Bishu Kalkidan, Agarwal Rajiv
Department of Medicine, Indiana University School of Medicine, and Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA.
Clin J Am Soc Nephrol. 2006 Sep;1 Suppl 1:S19-23. doi: 10.2215/CJN.01420406.
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.
静脉注射铁剂被广泛用于维持慢性肾脏病患者充足的铁储备并预防缺铁性贫血，但对于其在氧化应激、肾损伤和加速动脉粥样硬化方面的长期安全性仍存在担忧，这些正是本综述的主题。在美国有三种胃肠外铁剂可供使用：右旋糖酐铁、葡萄糖酸铁和蔗糖铁。右旋糖酐铁，尤其是高分子形式，与类过敏反应和过敏反应有关，其使用一直在减少。一部分静脉注射铁制剂具有氧化还原活性，即不稳定铁，可直接供体转铁蛋白。体外试验表明，常见的静脉注射铁制剂直接饱和转铁蛋白的能力不同：葡萄糖酸铁＞蔗糖铁＞右旋糖酐铁。静脉注射铁剂治疗会产生氧化应激，脂质过氧化产物（丙二醛）血浆水平升高就证明了这一点，这一情况比催化活性铁达到峰值浓度的时间要早得多，表明蔗糖铁对氧化应激有直接作用。此外，输注蔗糖铁会导致内皮功能障碍，其峰值似乎比游离铁的血清水平出现得更早。静脉输注蔗糖铁还被证明会导致急性肾损伤和炎症，尿白蛋白、酶（N - 乙酰 - 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）排泄增加就证明了这一点。虽然静脉注射铁剂的长期危害尚未得到证实，但这些数据呼吁对静脉注射铁剂对慢性肾脏病患者长期潜在危害的影响进行研究。
