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ETIOLOGY AND PATHOGENESIS

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  • Reduced production of erythropoietin (EPO) is the most significant factor 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. Further, increased hepcidin blocks iron absorption in the gut and iron release from macrophage stores (ameliorated by EPO therapy).

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

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CLINICAL AND LABORATORY FEATURES

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  • The anemia is normocytic and normochromic with a reduced number of reticulocytes relative to the degree of anemia (result of EPO deficiency). 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 and effectiveness of dialysis. Dialysis corrects, and EPO-therapy and or red cell transfusions ameliorate both the laboratory and clinical manifestations of abnormal platelet function.

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

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THERAPY, COURSE, AND PROGNOSIS

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  • Replacement therapy with EPO corrects the anemia in nearly all patients. Amelioration of the anemia improves the quality of life for uremic patients and leads to a decrease in bleeding time and to favorable endocrine changes.

  • EPO is usually given intravenously in dialysis patients. A target hemoglobin level of 11 to 12 g/dL is recommended.

  • Adequate iron and folate supply should be maintained to achieve an optimal response with EPO therapy.

  • Long-acting preparations (darbepoietin) given subcutaneously may be more convenient for patients not undergoing dialysis because no peaks are observed and plasma levels are lower but more sustained.

  • The National Kidney Foundation recommends subcutaneous EPO administration as the preferred route and, if needed, intravenous (rather than oral) iron supplementation to optimize response.

  • Complications of EPO therapy include hypertension, seizures, and thrombosis of shunts; hemoglobin levels of >12 g/dL should be avoided. Blood pressure should be carefully monitored throughout the treatment.

  • A small number of patients do not respond to EPO, most often because of iron deficiency but also because of aluminum toxicity or marrow fibrosis secondary to hyperparathyroidism or other causes (see Table 5–1). Common causes of EPO hyporesponsiveness are listed in Table 5–1.

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Table Graphic Jump Location
TABLE 5–1COMMON CAUSES OF ERYTHROPOIETIN HYPORESPONSIVENESS
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