Biomedical Research Core 1

临床表型核心 摘要 慢性肾脏病（CKD）与生长和成熟、骨代谢和免疫功能的进行性障碍有关。 增加和质量、营养状况和心血管健康。迫切需要开发经过验证的 预防和治疗这些并发症的策略，优化生长和发育，并改善长期 这一高风险人群的长期结果。成长中的儿童特别容易受到 肾病鉴于成长期儿童的独特生理学，现有的儿科肾脏病临床实践 指南-主要是基于意见和从成人数据推断-需要更有力的证据， 基地拟议的儿科肾脏病学卓越中心（PCEN）旨在关注以下障碍： 在儿童中进行临床试验。由于进行审判的结果如 骨折或心血管事件，开发敏感和有效的临床生物标志物， 血管疾病是进行介入研究的关键。本临床表型分析核心将 利用费城儿童医院临床和转化研究中心的资源， 用于评估骨质量、身体组成、生物营养素和血管健康的最先进方法。 肌肉骨骼成像包括DXA测量骨密度（BMD）和骨矿物质含量 在多个解剖部位和外周定量计算机断层扫描（pQCT）测量体积 BMD。第二代高分辨率pQCT（XCTII）设备提供了骨微结构的测量， 与离体高度相关的骨强度（失效载荷）的微观有限元分析估计 生物力学测试除了动态血压监测和超声心动图外， 表型包括动脉僵硬标志物（脉搏波速度/分析）、亚临床动脉粥样硬化 （颈动脉内膜中层厚度）和内皮功能（EndoPAT），所有这些都已被证明是 独立预测成人心血管事件，但需要在儿童中进一步评估。具体 临床表型分析核心的目的是：1）为中心研究者提供有关临床 儿童肾脏疾病观察性研究和临床试验的表型分析方案; 2）促进 中心研究者通过获得最先进和全面的 用于评估生长和营养、身体组成、骨骼质量和心血管疾病的核心资源 3）促进扩大和生成强有力的规范性纵向数据来源， 临床表型测定。核心研究者有实施骨研究的跟踪记录 健康、矿物质代谢、身体成分、营养、高血压和肾脏疾病中的血管疾病， 其他儿童慢性疾病和健康的儿童和青少年。通过与其他PCEN集成 临床表型分析核心将通过研究基地的核心和合作，减少 实施临床试验，以促进儿童肾病患者的骨生成和血管健康。

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.