The role of HIF in the kidney is of particular interest, since (i) renal oxygen tensions are extremely heterogeneous, (ii) erythropoietin (EPO) produced in the kidney cortex plays a central role in systemic adaptation to reduced oxygen availability,(iii) hypoxia is considered to play an important role in acute and chronic renal injury. HIFa protein was not detectable in kidneys under "normoxic" baseline conditions, but accumulated markedly under regional and systemic hypoxia, with a specific distribution: HIF-1a is found in tubular and HIF-2a in endothelial, glomerular and interstitial cells, including those producing EPO.HIF expression is thus apparently determined by both intrinsic properties of different renal cell populations and local oxygen gradients. Additionally, HIF expression is most marked in the border zone of hypoxic/ischemic areas, indicating its stabilization in a specific range of oxygen tensions. In experimental acute kidney injury, upregulation of HIF through endogenous hypoxia- sensing or following pharmacological HIF-stabilisation by prolyl- hydroxylase inhibitors (PHD-I) confers tissue protection. Thus, HIF stabilization offers a promising novel and clinically feasible approach for nephroprotection. Furthermore, stimulation of endogenous EPO by use of PHD-I is being explored as a novel treatment approach for anaemia.