Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
Medical Sciences, Uppsala University, Uppsala, Sweden.
BMC Nephrol. 2023 Jan 25;24(1):20. doi: 10.1186/s12882-022-03014-z.
BACKGROUND: Hepcidin is considered to play a central role in the pathophysiology of renal anemia. Recent studies in healthy individuals have demonstrated a suppressive effect of vitamin D (VD) on the expression of hepcidin. In this post-hoc analysis based on a randomized controlled study, we evaluated the effect of supplementing chronic kidney disease (CKD) patients (stage G3-G4) with a high daily dose of native VD on serum levels of hepcidin-25, the hepcidin/ferritin ratio, as well as on markers of erythropoiesis. METHODS: Patients with CKD stage G3-G4 included in a double blind, randomized, placebo (PBO) controlled study with available hepcidin measurements were analyzed. Study subjects received either 8000 international units (IU) of cholecalciferol daily or PBO for 12 weeks. We evaluated the change in markers of hepcidin expression, erythropoiesis, and iron status from baseline to week 12 and compared the change between the groups. RESULTS: Eighty five patients completed the study. Calcitriol, but not 25-hydroxyvitamin D (25(OH) D), was inversely correlated with serum levels of hepcidin-25 (rho = -0,38; p = < 0, 01 and rho = -0,02; p = 0, 89, respectively) at baseline. Supplementation with VD significantly raised the serum concentration of serum 25(OH)D in the treatment group (from 54 (39-71) to 156 (120-190) nmol/L; p = < 0, 01)) but had no effect on any of the markers of hepcidin, erythropoiesis, or iron status in the entire cohort. However, we did observe an increase in hemoglobin (HB) levels and transferrin saturation (TSAT) as compared to the PBO group in a subgroup of patients with low baseline 25(OH)D levels (< 56 nmol/L). In contrast, in patients with high baseline 25(OH)D values (≥ 56 nmol/L), VD supplementation associated with a decrease in HB levels and TSAT (p = 0,056) within the VD group in addition to a decrease in hepcidin levels as compared to the PBO group. CONCLUSION: High-dose VD supplementation had no discernible effect on markers of hepcidin or erythropoiesis in the entire study cohort. However, in patients with low baseline 25(OH)D levels, high-dose VD supplementation associated with beneficial effects on erythropoiesis and iron availability. In contrast, in patients with elevated baseline 25(OH)D levels, high-dose VD supplementation resulted in a decrease in hepcidin levels, most likely due to a deterioration in iron status.
背景：铁调素被认为在肾脏贫血的病理生理学中起核心作用。最近在健康个体中的研究表明维生素 D（VD）对铁调素的表达具有抑制作用。在这项基于随机对照研究的事后分析中，我们评估了补充慢性肾脏病（CKD）患者（G3-G4 期）高剂量天然 VD 对血清铁调素-25、铁调素/铁蛋白比值以及红细胞生成标志物的影响。
方法：对一项双盲、随机、安慰剂（PBO）对照研究中具有可用铁调素测量值的 CKD G3-G4 期患者进行分析。研究对象接受 8000 国际单位（IU）胆钙化醇或 PBO 每日治疗 12 周。我们评估了从基线到第 12 周铁调素表达、红细胞生成和铁状态标志物的变化，并比较了两组之间的变化。
结果：85 例患者完成了研究。钙三醇而非 25-羟维生素 D（25（OH）D）与基线时血清铁调素-25水平呈负相关（rho=-0.38；p= <0.01 和 rho=-0.02；p=0.89）。VD 补充显著提高了治疗组血清 25（OH）D 浓度（从 54（39-71）增加至 156（120-190）nmol/L；p= <0.01），但对整个队列中铁调素、红细胞生成或铁状态的任何标志物均无影响。然而，与 PBO 组相比，我们在基线 25（OH）D 水平较低（<56 nmol/L）的患者亚组中观察到血红蛋白（HB）水平和转铁蛋白饱和度（TSAT）升高。相比之下，在基线 25（OH）D 值较高（≥56 nmol/L）的患者中，VD 补充与 HB 水平和 TSAT 的降低相关（p=0.056），此外与 PBO 组相比，铁调素水平也降低。
结论：高剂量 VD 补充对整个研究队列的铁调素或红细胞生成标志物没有明显影响。然而，在基线 25（OH）D 水平较低的患者中，高剂量 VD 补充与红细胞生成和铁可用性的有益作用相关。相比之下，在基线 25（OH）D 水平升高的患者中，高剂量 VD 补充导致铁调素水平降低，这很可能是由于铁状态恶化所致。
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