Tsuchiya Ken, Nitta Kosaku
Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.
Ther Apher Dial. 2013 Feb;17(1):1-8. doi: 10.1111/1744-9987.12001. Epub 2012 Dec 16.
Hepcidin is a small defensin-like peptide produced primarily by hepatocytes, but also by other cells, including macrophages. In addition to hepcidin's antimicrobial properties, it is the main regulator of iron metabolism and controls both the amount of dietary iron absorbed in the duodenum and the iron release by reticuloendothelial cells. Hepcidin expression is upregulated by a variety of stimuli, including inflammation and iron overload, and downregulated by anemia, hypoxia, and iron deficiency. Chronic kidney disease (CKD) is associated with increased serum hepcidin levels, and the increased levels may contribute to the development and severity of anemia and to resistance to erythropoiesis-stimulating agents (ESAs). Elevated serum hepcidin levels contribute to the dysregulation of iron homeostasis in CKD patients. Although parenteral iron supplementation can bypass some of the iron-blocking effects of hepcidin in CKD patients with anemia, and free iron and iron stores increase as a result, the anemia is only partially corrected, and the ESA dose requirements remain significantly higher than needed for physiological replacement. Treatment with agents that lower serum hepcidin levels or inhibit its actions may be an effective strategy for restoring normal iron homeostasis and improving anemia in CKD patients. The aim of this article was to review the regulation of hepcidin levels and the role of hepcidin in CKD-related anemia, and to discuss hepcidin's potential as a clinical biomarker and several investigational treatments designed to lower serum hepcidin levels.
铁调素是一种主要由肝细胞产生的、类似防御素的小肽，但其他细胞（包括巨噬细胞）也能产生。除了具有抗菌特性外，铁调素还是铁代谢的主要调节因子，它既能控制十二指肠吸收的膳食铁量，也能控制网状内皮细胞释放的铁量。铁调素的表达受多种刺激上调，包括炎症和铁过载，而受贫血、缺氧和缺铁下调。慢性肾脏病（CKD）与血清铁调素水平升高有关，升高的水平可能导致贫血的发生和严重程度增加，并导致对促红细胞生成素（ESA）产生抵抗。血清铁调素水平升高会导致CKD患者铁稳态失调。虽然静脉补铁可以绕过铁调素对CKD贫血患者的一些铁阻断作用，结果游离铁和铁储存增加，但贫血仅得到部分纠正，且ESA剂量需求仍显著高于生理替代所需剂量。使用降低血清铁调素水平或抑制其作用的药物进行治疗可能是恢复CKD患者正常铁稳态和改善贫血的有效策略。本文旨在综述铁调素水平的调节及其在CKD相关贫血中的作用，并讨论铁调素作为临床生物标志物的潜力以及几种旨在降低血清铁调素水平的研究性治疗方法。
