The role of hypoxia in chronic kidney disease: a nuanced perspective.

Abstract

This review critically examines the role of hypoxia in chronic kidney disease (CKD). While traditionally viewed as detrimental, recent insights suggest a more nuanced understanding of hypoxia's role during renal disease. Emerging evidence challenges the traditional view that hypoxia is universally harmful in CKD context. We review here the recent evidence about hypoxia and HIF activation in CKD. We also discuss the effect of hypoxia on the renal tissue, and the relative inhibition of different HIF isoforms. Recent advancements in therapies, such as HIF prolyl hydroxylase inhibitors (HIF-PHIs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors seem to target the HIF pathway. These drugs impact anemia associated with CKDbut also renoprotection, hinting at a more complex interplay between hypoxia, HIF activation, and renal health. A certain level of hypoxia and specific HIF pathway activation, especially HIF-α, can be beneficial in CKD progression. Therapeutic strategies targeting HIF stabilization, such as with HIF-PHIs and SGLT2 inhibitors, offer promising avenues for enhancing renal protection. Future investigations should aim at better understanding the precise effects on HIF pathway and optimize their clinical application to improve outcomes for CKD patients.