Role of hypoxia in the pathogenesis of renal disease.
Despite a high overall oxygen supply, the tissue oxygen tensions in the kidney are comparatively low and render the kidneys prone to hypoxic injury. However, the role of hypoxia in the pathogenesis of different types of renal disease remains incompletely understood. The importance of hypoxic cell injury is most obvious in renal vascular disease, in which occlusion of the renal artery or one of its branches can induce tissue necrosis. In acute renal failure, circumstantial evidence suggests that hypoxic injury to the renal medulla plays a significant role. In addition, chronically impaired oxygenation may also be an important factor in the progression of chronic renal disease. Destruction of the glomerular capillaries leads to hypoperfusion of the peritubular interstitium. Moreover, in focal disease, a compensatory increase in perfusion of other glomeruli may increase flow and pressure in peritubular capillaries derived from their vasa efferentia which could be a cause of microvascular injury. The interstitial capillary density is reduced in chronic renal disease, and results of animal experiments suggest that this is due to an imbalance in the expression of pro- and antiangiogenic factors. Besides its essential role in energy generation, oxygen is increasingly recognized as an important regulator of cellular functions. Hypoxia induces specific genes through increased expression of hypoxia-inducible transcription factors (HIF). Different HIF isoforms have recently been shown to be inducible in glomerular, tubular, and interstitial cells of the kidney. While the majority of HIF-dependent genes confer protection against hypoxia, hypoxia-inducible gene expression has been suggested to contribute also to increased interstitial matrix deposition.
Eckardt
Kai-Uwe
KU
Department of Nephrology and Medical Intensive Care, Charité, Humboldt University, Berlin, Germany. kai-uwe.eckardt@charite.de
Rosenberger
Christian
C
Jürgensen
Jan Steffen
JS
Wiesener
Michael S
MS
D002196:Capillaries / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000235:genetics / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology*; D012079:Renal Circulation