Treatment of renal anemia by erythropoietin substitution. The effects on the cardiovascular system.

Recombinant human erythropoietin (r-HuEPO) effectively corrects the anemia of end stage renal disease (ESRD). Development or aggravation of hypertension has been the most commonly reported side-effect of r-HuEPO treatment. Placebo controlled trials have shown incidence rates ranging from 16-21%. Renal failure itself obviously is a prerequisite in the pathogenesis of r-HuEPO-induced hypertension, since it was never observed in anemic patients without renal disease. Increased whole blood viscosity and/or reduced hypoxic vasodilatation due to the rise in hematocrit may play a role in the development of hypertension at high concentrations of hematocrit. However, at hematocrit levels around 30% additional hypertensinogenic effects of r-HuEPO treatment seem likely. Endothelin and prostanoids are possible mediators of this effect. Left ventricular hypertrophy (concentric and eccentric), which can be due to hypertension and anemia, is commonly observed in ESRD patients and has been shown to be a predictor of cardiac morbidity and mortality in these patients. Following correction of anemia with r-HuEPO measures of left ventricular hypertrophy decrease by about 18% within a year. Normalization, though, is generally not achieved and in patients with r-HuEPO induced hypertension the increase of blood pressure may oppose the beneficial effects of r-HuEPO treatment on cardiac hypertrophy.