Ferroptosis and Necroptosis in the Kidney

Cell Chem Biol. 2020 Apr 16;27(4):448-462. doi: 10.1016/j.chembiol.2020.03.016.


In the last decade, the role of apoptosis in the pathophysiology of acute kidney injury (AKI) and AKI to chronic kidney disease (CKD) progression has been revisited as our understanding of ferroptosis and necroptosis has emerged. A growing body of evidence, reviewed here, ascribes a central pathophysiological role for ferroptosis and necroptosis to AKI, nephron loss, and acute tubular necrosis. We will introduce concepts to the non-cell-autonomous manner of kidney tubular injury during ferroptosis, a phenomenon that we refer to as a "wave of death." We hypothesize that necroptosis might initiate cell death propagation through ferroptosis. The remaining necrotic debris requires effective removal processes to prevent a secondary inflammatory response, referred to as necroinflammation. Open questions include the differences in the immunogenicity of ferroptosis and necroptosis, and the specificity of necrostatins and ferrostatins to therapeutically target these processes to prevent AKI-to-CKD progression and end-stage renal disease.

Keywords: ANCA-associated vasculitis; acute tubular necrosis; necrotizing vasculitis; programmed necrosis; regulated cell death; regulated necrosis; transplantation; xenotransplantation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology*
  • Autophagy-Related Proteins / metabolism
  • Ferroptosis*
  • Humans
  • Necroptosis*
  • Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / pathology*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Respiratory Distress Syndrome / metabolism
  • Respiratory Distress Syndrome / pathology
  • Signal Transduction


  • Autophagy-Related Proteins
  • Phospholipid Hydroperoxide Glutathione Peroxidase