Patient Oriented Research in Vitamin D and Physical Functioning in CKD

描述(由申请人提供)： 申请人是美国宾夕法尼亚大学生物统计和流行病学系儿科副教授和流行病学副教授。她是一位久负盛名的临床研究人员，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以患者为导向的研究和指导环境，包括多个机构培训拨款、K30临床研究课程奖、非常成功的临床流行病学理学硕士培训计划、生物统计学和数据管理支持，以及用于评估骨骼结构和身体成分的最先进方法。她目前的一项以患者为导向的、由NIDDK资助的R01是对325名患有CKD的成年人和500名对照组的骨结构进行的前瞻性队列研究。慢性肾脏病的骨折风险显著增加，并与相当高的发病率相关。这项研究通过定量计算机断层扫描评估肾脏疾病的严重程度、性腺功能减退、甲状旁腺功能亢进症、并存状态和药物对骨密度和骨结构的影响。大量研究表明，缺乏CKD的维生素D缺乏与肌肉无力有关。慢性肾脏病患者有许多维生素D缺乏的危险因素。透析患者跌倒和骨折的几率增加，身体功能严重受限。CKD患者维生素D[25(OH)D和1，25(OH)2D]与甲状旁腺激素(PTH)水平和身体功能的关系尚未得到研究。这项应用提出了一项关于她的CKD队列中维生素D水平和身体表现的辅助研究，增加了经过验证的身体表现(步态速度、站立平衡、定时坐站)和虚弱(非自愿体重减轻、自我报告的疲惫、低体力、握力和步态速度)的标准化测量，这些测量可以预测不同人群中的跌倒、残疾、住院和死亡率。维生素D缺乏可能是慢性肾脏病肌肉骨骼并发症的主要负担。阐明维生素D水平和身体功能结果之间的关系是必要的，以便开发补充维生素D治疗慢性肾脏病的预期随机试验。

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.