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.