Role of hypoxia in the pathogenesis of renal disease

Kidney Int Suppl. 2005 Dec;(99):S46-51. doi: 10.1111/j.1523-1755.2005.09909.x.


The kidney shows a remarkable discrepancy between blood supply and oxygenation. Despite high blood flow and oxygen delivery, oxygen tensions in the kidney are comparatively low, in particular in the renal medulla. The reason for this lies in the parallel arrangement of arterial and venous preglomerular and postglomerular vessels, which allows oxygen to pass from arterioles into the postcapillary venous system via shunt diffusion. The limitation in renal tissue oxygen supply renders the kidney susceptible to hypoxia and has long been recognized as an important factor in the pathogenesis of acute renal injury. In recent years, evidence has accumulated that hypoxia does also play a significant role in the pathogenesis and progression of chronic renal disease, because different types of kidney disease are usually associated with a rarefication of postglomerular capillaries. In both acute and chronic diseases, tissue hypoxia does not only imply the risk of energy deprivation but also induces regulatory mechanisms and has a profound influence on gene expression. In particular, the transcription factor hypoxia inducible factor (HIF) is involved in cellular regulation of angiogenesis, vasotone, glucose metabolism, and cell death and survival decisions. HIF has been shown to be activated in renal disease and presumably plays a major role in protective responses to oxygen deprivation. Recent insights into the regulation of HIF increase our understanding of the role of hypoxia in disease progression and open new options to improve hypoxia tolerance and to induce nephroprotection.

Publication types

  • Review

MeSH terms

  • Cell Hypoxia
  • Chronic Disease
  • Disease Progression
  • Gene Expression Regulation
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology*
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / physiopathology
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiology
  • Kidney Glomerulus / physiopathology
  • Kidney Tubules / blood supply
  • Kidney Tubules / pathology
  • Kidney Tubules / physiopathology
  • Neovascularization, Physiologic
  • Oxygen / physiology*


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oxygen