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.

Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis

“…Iron chelators have been shown to prevent or attenuate acute kidney injury. A pretreatment with deferoxamine protects against acute kidney injury in various mouse models (Sharma & Leaf, 2019). Here, nuciferine reduced iron accumulation induced either by folic acid treatment in mice or by RSL3 treatment in cells (Figures 3 and 6).…”

Feasibility study and direct extraction of endogenous free metallic cations combining hemodialysis and chelating polymer

“…For acute-on-chronic liver failure, higher incidence of multiorgans failure and consequent mortality is observed for patients with dysregulated iron homeostasis 19 . Kidney is another organ at risk for iron dysregulation 20 . Acute kidney injury is a relatively common disease associated with high mortality; it can be seen in 5–7% of hospitalized patients and in 57% of patients in intensive care units.…”

Iron and Cadmium Entry Into Renal Mitochondria: Physiological and Toxicological Implications

“…Two treatment approaches found their way in the literature: (1) metal chelating agents without or (2) with antioxidants. The Fe chelating agents currently in use for prevention and management of AKI include deferoxamine, deferasirox and deferiprone, all of which are highly specific for Fe ( Sharma and Leaf, 2019 ). A combination of Fe chelators and antioxidant treatment (e.g., N-acetylcysteine or ascorbic acid) has been proposed for myoglobin-induced AKI ( Panizo et al, 2015 ).…”