말기 신부전 환자에서 투여 경로에 따른 유전자 재조합 인 Erythropoietin(Epokine^(�))의 효과와 안정성에 대한 연구 : 제 4상 연구 A Phase 4 Single Center Study = Comparative Prospective Study of Intravenously and Subcutaneously Administered Recombinant Human Erythropoietin(Epokine^(�)) in End-Stage Renal Disease Patients

국문 초록 (Abstract)

목 적 : 국내 독자적 기술로 첫 개발된 유전자 재조합 인 에리트로포에틴(Epokineⓡ)의 투여방법에 따른 유효성과 안정성을 알아보고자 하였다.
방 법 : Epokineⓡ을 주당 100-150 U/kg, 주 2회, 12주간 피하 주사하여 목표 또는 안정된 혈색소치 유지 후 무작위로 피하 및 정맥 주사군으로 나누어 12주간 혈액투석 및 복막투석 환자13명, 28명에서 유효성, 안정성을 분석하였다.
결 과 : 양군에서 혈색소치와 헤마토크릿은 Epokineⓡ 투여 2주 후부터 증가, 혈색소치가 혈액투석 환자는 투여 전 7.3 g/dL, 투여 12주 9.5 g/dL, 24주 10.6 g/dL로, 복막투석 환자는 6.8g/dL에서 12주 10.2 g/dL, 24주 10.8 g/dL로 증가하였다. 양군에서 교정 망상적혈구수(%)는투여 1주 후부터 전 기간동안 증가하였다. 혈청 내 철분, ferritin치는 양군에서 투여 2주 후부터감소, 총 철분 결합능은 투여 2주 후부터 증가하였다. 12주째 혈액투석 환자에서 많은 Epokineⓡ용량이 필요했으나(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001) 24주 후 양군의 용량차이는 없었다(123.6±41.5 vs 99.2±49.3 U/kg/wk, p>0.05). 혈액투석 환자에서 피하 주사가Epokineⓡ 투여용량이 더 적었으나(97.4±15.4 vs 145.4±2.9 U/kg/wk, p<0.002) 복막투석 환자는 차이가 없었다(93.0±60.2 vs 105.4±9.7 U/kg/wk, p>0.05) 연구기간 중 9명(18.8%)에서혈압강하제 추가가 필요한 혈압상승, 근육통 동반 상기도 감염 유사증상 및 두통 등의 부작용이 있었다. 대부분 자연소실 혹은 대증요법으로 치유되었고 2명이 부작용으로 탈락하였다.
결 론 : 말기 신부전 환자의 빈혈 개선에 사용하는 Epokineⓡ의 효과는 복막투석 환자에서 더 좋았으며 투여 경로는 정맥주사보다 피하주사가 높음을 알 수 있었다.

다국어 초록 (Multilingual Abstract)

Background : We evaluated the clinical efficacy and safety of recombinant human erythropoietin(Epokine^(ⓡ)).
Methods : A comparative prospective study of intravenously and subcutaneously administrated Epokine^(ⓡ) conducted 13 patients performing hemodialysis and 28 patients performing continuous ambulatory peritoneal dialysis with end-stage renal disease. Epokine^(ⓡ) was given initially at a dosage of 100 unit/kg, subcutaneously, two times a week. The patients had achieved stable or more than 10 g/dL of hemoglobin level for 12 weeks and then we randomized switching intravenously or subcutaneously administrated Epokine^(ⓡ) for another 12 weeks.
Results : Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine^(ⓡ) administration. In HD patients, hemoglobin increased significantly from 7.3 to 9.5 after 12 weeks and to 10.6 after 24 weeks. In CAPD patients, hemoglobin increased significantly from 6.8 to 10.2 after 12 weeks and then 10.8 after 24 weeks(p<0.05). Corrected reticulocyte count(%) was significantly increased from baseline levels beginning from 1 week after Epokine^(ⓡ) administration and continuously increased during study period in both group. Serum ferritin and serum iron decreased significantly and total iron binding capacity increased significantly after 2 weeks. At 12 weeks, HD patients were significantly needed more dosage of Epokine^(ⓡ) than CAPD patients(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001), but at 24 weeks, the dosage was not different(123.6±41.5 vs 99.2±49.3 U/kg/wk, p> 0.05). In HD patients, intravenously administrated Epokine^(ⓡ) group was more dosage than subcutaneously group(97.4±15.4 vs 145.4±2.9 U/kg/wk, p< 0.002), but CAPD patients were not different by administration method(93.0±60.2 vs 105.4±9.7 U/kg/ wk, p>0.05). The 9 cases(18.8%) were suffered from headache and flu-like syndrome, but these side effects were not severe and disappeared from conventional therapy.
Conclusion : Epokine^(ⓡ) administration is safe and effective in treating anemia of ESRD patients and subcutaneously administration is significantly more effective than intravenously. (Korean J Nephrol 2002;21(2):190-198)