Acute injury with intravenous iron and concerns regarding long-term safety
Acute injury with intravenous iron and concerns regarding long-term safety
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DOI：
10.2215/cjn.01420406
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发表时间：
2006-09-01
影响因子：
9.8
通讯作者：
Agarwal, Rajiv
中科院分区：
文献类型：
--
作者：
Bishu, Kalkidan;Agarwal, Rajiv
静脉铁剂被广泛用于维持足够的铁储备和预防慢性肾脏疾病患者的缺铁性贫血，但人们仍然担心其长期安全性与氧化应激，肾损伤和加速动脉粥样硬化，这是本次审查的主题。在美国有三种肠外铁制剂可供使用：右旋糖酐铁、葡萄糖酸铁和蔗糖铁。右旋糖酐铁，尤其是高分子右旋糖酐铁，与类过敏反应和过敏反应有关，其使用量一直在下降。一部分静脉内铁制剂是氧化还原活性的，不稳定的铁可直接捐赠给转铁蛋白。体外试验表明，常用的静脉内铁制剂具有不同的能力，以饱和转铁蛋白直接：葡萄糖酸铁>蔗糖铁>右旋糖酐铁。静脉内铁治疗产生氧化应激，如脂质过氧化产物（丙二醛）的血浆水平增加所示，在比催化活性铁达到峰值浓度的时间早得多的时间点，表明蔗糖铁对氧化应激的直接影响。此外，铁蔗糖输注产生内皮功能障碍，似乎比游离铁的血清水平更早达到峰值。静脉内蔗糖铁输注也已显示产生急性肾损伤和炎症，如尿白蛋白、酶（N-乙酰基-β-氨基葡萄糖苷酶）和细胞因子（趋化因子单核细胞趋化蛋白-1）排泄增加所证明。尽管静脉注射铁剂的长期危险性尚未得到证实，但这些数据要求检查静脉注射铁剂对慢性肾脏疾病患者长期危害的潜在影响。
Intravenous iron is widely used to maintain adequate iron stores and prevent iron deficiency anemia in patients with chronic kidney disease, yet concerns remain about its long-term safety with respect to oxidative stress, kidney injury, and accelerated atherosclerosis, which are the subjects of this review. Three parenteral iron formulations are available for use in the United States: Iron dextran, iron gluconate, and iron sucrose. Iron dextran, especially the high molecular form, has been linked with anaphylactoid and anaphylactic reactions, and its use has been declining. A portion of intravenous iron preparations is redox-active, labile iron available for direct donation to transferrin. In vitro tests show that commonly available intravenous iron formulations have differing capacities to saturate transferrin directly: Iron gluconate > iron sucrose > iron dextran. Intravenous iron treatment produces oxidative stress, as demonstrated by increases in plasma levels of lipid peroxidation products (malondialdehyde), at a point that is much earlier than the time to peak concentration of catalytically active iron, suggesting a direct effect of iron sucrose on oxidative stress. Furthermore, iron sucrose infusion produces endothelial dysfunction that seems to peak earlier than the serum level of free iron. Intravenous iron sucrose infusion also has been shown to produce acute renal injury and inflammation as demonstrated by increased urinary albumin, enzyme (N-acetyl-beta-glucosaminidase), and cytokine (chemokine monocyte chemoattractant protein-1) excretions. Although the long-term dangers of intravenous iron are unproved, these data call for examination of effects of intravenous iron on the potential for long-term harm in patients with chronic kidney disease.