Abstract
BACKGROUND AND OBJECTIVES: Vitamin D supplements are prescribed to correct low circulating concentrations of 25-hydroxyvitamin D. In CKD, vitamin D metabolism is complicated by decreased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by CYP27B1 and possibly decreased conversion of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D by CYP24A1. The aim of this study was to determine the effects of vitamin D(2) supplementation on vitamin D metabolism in health and CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a treatment-only intervention study of 25 individuals with CKD (eGFR<60 ml/min per 1.73 m(2)) and 44 individuals without CKD from three academic centers, all with screening 25-hydroxyvitamin D <30 ng/ml. Each participant was prescribed vitamin D(2) (ergocalciferol) 50,000 IU orally twice weekly for 5 weeks. We tested whether changes in plasma concentrations of vitamin D metabolites and vitamin D metabolic ratios differed by CKD status. Plasma 1,25-dihydroxyvitamin D(3)-to-25-hydroxyvitamin D(3) ratio and 24,25-dihydroxyvitamin D(3)-to-25-hydroxyvitamin D(3) ratio were calculated as estimates of CYP27B1 and CYP24A1 function, respectively. RESULTS: With treatment, plasma 25-hydroxyvitamin D(2) and total 25-hydroxyvitamin D concentrations increased similarly for participants with and without CKD. For participants without CKD, 1,25-dihydroxyvitamin D(2) increased (2.8±1.3-32.9±1.4 pg/ml), whereas 1,25-dihydroxyvitamin D(3) decreased (45.6±1.9-14.6±1.9 pg/ml), resulting in no significant change in total 1,25-dihydroxyvitamin D; 1,25-dihydroxyvitamin D(3)-to-25-hydroxyvitamin D(3) ratio decreased (3.0±0.2-1.7±0.2 pg/ng), and 24,25-dihydroxyvitamin D(3)-to-25-hydroxyvitamin D(3) ratio increased (115.7±7.8-195.2±7.9 pg/ng). Individuals with CKD had lower baseline levels and smaller changes in magnitude for 1,25-dihydroxyvitamin D(2) (2.1±1.6-24.4±1.6 pg/ml; P interaction =0.01), 1,25-dihydroxyvitamin D(3)-to-25-hydroxyvitamin D(3) ratio (1.8±0.2-1.1±0.2 pg/ng; P interaction =0.05), and 24,25-dihydroxyvitamin D(3)-to-25-hydroxyvitamin D(3) ratio (72.0±9.1-110.3±9.3 pg/ng; P interaction <0.001). Fibroblast growth factor-23 and parathyroid hormone were not significantly changed in either group. CONCLUSIONS: Vitamin D(2) supplementation decreases conversion of 25-hydroxyvitamin D(3) to 1,25-dihydroxyvitamin D(3) and induces vitamin D(3) catabolism as evidenced by changes in D(3) metabolites and vitamin D metabolic ratios. These effects occur without significant changes in fibroblast growth factor-23 or parathyroid hormone and are blunted in CKD. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_02_CJASNPodcast_17_09.mp3.