Chapter 443 Anemia of Chronic Disorders (ACD) and

Renal Disease
Anemia complicates a number of chronic systemic diseases associated with infection, inflammation,
or tissue breakdown. Examples include chronic pyogenic infections, such as bronchiectasis and
osteomyelitis, and chronic inflammatory processes, such as rheumatoid arthritis, systemic lupus
erythematosus, and ulcerative colitis. Despite diverse underlying causes, the erythroid abnormalities
are similar, although incompletely understood. The red blood cell (RBC) life span is mildly decreased,
but this increased hemolysis is not the major problem. More importantly, there is a relative failure of
bone marrow to respond adequately to the anemia.
This impaired erythropoietic response is believed to be related to three factors:
First, iron is trapped in the macrophages and is unavailable for hemoglobin synthesis.
Second, despite slightly increased erythropoietin (EPO) levels the morphologically appearing normal
marrow is unable to increase erythropoiesis.
Third, although EPO production is slightly increased, this elevation is inadequate for the degree of
anemia.
A unifying explanation for the abnormal findings in this type of anemia is not available. One hypothesis
is that the underlying medical conditions cause the release of interleukin-1 (IL-1) and tumor necrosis
factor (TNF), and, subsequently, these cytokines lead to the production of interferon-beta (IFN-) and
interferon-gamma (IFN-). This hypothesis is supported by the observation that IFN- and IFN- given
to experimental animals causes a disorder similar to the anemia of chronic disease. The specific
stimulant of increased TNF and IL-1 production in these patients has not been identified.
The anemia seen in chronic renal disease shares some features with the anemia of chronic disease,
such as a mild degree of hemolysis. However, the major component of this anemia is decreased EPO
production owing to damage of the renal cells producing this cytokine.
Clinical Manifestations.
Although the important symptoms and signs are those of the underlying disease, the quality of life
may be affected by the mild to moderate anemia that is present.
Laboratory Findings.
Hemoglobin concentrations are usually 69g/dL. The anemia is usually normochromic and
normocytic, although occasionally some patients may have modest hypochromia and microcytosis.
Absolute reticulocyte counts are normal or low, and leukocytosis is common. The serum iron level is
low, without the increase in total iron-binding capacity (serum transferrin) that occurs in iron
deficiency. This pattern of low serum iron and low to normal iron-binding protein (serum transferrin) is
a regular and valuable diagnostic feature. The serum ferritin level may be elevated. The bone marrow
has normal cellularity; the RBC precursors are low to adequate, marrow hemosiderin may be
increased, and granulocytic hyperplasia may be present. A frequent clinical challenge is to identify
concomitant iron deficiency in patients with an inflammatory disease. Measurement of the TfR/ferritin
ratio may be useful, because it is elevated when iron deficiency is present (see Chapter 439 ). A trial
of iron therapy also may help resolve the issue, although there may be no response when
inflammation caused by the primary disease persists.
Treatment and Prognosis.

Because these anemias are secondary to other disease processes, they do not respond to iron or
hematinics unless there is concomitant deficiency. Transfusions raise the hemoglobin concentration
temporarily, but they are rarely indicated. If the underlying systemic disease can be controlled, the
anemia will resolve. Recombinant human EPO can increase the hemoglobin level and improve activity
and the sense of well-being in patients with cancer and end-stage renal failure and in those with
anemia of chronic inflammation. Treatment with iron is usually necessary for an optimal EPO effect.