Biology Reference
In-Depth Information
increasing the circulating red cell count and hemoglobin concentration in
patients receiving this therapy.
Hematologic response to erythropoietic therapy
Within a few days of starting erythropoietic therapy, circulating reticulocyte
counts are measurably increased in the blood approximately two to three times
over baseline value, depending on the dose administered. The erythropoietic
response is dose dependent, as shown in the first clinical study done with
rHuEPO in patients with renal disease [1]. The increase in circulating reticu-
locytes is followed by a more delayed increase in hemoglobin and red blood
cell count, which is evident after approximately two to three weeks of therapy
in most patients. The large multicenter clinical trials of rHuEPO therapy con-
ducted in the United States [2] and Europe [3] suggested that 90% to 95% of
patients with anemia due to renal disease will respond to treatment with a sig-
nificant improvement in their anemia. In addition to stimulation of the bone
marrow by erythropoietic therapy, erythropoiesis is also dependent on an ade-
quate supply of vitamins and minerals, particularly iron, vitamin B
12
, and folic
acid. Thus, patients receiving erythropoietic therapy should have an adequate
supply of these nutrients, which may also be supplemented if required.
Vitamin B
12
and/or folate deficiency affects the response to rHuEPO much
less commonly than iron deficiency, but replacement of these vitamins, if
required,will certainly enhance the response to erythropoietic therapy [4]. The
role of iron deficiency in inhibiting the response to erythropoietic therapy has
been increasingly recognized over the last decade [5, 6], and this may be either
absolute (where there is a deficiency of iron stores in the body), or functional
(where there are adequate iron stores, but a failure of these stores to release
iron rapidly enough to satisfy the demands of the proliferating bone marrow).
In both types of iron deficiency, supplementation with iron is mandatory to
ensure an optimal response to erythropoietic therapy, and this may be admin-
istered orally, intramuscularly, or intravenously. Oral iron is simple and rela-
tively inexpensive, but unfortunately is ineffective in most patients with renal
disease, partly due to poor absorption from the gastrointestinal tract and part-
ly due to the amount of iron required in patients receiving erythropoietic ther-
apy. Thus, in many patients, intravenous iron supplementation is required to
optimize the response to rHuEPO [7, 8]. Now that non-dextran-containing
intravenous iron preparations are available, this has become the mainstay of
iron supplementation in many patients receiving rHuEPO therapy.
Other factors that may affect the response to rHuEPO include acute or
chronic infections, other inflammatory disease, malignancy, and inadequate
dialysis. Hyperparathyroidism may inhibit the response to rHuEPO [9], partly
due to its role in causing osteitis fibrosa cystica: parathyroidectomy may
improve the response to erythropoietic therapy in some patients. Aluminum
toxicity is now less common than it was previously due to the decreased use
