Department of Nephrology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology, Pneumonology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
Front Endocrinol (Lausanne). 2023 May 31;14:1178166. doi: 10.3389/fendo.2023.1178166. eCollection 2023.
25-hydroxyvitamin D (25(OH)D) and potentially also 1,25-dihydroxyvitamin D (1,25(OH)2D) inhibits the synthesis of parathyroid hormone (PTH) in the chief cells of the parathyroid gland. Clinical studies showing a negative correlation between (25(OH)D and PTH are in good agreement with these findings in basic science studies. However, PTH was measured in these studies with the currently clinically used 2nd or 3rd generation intact PTH (iPTH) assay systems. iPTH assays cannot distinguish between oxidized forms of PTH and non-oxidized PTH. Oxidized forms of PTH are the by far most abundant form of PTH in the circulation of patients with impaired kidney function. Oxidation of PTH causes a loss of function of PTH. Given that the clinical studies done so far were performed with an PTH assay systems that mainly detect oxidized forms of PTH, the real relationship between bioactive non-oxidized PTH and 25(OH)D as well as 1,25(OH)2D is still unknown.
To address this topic, we compared for the first time the relationship between 25(OH)D as well as 1,25(OH)2D and iPTH, oxPTH as well as fully bioactive n-oxPTH in 531 stable kidney transplant recipients in the central clinical laboratories of the Charité. Samples were assessed either directly (iPTH) or after oxPTH (n-oxPTH) was removed using a column that used anti-human oxPTH monoclonal antibodies, a monoclonal rat/mouse parathyroid hormone antibody (MAB) was immobilized onto a column with 500 liters of plasma samples. Spearman correlation analysis and Multivariate linear regression were used to evaluate the correlations between the variables.
There was an inverse correlation between 25(OH)D and all forms of PTH, including oxPTH (iPTH: r=-0.197, p<0.0001; oxPTH: r=-0.203, p<0.0001; n-oxPTH: r=-0.146, p=0.001). No significant correlation was observed between 1,25(OH)2D and all forms of PTH. Multiple linear regression analysis considering age, PTH (iPTH, oxPTH and n-oxPTH), serum calcium, serum phosphor, serum creatinine, fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), albumin, and sclerostin as confounding factors confirmed these findings. Subgroup analysis showed that our results are not affected by sex and age.
In our study, all forms of PTH are inversely correlated with 25-hydroxyvitamin D (25(OH)D). This finding would be in line with an inhibition of the synthesis of all forms of PTH (bioactive n-oxPTH and oxidized forms of PTH with minor or no bioactivity) in the chief cells of the parathyroid glad.
25-羟维生素 D（25（OH）D），以及可能的 1,25-二羟维生素 D（1,25（OH）2D），可抑制甲状旁腺主细胞中甲状旁腺激素（PTH）的合成。临床研究表明，（25（OH）D 和 PTH 之间存在负相关，这与基础科学研究中的发现一致。然而，这些研究中使用的是目前临床使用的第二代或第三代完整 PTH（iPTH）检测系统来检测 PTH。iPTH 检测法无法区分 PTH 的氧化形式和非氧化形式。氧化形式的 PTH 是肾功能受损患者循环中含量最丰富的 PTH 形式。PTH 的氧化会导致其功能丧失。鉴于迄今为止进行的临床研究是使用主要检测氧化形式 PTH 的 iPTH 检测系统进行的，因此，生物活性非氧化 PTH 与 25（OH）D 以及 1,25（OH）2D 之间的真正关系仍不清楚。
为了解决这个问题，我们首次比较了 531 例稳定的肾移植受者在 Charité 中心临床实验室中 25（OH）D 以及 1,25（OH）2D 与 iPTH、oxPTH 和完全生物活性 n-oxPTH 之间的关系。样品要么直接评估（iPTH），要么使用 oxPTH（n-oxPTH），使用抗人 oxPTH 单克隆抗体的柱子去除 oxPTH（n-oxPTH），将单克隆大鼠/小鼠甲状旁腺激素抗体（MAB）固定在一个带有 500 升血浆样本的柱子上。使用 Spearman 相关分析和多元线性回归来评估变量之间的相关性。
25（OH）D 与所有形式的 PTH（包括 oxPTH）呈负相关，iPTH：r=-0.197，p<0.0001；oxPTH：r=-0.203，p<0.0001；n-oxPTH：r=-0.146，p=0.001）。1,25（OH）2D 与所有形式的 PTH 均无显著相关性。考虑年龄、PTH（iPTH、oxPTH 和 n-oxPTH）、血清钙、血清磷、血清肌酐、成纤维细胞生长因子 23（FGF23）、骨保护素（OPG）、白蛋白和硬化蛋白等混杂因素的多元线性回归分析证实了这些发现。亚组分析表明，我们的结果不受性别和年龄的影响。
在我们的研究中，所有形式的 PTH 与 25-羟维生素 D（25（OH）D）呈负相关。这一发现与甲状旁腺主细胞中所有形式的 PTH（具有较小或无生物活性的生物活性 n-oxPTH 和氧化形式的 PTH）的合成抑制一致。
