Iron Chelation as a Potential Therapeutic Strategy for AKI Prevention

Abstract

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.