EPO

One of the most common and chronic hypoproliferative anemia is the anemia of CKD. This is a hormone deficiency state, in which the diseased kidney is incapable of meeting the endogenous erythropoietin needs of the patient. As a result of erythropoietin deficiency, the moderately shortened lifespan of the circulating red cells, and the obligatory blood loss that accompanies dialysis, CKD patients can experience profound, debilitating anemia. Such patients have benefited greatly from the availability of epo, a recombinant human erythropoietin.

Epo is a 165-amino-acid glycoprotein manufactured by recombinant DNA technology and is identical in structure and biological activity to native erythropoietin. Originally approved by the Food and Drug Administration (FDA) for the treatment of anemia in CKD patients on dialysis, epo is currently indicated for treating anemia in CKD patients whether on dialysis or not, in cancer patients on chemotherapy, and in zidovudine-treated HIV-infected patients. It is also approved for reducing allogeneic blood transfusions in anemic patients undergoing elective, noncardiac, nonvascular surgery.

Epo beta and epo omega are other forms of recombinant human erythropoietin used outside of the United States. Because European researchers sometimes include data on epo beta, epo in this monograph refers to epo and epo beta.

For more than a decade, epo has been used successfully to manage the anemia of patients with CKD or cancer-related anemia. epo therapy has dramatically reduced the need for transfusions in these patient groups, has led to an improvement in QOL for those who have responded, and has decreased anemia-associated morbidity.61 epo has also been shown to be of benefit in managing anemia in patients with HIV/AIDS,22-24 inflammatory bowel disease,18 and rheumatoid arthritis.16,62 The anemia of the elderly and those undergoing surgery63,64 has also been responsive to therapy with epo. In some cases, epo is given with supplemental iron, a strategy that has been of proven value for a variety of patients, including patients with ESRD on dialysis, patients with rheumatoid arthritis, and some surgical patients.

epo

Epo, however, has a relatively short circulating half-life and, consequently, it is usually administered several times a week or at least weekly. Most recently, a novel erythropoiesis-stimulating protein (NESP) has been developed that addresses some of the inconvenience of frequent epo dosing. Engineered specifically for increased biological activity, darbepo has the same number of amino acids as epo, but they have been molecularly modified to add two additional

N-linked glycosylation sites to the molecule, bringing the total number to five, instead of the usual three. This results in a threefold increase in terminal elimination half-life (23.5 hours vs. 8.5 hours). As a result, darbepoetin alfa allows less frequent dosing than epo and is well tolerated. Darbepoetin alfa was approved by the FDA in 2001 for the treatment of patients with the anemia of CKD whether on dialysis or not.65 Study findings to date have shown the medication also to be of benefit in patients with nonmyeloid hematological malignancies or solid tumors.66,67 Darbepoetin alfa is currently undergoing FDA review for use in the treatment of anemia in cancer patients receiving chemotherapy.

Replacement therapy, whether it is iron or epo, takes time to correct the anemia. Thus, if the anemia is severe and the patient is symptomatic, transfusion therapy with packed red blood cells is an option. Although the safety of blood transfusions has been brought to an extremely high level, exposure to red cell transfusions still carries a measurable risk of allosensitization, and in some patient groups, such as those with HIV/AIDS and cancer, it can have an adverse effect on mortality.