Molecular Medicine

, Volume 14, Issue 7–8, pp 502–516 | Cite as

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

  • Matthieu Legrand
  • Egbert G. Mik
  • Tanja Johannes
  • Didier Payen
  • Can Ince
Review Article


Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium-leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways’ alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed.



The authors acknowledge Richard Milstein from Skylab Industry for help with the illustration in Figure 2.


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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Matthieu Legrand
    • 1
    • 2
  • Egbert G. Mik
    • 3
  • Tanja Johannes
    • 4
  • Didier Payen
    • 2
  • Can Ince
    • 1
  1. 1.Department of Physiology, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Anesthesiology and Critical Care, Lariboisière HospitalUniversity of Paris VIIParisFrance
  3. 3.Department of Anesthesiology, Erasmus Medical CenterUniversity of RotterdamRotterdamThe Netherlands
  4. 4.Department of Anesthesiology and Critical CareUniversity Hospital TuebingenTuebingenGermany

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