Impaired vitamin D metabolism is a promising therapeutic target to reduce the marked morbidity and mortality of chronic kidney disease (CKD). However, the evaluation and treatment of impaired vitamin D metabolism is currently limited by a lack of effective biomarkers. Our preliminary data suggest that reduced vitamin D catabolism accompanies reduced 1, 25- dihydroxyvitamin D production in CKD and that evaluation of vitamin D catabolism may offer a valuable new tool to guide clinical diagnosis and treatment. We propose to define vitamin D catabolism across glomerular filtration rate and race and test whether a low circulating concentration of 24, 25-dihydroxyvitamin D, the most abundant product of 25-hydroxyvitamin D catabolism by CYP24A1, is a modifiable risk factor for adverse health outcomes in CKD. Gold standard pharmacokinetic studies will define whether and to what extent vitamin D catabolism is impaired in CKD. Synergistic ancillary studies to existing epidemiologic studies and clinical trials will test associations of 24,25-dihydroxyvitamin D concentration with adverse health outcomes, examine the effects of a broad range of common vitamin D-related interventions on circulating 24,25-dihydroxyvitamin D, and explore whether baseline 24,25-dihydroxyvitamin D concentration identifies patients who have biochemical responses to such common interventions. This combination of experiments will comprehensively evaluate vitamin D catabolism in CKD and determine whether 24,25-dihydroxyvitamin D may fill an important void in the clinical assessment of vitamin D metabolism in this population.

Public Health Relevance

Patients with CKD are at high risk of adverse health outcomes, including progression to end stage renal disease, cardiovascular disease events, and death. Impaired vitamin D metabolism is a promising therapeutic target to prevent these complications. This project seeks to define vitamin D catabolism in CKD and evaluate a novel biomarker of vitamin D catabolism. The goal of this work is to better understand the pathophysiology of impaired vitamin D metabolism in CKD and develop an improved biomarker to help guide its evaluation and treatment.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Kidney, Nutrition, Obesity and Diabetes Study Section (KNOD)
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Flessner, Michael Francis
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University of Washington
United States
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