The naturally occurring hormone erythropoietin is PRIMARILY produced by which of the following?
- □ (A) Kidneys
- □ (B) Adrenal glands
- □ (C) Bone marrow
In addition to accounting for fluid, electrolyte, and acid-base homeostasis, the kidneys also provide neurohormonal activity such as erythropoietin (EPO) synthesis and vitamin D activation. EPO is a glycoprotein produced primarily by peritubular cells in the kidneys, with a small amount (10%) also produced in perisinusoidal cells of the liver (Figure). EPO stimulates the formation of red blood cells by increasing the number of erythroid precursors and accelerating the release of reticulocytes from the bone marrow. EPO production is stimulated by hypoxia and can be suppressed by polycythemia. Under normal circumstances, the body produces just enough EPO to maintain the red cell mass and replace senescent (old) and dying red cells. In patients with chronic kidney disease, the amount of EPO synthesized can be severely decreased, leading to anemia. There is also emerging evidence that EPO has additional roles in the body, including cytoprotective effects in multiple organs. Research is ongoing in these areas.
Recombinant human EPO (rHuEPO) was approved for the treatment of anemia of chronic renal failure in the United States in 1989. Other applications include the preoperative treatment of patients with anemia to avoid homologous blood transfusions and preoperative enhancement of autologous blood donations. It has also been used with variable results in patients with AIDS who are treated with zidovudine, which causes bone marrow suppression. Patients with anemia related to cancer or chemotherapy may also be treated with rHuEPO. rHuEPO has also been used to optimize preoperative hemoglobin levels in Jehovah’s Witnesses who refuse blood transfusions. However, some preparations of rHuEPO use human albumin as a diluent, which may make it unacceptable to some Jehovah’s Witnesses. It should be noted that anemia may take several weeks to improve after treatment with rHuEPO.
Several complications have been associated with rHuEPO. The U.S. Food and Drug Administration issued a black box warning of the increased risk of myocardial infarction, stroke, heart failure, and thrombotic events with the use of rHuEPO, especially when hemoglobin levels exceed 12 g/dL.
EPO is not synthesized in the bone marrow. However, bone marrow is an important site of action for EPO to increase production of red blood cells. The adrenal glands, though in close proximity to the kidneys, do not play a role in the production of EPO.