Anemia of CKD is a form of normocytic normochromic, hyperproliferative anemia. The pathogenesis of anemia is impaired EPO production and functional iron deficiency. EPO is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia, in order to stimulate red blood cell production (erythropoiesis) in the bone marrow.
Widespread use of erythropoietin stimulating agents (ESA) improved overall quality of life and reduced the need for blood transfusions.

Liberal administration of ESA was associated with increased risk of cardiovascular events, CKD progression, vascular access thrombosis, and overall mortality. Additional issues include, high cost of EPO analogs and associated resistance as well as side effects.
Alternatively, PHD inhibitors can be used to treat anemia by enhancing EPO secretion via upregulation of HIF-1α.