Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, United States; Kidney Research Institute, University of Washington, Seattle, WA, United States.
Division of Nephrology, Department of Medicine, University of Washington, Seattle, WA, United States; Kidney Research Institute, University of Washington, Seattle, WA, United States.
J Steroid Biochem Mol Biol. 2022 Mar;217:106047. doi: 10.1016/j.jsbmb.2021.106047. Epub 2021 Dec 22.
The formation of 24,25-dihydroxyvitamin D (24,25(OH)D) from 25-hydroxyvitamin D (25(OH)D) is the primary mechanism for the metabolic clearance of 25(OH)D, and is regulated by tissue-level vitamin D activity. The ratio of 24,25(OH)D to 25(OH)D in blood (vitamin D metabolite ratio, VDMR) is postulated to be a marker of 25(OH)D clearance, however this has never been tested. We measured baseline 24,25(OH)D and 25(OH)D concentrations in 87 participants by liquid chromatography-tandem mass spectrometry. Following an infusion of deuterated 25(OH)D, blood samples for each participant were collected over 56 days and analyzed for deuterated vitamin D metabolites. 25(OH)D clearance and the deuterated metabolite-to-parent AUC ratio (ratio of the AUC of deuterated 24,25(OH)D to that of deuterated 25(OH)D) were calculated. We compared the VDMR with these two measures using correlation coefficients and linear regression. Participants had a mean age of 64 ± 11years, 41 % were female, 30 % were self-described Black, 28 % had non-dialysis chronic kidney disease (CKD) and 23 % had kidney failure treated with hemodialysis. The VDMR was strongly correlated with 25(OH)D clearance and the deuterated metabolite-to-parent AUC ratio (r = 0.51 and 0.76, respectively). Adjusting for 25(OH)D clearance or the deuterated metabolite-to-parent AUC ratio in addition to clinical covariates, lower VDMR was observed in participants with CKD and kidney failure than in healthy controls; in Black than White participants; and in those with lower serum albumin. Our findings validate the VDMR as a measure of 25(OH)D clearance. This relationship was biased by characteristics including race and kidney disease, which warrant consideration in studies assessing the VDMR.
24,25-二羟维生素 D（24,25(OH)D）的形成是 25-羟维生素 D（25(OH)D）代谢清除的主要机制，并且受组织水平维生素 D 活性的调节。血液中 24,25(OH)D 与 25(OH)D 的比值（维生素 D 代谢物比值，VDMR）被认为是 25(OH)D 清除率的标志物，但这从未经过测试。我们通过液相色谱-串联质谱法测量了 87 名参与者的基线 24,25(OH)D 和 25(OH)D 浓度。在对每个参与者进行氘代 25(OH)D 输注后，在 56 天内采集每个参与者的血液样本，并对氘代维生素 D 代谢物进行分析。计算了 25(OH)D 清除率和氘代代谢物与母体 AUC 比值（氘代 24,25(OH)D 的 AUC 与氘代 25(OH)D 的 AUC 比值）。我们使用相关系数和线性回归比较了 VDMR 与这两个指标。参与者的平均年龄为 64 ± 11 岁，41%为女性，30%自称为黑人，28%患有非透析性慢性肾脏病（CKD），23%患有接受血液透析治疗的肾衰竭。VDMR 与 25(OH)D 清除率和氘代代谢物与母体 AUC 比值密切相关（r = 0.51 和 0.76）。在调整了 25(OH)D 清除率或氘代代谢物与母体 AUC 比值以及临床协变量后，与健康对照组相比，CKD 和肾衰竭患者的 VDMR 较低；与白人参与者相比，黑人参与者的 VDMR 较低；与血清白蛋白较低的参与者相比，其 VDMR 也较低。我们的发现验证了 VDMR 作为 25(OH)D 清除率的衡量标准。这种关系受到种族和肾脏疾病等特征的影响，在评估 VDMR 的研究中需要考虑这些特征。
