Tissue hypoxia has been pointed out as a major pathogenic factor in chronic kidney disease (CKD). However, epidemiological and experimental evidence inconsistent with this notion has been described. We reported previously that chronic exposure to low ambient pO2 promoted no renal injury in normal rats and, in rats with 5/6 renal ablation, unexpectedly attenuated renal injury. In the present study, we investigated whether chronic exposure to low ambient pO2 would also be renoprotective in two additional models of CKD: adenine excess and chronic nitric oxide inhibition. In both models, normobaric ambient hypoxia attenuated the development of renal injury and inflammation. In addition, renal hypoxia limited the activation of the NF-κB and NLRP3 inflammasome cascades, as well as oxidative stress and intrarenal infiltration by angiotensin II-positive cells. Renal activation of HIF-2α, along with other adaptive mechanisms to hypoxia, may have contributed to these renoprotective effects. The present findings may contribute to unravel the pathogenesis of CKD and to the development of innovative strategies to arrest its progression.

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