Biomedical Research Core 1

生物医学研究核心1

• 批准号: 10241468
• 负责人: KEVIN Edward MEYERS
• 金额: $ 6.48万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-18 至 2022-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241468
• 关键词: Adolescent; Adult; Age; Ambulatory Blood Pressure Monitoring; Atherosclerosis; Biomechanics; Biomedical Research; Blood Vessels; Body Composition; Bone Density; Bone Mineral Contents; Cardiovascular system; Center for Translational Science Activities; Child; Childhood; Chronic Disease; Chronic Kidney Failure; Clinical Data; Clinical Practice Guideline; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Consultations; Crohn' s disease; Data; Devices; Diabetes Mellitus; Disease; Dual-Energy X-Ray Absorptiometry; Echocardiography; End stage renal failure; Endothelium; Evaluation; Event; Failure; Finite Element Analysis; Fracture; Generations; Growth; Growth and Development function; Health; Hip region structure; Hypertension; Intervention Studies; Intervention Trial; Kidney Diseases; Life Expectancy; Measures; Medical; Metabolism; Methods; Minerals; Morbidity - disease rate; Multiple Anatomic Sites; Musculoskeletal Diseases; Nephrology; Nephrotic Syndrome; Nutritional status; Observational Study; Outcome; Pediatric Hospitals; Pediatric Research; Peripheral; Phenotype; Philadelphia; Physiologic pulse; Physiology; Protocols documentation; Race; Radial; Research; Research Personnel; Resolution; Resources; Site; Source; Testing; Thick; Urinary Calculi; Vascular Diseases; Vertebral column; X-Ray Computed Tomography; arterial stiffness; base; bone; bone health; bone quality; bone strength; cardiovascular health; carotid intima-media thickness; clinical biomarkers; clinical phenotype; design; early detection biomarkers; evidence base; experience; high risk population; implementation facilitation; improved; musculoskeletal imaging; nutrition; prevent; sex

CLINICAL PHENOTYPING CORE ABSTRACT Chronic kidney disease (CKD) is associated with progressive disturbances to growth and maturation, bone accrual and quality, nutritional status, and cardiovascular health. There is a critical need to develop validated strategies to prevent and treat these complications, to optimize growth and development, and to improve long- term outcomes for this high-risk population. Growing children are particularly vulnerable to the complications of kidney disease. Given the unique physiology of growing children, existing pediatric nephrology clinical practice guidelines – which are largely opinion-based and extrapolated from data in adults – need a stronger evidence- base. The proposed Pediatric Center of Excellence in Nephrology (PCEN) is designed to focus on barriers to implementing clinical trials in children. Since it would be impracticable to conduct trials with outcomes such as fractures or cardiovascular events, developing sensitive and valid clinical biomarkers of early musculoskeletal and vascular disease is essential to conducting interventional studies. This Clinical Phenotyping Core will leverage the resources of the Children’s Hospital of Philadelphia Clinical and Translational Research Center and state-of-the-art methods for the assessment of bone quality, body composition, bionutrition, and vascular health. Musculoskeletal imaging includes DXA measures of areal bone mineral density (BMD) and bone mineral content at multiple anatomic sites and peripheral quantitative computed tomography (pQCT) measures of volumetric BMD. The 2nd generation high-resolution pQCT (XCTII) device provides measures of bone microarchitecture and micro-finite element analysis estimates of bone strength (failure load) that are highly correlated with ex vivo biomechanical testing. In addition to ambulatory blood pressure monitoring and echocardiography, vascular phenotyping includes markers of arterial stiffness (pulse wave velocity/analysis), sub-clinical atherosclerosis (carotid intima-media thickness), and endothelial function (EndoPAT), all of which have been shown to independently predict cardiovascular events in adults, but need to be further evaluated in children. The specific aims of the Clinical Phenotyping Core are: 1) To provide expert consultation to center investigators on clinical phenotyping protocols for observational studies and clinical trials in childhood kidney diseases; 2) To facilitate implementation of clinical research by center investigators through access to state-of-the-art and comprehensive core resources for assessment of growth and nutrition, body composition, bone quality, and cardiovascular health; and 3) To contribute to the expansion and generation of robust sources of normative longitudinal data for the clinical phenotyping measures. Core Investigators have a track record of implementing studies of bone health, mineral metabolism, body composition, nutrition, hypertension, and vascular disease in kidney disease, other childhood chronic diseases, and healthy children and adolescents. Through integration with other PCEN Cores and collaboration across the Research Base, the Clinical Phenotyping Core will decrease the barriers to implementing clinical trials to promote bone accrual and vascular health in childhood kidney disease.

临床表型核心 抽象的 慢性肾脏疾病（CKD）与渐进式干扰对生长和成熟，骨骼有关 应计和质量，营养状况和心血管健康。 预防和惹恼并发症，优化增长和发展并改善长期的策略 这个高风险人群的期限尤其容易发生 肾脏疾病。 指南 - 基本上是基于意见的基于意见的，并且是从成人需要的数据中的数据中提出的 - 基地。 在儿童中实施临床试验。 骨折或心血管事件，发展早期肌肉骨骼的敏感和有效的临床生物标志物 血管疾病对于进行干预研究至关重要。 利用费城儿童医院的资源 评估骨骼质量，身体成分，倍育和血管健康的最新方法。 肌肉骨骼成像包括DXA的骨骼矿物质密度（BMD）和骨矿物质含量 在多个解剖位点和外周质量计算机断层扫描（PQCT）的体积测量 BMD。 与离体高度合并的骨强度（失败负载）的微型元素分析估计值 生物力学测试。 表型包括动脉刚度（脉搏波速度/分析），次临界动脉粥样硬化 （颈动脉内膜厚度）和内皮功能（内皮），所有这些功能都已显示为to。 不明显地预测成年人的心血管事件，但需要进一步评估儿童。 临床表型核心的目的是：1）为中心研究人员提供临床研究者 用于儿童肾脏疾病的观察性研究的表型方案； 中心研究人员通过获得最新和全面的临床研究实施 评估生长和营养，身体成分，骨质质量和心血管的核心资源 健康和3）为扩展和生成正常数据的范围 临床表型措施。 肾脏疾病中的健康，矿物质代谢，身体成分，营养，高血压和血管疾病， 其他童年慢性疾病以及健康的儿童和青少年。 核心和整个研究基础的协作，临床表型核心核心将减少障碍 实施临床STO促进儿童肾脏疾病中的骨骨骨骨骨骼和血管健康。