Erythropoietin therapy is one of the greatest inventions in Nephrology and it changed the way we treat anemic patients, which we were only dependent on blood transfusions in the past. Erythropoietin therapy is the easiest way to treat anemia in CKD, some of the effects of erythropoietin in CKD are followed;
HEMATOLOGICAL EFFECTS
A significant increase in the reticulocyte count of around two to three times baseline is usually seen at 1 week, and an increase in hemoglobin concentration is seen at 2–3 weeks after starting recombinant human erythropoietin therapy and approximately 90–95% of dialysis patients treated with erythropoietin respond with an improvement in their anemia. The increase in hemoglobin concentration is dose-dependent, and most clinicians aim for an increment of not more than 1 g/dL/month in order to minimize adverse effects. The target hemoglobin of 10-12 g/dL is usually achieved after 4-6 months of therapy and reduction of dosage is necessary to maintain the optimum level of hemoglobin once target hemoglobin is achieved.
After initiation of erythropoietin therapy increase in hemoglobin concentration is associated with an increase in red cell count and no significant changes are seen in the white cell or platelet counts are usually seen, although a clinically insignificant increase in the platelet count has been documented in a few patients.
Following the commencement of erythropoietin therapy, serum ferritin concentration and transferrin saturation start to drop as large quantities of iron are utilized in the manufacture of new red cells.
Blood volume studies have confirmed that there is an increase in the red cell mass, Ferrokinetic study indicate an increase in the marrow erythropoietic activity and little or no change is seen in the mean red cell lifespan after erythropoietin therapy.
FACTORS AFFECTING RESPONSE TO ERYTHROPOIETIN
There are many factors that influence the response to erythropoietin; these factors are divided into two groups for better management of anemia.
Major: Iron deficiency and Blood loss
Minor: Hyperparathyroidism (with marrow fibrosis), Aluminum toxicity, Infection/ Inflammation, Vitamin B12/Folate deficiency, Hemolysis, Marrow disorders, Hemoglobinopathies, Underdialysis, Carnitine deficiency, Poor nutrition, Obesity/Poor subcutaneous absorption, ACE inhibitors/Angiotensin II blockers and Erythropoietin antibodies.
All these factors have to be considered in a patient failing to respond to treating anemia. Patients with more severe anemia (hemoglobin <6 g/dL) at the onset of treatment generally require larger doses than necessary than those with mild anemia (hemoglobin 6–8 g/dL). Functional iron deficiency is commonly diagnosed in CKD patients on erythropoietin therapy; many individuals who are iron-replete at the start of treatment become deficient under the influence of erythropoietin and require intravenous iron supplementation in order to maintain a hemoglobin response. CKD patients on dialysis often have gastrointestinal blood loss due to gastritis and peptic ulcer and have increased bleeding tendency because of uremic condition and administration of heparin during dialysis. Response to erythropoietin even under larger dose is inhibited in the presence of acute or chronic infection, the presence of inflammatory disease or malignancy.
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