Ferroptosis and Acute Kidney Injury (AKI): Molecular Mechanisms and Therapeutic Potentials

Abstract

Acute kidney injury (AKI), a common and serious clinical kidney syndrome with high incidence and mortality, is caused by multiple pathogenic factors, such as ischemia, nephrotoxic drugs, oxidative stress, inflammation, and urinary tract obstruction. Cell death, which is divided into several types, is critical for normal growth and development and maintaining dynamic balance. Ferroptosis, an iron-dependent nonapoptotic type of cell death, is characterized by iron overload, reactive oxygen species accumulation, and lipid peroxidation. Recently, growing evidence demonstrated the important role of ferroptosis in the development of various kidney diseases, including renal clear cell carcinoma, diabetic nephropathy, and AKI. However, the exact mechanism of ferroptosis participating in the initiation and progression of AKI has not been fully revealed. Herein, we aim to systematically discuss the definition of ferroptosis, the associated mechanisms and key regulators, and pharmacological progress and summarize the most recent discoveries about the role and mechanism of ferroptosis in AKI development. We further conclude its potential therapeutic strategies in AKI.

The anti-inflammatory activity of resveratrol in acute kidney injury: a systematic review and meta‐analysis of animal studies

“… 2021 ; Feng et al. 2022 ; Levey 2022 ). AKI describes a sudden loss of kidney function that is determined on the basis of increased serum creatinine levels (a marker of kidney excretory function) and reduced urinary output (oliguria) (a quantitative marker of urine production) and is limited to a duration of 7 days.…”

Preparation, structural characterization, antioxidant activity and protection against cisplatin-induced acute kidney injury by polysaccharides from the lateral root of Aconitum carmichaelii

“…Acute kidney injury (AKI), a common and serious clinical kidney syndrome with high incidence and mortality. Many studies have shown that lipid peroxidation occurs after acute kidney injury ( Feng et al, 2022 ). The concept of ferroptosis was first proposed in 2012 by Dixon et al (2012) .…”

Pathogenesis of intrinsic acute kidney injury

“…Several novel therapeutic agents that inhibit necroptosis have already shown efficacy in experimental studies, and human translation appears to be promising [13 && ]. Ferroptosis, a distinct form of nonapoptotic irondependent cell death now well described in AKI, is characterized primarily by intracellular accumulation of labile, catalytic iron, with subsequent lipid peroxidation, membrane rupture and cell death [12,15,16]. Targeted inhibition of ferroptosis via widely available lipophilic antioxidants and iron chelators are achieving promising preliminary results.…”