대한내과학회지 : 제 82 권제 2 호 2012 http://dx.doi.org/10.3904/kjm.2012.82.2.185 신장기능이저하된급성관상동맥증후군환자에서조영제유발신증의발생예측인자 1 전남대학교병원심장센터, 2 보건복지부지정심장질환특성화연구센터, 3 전남대학교의과대학예방의학교실 박수환 1,2 정명호 1,2 이정애 3 최진수 3 황승환 1,2 고점석 1,2 이민구 1,2 심두선 1,2 박근호 1,2 윤남식 1,2 윤현주 1,2 김계훈 1,2 홍영준 1,2 김주한 1,2 안영근 1,2 조정관 1,2 박종춘 1,2 강정채 1,2 Predictors of Contrast-Induced Nephropathy in Acute Coronary Syndrome Patients with Renal Dysfunction Soo-Hwan Park 1,2, Myung Ho Jeong 1,2, Jung Ae Rhee 3, Jin Su Choi 3, Seung Hwan Hwang 1,2, Jum Suk Ko 1,2, Min Goo Lee 1,2, Doo Sun Sim 1,2, Keun-Ho Park 1,2, Nam Sik Yoon 1,2, Hyun Ju Yoon 1,2, Kye Hun Kim 1,2, Young Joon Hong 1,2, Ju Han Kim 1,2, Youngkeun Ahn 1,2, Jeong Gwan Cho 1,2, Jong Chun Park 1,2, and Jung Chaee Kang 1,2 1 The Heart Center of Chonnam National University Hospital; 2 The Heart Research Center Designated by Korea Ministry of Health and Welfare; 3 Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea Background/Aims: Contrast-induced nephropathy (CIN) is an important complication of diagnostic coronary angiography (CAG) and percutaneous coronary intervention (PCI). We investigated the incidence and predictors of the development of CIN in acute coronary syndrome (ACS) patients with renal dysfunction undergoing PCI. Methods: From January 2005 to June 2010, we evaluated the clinical, laboratory, and angiographic data of 406 patients with ACS who had a serum creatinine 1.3 mg/dl and underwent CAG or PCI. The patients were divided into two groups according to the development of CIN (CIN, n = 92; no CIN, n = 314). Results: Of the 406 patients, 92 (22.7%) developed CIN. The development of CIN was associated with a lower baseline body mass index (p = 0.001), decreased left ventricular ejection fraction (LVEF) (p < 0.001), decreased creatinine clearance (CrCl) (p < 0.001), lower albumin (p < 0.001), lower hemoglobin (p = 0.003), higher N-terminal pro B type natriuretic peptide (p = 0.001), and greater contrast medium volume (CMV) (p = 0.021). On multiple logistic regression analysis, LVEF < 40% (OR, 4.080; 95% CI, 2.087-7.977; p < 0.001), albumin < 3.5 g/dl (OR, 2.042; 95% CI, 1.211-3.440; p = 0.007), and CMV/CrCl 3.5 (OR, 1.964; 95% CI, 1.243-3.101; p = 0.004) were independent predictors of CIN. The cut-off value for CMV/CrCl was 3.5, and Received: 2011. 9. 18 Revised: 2011. 12. 5 Accepted: 2012. 1. 9 Correspondence to Myung Ho Jeong, M.D., Ph.D., F.A.C.C., F.A.H.A., F.E.S.C., F.S.C.A.I., F.A.P.S.I.C. Professor, Director of the Heart Research Center Nominated by Korea Ministry of Health and Welfare, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Korea Tel: +82-62-220-6243, Fax: +82-62-228-7174, E-mail: myungho@chollian.net * This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs (A084869). - 185 -
- The Korean Journal of Medicine: Vol. 82, No. 2, 2012 - that for albumin was 3.55 g/dl. Conclusions: CIN occurred in 22.7% of the patients with ACS and renal dysfunction who underwent CAG or PCI. Independent predictors of CIN were decreased LVEF, decreased albumin, and increased CMV/CrCl ratio. (Korean J Med 2012;82:185-193) Keywords: Contrast-induced nephropathy; Acute coronary syndrome; Renal dysfunction 서론관상동맥질환환자가증가함에따라관상동맥질환의진단및치료가증가하고있으며검사시사용되는조영제에대한노출빈도또한증가하여조영제유발성신증 (contrast-induced nephropathy, CIN) 의발생률이증가하고있는추세이다 [1]. CIN의발생여부는대상환자의나이, 당뇨병, 심부전, 신부전증, 조영제의양, 조영제의종류, 빈혈유무, 조영제노출전의저혈압, intra-aortic balloon pump (IABP) 사용유무, 그리고짧은시간안에반복적인조영제의노출유무에따라서발생위험이증가한다 [2-6]. 대상환자및연구조건에따라서 CIN의발생빈도는다양한차이를보이게되는데, 일반적으로조영제를이용한모든검사를시행받은환자의 3% 정도에서발생하는것으로알려져있다. 특히, 신장기능이저하된환자에서는 CIN의발생빈도가높아 12-50% 에이른다 [7]. CIN은병원에서발생하는급성신부전증의 11% 정도를차지하고, 세번째의급성신부전증의흔한원인이다 [8]. 관상동맥조영술은관상동맥질환의진단및치료에필요하며, 대상이되는환자역시당뇨병과고혈압등의동반질환이많고, 다른조영술보다조영제의사용량이비교적많아 CIN의발생이증가할것으로예상된다. 본연구는관상동맥조영술혹은중재술을시행받은신장기능이저하된급성관상동맥증후군 (acute coronary syndrome, ACS) 환자를대상으로조영제에의한 CIN 발생빈도와임상양상, 그리고 CIN 발생위험인자를알아보고자하였다. 대상및방법대상 2005년 1월 1일부터 2010년 6월 31일까지전남대학교병원심장센터에서관상동맥조영술및중재술을시행한환자중내원시기준치혈청크레아티닌이 1.3 mg/dl 이상으로 신장기능이저하된 ACS (ST 분절상승심근경색증, 비 ST 분절상승심근경색증, 불안정형협심증 ) 환자 406명을대상으로환자의무기록을후향적조사를실시하여 CIN 발생유무에따라발생군 (I군, 72.1 ± 7.7, 남 : 여 = 58:34) 과발생하지않은군 (II군, 69.0 ± 9.4, 남 : 여 = 233:81) 으로분류하여두군간의특징을조사하였다. 만성신부전증 (chronic kidney disease) 환자로서투석이나복막투석을받고있는환자는제외시켰다. 방법대상환자의의무기록을검토하여관상동맥조영술및중재술을시행전에의무기록을통하여연령, 성, 키, 체중, 체질량지수 (body mass index, BMI), 고혈압, 당뇨병, 고지혈증, 흡연여부, 심혈관조영술전의고혈압유무 ( 수축기협압 140 mmhg 이거나이완기혈압 90 mmhg 또는고혈압약제를복용하고있는경우 ), 응급조영술유무, 심박출량등의임상소견과혈청크레아티닌, 헤마토크릿, 헤모글로빈, 단백질, 알부민, 혈중요소질소, 요산, high sensitive C-reactive protein (hs-crp), 혈당, A1c형혈색소, 콜레스테롤, Apolipoprotein A-1 (ApoA1), Apolipoprotein B (ApoB), lipoprotein (a) [Lp (a)], creatine kinase (CK), CK-MB Fraction (CK-MB), troponin T, troponin I, N-terminal pro B-type natriuretic peptide (NT-proBNP) 을조사하였다. 심혈관조영술에대한기록으로는심혈관조영술시중재시술의유무, 협착이있는병변, 병변이있는혈관수, 스텐트삽입여부, 스텐트종류, 스텐트개수, 조영제종류, 조영제사용량, 크레아티닌청소율, 크레아티닌청소율에대한조영제사용량비 [9] 를조사하였다. 관상동맥질환은관상동맥의내경이 75% 이상협착이있는것으로정의하였다. 관상동맥조영술및중재술후전체환자를대상으로조영제에의한신증유발여부를확인하기위해혈청크레아티닌을추적검사하였고검사실소견, 임상 - 186 -
- Soo-Hwan Park, et al. Contrast-induced nephropathy in ACS - 양상, 회복유무와사망유무등을조사하였다. 크레아티닌청소율은혈청크레아티닌수치, 연령, 체중으로부터 Cockroft- Gault 식을이용하여구하였다 [10]. 조영제는비이온성, 등장성 (non-ionic, iso-osmolar contrast media) 조영제인 iodixanol (Visipaque 320, Amersham Health, Cork, Ireland) 만을사용하였다. CIN은방사선조영제에노출된후 48-72시간이내에혈청크레아티닌값이기저치의 25% 이상증가하거나혈청크레아티닌절대값이 0.5 mg/dl 이상증가하는경우로정의하였다 [11]. 통계학적분석자료는 SPSS (ver18.0 for Windows, SPSS Inc, Chicago, IL, USA) 를이용하였고, 기술통계값은백분율 (%) 또는평균 ± 표준편차 (mean ± SD) 로표시하였다. 두군간의연속변수는 Student's t-test 를이용하여검증하였고, 범주형변수의비교는 Chi-square test 를이용하여비교분석하였다. CIN과위험인자의연관성의분석을위해 logistic regression analysis를이용한단변량분석을시행후의미있는위험인자에대해다변량분석을시행하였으며, 결과는 odds ratios (OR) 와 95% confidence interval (CI) 으로제시하였다. 통계적유의성은 p value가 0.05 미만인경우로간주하였다. 결과대상환자의임상적특성과검사실소견관상동맥조영술및중재술을시행받은신장기능이저하된 ACS 환자는 406명이었으며, 남자 291명, 여자 115명으로평균연령은 69.7 ± 9.1세였다. CIN은 92명이발생하여발생률은 22.7% 이었다. CIN이발생한군을 I군으로발생하지않은군을 II군으로분류하였으며, 평균연령은 I군 72.1 ± 7.7 세, II군 69.0 ± 9.4세로유의한차이는없었으나, 성별은남자가 I군 58명, II군 233명으로유의한차이를보였다 (p < 0.048). 체질량계수와좌심실구혈률은 I군에서유의하게낮았으며, 입원기간은 I군에서유의하게길었다 (Table 1). 기준치혈청크레아티닌은 I군과 II군사이에차이가없었으나, 최고치혈청크레아티닌은 I군에서유의하게높았으며, 기준치헤마토크릿, 최저치헤마토크릿, 기준치크레아티닌청소율, 혈중알부민은 I군에서유의하게낮았고, 혈중요소질소, 혈중 NT-proBNP 는 I군에서유의하게높았다 (Table 2). 중재적시술에따른두군간의특성으로혈관에삽입한 Table 1. Baseline clinical characteristics Characteristic CIN (n = 92) No CIN (n = 314) p value Age, yr 72.1 ± 7.7 69.0 ± 9.4 0.058 Male gender, n (%) 58 (63.0) 233 (74.2) 0.048 Body mass index, kg/m 2 22.6 ± 2.9 23.9 ± 3.3 0.001 Risk factor, n (%) Hypertension 71 (77.2) 226 (72.0) 0.322 Diabetes mellitus 48 (50.2) 156 (49.7) 0.674 Hyperlipidemia 11 (12.0) 35 (11.1) 0.829 Smoking, n (%) 31 (33.7) 137 (43.6) 0.089 Percutaneous coronary intervention, n (%) 67 (72.8) 205 (65.3) 0.176 Heart rate, bpm 80.7 ± 17.5 76.2 ± 16.4 0.028 Systolic blood pressure, mmhg 130.2 ± 23.7 128.0 ± 22.5 0.43 Diastolic blood pressure, mmhg 79.6 ± 15.7 78.8 ± 15.7 0.696 Left ventricular ejection fraction, % 49.6 ± 14.5 57.6 ± 12.6 < 0.001 Length of hospital stay, day 15.6 ± 14.4 9.5 ± 7.6 < 0.001 Values are expressed as the number (%) of patients or mean ± SD. BPM, beats per minute. - 187 -
- 대한내과학회지 : 제 82 권제 2 호통권제 618 호 2012 - Table 2. Baseline laboratory findings Variable CIN (n = 92) No CIN (n = 314) p value Baseline creatinine, mg/dl 1.5 ± 0.3 1.5 ± 0.2 0.115 Maximum creatinine, mg/dl 2.3 ± 1.0 1.5 ± 0.3 < 0.001 Baseline hematocrit, % 33.8 ± 5.1 36.6 ± 5.8 < 0.001 Minimum hematocrit, % 30.0 ± 5.39 32.3 ± 5.8 0.001 Albumin, g/dl 3.5 ± 0.5 3.8 ± 0.6 < 0.001 Blood urea nitrogen, mg/dl 26.5 ± 9.3 24.0 ± 8.2 0.017 High-sensitivity C-reactive protein, mg/dl 3.2 ± 6.3 2.0 ± 3.3 0.136 Sodium, meq/l 136.9 ± 12.0 138.1 ± 3.5 0.117 Potassium, meq/l 4.3 ± 0.6 4.2 ± 0.6 0.701 Homocysteine, µmol/l 15.7 ± 11.7 13.6 ± 6.7 0.072 Hemoglobin A1C, g/dl 6.7 ± 1.4 6.6 ± 1.4 0.495 Uric acid, g/dl 7.5 ± 2.7 6.7 ± 1.8 0.107 N-terminal pro B type natriuretic peptide, pg/ml 6674.8 ± 7809.2 3444.9 ± 5103.8 0.001 Values are expressed as the mean ± SD. Table 3. Baseline coronary angiographic findings Variable CIN (n = 92) No CIN (n = 314) p value Culprit lesion, n (%) Left main 6(6.5) 10 (3.2) 0.148 Left anterior descending artery 27 (29.3) 81 (25.8) 0.498 Left circumflex artery 12 (13.0) 38 (12.1) 0.809 Right coronary artery 29 (31.5) 93 (29.6) 0.726 Pre-thrombolysis in myocardial infarction flow, n (%) 0 17 (18.5) 69 (22.0) 0.470 1 6(6.5) 11 (3.5) 0.204 2 18 (19.6) 56 (17.8) 0.705 3 32 (34.8) 87 (27.7) 0.190 ACC/AHA lesion type, n (%) B1 7(7.6) 43 (13.7) 0.118 B2 40 (43.5) 105 (33.4) 0.077 C 26 (28.3) 74 (23.6) 0.358 Stent profile Stent diameter, mm 3.1 ± 0.4 3.1 ± 0.4 0.682 Stent length, mm 25.9 ± 6.8 24.0 ± 6.8 0.067 Number of vessels per patient 1.7 ± 0.7 1.6 ± 0.7 0.223 Number of stents per patient 2.0 ± 1.0 1.6 ± 0.8 0.004 Contrast medium type (iodixanol a ), n (%) 92 (100) 314 (100) 1.000 CMV, ml 154.9 ± 69.5 136.2 ± 67.4 0.021 CrCl, ml/min 37.5 ± 10.4 42.8 ± 13.4 < 0.001 CMV/CrCl ratio 4.4 ± 2.3 3.5 ± 2.0 < 0.001 Values are expressed as the number (%) of patients or mean ± SD. ACC/AHA, American College of Cardiology/American Heart Association; CMV, contrast medium volume; CrCl, creatinine clearance; CMV/CrCl, contrast medium volume/creatinine clearance ratio. a Iodixanol, Visipaque 320, Amersham Health, Cork, Ireland. - 188 -
- 박수환외 17 인. 급성관상동맥증후군에서조영제유발신증 - Table 4. Medications taken during the admissions period Medication CIN (n = 92) No CIN (n = 314) p value N-acetylcysteine 25 (27.2) 59 (18.8) 0.081 Aspirin 91 (98.9) 305 (97.1) 0.333 Calcium channel blockers 15 (16.3) 59 (18.8) 0.587 Beta-blockers 34 (37.0) 95 (30.3) 0.225 Angiotensin-converting enzyme inhibitors 24 (26.1) 73 (23.2) 0.574 Statins 31 (33.7) 88 (28.0) 0.293 Vasopressors 57 (62.0) 201 (64.0) 0.719 Diuretics 42 (45.7) 87 (27.7) 0.001 Alpha-lipoic acid 27 (29.3) 120 (38.2) 0.12 Abciximab 10 (10.9) 29 (9.2) 0.64 Values are expressed as the number (%) of patients. Table 5. Univariate analysis of risk factor for the development of contrast-induced nephropathy Factor OR 95% CL p value Age (yr) 1.041 1.012-1.071 0.005 Male gender 1.800 1.008-3.216 0.047 Body mass index 0.879 0.814-0.950 0.001 Left ventricular ejection fraction 0.957 0.940-0.974 < 0.001 Contrast medium 1.004 1.001-1.007 0.021 Creatinine clearance 0.964 0.943-0.984 0.001 Baseline hematocrit 0.914 0.875-0.955 < 0.001 Albumin 0.401 0.260-0.618 < 0.001 Blood urea nitrogen 1.033 1.006-1.061 0.018 OR, odds ratio; CI, confidence interval. 스텐트개수, 조영제사용량은 I군에서유의하게많았으며, 관상동맥조영술검사에서병변혈관, thrombolysis in myocardial infarction (TIMI) 혈류 [12], American College of Cardiology/American Heart Association (ACC/AHA) 의병변분류 [13] 는 I군과 II군사이에유의한차이는없었다 (Table 3). 시술전이뇨제의사용은 I군에서유의하게많았으나 N-acetylcysteine, 칼슘통로차단제, 베타차단제, 안지오텐신전환효소억제제, 스타틴, 혈관확장제의약물복용은양군간의유의한차이는보이지않았다 (Table 4). 조영제유발신증위험요인의단변량분석 CIN이발생한군과발생하지않은군사이에유의한차 이가있는위험요인에대해단변량분석을시행하였다. 단변량분석에서나이 (OR 1.041; 95% CI 1.012-1.071; p = 0.005), 성별 (OR 1.800; 95% CI 1.008-3.216; p = 0.047), 체질량지수 (OR 0.879; 95% CI 0.814-0.950; p = 0.001), 좌심실구혈률 (OR 0.957; 95% CI 0.940-0.974; p < 0.001), 조영제사용량 (OR 1.004; 95% CI 1.001-1.007; p = 0.021), 크레아티닌청소율 (OR 0.964; 95% CI 0.943-0.984; p = 0.001), 기준치헤마토크릿 (OR 0.914; 95% CI 0.875-0.955; p < 0.001), 혈중알부민 (OR 0.401; 95% CI 0.260-0.618; p < 0.001), 혈중요소질소 (OR 1.033; 95% CI 1.006-1.061; p = 0.018) 등이 CIN 발생과연관성이있었다 (Table 5). - 189 -
- The Korean Journal of Medicine: Vol. 82, No. 2, 2012 - Table 6. Multivariate analysis of risk factors for the development of contrast-induced nephropathy Factor OR 95% CI p value Left ventricular ejection fraction (< 40%) 4.080 2.087-7.977 < 0.001 Albumin (< 3.5 g/dl) 2.042 1.211-3.440 0.007 CMV/CrCl ratio (< 3.5) 1.964 1.243-3.101 0.004 OR, odds ratio; CI, confidence interval; CMV/CrCl, contrast medium volume/creatinine clearance. Figure 1. The incidence of contrast-induced nephropathy according to the creatinine clearance (CrCl, ml/min) and left ventricular ejection fraction (LVEF, %). 조영제유발성신증위험요인의다변량분석 단변량분석에서유의하게연관성이있던위험요인항목에대해다변량분석을시행하였다. 다변량분석에서좌심실구혈률 (< 40%) (OR 4.080; 95% CI 2.087-7.977; p < 0.001), 혈중알부민 (< 3.5 g/dl) (OR 2.042; 95% CI 1.211-3.440; p = 0.007), 크레아티닌청소율에대한조영제사용량비 ( 3.5) (OR 1.964; 95% CI 1.243-3.101; p = 0.004) 등은 CIN과연관성이있었다 (Table 6). 조영제유발성신증과크레아티닌청소율, 좌심실구혈률의연관성 크레아티닌청소율과좌심실구혈률의연관성 CIN의발생률을알아보기위해좌심실구혈률 55% 미만과크레아티닌청소율 60 ml/min 미만군에서 164명중 55명 (33.5%), 좌심실구혈률 55% 미만과크레아티닌청소율 60 ml/min 이상군에서 14명중 3명 (21.4%), 좌심실구혈률 55% 이상과크레아티닌청소율 60 ml/min 미만군에서 203명중 32명 (15.8%), 좌심실구혈률 55% 이상과크레아티닌청소율 Figure 2. The distribution of the ratio of the contrast medium volume to the creatinine clearance (CMV/CrCl) in patients with and without contrast-induced nephropathy. 60 ml/min 이상군에서 25명중 2명 (8.0%) 으로크레아티닌청소율과좌심실구혈률이동시에저하된군에서 CIN의발생빈도가유의하게높았다 (p < 0.001, Fig. 1). 조영제유발성신증과크레아티닌청소율에대한조영제사용량비의연관성 크레아티닌청소율에대한조영제사용량비가낮은값에서높은값으로증가함으로써조영제유발성신증유발된환자와유발되지않은환자의비율이유의하게변화됨을알수있었다 (Fig. 2). 크레아티닌청소율에대한조영제사용량비에대한 ROC 곡선분석 다변량분석에서유의한연관성이있는크레아티닌청소율에대한조영제사용량비의 ROC 곡선분석을시행하였으며, CIN을예측할수있는한계 (cut-off) 비는 3.5이었으며, 민감도 0.630, 특이도 0.411, 곡선아래영역은 0.625이었다 (Fig. 3). - 190 -
- Soo-Hwan Park, et al. Contrast-induced nephropathy in ACS - Figure 3. Receiver-operating characteristic (ROC) curve analysis for predicting contrast-induced nephropathy according to ratio of the contrast medium volume to the creatinine clearance (CMV/ rcl) (Sensitivity, 63.0%; Specificity, 41.1%; Area under the curve, 0.625; = cut-off value for the CMV/CrCl ratio, 3.5). Figure 4. Receiver-operating characteristic (ROC) curve analysis for predicting contrast-induced nephropathy according to the serum albumin level (Sensitivity, 70.6%; Specificity, 52.4%; Area under the curve, 0.654; = cut-off value of for serum albumin, 3.55 g/dl). 혈중알부민에대한 ROC 곡선분석다변량분석에서유의한연관성이있는혈중알부민에대해 ROC 곡선분석을시행하였으며, CIN을예측할수있는한계 (cut-off) 혈중알부민수치는 3.55 g/dl이었으며, 민감도 0.706, 특이도 0.524, 곡선아래영역은 0.654이었다 (Fig. 4). 고찰신장기능이저하된 ACS 환자에서관상동맥조영술혹은중재술후에 CIN의발생예측인자를알아보고자하였으며, 낮은좌심실구혈률, 감소된크레아티닌청소율, 135 ml 이상의조영제사용량과저알부민증등이 CIN의발생예측인자이었다. 조영술의발달로질병의진단과치료목적으로조영제의사용량과빈도가많아지면서 CIN도증가하고, 특히노인환자와당뇨병환자의증가로심혈관조영술이활발해지면서 CIN 발생이증가하는추세이다. 대부분의 CIN은외국의연구사례이며, 국내의연구사례도심혈관조영술후급성신부전증의빈도에대한연구결과보다는동맥조영술후조영제에의한신부전증의연구조사와전산화단층촬영후신부전증에대한연구조사가보고되었다 [14,15]. CIN은관상동맥조영술이나중재시술의합병증으로입원기간연장, 사망률증가, 장기적인신장기능손상등을유발하는것으로 알려져있다. 현재까지알려진 CIN의위험인자로는환자의나이, 당뇨병, 신부전증, 사용한조영제의양과종류, 빈혈여부, 조영제노출전의저혈압, 대동맥내풍선펌프의사용여부, 반복적인조영제의사용이다 [9,10,14,15]. CIN의발생은혈청크레아티닌수치에따라다르다고알려져있으며, 정상신장기능을가진경우에 0-10% 정도로낮지만, 혈청크레아티닌수치가 1.5-2.0 mg/dl인환자에서는약 20% 정도로증가한다 [16]. 본연구에서는혈청크레아티닌 1.3 mg/dl 이상으로신장기능이저하된 ACS 환자를대상으로한결과에서 CIN의발생률은 22.7% 이었다. CIN은위험요인에의해발생률이달라지며, 위험요인에대한다변량분석을시행한결과좌심실구혈률의저하, 혈중알부민의저하, 크레아티닌청소율에대한조영제사용량비의증가가강력한연관성이있었다. 좌심실구혈률의저하로심박출량의감소는간접적으로도허혈을유발시키고저혈압이중추신경계에영향을미치며, 신장혈류가감소하면혈액요소질소가증가하고항이뇨호르몬분비가자극된다. 요독증과저나트륨혈증을유발하여피로와무기력감이생길수있다. 신장기능저하가오래되는경우적혈구생성소 (erythropoietin) 의감소및빈혈이발생하며본연구에서도 CIN이발생한군에서좌심실구혈률이유의하게낮게확인되었다. - 191 -
- 대한내과학회지 : 제 82 권제 2 호통권제 618 호 2012 - 크레아티닌은근육에서만들어지는단백질로서혈청크레아티닌수치는식사나체액량에따라서다르지않기때문에신장기능을평가하는지표이다. 신장에서재흡수되지않기때문에빠져나가는속도즉, 청소율로신장기능을판단한다. 크레아티닌수치가높은환자에서의크레아티닌청소율은감소하고 30 ml/min에서 CIN이유의하게발생한다고보고하고있으며, 본연구에서도크레아티닌청소율을 < 30 ml/min, 30-59 ml/min, 60 ml/min으로세군으로구분할때, CIN 발생빈도는 33.8%, 21.4%, 12.8% 로서세군간에 CIN 발생률은유의한차이가있었다. 관상동맥조영술혹은중재술을시행할경우에는 CIN을예방하기위해서조영제의양을최소화하는것이중요하다. 한연구보고에따르면 5 body weight (kg)/scr 을최대허용조영제용량 (maximum contrast media, MCD) 이라정의하였을때실제투여된조영제양을 MCD로나눈값이 1보다큰경우병원내임상경과와사망이그렇지않은경우보다 4배이상높았다고보고하였다 [17]. CIN은 30 ml의적은용량에서도발생할수있으나, 여러연구에서 140 ml 이상의고용량의조영제사용기준으로삼고있으며, 본연구에서는크레아티닌청소율에대한조영제사용량비는 I군 4.4 ± 2.3과 II군 3.5 ± 2.0로서유의한차이를보였으며, receiver operating characteristic (ROC) 곡선을이용하여 CIN을예측할수있는 cut-off value는 3.5이었다. 저알부민혈증시 CIN의발생기전은알려져있지않지만, 저알부민혈증이혈관내피세포의기능장애, 신혈관수축, nitric oxide 억제, 항산화제효소작용억제와연관있다는보고가있다 [18,19]. 저알부민혈증 ( 혈중알부민 < 3.5 g/dl) 환자군에서 CIN의발생률이높았다는보고가있으며 [19,20], 본연구의다변량분석에서도 CIN의위험요인으로분석되었다. 그러나 CIN이발생한군과발생하지않은군의평균수치가 3.5 ± 0.5 g/dl와 3.8 ± 0.6 g/dl로두군에서유의한차이를보였으나, 두군의값은정상범위이기때문에임상적가치로서의의미는적을것으로생각되었으며, 추후더많은환자를대상으로연구해볼가치는있을것으로생각된다. 빈혈과 CIN의연관성에대해낮은헤마토크릿수치가위험요인으로작용한다는보고가있으며, 시술시출혈로인한순환혈액량의감소및신경색을발생기전으로보고하고있다 [20]. 단변량분석에서빈혈이 CIN의위험요인이었지만, 다변량분석에서는연관성이없었다. 본연구의제한점으로는단일기관에서시행한후향적연구이었고, 응급실에서당일입원당일퇴원한환자에대해서는관상동맥조영술후크레아티닌검사가정확하게이루어지지않아연구대상에서제외된경우가많았다. 또한퇴원후크레아티닌에대한정기적추적검사가부족하여 CIN의지속여부를확인하기못하였다. 신장기능이정상인혈청크레아티닌이 1.3 mg/dl 미만인환자를비교하여 CIN의발생률을조사하지못하였다는점등이었다. 결론적으로혈청크레아티닌이 1.3 mg/dl 이상으로신장기능이저하된 ACS 환자에서 CIN의발생률은 22.7% 이었다. 좌심실구혈률의저하, 혈중알부민이저하, 크레아티닌청소율에대한조영제사용량비가증가된환자에서 CIN의발생빈도가유의하게높음을알수있었으며, 이런환자들에서유의한관찰이필요할것으로생각되었다. 요약목적 : 관상동맥질환환자가증가함에따라관상동맥질환의진단및치료가증가하고있으며검사시사용되는조영제에대한노출빈도또한증가하여조영제유발성신증 (contrast-induced nephropathy, CIN) 의발생률이증가하고있는추세이다. 신장기능이저하된급성관상동맥증후군 (acute coronary syndrome, ACS) 환자의 CIN 발생빈도는정상인환자보다높아서 CIN 유발인자를찾아보고자하였다. 방법 : 2005년 1월 1일부터 2010년 6월 31일까지전남대학교병원심장센터에서관상동맥조영술및중재술을시행한환자중혈청크레아티닌이 1.3 mg/dl 이상으로증가된 ACS 환자 406명을대상으로 CIN이발생한군 (I군) 과발생하지않은군 (II군) 으로분류하여두군간의특징을조사하였다. 결과 : 관상동맥조영술및중재술을시행받은신장기능이저하된 ACS 환자는 406명 ( 평균연령은 69.7 ± 9.1세, 남 : 여 = 291명 :115명) 이었고, CIN은 92명이발생하여발생률은 22.7% 이었다. 체질량지수는 I군 22.6 ± 2.9 kg/m 2, II군 23.9 ± 3.3 kg/m 2 (p = 0.001), 좌심실구혈률 I군 49.6 ± 14.5%, II군 57.6 ± 12.6% (p < 0.001), 크레아티닌청소율 I군 37.5 ± 10.4 ml/min, II군 42.8 ± 13.4 ml/min (p < 0.001), 혈중알부민 I 군 3.5 ± 0.5 g/dl, II군 3.8 ± 0.6 g/dl (p < 0.001), 헤모글로빈 I군 11.4 ± 1.9 g/dl, II군 12.2 ± 2.2 g/dl (p = 0.003), 비활성단백질혈중 NT-proBNP I군 6,674.8 ± 7,809.2 pg/ml, II군 - 192 -
- 박수환외 17 인. 급성관상동맥증후군에서조영제유발신증 - 3,444.9 ± 5103.8 pg/ml (p = 0.001), 입원기간 I군 15.6 ± 14.4 일, II군 9.5 ± 7.6일 (p < 0.001) 으로서양군간에유의한차이가있었다. CIN 발생예측인자는다변량분석에서다변량분석에서좌심실구혈률 (< 40%) (OR 4.080; 95% CI 2.087-7.977; p < 0.001), 혈중알부민 (< 3.5 g/dl) (OR 2.042; 95% CI 1.211-3.440; p = 0.007), 크레아티닌청소율에대한조영제사용량비 ( 3.5) (OR 1.964; 95% CI 1.243-3.101; p = 0.004) 등은 CIN 과유의한연관성이있었다. CIN을예측할수있는한계크레아티닌청소율에대한조영제사용량비는 3.5이었으며, 민감도 0.630, 특이도 0.411, 곡선아래영역은 0.625이었다. CIN을예측할수있는한계혈중알부민수치는 3.55 g/dl이었으며, 민감도 0.706, 특이도 0.524, 곡선아래영역은 0.654 이었다. 결론 : ACS 환자에서 CIN의발생률은 22.7% 이었고, 저하된좌심실구혈률, 크레아티닌청소율에대한조영제사용량비의증가, 낮은혈중알부민수치등이 CIN의발생과연관성이있었다. 중심단어 : 조영제유발성신증 ; 급성관상동맥증후군 ; 신장기능장애 REFERENCES 1. Anderson RJ, Linas SL, Berns AS, et al. Nonoliguric acute renal failure. N Engl J Med 1997;296:1134-1138. 2. Cho JY, Jeong MH, Park SH, et al. Effect of contrastinduced nephropathy on cardiac outcomes after use of nonionic isosmolar contrast media during coronary procedure. J Cardiol 2010;56:300-306. 3. Pannu N, Wiebe N, Tonelli M; Alberta Kidney Disease Network. Prophylaxis strategies for contrast-induced nephropathy. JAMA 2006;295:2765-2779. 4. Weisberg LS, Kurnik PB, Kurnik BR. Risk of radiocontrast nephropathy in patients with and without diabetes mellitus. Kidney Int 1994;45:259-265. 5. Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium-induced nephropathy. Kidney Int 2005;68:14-22. 6. McCullough PA, Soman SS. Contrast-induced nephropathy. Crit Care Clin 2005;21:261-280. 7. Choi W, Lim HM, Won HJ, et al. Contrast-induced nephropathy in patients undergoing percutaneous coronary angiography and its clinical characteristics. Korean J Nephrol 2008;27:55-61. 8. Hou SH, Bushinsky DA, Wish JB, Cohen JJ, Harrington JT. Hospital-acquired renal insufficiency: a prospective study. Am J Med 1983;74:243-248. 9. Laskey WK, Jenkins C, Selzer F, et al. Volume-to-creatinine clearance ratio: a pharmacokinetically based risk factor for prediction of early creatinine increase after percutaneous coronary intervention. J Am Coll Cardiol 2007;50:584-590. 10. Szummer K, Lundman P, Jacobson SH, et al. Cockcroft- Gault is better than the Modification of Diet in Renal Disease study formula at predicting outcome after a myocardial infarction: data from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Am Heart J 2010;159:979-986. 11. McCullough PA. Contrast-induced acute kidney injury. J Am Coll Cardiol 2008;51:1419-1428. Erratum in: J Am Coll Cardiol 2008;51:2197. 12. Zijlstra F, de Boer MJ, Hoorntje JC, Reiffers S, Reiber JH, Suryapranata H. A comparison of immediate coronary angioplasty with intravenous streptokinase in acute myocardial infarction. N Engl J Med 1993;328:680-684. 13. Ellis SG, Vandormael MG, Cowley MJ, et al. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection: Multivessel Angioplasty Prognosis Study Group. Circulation 1990;82:1193-1202. 14. Kim YS, Song SW, Ku YM, et al. Clinical characteristics and risk factors of contrast dye nephrotoxicity in patients performing arteriography. Korean J Nephrol 2004;23: 248-255. 15. Cho YS, Chung TN, Sohn DK, Kim SH. Contrast nephrotoxicity associated with emergency CT scans. J Korean Soc Emerg Med 2003;14:157-161. 16. Davidson CJ, Hlatky M, Morris KG, et al. Cardiovascular and renal toxicity of a nonionic radiographic contrast agent after cardiac catheterization: a prospective trial. Ann Intern Med 1989;110:119-124. 17. Cigarroa RG, Lange RA, Williams RH, Hillis LD. Dosing of contrast material to prevent contrast nephropathy in patients with renal disease. Am J Med 1989;86(6 Pt 1):649-652. 18. Shaper AG, Wannamethee SG, Whincup PH. Serum albumin and risk of stroke, coronary heart disease, and mortality: the role of cigarette smoking. J Clin Epidemiol 2004;57:195-202. 19. Vuong TD, Braam B, Willekes-Koolschijn N, Boer P, Koomans HA, Joles JA. Hypoalbuminaemia enhances the renal vasoconstrictor effect of lysophosphatidylcholine. Nephrol Dial Transplant 2003;18:1485-1492. 20. Nikolsky E, Mehran R, Lasic Z, et al. Low hematocrit predicts contrast-induced nephropathy after percutaneous coronary interventions. Kindey Int 2005;67:706-713. - 193 -