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.
References:
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