Vitamin D Deficiency, Physical Performance and Cardiovascular Outcomes in CRIC

描述（由申请人提供）：维生素D和矿物质代谢紊乱是慢性肾功能不全（CRI）的早期普遍并发症，与终末期肾病（ESRD）患者的骨折、血管钙化和死亡率相关。维生素D的经典功能是通过调节肠道和肾脏钙转运、甲状旁腺激素（PTH）分泌和骨矿化来维持钙稳态。然而，维生素D受体在其他组织中广泛表达，包括肌肉和心肌细胞。大量观察性研究、临床试验和动物研究表明，缺乏CRI的维生素D缺乏与肌肉无力、高血压和左心室肥厚（LVH）有关。CRI患者有许多维生素D缺乏的危险因素。透析患者的跌倒和骨折发生率增加，身体功能严重受限，心血管疾病（CVD）死亡率显著增加。CRI患者维生素D [25(OH)D和1,25(OH)2D]与甲状旁腺激素水平、生理功能和心血管疾病的关系尚未研究。NIDDK CRI队列（CRIC）研究于2003年启动，旨在确定轻度至重度CRI成人CVD和CRI进展的危险因素。这个队列提供了一个前所未有的、时间有限的机会来调查CRI中维生素D缺乏的风险因素和后果。拟议的横断面辅助研究将在4个临床站点的1780名受试者中增加25(OH)D, 1,25(OH)2D和PTH的测量，以及经过验证的，标准化的身体表现测量（步态速度，站立平衡，时间坐到站）和虚弱（非自愿体重减轻，自我报告的疲劳，低体力活动，握力和步态速度），预测跌倒，残疾，住院和死亡率在不同人群中。该研究的目的是：确定CRI中25(OH)D缺乏症的患病率和危险因素；根据肾功能和甲状旁腺激素水平确定25(OH)D与1,25(OH)2D的关系；并确定25(OH)D和125 (OH)2D水平对CRI患者CVD、身体机能和虚弱的独立影响。维生素D缺乏可能导致CRI的肌肉骨骼和心血管并发症的严重负担。描述25(OH)D和125 (OH)2D与临床结果之间的关系是必要的，以便在CRI中开展维生素D补充的预期随机试验。

DESCRIPTION (provided by applicant): Disturbances in vitamin D and mineral metabolism are early, pervasive complications of chronic renal insufficiency (CRI), and are associated with fractures, vascular calcification and mortality in patients with end-stage renal disease (ESRD). The classical function of vitamin D is to maintain calcium homeostasis by regulating intestinal and renal calcium transport, parathyroid hormne (PTH) secretion, and bone mineralization. However, the vitamin D receptor is widely expressed in other tissues, including muscle and myocardial cells. Numerous observational studies, clinical trials and animal studies have demonstrated that vitamin D deficiency in the absence of CRI is associated with muscle weakness, hypertension and left ventricular hypertrophy (LVH). Patients with CRI have numerous risk factors for vitamin D deficiency. Dialysis patients suffer increased fall and fracture rates, severely limited physical function, and markedly increased cardiovascular disease (CVD) mortality. The relations between vitamin D [25(OH)D and 1,25(OH)2D] and PTH levels, physical function and CVD have not been examined in CRI. The NIDDK CRI Cohort (CRIC) study was initiated in 2003 to identify risk factors for CVD and progression of CRI in adults with mild to severe CRI. This cohort provides an unprecedented, time-limited opportunity to investigate the risk factors and consequences of vitamin D deficiency in CRI. The proposed cross-sectional ancillary study in 1780 subjects at 4 clinical sites will add measures of 25(OH)D, 1,25(OH)2D, and PTH, as well as 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. The aims of the study are: to determine the prevalence and risk factors for 25(OH)D deficiency in CRI; to determine the relations between 25(OH)D and 1,25(OH)2D according to renal function and PTH levels; and to determine the independent effects of 25(OH)D and 1,25(OH)2D levels on CVD, physical performance and frailty in CRI. Vitamin D deficiency likely contributes to the substantial burden of musculoskeletal and cardiovascular complications of CRI. Delineation of the relations between 25(OH)D and 1,25(OH)2D and clinical outcomes is necessary in order to develop anticipated randomized trials of vitamin D supplementation in CRI.