Elevated serum phosphorus (P) and related abnormalities in P homeostasis due to progressive loss of kidney function are primary driving forces behind cardiovascular dysfunction and mortality in chronic kidney disease (CKD) patients. In addition, elevated serum P is associated with increased mortality in the healthy general population. Intestinal P absorption is a critical, yet understudied component in P metabolism. Elucidating factors that influence and regulate P absorption is essential for developing strategies to control abnormal P metabolism and associated consequences in CKD patients, and in the general population. The principle investigator (PI)'s long-term career goal is to develop an independent clinical and translational research program focused on determining the factors that influence and regulate intestinal P absorption in healthy and CKD populations. To achieve this, the PI will conduct a series of clinical studies in healthy subjects and patients with CKD, supported by complementary experiments in animal models of CKD. This fits well within the mission of the NIDDK to improve health and quality of life through support of research and research training in kidney disease and endocrine and metabolic diseases. The goals of the specific aims of this project are: 1) to determine intestinal P absorption efficiency in patients wth early stages of CKD in comparison to healthy adults, how P absorption is affected when dietary P is restricted, and to determine P bioavailability from organic and inorganic dietary sources; 2) to determine P absorption efficiency and response to dietary P intake on P absorption in a mechanistic study using the Cy/+ rat model of progressive CKD-MBD, and determine the role of localization of the intestinal P transporter NaPi-2b on P absorption; and 3) to determine total-body P balance in normal children and the effects of dietary Ca intake, demographic, and biochemical factors on P balance leading to future studies in children with CKD. A team of mentors with complementary expertise relevant to this project will oversee the PI's research training in P absorption and metabolism, as well as career development guidance during the mentored award period. The PI will partake in educational experiences in bone and mineral metabolism, chronic kidney disease, clinical research, and responsible conduct of research. Purdue University and Indiana University School of Medicine, along with the Indiana Clinical Research Center, provide excellent environments in terms of research and intellectual resources for clinical and basic studies in mineral metabolism.

Public Health Relevance

Chronic kidney disease (CKD) affects 10 % of the U.S. population, and leads to considerable morbidity and mortality. Elevated serum phosphorus and associated abnormalities in phosphorus metabolism due to progressive loss of kidney function are primary driving forces behind the secondary consequences of CKD, particularly vascular calcification and heart enlargement; additionally, serum phosphorus is positively associated with mortality in the healthy non-CKD population. Increasing the understanding of intestinal phosphorus absorption and metabolism is critical to developing strategies to reduce the morbidity and mortality related to phosphorus in both general and CKD populations.

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 #
1K01DK102864-01A1
Application #
8914299
Study Section
Kidney, Urologic and Hematologic Diseases D Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2015-06-01
Project End
2020-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Purdue University
Department
Nutrition
Type
Schools of Public Health
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907
Choi, Mun Sun; Kistler, Brandon; Wiese, Gretchen N et al. (2018) Pilot Study of the Effects of High-Protein Meals During Hemodialysis on Intradialytic Hypotension in Patients Undergoing Maintenance Hemodialysis. J Ren Nutr :
Vorland, Colby J; Martin, Berdine R; Weaver, Connie M et al. (2018) Phosphorus Balance in Adolescent Girls and the Effect of Supplemental Dietary Calcium. JBMR Plus 2:103-108
Stremke, Elizabeth R; McCabe, Linda D; McCabe, George P et al. (2018) Twenty-Four-Hour Urine Phosphorus as a Biomarker of Dietary Phosphorus Intake and Absorption in CKD: A Secondary Analysis from a Controlled Diet Balance Study. Clin J Am Soc Nephrol 13:1002-1012
Coheley, L M; Kindler, J M; Laing, E M et al. (2018) Whole egg consumption and cortical bone in healthy children. Osteoporos Int 29:1783-1791
Moorthi, Ranjani N; Vorland, Colby J; Hill Gallant, Kathleen M (2017) Diet and Diabetic Kidney Disease: Plant Versus Animal Protein. Curr Diab Rep 17:15
Kindler, Joseph M; Pollock, Norman K; Laing, Emma M et al. (2017) Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years. J Bone Miner Res 32:1537-1545
Giudici, Kelly Virecoulon; Kindler, Joseph M; Martin, Berdine R et al. (2017) Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States. Nutr Metab (Lond) 14:25
Vorland, Colby J; Stremke, Elizabeth R; Moorthi, Ranjani N et al. (2017) Effects of Excessive Dietary Phosphorus Intake on Bone Health. Curr Osteoporos Rep 15:473-482
Hill Gallant, Kathleen M; Spiegel, David M (2017) Calcium Balance in Chronic Kidney Disease. Curr Osteoporos Rep 15:214-221
Hill Gallant, Kathleen M; Weaver, Connie M; Towler, Dwight A et al. (2016) Nutrition in Cardioskeletal Health. Adv Nutr 7:544-55

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