Hypoxia-inducible factor signaling in vascular calcification in chronic kidney disease patients.

Abstract

Chronic kidney disease (CKD) affects approximately 15% of the adult population in high-income countries and is associated with significant comorbidities, including increased vascular calcifications which is associated with a higher risk for cardiovascular events. Even though the underlying pathophysiology is unclear, hypoxia-inducible factor (HIF) signaling appears to play a central role in inflammation, angiogenesis, fibrosis, cellular proliferation, apoptosis and vascular calcifications which is influenced by multiple variables such as iron deficiency anemia, serum phosphorus and calcium levels, fibroblast growth factor-23 (FGF-23) and Klotho. Along with the growing understanding of the pathology, potential therapeutic alternatives have emerged including HIF stabilizers and SGLT-2 inhibitors. The aim of this review is to discuss the role of HIF signaling in the pathophysiology of vascular calcification in CKD patients and to identify potential therapeutic approaches.