metab 102:4648-4657
Rebholz, Casey M; Inker, Lesley A; Chen, Yuan et al. (2017) Risk of ESRD and Mortality Associated With Change in Filtration Markers. Am J Kidney Dis 70:551-560
Grams, Morgan E; Yang, Wei; Rebholz, Casey M et al. (2017) Risks of Adverse Events in Advanced CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis 70:337-346
Grams, Morgan E; Tin, Adrienne; Rebholz, Casey M et al. (2017) Metabolomic Alterations Associated with Cause of CKD. Clin J Am Soc Nephrol 12:1787-1794
Rebholz, Casey M; Grams, Morgan E; Steffen, Lyn M et al. (2017) Diet Soda Consumption and Risk of Incident End Stage Renal Disease. Clin J Am Soc Nephrol 12:79-86
McClure, Scott T; Chang, Alex R; Selvin, Elizabeth et al. (2017) Dietary Sources of Phosphorus among Adults in the United States: Results from NHANES 2001-2014. Nutrients 9:
Haring, Bernhard; Selvin, Elizabeth; Liang, Menglu et al. (2017) Dietary Protein Sources and Risk for Incident Chronic Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study. J Ren Nutr 27:233-242
Jung, Molly; Warren, Bethany; Grams, Morgan et al. (2017) 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 :
Rebholz, Casey M; Crews, Deidra C; Grams, Morgan E et al. (2016) DASH (Dietary Approaches to Stop Hypertension) Diet and Risk of Subsequent Kidney Disease. Am J Kidney Dis 68:853-861

Showing the most recent 10 out of 11 publications