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.
|Robinson-Cohen, Cassianne; Zelnick, Leila R; Hoofnagle, Andrew N et al. (2017) Associations of Vitamin D-Binding Globulin and Bioavailable Vitamin D Concentrations With Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis (MESA). J Clin Endocrinol Metab 102:3075-3084|
|Hallan, Stein; Afkarian, Maryam; Zelnick, Leila R et al. (2017) Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients. EBioMedicine 26:68-77|
|Kendrick, Jessica; Andrews, Emily; You, Zhiying et al. (2017) Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial. Clin J Am Soc Nephrol 12:1438-1446|
|de Boer, Ian H; Kahn, Steven E (2017) SGLT2 Inhibitors-Sweet Success for Diabetic Kidney Disease? J Am Soc Nephrol 28:7-10|
|Batacchi, Zona; Robinson-Cohen, Cassianne; Hoofnagle, Andrew N et al. (2017) Effects of Vitamin D2 Supplementation on Vitamin D3 Metabolism in Health and CKD. Clin J Am Soc Nephrol 12:1498-1506|
|Kendrick, Jessica B; Zelnick, Leila; Chonchol, Michel B et al. (2017) Serum Bicarbonate Is Associated with Heart Failure in the Multi-Ethnic Study of Atherosclerosis. Am J Nephrol 45:118-126|
|Gao, Chunying; Bergagnini-Kolev, Mackenzie C; Liao, Michael Z et al. (2017) Simultaneous quantification of 25-hydroxyvitamin D3-3-sulfate and 25-hydroxyvitamin D3-3-glucuronide in human serum and plasma using liquid chromatography-tandem mass spectrometry coupled with DAPTAD-derivatization. J Chromatogr B Analyt Technol Biomed Life Sci 1060:158-165|
|Hoofnagle, Andrew N; Laha, Thomas J; de Boer, Ian H (2016) Recalibration of 24,25-Dihydroxyvitamin D3 Results Based on NIST Standard Reference Material 972a. Am J Kidney Dis 67:812-3|
|Afkarian, Maryam; Zelnick, Leila R; Hall, Yoshio N et al. (2016) Clinical Manifestations of Kidney Disease Among US Adults With Diabetes, 1988-2014. JAMA 316:602-10|
|de Boer, Ian H; Afkarian, Maryam; Tuttle, Katherine R (2016) The Surging Tide of Diabetes: Implications for Nephrology. Am J Kidney Dis 67:364-6|
Showing the most recent 10 out of 14 publications