Korean Journal of Nephrology 1995;14(4):473-484.

혈액투석 환자에서 Recombinant Human Erythro-poietin (rHuEpo)치료에 따른 혈증 Endothelin농도의 변화와 고혈압 발생의 상간 관계에 관한 연구

강덕희 , 최규복 ,윤견일

Abstract

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 vasocons- trictor, 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 increase of blood pressure during rHuEpo administration in 16 hernodialysis patients (M:F 9:7) with the mea- surement of hemodynamic parameters. rHuEpo was started at a dose of 50-100 unit/kg, given subcu- taneously 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 evaluated stroke volume (SV), cardiac index (CI) and total peripheral vascular resistance (TPVR) by doppler echocardiography be- fore and eight weeks after rHuEpo. Mean Hct and erythropoietin level before rHuEpo was 20.9±8.7 M 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 chang@es in plasma ET were found during rHuEpo. After eight weeks of rHuEpo, SV (58.4±7.3 vs. 49.7±6.5 mVm, p<0.01) and CI (4.22±0.66 vs. 3.17 ±0.71 L/min/m, p<0.05) decreased significantly with an increase of TPVR (1223±51 vs. 1719±34 dyn.sec/cm', 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 LHct, "erythropoietin, and ''5TPVR according to the presence of rHuEpo-induced hypertension. Baseline ET level was elevated in rHuEpo-induced hyper tension 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, ery- thropoietin 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 correc- tion of anemia with rHuEpo in hemodialysis patients.