The pathogenesis of hypertension occurring during correction of anemia with rhuEpo in end stage renal disease patients still remains unclear. Endothelial cells have receptors for rHuEpo and release endothelin (ET), one of the most potent
vasoconstrictor, with endothelial. damage. Although several studies revealed the possible link of rHuEpo treatment and ET release, there were discordant results about rHuEpo-induced hypertension and plasma ET concentration. The present study was
undertaken to evaluate the correlation between changes in plasma ET concentration and an incerease of blood pressure during rHuEpo administration in 16 hemodialysis patients (M:F 9:7) with the measurement of hemodynamic parameters. rHuEpo was
started at
a dose of 50-100 unit/kg, given subcutaneously two or three times a week, at the end of each dialysis session. Various parameters including hematocrit (Hct), erythropoietin and ET concentration were measured before treatment and every two weeks
interval
during the first eight weeks of rHuEpo. We also evaiuated strcke volume (SV), cardiac index (CI) and total peripheral vascular resistance (TPVR) by doppler echocardiography before and eight weeks after rHuEpo.
Mean Hct and erythropoietio level before rHuEpo was 20.9 ±8.7 % and 5.5±2.1 mU/ml respectively, and started to increase significantly 2 weeks after rHuEpo. Median value of plasma ET concentration before rHuEpo was 6.7 pg/ml. and there was no
significant correlation between ET level and systolic or diastolic blood pressure. No significant changes in plasma ET were found during rHuFpo.
After eight weeks of rHuEpo, SV (58.4±7.3 vs. 49.7±6.5 ml/㎡, p<0.01) and CI (4.22±0.66 vs. 3.17±0.71 L/min/㎡, p<0.05) decreased significantly with an increase of TPVR (1223±51 vs. 1719±34 dyn. sec/cm5, p<0.01). An elevation in blood
pressure was
found in five patients (31.3 %) In these rHuEpo-induced hypertension group, absolute value of △SV before and eight weeks after rHuEpo was significantly lower compared to the group without rHuEpo-induced hypertension (10.1±4.1 vs. 0.5±2.4,
p<0.01) in
spite of no significant differences of △Hct, △erythropoietin, and △TPVR according to the presence of rHuEpo-induced hypertension. Baseline ET level was elevated in rHuEpo-induced hypertension group (6.1±2.1 vs. 11.7±4.3 pg/ml, p<0.01), but
there
was no significant difference in△ET.
In conclusion, rHuEpo-induced hypertension was not related with the rate of hct increase, erythropoietin and endothelin concentration during rHuEpo administration. The most important factor which distinguished those patients whose blood pressure
rised
from the remainder was a failure of stoke volume to fall. Therefore volume status of patients should be carefully monitored with correction of anemia with rHuEpo in hemodialysis patients.
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