Rostoker Guy, Vaziri Nosratola D
Hôpital Privé Claude-Galien, Ramsay-Générale de Santé, Division of Nephrology and Dialysis, 91480 Quincy-sous-Sénart, France.
University of California, Division of Nephrology and Hypertension, Irvine, USA.
Presse Med. 2017 Dec;46(12 Pt 2):e312-e328. doi: 10.1016/j.lpm.2017.10.014. Epub 2017 Nov 16.
Iron overload was considered rare in hemodialysis patients until recently, but its clinical frequency is now increasingly recognized. 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 hemosiderosis and genetic hemochromatosis. Magnetic resonance imaging (MRI) is now the gold standard method for estimating and monitoring LIC. Studies of LIC in hemodialysis patients by magnetic susceptometry thirteen years ago and recently by quantitative MRI have demonstrated a 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. Moreover, three recent long-term observational studies suggested that excessive IV iron doses might be associated with an increased risk of cardiovascular events and death in hemodialysis patients. It has been hypothesized that iatrogenic iron overload in the era of erythropoiesis-stimulating agents might silently increase complications in dialysis patients without creating obvious, clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It has been postulated that the main pathophysiological pathway leading to these events might involve the pleiotropic master hormone hepcidin, which regulates iron metabolism, leading to activation of macrophages in atherosclerotic plaques and then to clinical cardiovascular events. Thus, the potential iron overload toxicity linked to chronic administration of IV iron therapy is now becoming one of the most controversial topics in the management of anemia in hemodialysis patients.
直到最近，铁过载在血液透析患者中还被认为很罕见，但现在其临床发生率越来越受到认可。肝脏是铁储存的主要部位，在继发性含铁血黄素沉着症和遗传性血色素沉着症患者中，肝脏铁浓度（LIC）与总铁储存密切相关。磁共振成像（MRI）现在是估计和监测LIC的金标准方法。13年前通过磁测法以及最近通过定量MRI对血液透析患者的LIC进行的研究表明，铁过载风险与按照当前贫血管理指南中所含铁生物标志物临界值确定的剂量开具的静脉注射（IV）铁剂的使用之间存在关联。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，尤其是在推荐的IV铁剂剂量方面。此外，最近的三项长期观察性研究表明，过量的IV铁剂剂量可能与血液透析患者心血管事件和死亡风险增加有关。据推测，在促红细胞生成素时代的医源性铁过载可能会在透析患者中悄然增加并发症，而不会产生明显的临床体征和症状。最近，高铁调素-25水平与透析患者的致命和非致命心血管事件有关。据推测，导致这些事件的主要病理生理途径可能涉及多效性主激素铁调素，它调节铁代谢，导致动脉粥样硬化斑块中的巨噬细胞活化，进而引发临床心血管事件。因此，与长期静脉注射铁剂治疗相关的潜在铁过载毒性现在正成为血液透析患者贫血管理中最具争议的话题之一。
