Nephrol Dial Transplant. 2011 Oct;26(10):3092-100. doi: 10.1093/ndt/gfr410. Epub 2011 Jul 22.
Hepcidin has been established as a central regulator of iron metabolism. In most patients with chronic kidney disease (CKD), serum hepcidin levels are relatively high, favoring iron sequestration in several cell types and organs and thereby leading to iron-related complications. In the absence of overt inflammation, serum hepcidin has been found to be most closely associated with serum ferritin in healthy subjects and in CKD patients. Intestinal iron absorption is tightly regulated by both iron stores and hepcidin. The expression of the mammalian iron exporter, ferroportin (FPN), limits the growth of intracellular bacteria by depleting cytosolic iron. An upregulation of hepcidin could diminish FPN and favor bacterial growth. Of note, in patients with hyperferritinemia impaired hepcidin expression caused by a mutation in the hemochromatosis gene associates with an attenuation of atherosclerosis. Thus, hepcidin might accelerate atherosclerosis by preventing iron exit from macrophages or other cells in the arterial wall. High hepcidin levels have also been found to be linked to good erythropoiesis-stimulating agents (ESAs) response, in conjunction with the strong hepcidin-ferritin correlation. Finally, hepcidin may also play a significant role by itself in the pathogenesis of CKD complications associated with disturbed iron metabolism, i.e. unrelated to ESA hyporesponsiveness, such as bacterial infections and atherosclerosis.
铁调素已被确定为铁代谢的中心调节剂。在大多数慢性肾脏病（CKD）患者中，血清铁调素水平相对较高，有利于几种细胞类型和器官中铁的蓄积，从而导致与铁相关的并发症。在没有明显炎症的情况下，在健康受试者和 CKD 患者中，血清铁调素与血清铁蛋白的相关性最强。肠道铁吸收受铁储存和铁调素的严格调节。哺乳动物铁输出蛋白，亚铁转运蛋白（FPN）的表达通过耗尽细胞质铁来限制细胞内细菌的生长。铁调素的上调可能会降低 FPN 并有利于细菌生长。值得注意的是，在因血色病基因突变导致高血铁蛋白血症的患者中，铁调素表达受损与动脉粥样硬化程度减轻有关。因此，铁调素可能通过阻止巨噬细胞或动脉壁中其他细胞中铁的外排而加速动脉粥样硬化的发生。高水平的铁调素也与良好的促红细胞生成素刺激剂（ESA）反应有关，同时与铁调素-铁蛋白的强烈相关性有关。最后，铁调素本身也可能在与 ESA 低反应性无关的与铁代谢紊乱相关的 CKD 并发症的发病机制中发挥重要作用，例如细菌感染和动脉粥样硬化。
