Vitamin D Deficiency, Physical Performance and Cardiovascular Outcomes in CRIC

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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.