Vitamin D Deficiency, Physical Performance and Cardiovascular Outcomes in CRIC

描述（由申请方提供）：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和肾钙转运、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。许多观察性研究、临床试验和动物研究已经证明，在缺乏CRI的情况下，维生素D缺乏与肌无力、高血压和左心室肥大（LVH）有关。CRI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。维生素D [25（OH）D和1，25（OH）2D]与PTH水平、身体功能和CVD之间的关系尚未在CRI中进行研究。NIDDK CRI队列（CRIC）研究于2003年启动，旨在确定轻度至重度CRI成人中CVD和CRI进展的风险因素。该队列研究提供了一个前所未有的、有时间限制的机会来研究CRI中维生素D缺乏的风险因素和后果。在4个临床试验机构的1780例受试者中进行的拟定横断面辅助研究将增加25（OH）D、1，25（OH）2D和PTH的测量，以及经验证的标准化体能测量（步态速度、站立平衡、定时坐立）和虚弱（不自主的体重减轻，自我报告的疲惫，体力活动，握力和步态速度低），预测福尔斯，残疾，住院率和死亡率。这项研究的目的是：确定CRI患者25（OH）D缺乏的患病率和危险因素，根据肾功能和PTH水平确定25（OH）D和1，25（OH）2D之间的关系，确定25（OH）D和1，25（OH）2D水平对CRI患者心血管疾病、体力活动和虚弱的独立影响。维生素D缺乏可能导致CRI的肌肉骨骼和心血管并发症的巨大负担。为了开展CRI患者补充维生素D的预期随机试验，有必要描述25（OH）D和1，25（OH）2D与临床结局之间的关系。

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.