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.
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.
|de Boer, Ian H; Mehrotra, Rajnish (2014) Insulin resistance in chronic kidney disease: a step closer to effective evaluation and treatment. Kidney Int 86:243-5|