Mitochondrial mechanisms and therapeutics in ischaemia reperfusion injury

Pediatr Nephrol. 2019 Jul;34(7):1167-1174. doi: 10.1007/s00467-018-3984-5. Epub 2018 Jun 2.

Abstract

Acute kidney injury (AKI) remains a major problem in critically unwell children and young adults. Ischaemia reperfusion (IR) injury is a major contributor to the development of AKI in a significant proportion of these cases and mitochondria are increasingly recognised as being central to this process through generation of a burst of reactive oxygen species early in reperfusion. Mitochondria have additionally been shown to have key roles in downstream processes including activation of the immune response, immunomodulation, and apoptosis and necrosis. The recognition of the central role of mitochondria in IR injury and an increased understanding of the pathophysiology that undermines these processes has resulted in identification of novel therapeutic targets and potential biomarkers. This review summarises a variety of therapeutic approaches that are currently under exploration and may have potential in ameliorating AKI in children in the future.

Keywords: Acute kidney injury; Children; Ischaemia reperfusion injury; Mitochondria; Reactive oxygen species; Succinate.

Publication types

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

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / prevention & control*
  • Antioxidants / therapeutic use
  • Apoptosis
  • Biomarkers / blood
  • DNA, Mitochondrial / blood
  • Humans
  • Kidney Tubules / pathology
  • Mitochondria / metabolism*
  • Mitophagy
  • Necrosis
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism*
  • Reperfusion Injury / complications
  • Reperfusion Injury / immunology
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / therapy

Substances

  • Antioxidants
  • Biomarkers
  • DNA, Mitochondrial
  • Reactive Oxygen Species