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内科儿科副教授、生物统计与流行病学系流行病学副教授。她是一位知名的临床研究员，在患有慢性肾病 (CKD) 和炎症性疾病的儿童和成人的营养和骨骼健康方面拥有广泛的成功研究记录。费城儿童医院和宾夕法尼亚大学致力于为她提供以患者为中心的研究和指导的强大环境，包括多项机构培训资助、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、由 NIDDK 资助的 R01 项目是一项针对 325 名 CKD 成人和 500 名对照者的骨骼结构的前瞻性队列研究。 CKD 患者的骨折风险显着增加，并且与高发病率相关。本研究通过定量计算机断层扫描评估肾病严重程度、性腺功能减退、甲状旁腺功能亢进、合并症和药物对骨密度和结构的影响。大量研究表明，在没有 CKD 的情况下，维生素 D 缺乏与肌肉无力有关。 CKD 患者存在多种维生素 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 中维生素 D [25(OH)D 和 1,25(OH)2D] 与 PTH 水平和身体功能之间的关系尚未得到研究。该申请提出了一项针对其 CKD 队列中维生素 D 水平和身体表现的辅助研究，添加了经过验证的标准化身体表现（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、体力活动低、握力和步态速度）的标准化测量，以预测不同人群的跌倒、残疾、住院和死亡率。维生素 D 缺乏可能会导致 CKD 肌肉骨骼并发症的沉重负担。为了开展 CKD 补充维生素 D 的预期随机试验，有必要描述维生素 D 水平与身体机能结果之间的关系。

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.