Effects of Dietary Phosphorus Restriction on Whole-Body Calcium and Phosphorus Balance and Kinetics in Patients with Moderate Chronic Kidney Disease

膳食磷限制对中度慢性肾病患者全身钙磷平衡和动力学的影响

• 批准号: 9809588
• 负责人: Kathleen M Hill Gallant
• 金额: $ 11.06万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2020-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9809588
• 关键词: Address; Adult; Affect; American diet; Blood; Bone Diseases; Calcitriol; Calcium; Calcium Isotopes; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Research; Collection; Comorbidity; Coupled; Crossover Design; Data; Development; Diet; Diet Research; Dietary Calcium; Dietary Intervention; Dietary Phosphorus; Dietary Proteins; Dietary intake; Dihydroxycholecalciferols; Dose; Eligibility Determination; Enrollment; Equilibrium; Event; Fracture; Funding; Future; Goals; Guidelines; Health; Homeostasis; Hormonal; Hour; Inpatients; Intake; Intervention; Intestinal Absorption; Intestines; Intravenous; Ions; Isotopes; Kidney; Kidney Diseases; Kinetics; Knowledge; Measurement; Metabolic; Methods; Minerals; Mission; Modeling; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Oral; Outcome; Outpatients; PTH gene; Parathyroid gland; Patients; Pharmacologic Substance; Pharmacology; Phosphorus; Phosphorus Isotopes; Physiology; Placebos; Protocols documentation; Quality of life; Race; Radioactive; Randomized; Research; Research Support; Sampling; Serum; Serum Phosphorus Level; Severities; Testing; Time; Tissues; Tracer; United States; Urine; Work; absorption; base; biological sex; bone; calcium intake; calcium metabolism; cardiovascular risk factor; dietary restriction; effective therapy; extracellular; feeding; fibroblast growth factor 23; improved; innovation; mortality; mortality risk; novel; phosphorus metabolism; prevent; screening; treatment strategy

PROJECT SUMMARY/ABSTRACT Abnormal calcium (Ca) and phosphorus (P) metabolism are central to the development of chronic kidney disease-mineral bone disorder (CKD-MBD), which causes cardiovascular and bone disease leading to cardiovascular events, bone fractures, and increased risk of death. The various dietary and pharmaceutical treatments for CKD-MBD affect both Ca and P metabolism, yet major knowledge gaps exist on how these treatments affect whole-body physiology of both ions. The lack of understanding on Ca and P metabolism in CKD-MBD progression precludes the development of effective therapies. The goal of this project is to produce preliminary data on the effects of the commonly prescribed dietary phosphorus restriction on whole-body Ca and P balance and kinetics in patients with CKD, to support a larger future clinical study. The specific aims are to determine 1) intestinal Ca and P fractional absorption and 2) Ca and P balance and full kinetics, effect sizes and variance estimates in patients with CKD on a low Ca diet with high P diet versus dietary P restriction. In a randomized cross-over design, four adult patients with moderate-stage CKD will be studied on a controlled diet of either low dietary Ca intake and high dietary P intake, representative of a typical American diet, or a low dietary Ca intake with a dietary P restriction as commonly prescribed. After screening to determine eligibility, enrolled patients will be given the randomly assigned controlled diet for 1 week as outpatients, and then admitted to the clinical research center for a 48-hour absorption testing protocol that will utilize oral and intravenous doses of stable Ca-44 and radioactive P-33 isotopes. Serial blood draws will be taken over the 48-hour inpatient period, along with timed urine and complete fecal collections. Fractional Ca and P intestinal absorption will be determined by kinetic modeling of serum and urine measurements of the isotopes after oral and intravenous dosing. Two patients will be studied for an additional 12-days as inpatient continuing on the controlled research diet with blood draws and timed, complete urine and fecal collections to determine whole-body Ca and P balance over 2-weeks, as well as full Ca and P kinetics obtained by modeling the serum, urine, and fecal isotopic data, which will give rates of Ca and P transfer to and from various body pools (e.g. to and from bone). Following a 1- week washout, patients will crossover to be studied on the other dietary condition. It is expected that this study will produce the necessary effect size and variance estimates on the effect of dietary P restriction on Ca and P absorption, balance, and kinetics to adequately power a future clinical study. The long-term goal of this research is to determine effects of a variety of current and novel dietary and pharmaceutical interventions on whole-body Ca and P physiology with the goal of improving treatments for CKD-MBD. This relates to the mission of the NIDDK to support research aimed at improving the health and quality of life of patients with kidney disease.

项目概要/摘要 钙 (Ca) 和磷 (P) 代谢异常是慢性肾病发展的核心 疾病-矿物质性骨病 (CKD-MBD)，它会导致心血管和骨骼疾病，从而导致 心血管事件、骨折和死亡风险增加。各种饮食和药物 CKD-MBD 的治疗会影响 Ca 和 P 代谢，但对于这些代谢如何影响，仍存在重大知识空白 治疗会影响两种离子的全身生理机能。对钙、磷代谢缺乏了解 CKD-MBD 的进展阻碍了有效疗法的开发。该项目的目标是生产 关于常用膳食磷限制对全身钙和钙的影响的初步数据 CKD 患者的 P 平衡和动力学，以支持未来更大规模的临床研究。具体目标是 确定 1) 肠道 Ca 和 P 吸收分数，以及 2) Ca 和 P 平衡和完整动力学、效应大小和 低钙饮食、高磷饮食与饮食磷限制的 CKD 患者的方差估计。在一个 随机交叉设计，四名成年中度 CKD 患者将接受控制饮食研究 低膳食钙摄入量和高膳食磷摄入量（代表典型的美国饮食）或低膳食摄入量 按照通常规定，钙摄入量应限制膳食磷的摄入量。经筛选确定资格后，报名 患者将作为门诊患者接受随机分配的控制饮食 1 周，然后入院 临床研究中心的 48 小时吸收测试方案将利用口服和静脉注射剂量 稳定的 Ca-44 和放射性 P-33 同位素。将在 48 小时住院期间进行连续抽血， 以及定时尿液和完整粪便收集。 Ca 和 P 肠道吸收分数为 通过口服和静脉注射后血清和尿液同位素测量的动力学模型确定 剂量。两名患者将作为住院患者继续进行为期 12 天的额外研究 通过抽血和定时、完整的尿液和粪便收集来确定全身钙和磷平衡的饮食 超过两周的时间，以及通过对血清、尿液和粪便同位素数据建模获得的完整 Ca 和 P 动力学， 这将给出 Ca 和 P 传入和传出不同身体池（例如传入和传出骨骼）的速率。继 1- 一周冲洗后，患者将交叉研究其他饮食条件。预计这项研究 将针对膳食 P 限制对 Ca 和 P 的影响产生必要的效应大小和方差估计 吸收、平衡和动力学，为未来的临床研究提供充足的动力。本研究的长期目标 是为了确定各种当前和新颖的饮食和药物干预措施对全身的影响 Ca 和 P 生理学，目标是改善 CKD-MBD 的治疗。这关系到我们的使命 NIDDK 支持旨在改善肾病患者健康和生活质量的研究。