Erythropoeitin use (Chronic Renal Failure, Anemia)

Use of recombinant erythropoietin (rhEPO) to improve chronic anemia has increased in several different disorders. Erythropoietin is a glycoprotein synthesized predominantly in the kidney. Its production is induced by hypoxia, and its primary effect is to stimulate erythroid progenitor cell proliferation. It was the first hematopoietic growth factor to be identified experimentally.

Initially rhEPO was used in patients who had chronic renal failure and could not produce adequate amounts of this cytokine. Administration of rhEPO parenterally three times a week allows most patients on dialysis to become transfusion-independent. Dosages have varied, but many centers start dialysis-dependent patients at 50 to 100 U/kg of body weight subcutaneously or intravenously three times a week. Subcutaneous administration may be more efficacious. The role of rhEPO in patients who have renal failure that does not yet require dialysis is less well defined.

The primary side effects of rhEPO in chronic renal failure are the development of iron deficiency (related to increased iron utilization), hypertension, and seizures. The administration of iron helps to prevent iron deficiency. The hypertension probably is due to reversal of the vasodilatory effects of the anemia and occurs in only a minority of  patients. The etiology of the seizures is not clear and may not differ from that seen in patients who have chronic renal failure and are not receiving rhEPO.

rhEPO also has been used in the treatment of anemia associated with chronic disease. Although concentrations of erythropoietin in affected patients may be normal, they are not elevated appropriately for the degree of anemia. rhEPO can improve anemia in patients who have chronic inflammatory disorders such as rheumatoid arthritis. Its efficacy also has been demonstrated in children infected with human immunodeficiency virus. These patients frequently develop anemia because of the chronic illness, opportunistic infections, and erythroid suppression from antiviral therapy, particularly zidovudine. rhEPO may increase hemoglobin concentrations and improve the patient's overall well-being when endogenous erythropoietin concentrations are below 500 U/L. 

rhEPO also may play a role in the prevention of anemia among children receiving chemotherapy. Both the hemoglobin concentration and the patient's overall well-being can be improved, particularly in those receiving platinum analogues. The initial studies investigating rhEPO use were performed in adults, but data on its use in children are accumulating. One issue is cost-effectiveness; transfusions are considerably less expensive than rhEPO, but their safety remains a concern.  

rhEPO has been evaluated in the treatment of anemia of prematurity. Erythropoietin concentrations in affected infants are not appropriately elevated for the severity of anemia. rhEPO results in a more rapid reticulocyte response, but its overall benefit in this otherwise self-limited disorder remains controversial. Patients who have bone marrow failure, particularly myelodysplastic syndromes, also have benefited from rhEPO, but these disorders are uncommon in children, and pediatric experience is limited. rhEPO also plays a preoperative role in certain situations. Erythropoietin can increase the size of autologous preoperative red cell donations, and it is useful pre- and postoperatively in patients who refuse to receive blood, such as Jehovah's Witnesses.

rhEPO is important therapeutically because it is specific in stimulating erythropoiesis. Iron, folate, and copper are effective in managing specific deficiencies of these substances, but they do not enhance red blood cell production. Red blood cell transfusions are useful in patients such as the girl in the vignette, but rhEPO can limit their use.

Abshire TC. The anemia of inflammation. A common cause of childhood
anemia. Pediatr Clin North Am. 1996;43:623-637
Brugnara C, Platt OS. The neonatal erythrocyte and its disorders. In:
Nathan DG, Orkin SH, Oski FA, Ginsburg D, eds. Nathan and Oski's
Hematology of Infancy and Childhood. 5th ed. Philadelphia, Pa: WB
Saunders Co; 1998:19-52
Gordon MS, Sosman JA. Clinical application of cytokines and biologic
response modifiers. In: Hoffman R, Benz EJ Jr, Shattil SJ, Furie B,
Cohen HJ, Silberstein LE, McGlave P, eds. Hematology: Basic Principles
and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:946-947