Hypoxia-inducible factor (HIF) is a transcription factor that serves as a master regulator of the adaptive response against hypoxia. The 2019 Nobel Prize in Physiology or Medicine was awarded to three physician scientists for their groundbreaking work revealing this pathway.
Chronic kidney disease decreases production of erythropoietin in the kidney. Erythropoietin is one of the representative target genes of HIF, and HIF prolyl hydroxylase (HIF-PH) inhibitors are launched as novel therapeutic agents for anemia in chronic kidney disease. In contrast to conventional exogenous erythropoietin administration, HIF-PH inhibitors stimulate endogenous EPO production and improve iron metabolism via stabilization of HIF. However, HIF activates a variety of target genes, and HIF-PH inhibitors work systemically. We need to understand potential consequences of HIF activation, which might lead to either beneficial or undesirable effects.