Hypoxia-Driven Responses in Chronic Kidney Disease

Chronic kidney disease (CKD) affects 10% of the population. Fibrosis is the hallmark of CKD, which is marked by the deposit of extracellular matrix (ECM). This response is the final outcome of an unbalanced reaction to inflammation and wound healing and can be induced by a variety of insults, including hypoxia. Vascular damage results in an impaired tissue oxygen supply, inducing immune cell infiltration, tubule injury and the activation of ECM-secreting myofibroblasts. In turn, tubulointerstitial fibrosis development worsens oxygen diffusion. Hypoxia-inducible factor (HIF) is the primary transcriptional regulator of hypoxia-associated responses, such as oxidative stress and metabolic reprogramming, triggering a proinflammatory and profibrotic landscape. In this review, we discuss hypoxia-driven reprogramming in CKD as well as potential therapeutic approaches to target chronic hypoxia.