Patient Oriented Research in Vitamin D and Physical Functioning in CKD

描述（由申请人提供）： 申请人是宾夕法尼亚大学肾脏科儿科副教授和生物统计学和流行病学系流行病学副教授。她是一位成熟的临床研究人员，拥有广泛的成功研究记录，专注于患有慢性肾脏疾病（CKD）和炎症性疾病的儿童和成人的营养和骨骼健康。费城儿童医院和宾夕法尼亚大学致力于为她提供一个强大的环境，以患者为导向的研究和指导，包括多个机构培训赠款，K30临床研究课程奖，非常成功的临床流行病学培训计划，生物统计和数据管理支持，以及用于评估骨结构和身体组成的现有技术方法。她目前的一项以患者为导向的NIDDK资助的R01是一项前瞻性队列研究，研究了325名成人CKD患者和500名对照者的骨结构。CKD患者骨折风险显著增加，并与大量发病率相关。本研究通过定量计算机断层扫描评估肾脏疾病严重程度、性腺功能减退、甲状旁腺功能亢进、共病和药物对骨密度和结构的影响。许多研究表明，在没有CKD的情况下，维生素D缺乏与肌肉无力有关。CKD患者有许多维生素D缺乏的风险因素。透析患者的跌倒和骨折率增加，身体功能严重受限。维生素D [25（OH）D和1，25（OH）2D]和PTH水平与身体功能之间的关系尚未在CKD中进行研究。该申请提出了在她的CKD队列中进行维生素D水平和身体表现的辅助研究，增加了身体表现（步态速度、站立平衡、定时坐立）和虚弱（非自愿体重减轻、自我报告的疲惫、低体力活动、握力和步态速度）的经验证的标准化测量，其预测不同人群中的福尔斯、残疾、住院和死亡。维生素D缺乏可能导致CKD肌肉骨骼并发症的严重负担。维生素D水平和身体功能结果之间的关系的描述是必要的，以开发预期的随机试验的维生素D补充CKD。

DESCRIPTION (provided by applicant): The applicant is an Associate Professor of Pediatrics in the Division of Nephrology, and an Associate Professor of Epidemiology in the Department of Biostatistics and Epidemiology at the University of Pennsylvania. She is an established clinical researcher with an extensive track record of successful research focused on nutrition and bone health in children and adults with chronic kidney disease (CKD) and inflammatory disorders. The Children's Hospital of Philadelphia and UPENN are committed to providing her with a strong environment for patient-oriented research and mentoring, including multiple institutional training grants, a K30 Clinical Research Curriculum Award, an extraordinarily successful Master's of Science in Clinical Epidemiology training program, biostatistical and data management support, and state of the art methods for the assessment of bone structure and body composition. One of her current patient-oriented, NIDDK-funded R01s is a prospective cohort study of bone structure in 325 adults with CKD and 500 controls. Fracture risk is markedly increased in CKD and is associated with substantial morbidity. This study is examining the effects of renal disease severity, hypogonadism, hyperparathyroidism, comorbid conditions and medications on bone density and structure as assessed by quantitative computed tomography. Numerous studies have demonstrated that vitamin D deficiency in the absence of CKD is associated with muscle weakness. Patients with CKD have numerous risk factors for vitamin D deficiency. Dialysis patients suffer increased fall and fracture rates and severely limited physical function. The relations between vitamin D [25(OH)D and 1,25(OH)2D] and PTH levels and physical function have not been examined in CKD. This application proposes an ancillary study of vitamin D levels and physical performance within her CKD cohort, adding validated, standardized measures of physical performance (gait speed, standing balance, timed sit- to-stand) and frailty (involuntary weight loss, self-reported exhaustion, low physical activity, grip strength and gait speed) that predicted falls, disability, hospitalizations and mortality in varied populations. Vitamin D deficiency likely contributes to the substantial burden of musculoskeletal complications of CKD. Delineation of the relations between vitamin D levels and physical functioning outcomes is necessary in order to develop anticipated randomized trials of vitamin D supplementation in CKD.