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혈액투석 환자에서 Recombinant Human Erythro-poietin(rHuEpo)치료에 따른 혈증 Endothelin농도의 변화와 고혈압 발생의 상간 관계에 관한 연구
강덕희,윤견일,최규복 대한신장학회 1995 Kidney Research and Clinical Practice Vol.14 No.4
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 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 changes in plasma ET were found during rHuEpo. After eight weeks of rHuEpo, SV (58.4±7.3 vs. 49.7±6.5 ml/m², p$lt;0.01) and CI (4.22±0.66 vs. 3.17±0.71 L/min/m², p$lt;0.05) decreased significantly with an increase of TPVR (1223?51 vs. 1719?34 dyn.sec/cm', p$lt;0.01). An elevation in blood pressure was found in five patients (31.3 %). In these rHuEpo-induced hypertension group, absolute value of ASV before and eight weeks after rHuEpo was significantly lower compared to the group without rHuEpo-iypertension (10.1±4.1 vs. 0.5?2.4, p$lt;0.01) in spite of no significant differences of LHct, $quot;erythropoietin, and △TPVR according to the presence of rHuEpo-induced hypertension. Baseline ET level was elevated in rHuEpo-induced hyper tension group (6.1±2.1 vs. 11.7?4.3 pg/ml, p$lt;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.
복막 투석액 내의 cancer antigen 125(CA125)의 농도 복막 중피세포의 용적 표지자로서의 의의
강덕희,윤견일 대한신장학회 1998 Kidney Research and Clinical Practice Vol.17 No.2
The longevity of the peritoneum has been an object of interests and speculation since the inception of CAPD. Peritoneal mesothelial cells(MC) are the mast important intraperitoneal cell quantitatively and have the capability to secret different types of substances including lubricant and various cytokines. It may therefore be essential to have information on the MC mass during peritoneal dialysis. However, there were no specific tools to evaluate the exact status of peritoneal membrane. CA125 is a 22kDa glycoprotein which is a clinically useful tumor marker of non-mucinous epithelial ovarian carcinoma. Recently, other cells including pleural and peritoneal MC have been proved to express CA125. This study was undertaken to determine whether CA125 can be used as a bulk marker of MC mass in clinically stable 23 CAPD patients. We also analyzed whether the observed intraperitoneal production of CA125 can be attributed to MC using the cultured human peritoneal MC from omentum. The CA125 production by MC in vitro was estimated with cultured MC of various number(10,000-5,000,000/well) for different period of time. The median concentration of CA125 was significantly higher in 24-hour spent dialysate than in serum(5.5 vs. 17.3U/ml, P$lt;0.05). There was signifcant negative correlation between the dialysate CA125 level and the incidence of peritonitis. In-vitro experiment using cultured MC cell showed an expo- nential increase of CA125 level during confluence(6th day of culture), and persistently increased till 15 days of culture, reaching a plateau. A linear relation between the number of MC and the amount of CA125 in supernatant was also observed. In conclusion, CA125 is locally produced in the peritoneal cavity and can be an useful marker of MC mass in stable CAPD patients. Since the clinical significance of the inverse correlation between the CA125 level and peritonitis incidence is uncertain(low CA125 as a second result of repeated peritonitis or the importance of MC mass to regulate the antibacterial defense mechanism?), a prospective follow-up study is nece- ssary to confirm the relation between dialysate CA125 and the incidence of peritonitis.
강덕희(Duk Hee Kang),윤견일(Kyun Il Yoon) 대한내과학회 1996 대한내과학회지 Vol.51 No.5
N/A Objectives: The efficacy of rHuEpo in the correction of renal anemia has been well established resulting in theoretical benefits on cardiac function with the regression of left ventricular dilatation. However, hypertension and thrombogenic complications can be developed with rHuEpo therapy, which impose the deleterious effects on cardiovascular system. Moreover there has been no study into the effects of rHuEpo on uremic dyslipidemia which may also contribute to an increased cardiovascular mortality in dialysis patients. Methods: The present prospective study was undertaken to evaluate the effects of rHuEpo on lipid profiles including Lp (a) in 22 (M:F 12:10) maintenance HD patients. rHuEpo was started at a dose of 2000 unit, given subcutaneously two or three times a week, at the end of each dialysis session. Lp (a) and other lipid profiles including total cholesterol (TC), triglyceride (Tg), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) were measured before treatment, and at two week intervals during the first eight weeks of rHuEpo. Results: Hct started to increase significantly 4 weeks after rHuEpo therapy. The concentrations of TC, Tg and LDL-cholesterol did not significantly change during rHuEpo. The median value of Lp (a) before rHuEpo therapy was 20.4㎎/dl with a distribution from 1.4 to 113.6㎎/dl. Five out of 22 patients (22.7%) had Lp (a) concentrations above 30㎎/dl, which value has been shown to be a high risk for atherosclerosis. The Lp (a) concentration also showed no statistically significant changes in spite of a tendency to decrease with rHuEpo. However, it was interesting that Lp (a) levels in all of the five patients whose Lp (a) was above 30㎎/dl decreased significantly 8 weeks after rHuEpo therapy (58.8±4.5 vs. 32.5±7.9㎎/dl, p<0.05). Conclusions: rHuEpo may decrease the serum Lp (a) level, especially in the high Lp (a) subjects. Although the exact mechanism of this favorable effect on Lp (a) during rHuEpo administration is uncertain, it may contribute to a decrease in cardiovascular morbidity, independent of the effects of anemia correction itself.