INTRAVENOUS ERYTHROPOIETIN (RHUEPO) ADMINISTRATION INCREASES PLASMA ENDOTHELIN AND BLOOD-PRESSURE IN HEMODIALYSIS-PATIENTS

The correction of anemia in end stage renal disease with recombinant human erythropoietin (rHuEPO) is associated with hypertension in about a third of hemodialysis patients. In the present study, we investigated the role of endothelin (ET-1) on rHuEPO associated hypertension and the effect of the rHuEPO administration route on plasma ET-1 levels. We studied 50 stable chronic hemodialysis patients who were divided into three groups: 26 patients received rHuEPO intravenously (IV) and 21 subcutaneously (SC). The control group was nine patients who were treated with nandrolone decanoate (ND). Prehemodialysis ET-1 plasma levels were correlated with mean arterial pressure (MAP), hematocrit (Hct), time on dialysis, and rHuEPO doses. The antihypertensive therapeutic index (ATI) was used to determine the changes in blood pressure medication intake. We observed that the ET-1 levels were significantly higher in the IV group (19.3 +/- 2) than the SC (5.0 +/- 0.6) or ND groups (3.6 +/- 0.4 pg/mL) (P < 0.001, IV v SC or ND). After IV rHuEPO treatment, there were increases in both MAP (pre- v post-rHuEPO, P <.001) and in ATI (pre- v post-rHuEPO, P <.001). In the SC group, the increases in MAP and ATI were not significant. Only the IV group showed a significant correlation between MAP and ET-1 levels (r = .05, P = .02). To accomplish the same Hct, the IV group received higher rHuEPO doses than those of the SC (180 15 v 87 +/- 12 U/kg/week) (P <.001). No significant correlations were found between the plasma ET-1 levels and Hct, time on dialysis and rHuEPO doses. Results suggest that higher doses of rHuEPO IV than SC are necessary for the achievement of a similar correction of anemia; only the patients treated with rHuEPO IV showed a significant correlation between ET-1 levels and MAP; and the higher ET-1 levels and the administration route may play a role in rHuEPO associated hypertension.