Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century
Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century
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DOI：
10.1007/s40265-016-0569-0
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发表时间：
2016-05-01
期刊：
影响因子：
11.5
通讯作者：
Fishbane, Steven
中科院分区：
文献类型：
--
作者：
Rostoker, Guy;Vaziri, Nosratola D.;Fishbane, Steven
铁超载在血液透析患者中曾经被认为是罕见的，但其临床频率现在越来越多地认识到。肝脏是铁储存的主要部位，继发性铁血黄素沉着症和遗传性血色素沉着症患者的肝铁浓度（LIC）与总铁储存密切相关。磁共振成像现在是非肾脏患者LIC估计和监测的金标准方法。通过定量磁共振成像和磁导法对血液透析患者的LIC进行的研究表明，铁超载风险与静脉注射（IV）铁产品的使用之间存在密切关系，静脉注射铁产品的剂量由当前贫血管理指南中包含的铁生物标志物截止值确定。这些发现对铁生物标志物临界值和当前临床指南的有效性提出了挑战，特别是在推荐的静脉注射铁剂量方面。最近三项长期观察性研究表明，过量静脉注射铁可能与血液透析患者心血管事件和死亡风险增加有关。我们推测，在促红细胞生成剂时代，医源性铁超载可能会无声地增加透析患者的并发症，而不会产生明显的临床体征和症状。高hepcidin-25水平最近与透析患者的致命性和非致命性心血管事件有关。因此，我们很容易假设导致这些事件的主要病理生理途径可能涉及调节铁代谢的多效性主激素hepcidin（由成纤维细胞生长因子23协同作用）。静脉输铁和铁超载导致的氧化应激，通过释放不稳定的非转铁蛋白结合的铁，可能代表对血管床的“第二次打击”。最后，严重铁超载患者心肌中的铁沉积也可能在某些患者猝死的发病机制中发挥作用。
Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.