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INTRODUCTION

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ESSENTIALS OF DIAGNOSIS

  • Anemia is a comorbidity of progressive chronic kidney disease (CKD).

  • Anemia of CKD results from the inability of the kidney to produce significant quantities of erythropoietin.

  • Decreased red blood cell survival and iron deficiency are cofactors.

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GENERAL CONSIDERATIONS

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Since the initial observations by Richard Bright in 1836 on the relationship of anemia to renal inefficiency, anemia has remained as an ever-present comorbidity of progressive chronic kidney disease (CKD). The Kidney Disease Outcomes Quality Initiatives (K/DOQI) clinical practice guidelines for CKD first published in 2002 helped focus attention on CKD and its comorbidities, specifically anemia.

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Recent data support the direct relationship of anemia to cardiovascular disease and to patient mortality in end-stage renal disease (ESRD). Anemia of CKD is generally caused by the inability of the kidneys to produce significant quantities of erythropoietin, but other factors are frequently involved including decreased red blood cell survival and iron deficiency. Despite the clinical introduction of recombinant human erythropoietin (rHuEPO) in 1989, there is still an estimated 1.5 million individuals with anemia in the United States. Additionally, anemia (hemoglobin <12 mg/dL) is present in greater than 75% of dialysis patients.

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The availability of rHuEPO revolutionized our understanding of uremia and quickly became a major tool in the armamentarium of nephrologists to improve symptoms previously thought to be due to the “uremic syndrome.” Correction of anemia in these patients resulted in an improved sense of well-being, improved energy levels, a significant improvement in sleep disturbances, improved cognitive function, and an improvement in the ability to perform tasks of daily living. More significantly, improved hemoglobin levels in CKD patients have been correlated with decreased left ventricular hypertrophy (LVH) and improved cardiovascular outcomes.

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Although debate continues on the proper “target” hemoglobin, the FDA directed use of erythropoiesis-stimulating agents (ESAs) to avoid the need for transfusion has been generally accepted.

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PATHOGENESIS

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Under normal homeostatic conditions, the kidney very precisely regulates plasma volume through the reabsorption or excretion of salt and water. Hemoglobin levels are maintained in response to the production of erythropoietin to tissue hypoxia.

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Erythropoietin is known to be a multifunctional tropic factor with effects on not only the bone marrow but on the central nervous system where studies have shown both neurotrophic and neuroprotective functions. Its primary target although is the pluripotent hematopoietic stem cells of the bone marrow. This cell line is capable of forming erythrocytes, leukocytes, and megakaryocytes. Erythropoietin is produced by specialized fibroblasts in the interstitium of the kidney in response to hypoxia (Figure 19–1).

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Figure 19–1.

Erythropoiesis is divided into two stages. Erythropoietin (EPO) is needed in the first stage (from multipotential to progenitor cells in the burst-forming unit erythroid) but not in the second precursor cell stage. The site of action of EPO and other growth factors is shown. Dashed circles indicate potential apoptosis of progenitor cells. (Adapted with permission from ...

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