Effect of Subcutaneous and Intraperitoneal Administration of Recombinant Human Erythropoietin on Blood Pressure and Vasoactive Hormones in Patients on Continuous Ambulatory Peritoneal Dialysis

Abstract

The effect of subcutaneous and intraperitoneal administration of recombinant human erythropoietin (rHuEPO) on blood pressure was evaluated in 20 patients with renal failure on continuous ambulatory peritoneal dialysis. The two groups of patients were commenced on a 16-week course of twice weekly rHuEPO by either the subcutaneous (10 patients) or the intraperitoneal route (10 patients). One patient in the latter group was subsequently excluded because of operation and transfusion. The hemoglobulin increased significantly from 6.9 ± 0.3 g/dl to 9.8 ± 0.6 g/dl after subcutaneous rHuEPO treatment (p < 0.01) at an average dose of 84 ± 9 U/kg body weight/week. For the intraperitoneal group, despite a higher average rHuEPO dosage (133 ± 7 U/kg body weight/week), the hemoglobin level was not significantly altered (7.0 ± 0.4 g/dl to 8.0 ± 0.4 g/dl, p < 0.05). During the 16-week period of rHuEPO therapy, an increase in antihypertensive therapy was required more frequently in patients in the intraperitoneal group but the difference between groups failed to reach statistical significance. There was no conclusive evidence that the rise in hematocrit was an independent precipitant of hypertension. Patients who were hypertensive prior to rHuEPO therapy appeared most susceptible to the pressor effects in that 8 of 11 treated hypertensive patients required more intensive antihypertensive treatment during EPO administration whereas none of the untreated patients developed hypertension during the study (Fisher’s exact test, p = 0.007). Plasma levels of the vasoactive hormones, atrial natriuretic peptide (ANP), plasma renin activity (PRA), and endothelin (ET) remained unchanged during both subcutaneous and intraperitoneal rHuEPO therapy. These observations suggest that the presence of hypertension predisposes to the pressor effect of EPO, and that the vasoactive hormones ANP, PRA, and ET are unlikely to be involved in the pathophysiology of rHuEPO-induced hypertension.

Effects of Intravenous Administration of Recombinant Human Erythropoietin in Rats Subject to Hemorrhagic Shock

“…In the literature, there are contrast ing data about the effects of EPO on the plasmatic levels of endothelin. Lai et al [17], e.g., did not find any action of EPO on endothelin; others, such as Tkayama [18], found an increase in the plasmatic levels of endothelin in subjects treated with therapeutic doses of rHuEPO (from 5.6 ±4.7 to 14.1 ±2.9 pg/ml).…”

Intraperitoneal administration of recombinant human erythropoietin in children on continuous ambulatory peritoneal dialysis

“…In humans only a very limited absorption was observed [4,12,13]. Controversial results were obtained in therapeutic studies with intraperitoneal erythropoietin [6,9,10,12].…”

Arterial Hypertension in Uraemic Patients Treated with Erythropoietin

“…From this study, it seems that endothelin 1 may participate in the pathogenesis of rhuEPO-induced elevation of the blood pressure. In other studies no significant changes in plasma endothelin 1 levels were reported in patients on rhuEPO therapy [64], Summarizing, it seems that alterations in the secretion of blood pressure related hormones may be involved both in hypertensive and antihypertensive 129 mechanisms triggered by rliuEPO therapy. Controversial results observed sometimes in this respect seem to be due predominantly to a lack of standardization of conditions under which the individual hormones were assessed.…”

“…The atrial natriuretic peptide levels showed a tendency to increase at the beginning of rhuEPO therapy [63], but decreased to basal values after long-term administration of this hormone [63]. Other authors did not find similar alterations in plasma atrial natriuretic peptide levels in rhuEPO-treated patients [58,64]. It should be mentioned that short-term administration of rhuEPO to rats was accompanied by increased renin-specific mRNA in renal tissue and increased renin substrate mRNA in kidney and aorta [65], In both aorta and kidney a significant correla tion was observed between renin substrate mRNA and blood pressure [65].…”