Division of Systems Bioscience for Drug Discovery, Project Research Center, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
Mizuho Hospital, Tsubata 929-0346, Ishikawa, Japan.
Int J Mol Sci. 2023 Sep 7;24(18):13779. doi: 10.3390/ijms241813779.
Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, = 0.000; -0.648, -1.099 to -0.197, = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.
口服柠檬酸铁铵（FCH）对血液透析患者的缺铁有效；然而，体内铁平衡如何影响肠道内的铁吸收尚不清楚。这项前瞻性观察性研究（Riona-口服铁吸收试验，R-OIAT，UMIN 000031406）在日本的 42 个血液透析中心进行，其中招募了 268 名无炎症的血液透析患者，并接受固定剂量的 FCH 治疗 6 个月。我们评估了铁调素-25 对 FCH 治疗后铁吸收和铁在铁蛋白（FTN）和红细胞（RBC）之间转移的预测价值。FCH 摄入后 2 小时（ΔFe2h）血清铁的变化被评估为铁吸收。主要结局是定量描述与 ΔFe2h 相关的铁变量，次要结局是描述机体铁平衡的预测因素。广义估计方程（GEE）用于确定 FCH 治疗各阶段铁吸收的决定因素。铁调素-25 和转铁蛋白饱和度（TSAT）降低时，ΔFe2h 增加（-0.459，-0.643 至-0.276， = 0.000；-0.648，-1.099 至-0.197， = 0.005，分别）在 GEEs 中。当 RBC 减少（-1.392，-1.749 至-1.035， = 0.000）和铁调素-25 增加（0.297，0.239 至 0.355， = 0.000）时，FTN 增加。为维持血红蛋白水平限制红细胞生成会导致血液透析患者的 RBC 减少，从而导致铁调素-25 和 FTN 水平升高。铁调素-25 的产生可能促使铁从 RBC 铁转移到 FTN 铁，即使继续摄入 FCH，也会抑制铁吸收。
