Pathogenesis and treatment of anemia in chronic kidney disease.

Chronic kidney disease leads to dysfunction of renal erythropoietin-producing cells, resulting in a decrease in erythrocyte production. A decrease in oxygen delivery to vital organs due to anemia results in worse quality of life and is associated with poor prognosis of the patients. Treatment with human recombinant erythropoietin or its improved version of erythropoiesis-stimulating agent (ESA) with a longer half-life is effective. However, some patients show hyporesponsiveness to ESA. Hyporesponsiveness to ESA, which can be induced by factors such as inflammation and uremic toxins, is associated with poor prognosis. Production of erythropoietin in the kidney is regulated by a transcription factor, hypoxia-inducible factor (HIF). PHD regulates HIF activity, and recently developed PHD inhibitors need to be clinically used as drugs to ameliorate anemia in CKD by activating HIF.