Hypoxia as a final common pathway of kidney disease

Abstract

The kidney is susceptible to hypoxia due to a large amount of oxygen consumption and arterial-venous oxygen shunt with subsequent low efficiency of oxygen uptake. Thus, chronic hypoxia of the kidney induced by various mechanisms serves as a final common pathway to end stage kidney disease. Previous studies utilized different methods and demonstrated hypoxia of the kidney in experimental models of various kidney diseases. Recently BOLD-MRI showed hypoxia of the human kidney. Cells are endowed with a defensive mechanism against hypoxia, and hypoxia inducible factor (HIF) serves as a master transcriptional regulator of adaptive genes to hypoxia. Current therapeutic modalities show improvements of hypoxia in the kidney, and development of HIF activators is awaited. Hypoxia changes histone modifications and may induce gene expression in a long term. Epigenetic aspects of hypoxia are a very important issue to be pursued.