Molecular mechanisms of hepcidin regulation: implications for the anemia of CKD.
Molecular mechanisms of hepcidin regulation: implications for the anemia of CKD.
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DOI：
10.1053/j.ajkd.2009.12.030
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Lin HY
中科院分区：
文献类型：
--
作者：
Babitt JL;Lin HY
贫血在慢性肾脏疾病(CKD)患者中普遍存在，并与较低的生活质量和较高的不良结局风险相关，包括心血管疾病和死亡。CKD患者的贫血治疗目前围绕着红细胞生成刺激剂(ESA)和补铁的使用。然而，许多患者没有足够的反应和/或需要大剂量的这些药物。此外，最近的临床试验表明，以较高的血红蛋白水平为目标的传统疗法会导致心血管发病率和死亡率的增加，特别是在使用更大剂量的ESA时，以及在对治疗反应较差的患者中。一些患者对传统疗法反应不佳的一种解释是，这些疗法没有完全解决贫血的根本原因。在许多CKD患者中，就像其他慢性炎症性疾病的患者一样，饮食中铁的吸收不足和无法利用体内的铁储备导致了贫血。最近的研究表明，铁平衡的这些异常可能是由关键的铁调节激素海普西丁水平升高引起的。本文综述了慢性肾脏病贫血的发病机制、海普西丁在全身铁稳态中的作用和调节以及慢性肾脏病贫血，以及这些发现的潜在诊断和治疗意义。
Anemia is prevalent in patients with chronic kidney disease (CKD) and is associated with a lower quality of life and a higher risk of adverse outcomes including cardiovascular disease and death. Anemia management in CKD patients currently revolves around the use of erythropoiesis-stimulating agents (ESAs) and supplemental iron. However, many patients do not respond adequately and/or require high doses of these medications. Furthermore, recent clinical trials have shown that targeting higher hemoglobin levels with conventional therapies leads to increased cardiovascular morbidity and mortality, particularly when higher doses of ESAs are used, and in patients who are poorly responsive to therapy. One explanation for the poor response to conventional therapies in some patients is that these treatments do not fully address the underlying cause of the anemia. In many CKD patients, like patients with other chronic inflammatory diseases, poor absorption of dietary iron and inability to utilize the body's iron stores contributes to the anemia. Recent research suggests that these abnormalities in iron balance may be caused by elevated levels of the key iron regulatory hormone hepcidin. This article reviews the pathogenesis of anemia in CKD, the role and regulation of hepcidin in systemic iron homeostasis and the anemia of CKD, and the potential diagnostic and therapeutic implications of these findings.
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