Biology Reference
In-Depth Information
of aluminum-containing phosphate binders and improved dialysate water
purification. Aluminum toxicity can cause a severe rHuEPO-resistant micro-
cytic anemia. Despite improved water technology, contamination by such sub-
stances as chloramine may cause resistance to rHuEPO due to hemolysis [10],
and should be suspected if an entire dialysis population shows hyporespon-
siveness to rHuEPO.
The presence of a hemoglobinopathy may also impair the response to ery-
thropoietic therapy, particularly in homozygous sickle cell disease, where
there is an inherent genetic defect in hemoglobin synthesis. Likewise, bone
marrow disorders unrelated to the underlying renal disease such as myelodys-
plastic syndrome or myeloma, may cause some resistance to erythropoietic
therapy. Finally, pure red cell aplasia with anti-erythropoietin antibodies caus-
es severe resistance to rHuEPO therapy; this rare but important condition will
be discussed later in this chapter and in Chapter 14.
Secondary benefits of anemia correction by erythropoietins
Cardiovascular system
Longstanding severe anemia has profound effects on the cardiovascular sys-
tem, many of which have been shown to be reversed or improved after correc-
tion of anemia by rHuEPO (Tab. 1). The increased cardiac output returns
towards normal values with correction of the anemia [11], the compensatory
hypoxic vasodilatation is reversed (producing an increase in peripheral vascu-
lar resistance), and the mean arterial blood pressure increases in 20% to 30%
of patients. Oxygen delivery to the myocardium is improved, reducing symp-
toms of angina and exercise-induced myocardial ischemia [12, 13]. Left ven-
tricular mass also decreases progressively after rHuEPO therapy, particularly
when the left ventricle is grossly hypertrophied before treatment [12, 14, 15].
This latter finding may have long-term implications for cardiovascular mortal-
ity, since left ventricular hypertrophy has been shown to be an independent
determinant of survival in patients receiving dialysis [16]. The internal dimen-
Table 1. Cardiovascular effects of recombinant human erythropoietin (rHuEPO therapy)
Increased exercise tolerance
•
Normalization of increased cardiac output
•
Increased peripheral vascular resistance
•
Increased blood pressure (20% to 30% of patients)
•
Decreased symptoms of angina
•
Reduction in myocardial ischemia
•
Reduction in left ventricular hypertrophy
•
Reduction in left ventricular internal dimensions
•
Decreased cardiac size on chest radiograph
•
