유지 혈액투석 환자에서 Erythropoietin 저항성에 영향을 미치는 유전적 요인과 환경적 요인들 = Genetic and Environmental Factors that Influence on Erythropoietin Resistance in Patients on Hemodialysis

국문 초록 (Abstract)

배 경:유지 투석 환자에서 일정 수준 이상의 혈색소를 유지하기 위한 erythropoietin (EPO) 요구량은 개인차가 있으며 이는 여러 요인에 의해 결정된다. 한편, 안지오텐신 II는 EPO를 매개로 하여 적혈구의 분화를 촉진시키며 안지오텐신 II의 농도는 안지오텐신 전환효소의 유전자 다형성과 관련이 있다고 알려져 있다. 이에 저자들은 안지오텐신 전환효소의 유전자 다형성이 EPO 저항성과 상관관계가 있는지 여부와 EPO 저항성에 영향을 주는 인자들을 알아보고자 본 연구를 실시하였다.
방 법:안지오텐신 전환효소의 유전자 다형성 (II, ID, DD), EPO 요구량, EPO 저항 계수, high sensitivity CRP (hs-CRP), 페리틴, 알부민, 헤마토크리트, 부갑상선호르몬, Kt/V, nPCR, 원인 신질환, 안지오텐신 전환효소 억제제 및 안지오텐신 수용체 차단제 복용 유무, 체질량 지수, 성별, 나이, 투석기간 등의 자료를 수집하여 안지오텐신 전환효소의 유전자 다형성에 따른 각 임상 소견 및 검사실 소견을 비교하였다. EPO 저항 계수를 종속 변수로, 각 검사실 소견과 임상 소견을 독립 변수로 다중 선형 회귀 분석을 시행하였다.
결 과:본원에서 유지 혈액투석을 받는 199명 [남:여 94:105, 나이 61±13세, 투석기간 63 (3-287개월)] 중, DD군의 EPO 저항 계수는 II군과 ID군에 비해 의미있게 낮았다 (p=0.034). 그 외 나머지 인자에 관한 각 군간의 유의한 차이는 없었다. 다중 선형 회귀 분석시 non-DD형의 안지오텐신 전환효소의 유전자형 (non-DD vs. DD, p=0.027), 체질량 지수가 낮은 경우 (p<0.001), 여자인 경우 (p=0.001) 등이 EPO 저항 계수를 높이는 것으로 나타났다.

다국어 초록 (Multilingual Abstract)

Background:Erythropoietin (EPO) requirement to reach a specified target hemoglobin level varies in patients on dialysis, the reasons being multifactorial. Angiotensin II has been shown to stimulate proliferation of early erythroid progenitors via erythropoietin and the plasma level of angiotensin II has been strongly associated with angiotensin converting enzyme (ACE) gene polymorphism. EPO resistance index (ERI, weekly rhEPO dose/hematocrit/body weight) is a collective responsiveness between EPO and hematocrit. We have evaluated whether ACE gene polymorphism might exert effect on ERI and also have analysed various laboratory parameters that could affect erythropoietin requirement in HD patients.
Methods:We have compared various demographic data and laboratory parameters, including age, sex, months on dialysis, body mass index (BMI), EPO requirement, ERI, high sensitivity C-reactive protein (hsCRP), ferritin, albumin, hematocrit, iPTH, Kt/V, normalized protein catabolic rate (nPCR), cause of renal failure and whether or not patients were on ACE inhibitor or Angiotensin receptor blocker (ARB), in 199 patients on hemodialysis therapy [M:F 94:105, Age 61±13, duration of dialysis 63 (3-287 months)] according to ACE gene polymorphism (II, ID, DD). We also have assessed independent association of ERI with demographic variables and laboratory parameters using linear regression analysis.
Results:There was statistically significant difference (p=0.034) in ERI in the II/ID group compared to the DD group and it was lower in the DD group. But there was no statistically significant difference in other demographic data and laboratory parameters according to ACE gene polymorphism. In the linear regression analysis, lower BMI (p<0.001), female gender (p=0.001), and ACE gene polymorphism (non-DD vs. DD, p=0.027) were determined to be independent factors affecting high ERI.
Conclusion:ACE gene polymorphism could be determining factor of EPO requirement in patients on hemodialysis. Improving nutritional status might be helpful in reducing EPO requirement and we should consider the gender difference in determining EPO dose in patients on hemodialysis.

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