Phosphorus Absorption and Balance in Normal Physiology and Chronic Kidney Disease

正常生理和慢性肾脏病中的磷吸收和平衡

• 批准号: 9069837
• 负责人: Kathleen M Hill Gallant
• 金额: $ 13.81万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9069837
• 关键词: Adolescent; Adult; Adverse effects; Affect; Age; Animal Model; Award; Biochemical; Biological Availability; Blood Vessels; Bone Diseases; Cardiomegaly; Cardiovascular system; Carrier Proteins; Child; Chronic Kidney Failure; Clinical; Clinical Research; Data; Demographic Factors; Development; Diet; Dietary Calcium; Dietary Factors; Dietary Intervention; Dietary intake; Dihydroxycholecalciferols; Disease; Disease Progression; Endocrine System Diseases; Enterocytes; Environment; Equilibrium; Excretory function; Foundations; Functional disorder; Future; General Population; Goals; Health; Homeostasis; Hormones; Human; Impaired Renal Function; Indiana; Intake; Intestines; Kidney; Kidney Diseases; Laboratory Research; Longevity; Measures; Medical; Mentors; Mentorship; Metabolic Bone Diseases; Metabolic Diseases; Metabolism; Methods; Minerals; Mission; Modeling; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Nutritional Science; PTH gene; Patients; Phosphorus; Physiology; Population; Quality of life; Rattus; Renal function; Research; Research Personnel; Research Support; Research Training; Resources; Role; Sampling; Series; Serum; Signal Transduction; Source; Staging; Testing; Tissues; Training; Translational Research; Universities; Urine; Vascular calcification; Work; absorption; age group; base; bone; bone metabolism; brush border membrane; calcification; calcium intake; career; career development; dietary control; dietary excess; driving force; experience; fibroblast growth factor 23; improved; medical schools; mortality; normal aging; nutrition; phosphorus metabolism; prevent; professor; programs; radiotracer; research study; response; responsible research conduct; soft tissue; tenure track

 DESCRIPTION (provided by applicant): 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.