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Etiology and Pathogenesis

  • Reduced renal production of erythropoietin (EPO) and inflammation and hepcidin-induced iron restriction are the most significant factors in the development of anemia in renal insufficiency.

  • A modest reduction in red cell life span occurs in uremia, probably as a result of metabolic impairment of red cells.

  • Iron deficiency occurs from blood loss in dialysis tubing, laboratory testing, or external bleeding, sometimes as a result of uremia-induced platelet dysfunction. Furthermore, increased hepcidin blocks iron absorption in the gut and iron release from macrophage stores (in part ameliorated by therapy with EPO or other erythropoiesis-stimulating agents [ESAs]).

  • The plasma volume varies widely in renal failure, with consequent variations in the hemoglobin concentration.

Clinical and Laboratory Features

  • The anemia is normocytic and normochromic with a reduced blood concentration of reticulocytes relative to the degree of anemia. Gastrointestinal and gynecologic bleeding occurs in one third to one half of all patients with chronic renal failure.

  • Acanthocytes or schistocytes may be seen on the blood film.

  • Total and differential leukocyte count and platelet count are usually normal.

  • Platelet function is abnormal, in relationship to the degree of uremia.

  • Cellularity and blood cell maturation sequences in the marrow are normal. Despite the anemia, there is no compensatory erythroid hyperplasia.

Therapy, Course, and Prognosis

  • Replacement therapy with EPO or other ESA corrects the anemia in nearly all patients. Amelioration of the anemia improves the quality of life for uremic patients.

  • EPO and iron are usually given intravenously in dialysis patients. A target hemoglobin level of 10 to 11 g/dL is recommended.

  • Adequate iron and folate supply should be maintained to achieve an optimal response with ESA therapy. If transferrin iron saturation is less than 30% and ferritin is less than 300 ng/mL, intravenous iron therapy usually increases hemoglobin levels or decreases ESA doses required, whether or not patients are on hemodialysis.

  • Long-acting ESA preparations (eg, darbepoetin) given subcutaneously may be more convenient and, perhaps, safer for patients not undergoing dialysis because plasma ESA levels are lower but more sustained.

  • Complications of EPO therapy include hypertension, seizures, increased cardiovascular morbidity and mortality and thrombosis of shunts; hemoglobin levels of greater than 11 g/dL should be avoided. Blood pressure should be carefully monitored throughout the treatment.

  • A small number of patients do not respond to EPO or require higher doses, most often because of iron deficiency, infection, or inflammation. Common causes of EPO hyporesponsiveness are listed in Table 5–1.

  • Chronic hemodialysis may improve the platelet dysfunction.

TABLE 5–1Common Causes of Erythropoietin Hyporesponsiveness



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