The suffocating kidney: tubulointerstitial hypoxia in end-stage renal disease

Chronic kidney disease (CKD) is characterized by irreversible pathological processes that result in the development of end-stage renal disease (ESRD). Accumulating evidence has emphasized the important role of chronic hypoxia in the tubulointerstitium in the final common pathway that leads to development of ESRD. The causes of chronic hypoxia in the tubulointerstitium are multifactorial and include mechanisms such as hemodynamic changes and disturbed oxygen metabolism of resident kidney cells. Epidemiological studies have revealed an association between CKD and systemically hypoxic conditions, such as chronic obstructive pulmonary disease and sleep apnea syndrome. In addition to tubulointerstitial hypoxia, glomerular hypoxia can occur and is a crucial factor in the development of glomerular disorders. Chemical compounds, polarographic sensors, and radiographical methods can be used to detect hypoxia. Therapeutic approaches that target chronic hypoxia in the kidney should be effective against a broad range of kidney diseases. Amelioration of hypoxia is one mechanism of inhibiting the renin-angiotensin system, the current gold standard of CKD therapy. Future therapeutic approaches include protection of the vascular endothelium and appropriate activation of hypoxia-inducible factor, a key transcription factor involved in adaptive responses against hypoxia.