One of the most common symptoms of advanced renal disease is anemia, caused primarily by the inability of the kidney to respond to anemic conditions with a corresponding increase in [erythropoietin] (EPO) production.[A244165] The treatment of anemia associated with chronic kidney disease (CKD) has traditionally involved the administration of exogenous erythropoiesis-stimulating agents (ESAs), such as [darbepoetin alfa], to counter the decrease in endogenous EPO production. While efficacious, the overuse of ESAs has been associated with cardiovascular complications, progression of CKD, and increases in overall mortality.[A244165] A relatively new and alternative treatment option for patients with anemia associated with CKD is the use of small molecule inhibitors of hypoxia-inducible factor prolyl-hydroxylase (HIF-PH). These agents inhibit prolyl-hydroxylase domain oxygen sensors, mimicking hypoxic conditions and activating hypoxia-inducible factors. These transcription factors serve a multitude of roles, including the stimulation of erythropoiesis.[A244165] Vadadustat is an orally administered inhibitor of HIF-PH with a safety and efficacy profile non-inferior to [darbepoetin alfa] for the treatment of anemia in patients with CKD undergoing dialysis.[A244145,A244155] It was first approved in Japan, and in April 2023, it was approved by the EMA for the treatment of symptomatic anemia associated with CKD in adults on chronic maintenance dialysis.[L39610,L46936,L46951] Vadadustat is currently awaiting a regulatory decision by the FDA.[L39605] Vadadustat did not meet the prespecified noninferiority criterion for cardiovascular safety in patients with non-dialysis-dependent CKD.[A244150]