Martin-Malo Alejandro, Merino Ana, Carracedo Julia, Alvarez-Lara Maria Antonia, Ojeda Raquel, Soriano Sagrario, Crespo Rodolfo, Ramirez Rafael, Aljama Pedro
Nephrology Unit, Reina Sofia University Hospital, Córdoba, Spain.
Nephrol Dial Transplant. 2012 Jun;27(6):2465-71. doi: 10.1093/ndt/gfr711. Epub 2011 Dec 29.
This study analysed, in vivo and in vitro, the effects of four different intravenous iron preparations (iron gluconate, iron sucrose, iron dextran and ferric carboxymaltose) on activation and damage of mononuclear cells.
A randomized prospective study was conducted in 10 haemodialysis (HD) patients. Blood samples were collected at baseline (T0); 1 h after starting HD, just before the iron or saline administration (T1); 30 min after the iron or saline infusion (T2) and at the end of HD (T3). In addition, peripheral blood mononuclear cells from 10 healthy individuals and 9 chronic kidney disease Stage-5 (CKD-5) without HD treatment were cultured with the 4 iron preparations.
Iron infusion during the HD session increased the percentage of mononuclear cells with reactive oxygen species (ROS) production, Inter-Cellular Adhesion Molecule-1 (ICAM-1) and apoptosis. There were no significant differences between the four iron preparations. Culture of mononuclear cells from healthy individuals and CKD-5 patients with the different iron preparations resulted in a significant increase in ROS, ICAM-1 and apoptosis as compared with control. In an additional study, the effect of original iron sucrose formulation on mononuclear cells was compared with that of one generic formulation. The generic formulation produced a greater increase in ROS, ICAM-1 and apoptosis than the original iron sucrose.
Our results suggest that intravenous iron has deleterious effects on mononuclear cells. The four iron compounds evaluated produced similar effects on oxidative stress, cell activation and apoptosis. However, the effects of iron compounds with the same formulation were different, thus further investigation may be required to establish the safety of iron preparations that theoretically have the same composition.
本研究在体内和体外分析了四种不同静脉铁制剂（葡萄糖酸铁、蔗糖铁、右旋糖酐铁和羧基麦芽糖铁）对单核细胞活化和损伤的影响。
对10名血液透析（HD）患者进行了一项随机前瞻性研究。在基线（T0）、HD开始后1小时（恰好在给予铁剂或生理盐水之前，T1）、铁剂或生理盐水输注后30分钟（T2）以及HD结束时（T3）采集血样。此外，将来自10名健康个体和9名未接受HD治疗的慢性肾脏病5期（CKD-5）患者的外周血单核细胞与这4种铁制剂进行培养。
HD期间输注铁剂增加了产生活性氧（ROS）、细胞间黏附分子-1（ICAM-1）和凋亡的单核细胞百分比。四种铁制剂之间无显著差异。健康个体和CKD-5患者的单核细胞与不同铁制剂培养后，与对照组相比，ROS、ICAM-1和凋亡显著增加。在另一项研究中，将原蔗糖铁制剂与一种仿制药制剂对单核细胞的影响进行了比较。仿制药制剂比原蔗糖铁制剂在ROS、ICAM-1和凋亡方面产生更大的增加。
我们的结果表明静脉铁对单核细胞有有害影响。所评估的四种铁化合物对氧化应激、细胞活化和凋亡产生相似的影响。然而，相同制剂的铁化合物的影响不同，因此可能需要进一步研究以确定理论上具有相同成分的铁制剂的安全性。
