Divisions of Metabolism, Endocrinology and Nutrition and.
Kidney Research Institute, and.
Clin J Am Soc Nephrol. 2017 Sep 7;12(9):1498-1506. doi: 10.2215/CJN.00530117. Epub 2017 Aug 2.
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 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) and 44 individuals without CKD from three academic centers, all with screening 25-hydroxyvitamin D <30 ng/ml. Each participant was prescribed vitamin D (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-to-25-hydroxyvitamin D ratio and 24,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio were calculated as estimates of CYP27B1 and CYP24A1 function, respectively.
With treatment, plasma 25-hydroxyvitamin D and total 25-hydroxyvitamin D concentrations increased similarly for participants with and without CKD. For participants without CKD, 1,25-dihydroxyvitamin D increased (2.8±1.3-32.9±1.4 pg/ml), whereas 1,25-dihydroxyvitamin D 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-to-25-hydroxyvitamin D ratio decreased (3.0±0.2-1.7±0.2 pg/ng), and 24,25-dihydroxyvitamin D-to-25-hydroxyvitamin D 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 (2.1±1.6-24.4±1.6 pg/ml; interaction =0.01), 1,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio (1.8±0.2-1.1±0.2 pg/ng; interaction =0.05), and 24,25-dihydroxyvitamin D-to-25-hydroxyvitamin D ratio (72.0±9.1-110.3±9.3 pg/ng; interaction <0.001). Fibroblast growth factor-23 and parathyroid hormone were not significantly changed in either group.
Vitamin D supplementation decreases conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D and induces vitamin D catabolism as evidenced by changes in D 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.
This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017_08_02_CJASNPodcast_17_09.mp3.
维生素 D 补充剂用于纠正 25-羟维生素 D 循环浓度低的情况。在 CKD 中，维生素 D 代谢受到 CYP27B1 转化 25-羟维生素 D 为 1,25-二羟维生素 D 的减少和 CYP24A1 转化 25-羟维生素 D 为 24,25-二羟维生素 D 的减少的影响。本研究旨在确定维生素 D 补充对健康和 CKD 患者维生素 D 代谢的影响。
设计、地点、参与者和测量：我们对来自三个学术中心的 25 名 CKD 患者（eGFR<60 ml/min per 1.73 m）和 44 名无 CKD 的个体进行了一项仅治疗的干预研究，所有患者的筛选 25-羟维生素 D<30 ng/ml。每位参与者均口服每周两次 50,000 IU 麦角钙化醇，持续 5 周。我们测试了维生素 D 代谢产物和维生素 D 代谢比的变化是否因 CKD 状态而异。1,25-二羟维生素 D 与 25-羟维生素 D 的比值和 24,25-二羟维生素 D 与 25-羟维生素 D 的比值分别作为 CYP27B1 和 CYP24A1 功能的估计值。
随着治疗的进行，无论是否患有 CKD，参与者的血浆 25-羟维生素 D 和总 25-羟维生素 D 浓度均相似增加。对于没有 CKD 的参与者，1,25-二羟维生素 D 增加（2.8±1.3-32.9±1.4 pg/ml），而 1,25-二羟维生素 D 减少（45.6±1.9-14.6±1.9 pg/ml），导致总 1,25-二羟维生素 D 无明显变化；1,25-二羟维生素 D 与 25-羟维生素 D 的比值降低（3.0±0.2-1.7±0.2 pg/ng），24,25-二羟维生素 D 与 25-羟维生素 D 的比值升高（115.7±7.8-195.2±7.9 pg/ng）。患有 CKD 的个体基线水平较低，1,25-二羟维生素 D 的变化幅度较小（2.1±1.6-24.4±1.6 pg/ml； 交互作用=0.01），1,25-二羟维生素 D 与 25-羟维生素 D 的比值（1.8±0.2-1.1±0.2 pg/ng； 交互作用=0.05）和 24,25-二羟维生素 D 与 25-羟维生素 D 的比值（72.0±9.1-110.3±9.3 pg/ng； 交互作用<0.001）。两组纤维母细胞生长因子 23 和甲状旁腺激素均无明显变化。
维生素 D 补充剂减少了 25-羟维生素 D 向 1,25-二羟维生素 D 的转化，并诱导维生素 D 分解代谢，这可通过 D 代谢产物和维生素 D 代谢比的变化来证明。这些作用在纤维母细胞生长因子 23 或甲状旁腺激素无明显变化的情况下发生，并且在 CKD 中减弱。
本文包含一个播客，可在 https://www.asn-online.org/media/podcast/CJASN/2017_08_02_CJASNPodcast_17_09.mp3 上找到。
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