Influence of recombinant human erythropoietin therapy on plasma endothelin-1 levels during hemodialysis

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 hypertensi on is still uncertain, though evidence of the involvement of endothelial ce lls 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) w ith end stage renal disease were studied. Cuprophan dialysers (GFS 12(R), G ambro, Lund Sweden) were used for hemodialysis in all cases. rHuEPO (40U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and bl ood volume changes (Delta BV; hemoglobinometry %) were serially measured. S amples were taken before and every hour during hemodialysis. Plasma endothe lin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected f or 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) an d increased to 1.47 +/- 0.51 pg/ml by the end of the session (p<0.05). In p atients under rHuEPO-substitution plasma endothelin-1 was higher when compa red 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 Delta BV between the two groups during tr eatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a con tinuous rise in plasma endothelin-1 during a session. Comparison of two gro ups of hemodialysis patients with and without s.c. rHuEPO-replacement treat ment revealed a significantly higher plasma endothelin-1 concentration in p atients with s.c. rHuEPO treatment. However, the elevated endothelin-1 leve ls were not accompanied by arterial hypertension.