Do prolyl hydroxylase domain (PHD) enzyme inhibitors treat anemia associated with chronic diseases?
Prolyl hydroxylase inhibitors represent a novel oral therapeutic approach for anemia of chronic disease by stabilizing hypoxia-inducible factor and regulating iron homeostasis.
Chronic kidney disease, cancer, chronic inflammatory disorders, nutritional, and genetic deficiency can cause anemia. Hypoxia causes induction of hypoxia-inducible factor (HIF), which stimulates erythropoietin (EPO) synthesis. Prolyl hydroxylase domain (PHD) enzyme inhibition can stabilize hypoxia-inducible factor (HIF). HIF stabilization also decreases hepcidin, a hormone of hepatic origin, which regulates iron homeostasis. PHD inhibitors represent a novel pharmacological treatment of anemia associated with chronic diseases. Many orally active PHD inhibitors like roxadustat, molidustat, vadadustat, and desidustat are in late phase clinical trials. This review discusses the role of PHD inhibitors in the treatment of anemia associated with chronic diseases.
Joharapurkar et al. (Tue,) studied this question.