erytropoetin

Erytropoetin, also known as erythropoietin, is a glycoprotein hormone that regulates red blood cell production. In adults, the kidneys are the primary source of endogenous EPO, with a smaller contribution from the liver during fetal development. Specialized peritubular interstitial cells detect tissue hypoxia and increase EPO synthesis in response to low oxygen levels.

Erythropoietin works by binding to the erythropoietin receptor (EPOR) on erythroid progenitor cells in the bone marrow. This activates signaling pathways, notably JAK2-STAT5, which promote the survival, proliferation, and differentiation of these cells into mature red blood cells. The production of EPO is tightly regulated by hypoxia-inducible factors (HIF-1 and HIF-2); under hypoxic conditions, HIF stabilizes and enhances EPO gene expression.

Clinically, inadequate EPO production leads to anemia, seen in chronic kidney disease, inflammatory diseases, certain cancers undergoing chemotherapy, and other liver or renal disorders. Therapeutically, recombinant human erythropoietin and longer-acting analogs (such as epoetin alfa, epoetin beta, epoetin zeta, and darbepoetin alfa) are used to treat anemia associated with CKD, chemotherapy, and HIV therapy. Treatment aims to reduce the need for red blood cell transfusions while avoiding excessive rises in hemoglobin.

Safety and monitoring are important: ESAs can raise blood pressure and increase the risk of thromboembolic, cardiovascular, and other events in some patients. In rare cases, immune-mediated pure red cell aplasia can occur due to antibodies against erythropoietin. Therapy typically includes iron supplementation as needed and careful monitoring of hemoglobin and iron status to guide dosing. In cancer care, ESA use is guided by guidelines due to mixed effects on outcomes.