투석을 시작하는 말기 신부전증 환자에서 혈관 내피세포의 기능이상

Abstract

[한글]말기 신부전증 환자에서 동맥경화성 심혈관계 질환은 가장 중요한 사망 원인으로 알려져 있으며, 혈관 내피세포 기능이상은 동맥경화성 심혈관계 질환의 초기 병변일 뿐만 아니라 진행과도 밀접한 관련이 있는 것으로 보고되고 있다. 투석을 시행받고 있는 말기 신부전증 환자에서 혈관 내피세포 기능이상에 대한 연구는 종종 있었으나, 투석을 시작하는 말기 신부전증 환자를 대상으로 한 국내 연구는 아직까지 보고된 바가 없는 실정이다. 이에 본 연구에서는 투석을 시작하는 말기 신부전증 환자에서 비침습적 방법으로 혈관 내피세포 기능을 평가하고, 혈관 내피세포 기능이상에 영향을 미치는 인자들을 규명하고자 하였다.2005년 1월 1일부터 2005년 12월 31일까지 연세대학교 의과대학 부속 세브란스 병원에서 투석을 시작한 말기 신부전증 환자군 (ESRD군)과 정상 신기능을 가진 고혈압-대조군 (C군)을 대상으로 단면적 연구를 시행하였다. 혈관 내피세포 기능이상을 알아보기 위하여 상완 도플러 초음파 검사를 통한 비침습적 방법으로 혈류 매개성 혈관확장 (flow-mediated dilation, FMD)을 측정하였으며, FMD 측정 당시의 임상적 특징, 생화학적 지표, 사구체 여과율 (MDRD-GFR), 그리고 만성 염증의 지표인 C-반응 단백 (CRP)과 FMD 사이의 상관관계를 분석하였다.총 대상 환자는 68명이었으며, ESRD군이 35명 (평균연령 51.7±12.6세, 남:여=22:13), C군이 33명이었다 (평균연령 55.2±11.4세, 남:여=17:16). C군에 비하여 ESRD군에서 수축기 혈압과 맥압이 의의있게 높았으며 (수축기 혈압, 156.9±19.3 vs. 138.5±15.3 mmHg; 맥압, 69.9±13.6 vs. 53.5±12.3 mmHg)(p<0.001), 혈청 칼슘 및 알부민 농도는 의미있게 낮았다 (칼슘, 8.0±1.0 vs. 9.8±0.5 mg/dL; 알부민, 3.6±0.7 vs. 4.6±0.4 g/dL)(p<0.001). 혈색소도 ESRD군에서 8.0±1.5 g/dL로, C군의 13.7±1.5 g/dL에 비하여 유의하게 낮았다 (p<0.001). FMD는 ESRD군에서 C군에 비하여 의의있게 낮았다 (3.8±1.9 vs. 4.9±2.4%, p<0.05). ESRD군을 당뇨군과 비당뇨군으로 나누어 FMD를 비교한 결과, 비당뇨군에 비하여 당뇨군에서 FMD가 의미있게 낮았다 (3.1±1.9 vs. 4.4±1.9%, p<0.05). ESRD군에서 수축기 혈압 (r=-0.480, p<0.005), 평균 동맥압 (r=-0.342, p<0.05), 맥압 (r=-0.501, p<0.005), 그리고 당뇨 유병 기간 (r=-0.471, p<0.05)과 FMD 사이에 유의한 음의 상관관계가 있었다.이상의 결과로, 말기 신부전증 환자의 경우 투석 시작 당시에 이미 혈관 내피세포 기능이상이 동반되어 있으며, 이러한 기능이상은 비당뇨병 환자에 비하여 당뇨병 환자에서 심하다는 것을 알 수 있었다.

[영문]Patients with renal failure have increased cardiovascular risk due to accelerated atherosclerosis, resulting in higher cardiovascular (CV) morbidity and mortality. The underlying mechanism of this increased risk are not fully understood, but previous studies have shown that both traditional and non-traditional CV risk factors contribute to the early and rapid development of atherosclerosis.Endothelial dysfunction (ED) appears to be an important initiating event in the process of atherogenesis. ED was initially identified as impaired vasodilation to specific stimuli such as acetylcholine or bradykinin, but now a broader meaning of the term would include not only reduced vasodilation but also a proinflammatory and prothrombic state associated with dysfunction of the endothelium. Since 1990 when ED was first described in human hypertension in the forearm vasculature, it has been documented in patients with type 1 and type 2 diabetes, coronary heart disease, and congestive heart failure. In addition, ED has been reported in resistance and conduit arteries in patients receiving hemodialysis and peritoneal dialysis, transplant recipients, and even in predialysis chronic renal failure patients. So far, however, there has been no study on ED in new Korean ESRD patients. In this study, ED was assessed in patients starting dialysis treatment and the risk factors of ED were analyzed.Among the patients diagnosed as end-stage renal disease and started dialysis treatment at Severance Hospital of Yonsei University College of Medicine from January, 2005 to December, 2005, 35 patients (ESRD) underwent Doppler ultrasonography to assess endothelial function when they were clinically stable within 2 weeks after the initiation of dialysis. Flow-mediated dilation (FMD) was used as an index of ED. For the control group, 33 hypertensive patients with normal renal function were selected and FMD was also measured in them. A comparison of clinical, biochemical, and FMD was performed between the ESRD and the control groups, and correlation analysis was performed to identify the factors associated with ED.The mean age of the ESRD group was 51.7±12.6 years with sex ratio of 1.7:1. There were no significant differences in age, sex ratio, and the proportion of DM patients between the ESRD and the control groups. Compared to the control group, systolic blood pressure (156.9±19.3 vs. 138.5±15.3 mmHg, p<0.001) and pulse pressure (69.9±13.6 vs. 53.5±12.3 mmHg, p<0.001) were significantly higher in the ESRD group, whereas hemoglobin (8.0±1.5 vs. 13.7±1.5 g/dL, p<0.001), serum calcium (8.0±1.0 vs. 9.8±0.5 mg/dL, p<0.001), and serum albumin levels (3.6±0.7 vs. 4.6±0.4 g/dL, p<0.001) were significantly lower in the ESRD group. FMD, an index of ED, was significantly reduced in the ESRD group compared to the control group (3.8±1.9 vs. 4.9±2.4%, p<0.05). When the ESRD group was divided into DM and non-DM groups according to DM status, there was a significant difference in FMD between the two groups (DM, 3.1±1.9%; non-DM, 4.4±1.9%, p<0.05). In the ESRD group, FMD was inversely related to systolic blood pressure (r=-0.480, p<0.005), mean arterial pressure (r=-0.342, p<0.05), pulse pressure (r=-0.501, p<0.005), and to DM duration (r=-0.471, p<0.05).In conclusion, endothelial dysfunction was already present in new ESRD patients at the time of starting dialysis treatment and was more severe in DM compared to non-DM patients.