Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Renal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
J Am Soc Nephrol. 2019 Nov;30(11):2060-2071. doi: 10.1681/ASN.2019060595. Epub 2019 Sep 25.
AKI remains a major public health concern. Despite years of investigation, no intervention has been demonstrated to reliably prevent AKI in humans. Thus, development of novel therapeutic targets is urgently needed. An important role of iron in the pathophysiology of AKI has been recognized for over three decades. When present in excess and in nonphysiologic labile forms, iron is toxic to the kidneys and multiple other organs, whereas iron chelation is protective across a broad spectrum of insults. In humans, small studies have investigated iron chelation as a novel therapeutic strategy for prevention of AKI and extrarenal acute organ injury, and have demonstrated encouraging initial results. In this review, we examine the existing data on iron chelation for AKI prevention in both animal models and human studies. We discuss practical considerations for future clinical trials of AKI prevention using iron chelators, including selection of the ideal clinical setting, patient population, iron chelating agent, and dosing regimen. Finally, we compare the key differences among the currently available iron chelators, including pharmacokinetics, routes of administration, and adverse effects.
急性肾损伤仍然是一个主要的公共卫生问题。尽管经过多年的研究，仍没有干预措施被证明能可靠地预防人类的急性肾损伤。因此，迫切需要开发新的治疗靶点。铁在急性肾损伤的病理生理学中的重要作用已经被认识了三十多年。当铁过量存在且处于非生理不稳定形式时，对肾脏和其他多个器官有毒性，而铁螯合在广泛的损伤中具有保护作用。在人类中，一些小型研究已经探讨了铁螯合作为预防急性肾损伤和肾外急性器官损伤的新治疗策略，并取得了令人鼓舞的初步结果。在这篇综述中，我们检查了现有的关于铁螯合预防动物模型和人类研究中急性肾损伤的数据。我们讨论了使用铁螯合剂预防急性肾损伤的未来临床试验的实际考虑因素，包括选择理想的临床环境、患者人群、铁螯合剂和剂量方案。最后，我们比较了目前可用的铁螯合剂之间的关键差异，包括药代动力学、给药途径和不良反应。
