Safety concerns about intravenous iron therapy in patients with chronic kidney disease.
Safety concerns about intravenous iron therapy in patients with chronic kidney disease.
复制标题
DOI：
10.1093/ckj/sfv142
复制
发表时间：
2016-04
影响因子：
4.6
通讯作者：
Locatelli F
中科院分区：
文献类型：
--
作者：
Del Vecchio L;Longhi S;Locatelli F
慢性肾病（CKD）贫血主要通过红细胞生成刺激剂（ESA）和铁剂治疗。在关注ESA治疗后，静脉内（IV）铁剂在世界范围内越来越多地使用。然而，目前还不清楚这种方法在非常高的剂量或在非常高的铁蛋白水平存在下是否安全。一些观察性研究表明，高铁蛋白水平或高铁剂量与死亡、心血管事件、住院或感染风险增加之间存在关系。其他人无法证实这些调查结果。然而，它们受到指示偏差的影响。另一方面，大多数随机临床试验只有很短的随访（因此药物暴露），不足以评估死亡风险。他们都没有测试不同铁剂量对硬终点的作用。由于缺乏来自精心设计和大规模研究的明确证据，一些数据表明，过量的铁治疗可能在几个方面是有毒的，从铁过载到不稳定铁的组织损伤。大量的实验和临床数据表明，过量的铁治疗或铁超载可能是动脉粥样硬化形成的罪魁祸首。这一过程似乎是由氧化应激介导的。铁治疗在活动性感染的情况下也应该谨慎使用，因为铁对细菌生长至关重要。最近，欧洲药品管理局正式提出了对IV铁剂给药后罕见超敏反应的担忧。平衡一直有利于福利。在几个欧洲国家，这造成了很多混乱，并在一定程度上减缓了过度使用的速度。总而言之，IV铁剂仍然是CKD患者贫血治疗的主要药物。然而，在我们看来，应避免过度使用，特别是在铁蛋白水平高的患者和ESA药物不禁忌的情况下。
Anaemia in chronic kidney disease (CKD) is managed primarily with erythropoiesis-stimulating agents (ESAs) and iron therapy. Following concerns around ESA therapy, intravenous (IV) iron is being administered more and more worldwide. However, it is still unclear whether this approach is safe at very high doses or in the presence of very high ferritin levels. Some observational studies have shown a relationship between either high ferritin level or high iron dose and increased risk of death, cardiovascular events, hospitalization or infection. Others have not been able to confirm these findings. However, they suffer from indication biases. On the other hand, the majority of randomized clinical trials have only a very short follow-up (and thus drug exposure) and are inadequate to assess the mortality risk. None of them have tested the role of different iron doses on hard end points. With the lack of clear evidence coming from well-designed and large-scale studies, several data suggest that excessive iron therapy may be toxic in several aspects, ranging from iron overload to tissue damage from labile iron. A number of experimental and clinical data suggest that either excessive iron therapy or iron overload may be a possible culprit of atherogenesis. The process seems to be mediated by oxidative stress. Iron therapy should also be used cautiously in the presence of active infections, since iron is essential for bacterial growth. Recently, the European Medicines Agency officially raised concerns about rare hypersensitivity reactions following IV iron administration. The balance has been in favour of benefits. In several European countries, this has created a lot of confusion and somewhat slowed the run towards excessive use. Altogether, IV iron remains a mainstay of anaemia treatment in CKD patients. However, in our opinion, its excessive use should be avoided, especially in patients with high ferritin levels and when ESA agents are not contraindicated.