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: 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
• 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

 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（由适用提供）：由于肾脏功能的进行性丧失而导致P稳态的血清磷升高（P）和相关异常是心血管功能障碍和慢性肾脏病（CKD）患者的心血管功能障碍和死亡率的主要驱动力。此外，血清P升高与健康普通人群的死亡率升高有关。肠道P抽象是P代谢中的关键，但可以理解的成分。阐明影响和调节P绝对P的因素对于制定控制异常P代谢的策略以及CKD患者以及普通人群的相关后果至关重要。主要调查员（PI）的长期职业目标是 为了开发独立的临床和翻译研究计划，重点是确定影响和调节健康和CKD种群中肠道P抽象的因素。为此，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CKD动物模型的补充实验的支持。通过支持肾脏疾病，内分泌和代谢疾病的研究和研究培训，这非常适合NIDDK的使命，以改善健康和生活质量。该项目的具体目的的目标是：1）确定CKD早期阶段患者的肠道P吸收效率与健康成年人相比，当饮食P受到限制时如何影响P吸收，并确定P的生物利用度P的生物利用度。 2）在使用渐进性CKD-MBD的CY/+大鼠模型中，在机械研究中确定P吸收效率和对饮食P摄入的响应，并确定肠道P转运蛋白NAPI-2B对P抽象的定位作用； 3）为了确定正常儿童的全身P平衡，以及饮食CA摄入，人口统计学和生化因素对P平衡的影响，从而导致CKD儿童的未来研究。与该项目相关的具有完全专业知识的导师团队将监督PI在P抽象和代谢方面的研究培训，以及在修订奖励期内的职业发展指导。 PI将参与骨骼和矿物质代谢，慢性肾脏疾病，临床研究以及负责任的研究的教育经验。普渡大学和印第安纳大学医学院以及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了良好的环境。