Role of necroptosis in kidney health and disease

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Benedikt Kolbrink1, Friedrich A von Samson-Himmelstjerna1, James M Murphy2,3

  • 1Department of Nephrology and Hypertension, University Hospital Schleswig-Holstein, Kiel, Germany.

Nature Reviews. Nephrology
|January 3, 2023
PubMed

Insights

Necroptosis, a form of regulated cell death, drives kidney disease progression and inflammation. Targeting necroptosis could offer new therapeutic strategies for kidney injury.

Area of Science:

  • Nephrology
  • Cell Biology
  • Immunology

Background:

  • Cell death, especially of tubule epithelial cells, is central to kidney disease pathophysiology.
  • Necroptosis, a regulated necrosis, plays a key role in acute tubular necrosis, nephron loss, and renal fibrogenesis.
  • Unlike non-immunogenic apoptosis, necroptosis triggers inflammation via cellular content release, leading to organ dysfunction and lasting kidney injury.

Purpose of the Study:

  • To review the role of necroptosis in kidney diseases.
  • To highlight the lack of therapeutic options targeting necroptosis.
  • To emphasize the need for understanding necroptosis mechanisms for novel treatment development.

Main Methods:

  • Literature review of studies on necroptosis in kidney disease over the past 15 years.
  • Analysis of the molecular mechanisms and inflammatory consequences of necroptosis.
  • Evaluation of current therapeutic approaches and identification of shortcomings.

Main Results:

  • Necroptosis is increasingly recognized as a significant contributor to kidney injury and fibrosis.
  • The necroinflammatory environment resulting from necroptosis exacerbates kidney dysfunction.
  • Existing therapeutic strategies for targeting necroptosis regulators are insufficient.

Conclusions:

  • Greater understanding of necroptosis triggers and regulators in kidney disease is crucial.
  • Identifying shortcomings in current approaches may lead to innovative therapeutic strategies.
  • Targeting necroptosis offers a promising avenue for treating acute and chronic kidney diseases.

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