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

基本信息

批准号：
8914299
负责人：
Kathleen M Hill Gallant
金额：
$ 13.96万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
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/8914299
关键词：
1,25 (OH) vitamin D 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 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 Parathyroid gland 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 public health relevance radiotracer research study response responsible research conduct soft tissue

项目摘要

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.

描述（由申请人提供）：由于肾功能进行性丧失导致血清磷（P）升高和相关的磷稳态异常是慢性肾病（CKD）患者功能障碍和死亡的主要驱动因素。此外，血清磷升高。肠道磷吸收是磷代谢中一个重要但尚未得到充分研究的因素，对于制定控制异常磷代谢和相关的策略至关重要。首席研究员 (PI) 的长期职业目标是对 CKD 患者和普通人群的影响。开发一个独立的临床和转化研究项目，重点确定影响和调节健康和 CKD 人群肠道 P 吸收的因素。为了实现这一目标，PI 将在健康受试者和 CKD 患者中进行一系列临床研究，并得到以下机构的支持。这非常符合 NIDDK 通过支持肾脏疾病以及内分泌和代谢疾病的研究和研究培训来改善健康和生活质量的使命。该项目的具体目标是。 : 1)确定早期 CKD 患者与健康成人相比的肠道 P 吸收效率，限制膳食 P 时 P 吸收受到的影响，并确定有机和无机膳食来源的 P 生物利用度 2) 确定 P 吸收效率和在使用进行性 CKD-MBD 的 Cy/+ 大鼠模型的机制研究中，膳食磷摄入对磷吸收的反应，并确定肠道磷转运蛋白 NaPi-2b 的定位对磷吸收的作用；3) 确定正常儿童的全身磷平衡以及膳食钙摄入量、人口统计和生化因素对磷平衡的影响，从而促进未来对 CKD 儿童的研究具有与该项目相关的互补专业知识的导师团队将监督 PI 的研究培训。 PI 将参与骨和矿物质代谢、慢性肾病、临床研究以及负责任的研究开展方面的教育经验。医学部和印第安纳州临床研究中心，为矿物质代谢的临床和基础研究提供优良的科研环境和智力资源。