Biomedical Research Core 1

临床表型核心 摘要 慢性肾脏疾病(CKD)与生长和成熟、骨骼进行性紊乱有关。 应计收入和质量、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 这一高危人群的长期结局。成长中的儿童尤其容易受到 肾脏疾病。鉴于儿童生长发育的独特生理特点，现有的儿科肾病临床实践 指南-主要基于意见，并从成年人的数据推断-需要更有力的证据- 基地。拟议的儿科肾病卓越中心(PCEN)旨在关注以下障碍 在儿童中实施临床试验。因为以如下结果进行试验是不切实际的 骨折或心血管事件，开发敏感和有效的早期肌肉骨骼临床生物标志物 而血管疾病对于进行介入研究是必不可少的。这个临床表型核心将 利用费城临床和翻译研究中心儿童医院的资源， 用于评估骨骼质量、身体成分、生物营养和血管健康的最先进方法。 肌肉骨骼成像包括面积骨密度(BMD)和骨矿含量的DXA测量 多个解剖部位和外周定量计算机断层扫描测量体积 骨密度。第二代高分辨率pQCT(XCTII)设备提供了骨微结构和 与体外高度相关的骨强度(破坏载荷)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，血管 表型包括动脉僵硬的标记物(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(血管内皮细胞)，所有这些都已被证明 独立预测成人的心血管事件，但需要在儿童中进一步评估。具体的 临床表型核心的目标是：1)为临床中心研究人员提供专家咨询 儿童肾脏疾病的观察研究和临床试验的表型方案；2)促进 中心研究人员通过获取最先进的和全面的 用于评估生长和营养、身体成分、骨骼质量和心血管的核心资源 健康；以及3)促进扩大和产生可靠的规范性纵向数据来源 临床表型措施。核心研究人员有实施骨骼研究的跟踪记录 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， 其他儿童慢性病，以及健康的儿童和青少年。通过与其他PCEN集成 整个研究基地的核心和协作，临床表型核心将降低 实施临床试验以促进儿童肾脏疾病的骨积累和血管健康。

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.