Renal hypoxia in kidney disease: Cause or consequence?

C. P. C. Ow, J. P. Ngo, M. M. Ullah, L. M. Hilliard, R. G. Evans

Research output: Contribution to journalReview ArticleResearchpeer-review

87 Citations (Scopus)


Tissue hypoxia has been proposed as an important factor in the pathophysiology of both chronic kidney disease (CKD) and acute kidney injury (AKI), initiating and propagating a vicious cycle of tubular injury, vascular rarefaction, and fibrosis and thus exacerbation of hypoxia. Here, we critically evaluate this proposition by systematically reviewing the literature relevant to the following six questions: (i) Is kidney disease always associated with tissue hypoxia? (ii) Does tissue hypoxia drive signalling cascades that lead to tissue damage and dysfunction? (iii) Does tissue hypoxia per se lead to kidney disease? (iv) Does tissue hypoxia precede pathology? (v) Does tissue hypoxia colocalize with pathology? (vi) Does prevention of tissue hypoxia prevent kidney disease? We conclude that tissue hypoxia is a common feature of both AKI and CKD. Furthermore, at least under in vitro conditions, renal tissue hypoxia drives signalling cascades that lead to tissue damage and dysfunction. Tissue hypoxia itself can lead to renal pathology, independent of other known risk factors for kidney disease. There is also some evidence that tissue hypoxia precedes renal pathology, at least in some forms of kidney disease. However, we have made relatively little progress in determining the spatial relationships between tissue hypoxia and pathological processes (i.e. colocalization) or whether therapies targeted to reduce tissue hypoxia can prevent or delay the progression of renal disease. Thus, the hypothesis that tissue hypoxia is a “common pathway” to both AKI and CKD still remains to be adequately tested.

Original languageEnglish
Article numbere12999
Number of pages18
JournalActa Physiologica
Issue number4
Publication statusPublished - 1 Apr 2018


  • acute kidney injury
  • chronic kidney disease
  • hypoxia
  • hypoxia-inducible factors
  • oxygen consumption
  • oxygen delivery

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