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.
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