title: Influence of recombinant human erythropoietin therapy on plasma endothelin-1 levels during hemodialysis.
abstract: The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 +/- 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40 U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (deltaBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 +/- 0.36 pg/ml) when compared to healthy controls (ref. 0.3-0.9) and increased to 1.47 +/- 0.51 pg/ml by the end of the session (p<0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 +/- 0.3 vs. 1.05 +/- 0.3 pg/ml) and at the end of HD (1.62 +/- 0.5 vs. 1.28 +/- 0.3 pg/ml, p<0.05). There was no difference in BP and deltaBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.
authors.affiliation: Medical Clinic II, Technical University Hospital, Aachen, Germany. stefanid@med.uth.gr
authors.forename: I
authors.initials: I
authors.lastname: Stefanidis
authors.forename: P R
authors.initials: PR
authors.lastname: Mertens
authors.forename: P
authors.initials: P
authors.lastname: Wurth
authors.forename: R
authors.initials: R
authors.lastname: Bach
authors.forename: W
authors.initials: W
authors.lastname: Makropoulos
authors.forename: H
authors.initials: H
authors.lastname: Mann
authors.forename: B
authors.initials: B
authors.lastname: Heintz
mesh_terms: D000740:Anemia / Q000188:drug therapy / Q000209:etiology; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D018709:Statistics, Nonparametric
chemical_list: D019332:Endothelin-1; D011994:Recombinant Proteins; D004921:Erythropoietin