Journal of Radiation Industry 13 (1) : 9 ~ 15 (2019) Technical Paper 조영제증강 CT 검사환자에서 egfr 을적용한부작용분석 김명성 1 권대철 2, * 1 국립암센터영상의학과, 2 신한대학교바이오생태보건대학방사선학과 Analysis of egfr Calculator in Patients Undergoing Contrast Media Enhanced CT Examination Myeong Seong Kim 1 and Dae Cheol Kweon 2, * 1 Department of Radiology, National Cancer Center, Goyang 10408, Republic of Korea 2 Department of Radiological Science, College of Bioecological Health, Shinhan University, Uijeongbu 11644, Republic of Korea Abstract - The purpose of this study was to investigate creatinine and estimated glomerular filtration rate (egfr) in patients with CT using egfr, and to provide a baseline data to prevent contrast induced nephropathy (CIN) To provide basic data. Patients who visited the hospital for CT examination were injected with contrast medium and examined for side effects. Contrast medium injection rate, injection rate, adverse reations, type of contrast agent, sex, and creatinine were entered into egfr. The study of side effects of contrast media was conducted with the consent of the patients and the adverse effects following contrast injection were investigated according to the study ethics guidelines. Twenty-four patients with adverse drug reactions were included in the CT scan. Contrast medium was injected from a minimum of 80 ml to a maximum of 120 ml, and the injection rate per second was from 1.7 ml s -1 to 4.5 ml s -1. Among the patients, creatinine was measured variously according to the patient. In regression analysis of creatinine according to egfr, R 2 showed a distribution of 0.747 and showed a linear relationship of inverse. We investigated retrospectively the creatinine and egfr of patients with CT using egfr to prevent side effects of contrast agents and provide basic data. In the case of adverse effects in the CT contrast agent, egfr showed an inverse linear relationship in regression analysis according to creatinine. Key words : Computed tomography, Creatinine, egfr, Contrast media 서 CT (computed tomography) 에서는조영제를이용하여환 자의진단에활용되고있다. 이러한조영제는주입에따른 부작용을수반한다. 수용성및비이온성조영제가신장을통 해배설하고있다. 이러한배설은신장이중요한역할을하 고있다. 론 * Corresponding author: Dae Cheol Kweon, Tel. +82-31-870-3411, Fax. +82-31-870-3419, E-mail. dckweon@shinhan.ac.kr 사구체여과율 (egfr; estimated glomerular filtration rate) 은신장의기능을나타내는척도로서신장에적정투여용량결정을위한방법으로이러한사구체여과율은신장이일정한시간에특정물질을완전히제거할수있는혈장량으로정의하고있으며, 신장의기능평가에대한중요한척도로활용되고있다 (Song et al. 2008). 임상에서는몸에서생성되어배설되는크레아티닌 (creatinine) 의혈장농도를통해사구체여과율을평가하고있다. 만성신부전은전세계적으로증가하고있는추세이고 (Lysaght et al. 2002), 미국에서만 9
10 김명성 권대철 성신부전에의한사망에대한보고는 1990년에 30,400명에서 2010년은 60,300명으로증가하고있다 (Murray et al. 2013). 최근연구에서는만성신부전이말기신부전의진행뿐만아니라심혈관질환의위험을증가시킨다는보고도있다 (Keith et al. 2004; Vanholder et al. 2005). CT검사에서조영제부작용을줄이기위해여러방법으로신장기능을사전에검사하여크레아티닌및신기능검사로환자의상태여부를확인한다. 조영제가환자의신장기능에미치는영향을평가하기위한방법으로는사구체여과율이주로적용되어사용되고있다 (Kim et al. 2012). 조영제는혈관내에투여하여인체내혈관이나연부조직기관을대조도높게보기위하여사용되는약물로서대부분의배출이신장에서이루어진다. 대부분의조영제약물은수시간에서수일내에서배출이되지만인체에남아있는동안신장 ( 조영제주입후 24시간에서 5일이내 peaking up to creatinine level) 신장에독성물질로작용하여조영제투여환자중 5~20% 는급성신장손상 (acute kidney injury) 에대한유병률을보고하였다 (McCullough 2008). 본연구의목적은 CT검사환자에서 egfr을이용하여후향적으로크레아티닌및사구체여과율을조사하여임상에서 CIN (contrast induced nephropathy) 의조영제부작용을예방하는기초자료제공하고 CT 조영제부작용의예방효과를연구하여기초데이터를제공하고자한다. 대상및방법 1. 사구체여과율사구체여과율은인체의신장이 1분동안에깨끗하게걸러주는혈액의양으로정의하며신장의기능을평가하는가장중요한수치이다. 정상적인콩팥기능을가진사람의사구체여과율은분당 90~120 ml 정도이고, 하루에 180 liter로분당 125 ml의혈장을여과하며나이, 성별, 몸무게등에따라사람마다차이를보인다 (Stevens et al. 2006). 나이가들면정도의차이는있지만일년에 0.75 ml min -1 정도로감소하는것이일반적인현상으로고혈압환자는저하속도가더빠른경우가흔하게발생한다 (Coresh et al. 2003). 신장의기능에서사구체기능, 여과기능을나타내는중요한지표로서사구체여과율은정상치는 100 ml min -1 이다. 신장에이상이있으면사구체여과율이감소한다. 임상에서는내인성크레아티닌의청소율을구함으로써사구체여과율을계산한다. 사구체여과율은신기능평가에중요한지표이며, 임상에서는혈청크레아티닌 (S.Cr) 을기초로한공식을적용하여보정하였다 (Cockcroft et al. 1976; Levey et al. 2000). egfr (ml/min/1.73 m 2 ) =186 (S.Cr in μmol l -1 0.011312) -1.154 (age) -0.203 (0.742 if female) (1) 크레아티닌청소율 (Ccr: creatinine clearance) 을계측할때에는혈청크레아티닌 (S.Cr: serum creatinine) 을이용한경우에여자에서계산된크레아티닌청소율의 85% 이다. 사구체여과율은다음과같은수정된 Modification of Diet in Renal Disease (MDRD) 공식을이용하여간접적으로 GFR 을계산하여신기능을예측한다 (Levey et al. 1999). 사구체여과율 (GFR) =186 Scr -1.154 age -0.203 (0.742 if female) (2) 2. 대상및방법 CT검사를위해내원한환자를대상으로조영제주입하여검사하고부작용에대해조사하였다. CT검사를위해국립암센터영상의학과에내원한환자중에서조영제부작용이발생한환자 24명 ( 남 8명, 여 16명 ) 을대상으로크레아티닌을입력하여 egfr를계산하였고, 나이, 체중, 키, 성별, BMI (body mass index), 조영제종류, 조영제주입속도, 조영제주입용량, 부작용의증상을조사하였다. 조영제부작용에대한분석은기록을후향적으로분석하였다. 연구는환자의동의를획득하여 CT검사에서조영제주입후에발생하는부작용을조사하였다. 검사에사용된조영제는 Bonorex 300 (iohexol, Centrial Medical Service, Seoul, Korea), Pamiray 300 (iopamidol, Dongkook Pharm., Seoul, Korea), Iomeron 300 (iomeprol, Bracco, Milan, Italy), Ultravist 300 (iopromide, Schering AG, Berlin, Germany), Genetix로총 5종류로주입하였다. CT검사를위한조영제용량은최저 80 ml에서최대 120 ml 로주입하였고, 초당주입량은 1.7 ml s -1 에서최대 4.5 ml s -1 을자동주입기를이용하여주입하였다. 조영제부작용이발생한환자는 egfr (using the short version of the Modification of Diet in Renal Disease GFR calculator) 을이용하여 30~90 ml/min/1.73 m 2 사이의신장기능을반영하여산출하였고 (Levey et al. 2006), CKD (chronic kidney disease) stage는 Table 1과같이분류하였다. Table 1. Stage of CKD (chronic kidney disease) Stage GFR (ml/min/1.73 m 2 ) 1 >90 2 60 to 89 3 30 to 59 4 15 to 29 5 <15
조영제증강 CT 검사 egfr 부작용분석 11 Table 2. Summary of adverse reaction for injection of contrast media Identifier Creatinine (mg dl -1 ) Age Weight (kg) Height (m) Gender BMI egfr Contrast media Flow rate (ml s -1 ) Volume (ml) Symptom 1 0.8 53 60 158 F 37.97 79.7 Bonorex 2 80 Urticaria 2 0.8 47 52.7 145 F 36.34 81.7 Pamiray 4.5 100 Dizziness, Chill 3 1.2 70 50.8 154.7 F 32.83 47.2 Iomeron 1.7 115 Cough, Itching, Urticaria 4 0.8 43 52 158.4 F 32.82 83.2 Iomeron 3.0 110 Flush, Hypermia, Itching, Urticaria 5 0.9 53 57 150 F 38 69.6 Iomeron 2.0 110 Urticaria 6 0.9 69 48.5 163 M 29.75 88.9 Ultravist 3.0 120 Dyspnea 7 0.8 51 58 165 F 35.15 80.4 Bonorex 1.8 110 Vomiting, Orbital edema 8 0.7 65 52.8 157.5 F 33.52 89.3 Ultravist 300 1.8 80 Dizziness, Weakness 9 1.3 72 72 164.6 M 43.74 57.7 Ultravist 300 1.8 80 Flush, Dyspnea 10 1.3 81 58 164 M 35.36 56.3 Ultravist 300 2.0 90 Dyspnea 11 0.9 42 68 158 F 43.03 73 Ultravist 2.0 110 Itching, Facial edema 12 1.2 49 51 159 F 32.07 50.7 Ultravist 2.0 110 Dizziness 13 0.6 56 45 160 F 28.12 109.9 Ultravist 2.0 80 Dizziness 14 1.2 35 45 160 F 28.12 54.3 Pamiray 1.7 80 Dyspnea 15 1.1 72 72 164.6 M 43.74 69.9 Pamiray 1.7 50 Dyspnea, Abdominal pain 16 1.1 65 59.8 156.8 M 38.13 71.4 Ultravist 1.8 90 Dizziness, Urticaria 17 0.9 54 43.3 156.9 F 27.59 69.3 Iomeron 3.5 120 Urticaria, Itching, Chill 18 0.8 73 52 151.6 F 34.30 74.7 Pamiray 3.0 120 Hypermia, Urticaria 19 0.8 55 65 153 F 42.48 79.2 Pamiray 2.0 90 Weakness 20 1 56 65 153 F 42.48 61 Ultravist 2.0 120 Urticaria, Dizziness 21 0.6 35 48.3 142.8 F 33.82 120.9 Ultravist 2.0 100 Dizziness, Dyspnea 22 1.4 44 62 164 F 37.80 43.4 Ultravist 2.5 90 Seizure 23 0.8 64 56 154 F 36.36 76.8 Ultravist 3.0 130 Weakness 24 1.1 57 67.8 172 M 39.41 73.3 Ultravist 2.0 120 Dizziness, Cold sweating 25 1.1 20 56.5 168 M 33.63 90.7 Pamiray 4.5 120 Urticaria 26 1 77 50 163 M 30.67 77 Ultravist 2.0 80 Chill 27 1.2 54 38.1 159 F 23.96 49.8 Bonorex 2.7 100 Dyspnea, Nausea 28 0.9 45 65 156 F 41.66 72 Genetix 2.0 80 Dyspnea Mean±SD 0.97±0.21 55.6±14.2 56.12±8.8 158.28±6.52 35.46±5.33 73.2±17.7 2.35±0.77 99.46±18.97
12 김명성 권대철 Fig. 1. egfr calculator. 3. 통계분석혈청크레아티닌에따른 egfr은프로그램 Microsoft Excel 2010 (MS Excel; Microsoft, Redmond, MA, USA) 을사용하여그래프를그리고추세선에따른회귀방정식을산출하였다. 로그방정식 y=a ln x+b으로추세선을표시하였다. 이러한로그추세선은방사선선량의변동률이급격하게증감한후일정한값을유지하는경우에적합한곡선이다. 결과 CT검사에서조영제주입에따른조영제부작용이발생한환자의데이터의결과는 Table 2와같이 24명으로조사되었다. CT 조영제의주입에따른부작용이발생한환자의특성에서크레아티닌은 0.97±0.21, 나이는 55.6±14.2, 체중은 56.12±8.8, 키 158.28±6.52, BMI 35.46±5.33로조사되었다. CT 조영제의부작용이발생한환자의크레아티닌은환자에따라다양하게분석되었다. CT검사대상자의조영제에대한부작용발생대상자의크레아티닌과 egfr 수치가다소낮은편이긴하지만나이, 신장, 몸무게, 성별, 조영제종 류및주입속도, 총량에따라관계가없었다. 조영제부작용이발생한환자의 egfr calculator에나이, 성별, 인종을 Estimation of Glomerular Filtration Rate (GFR) using simplified Modification of Diet in Renal Disease (MDRD) formula (Giles et al. 2007) 을적용한 egfr calculator (Fig. 1) 에입력하여 egfr 73.2±17.7 ml/min/1.73 m 2 결과가산출되었다. 결과에서 Stage of CKD (chronic kidney disease) 인 30~59 ml/min/1.73 m 2 는 7명으로조사되었다 (Table 3). CT 조영제에대한부작용이발생한환자의데이터를 egfr calculator에입력하여혈중크레아티닌에대한 egfr 의회귀분석에서회귀식은 Y = - 68.752X +140.05, 상관계수 (R 2 ) 0.7024로역의선형관계를보였다 (Fig. 2). 고찰요오드기반의임상에사용되는조영제는 CT검사의진단에중요한역할을하고있으며이러한검사에서조영제부작용이발생하여기존연구에서는역학감시와함께조영제에대한부작용에대한문서화및연구가다양하게진행되
조영제증강 CT 검사 egfr 부작용분석 13 Table 3. Result summary of serum creatinine and egfr Identifier Age Gender M=Male F=Female Serum creatinine (μmol l -1 ) Ethnicity O=Other B=Black Estimated GFR (ml/min/1.73 m 2 ) Notes Notes about CKD stages or errors 1 53 F 70.72 O 79.7 2 47 F 70.72 O 81.7 3 70 F 106.08 O 47.2 Stage 3 CKD 4 43 F 70.72 O 83.2 5 53 F 79.56 O 69.6 6 69 M 79.56 O 88.9 7 51 F 70.72 O 80.4 8 65 F 61.88 O 89.3 9 72 M 114.92 O 57.7 Stage 3 CKD 10 81 M 114.92 O 56.3 Stage 3 CKD 11 42 F 79.56 O 73 12 49 F 106.08 O 50.7 Stage 3 CKD 13 56 F 53.04 O 109.9 14 35 F 106.08 O 54.3 Stage 3 CKD 15 72 M 97.24 O 69.9 16 65 M 97.24 O 71.4 17 54 F 79.56 O 69.3 18 73 F 70.72 O 74.7 19 55 F 70.72 O 79.2 20 56 F 88.4 O 61 21 35 F 53.04 O 120.9 22 44 F 123.76 O 43.4 Stage 3 CKD 23 64 F 70.72 O 76.8 24 57 M 97.24 O 73.3 25 20 M 97.24 O 90.7 26 77 M 88.4 O 77 27 54 F 106.08 O 49.8 Stage 3 CKD 28 45 F 79.56 O 72 egfr 140 120 100 80 60 40 20 y= -68.752x+140.05 R 2 =0.7024 0 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 Creatinine (mg dl -1 ) Fig. 2. Illustrate of log regression analysis of creatinine and egfr log counts. 었다 (Vogl et al. 2006; Kopp et al. 2008). 본연구에서는 CT 검사에서 egfr calculator 를이용하여부작용이발생한환 자 24 명을대상으로크레아티닌및사구체여과등을후향 적으로조사하여 CT 검사에서조영제의부작용을예방하고 기초자료로제공하기위해연구하였다. 사구체여과율은혈청크레아티닌, 나이, 인종등을 egfr 프로그램에입력하여산출하였다. 현대에영상의학의진단 기술의발달과함께 CT 조영제의사용이증가하고있고, 임상에서진단에적용되어응용되고있다. 미국 National Kidney Foundation은 Kidney disease/dialysis outcome quality improvement (K/DOQI) 지침은신장의사구체여과율을기준으로 CKD의병기 (stage) 를분류하였다. egfr이정상 (90 ml/min/1.73 m 2 이상 ), 경도감소 (60~89 ml/min/1.73 m 2 ), 중등도감소 (30~59 ml/min/1.73 m 2 ), 중증감소 (15~29 ml/ min/1.73 m 2 ), 투석하는신부전 (<15 ml/min/1.73 m 2 ) 으로정의하고있다 (National Kidney Foundation 2002; Levey et al. 2003). 본연구에서 CT 조영제부작용발생환자의평균 egfr 73.2±17.7 ml/min/1.73 m 2 로경도감소로정상신기능이하로볼수있고 seizure 반응을보였던환자의경우 egfr은 43 ml/min/1.73 m 2 로낮은결과값을나타냈다. 또한 Stage of CKD가 3인환자가 7명으로조사되었다. 본연구대상자수로 egfr 수치와조영제부작용발생과의연관성을관계를단언할수없지만인체에서독성물질을걸러주고외부로배출시키는역할을하고있는신장의기능이미약하다면조영제로인한부작용발생의확률은당연히높을수밖에없을것이다 (National Kidney Foundation 2002; Levey et al. 2003). 크레아티닌에대한 egfr에대한회귀분석에서회귀식은
14 김명성 권대철 Y = -71.841X +145.05, 상관계수 (R 2 ) 0.7157 로역의선형 관계를보였다. 크레아티닌이높을수록신사구체여과율이 높아지는역의상관관계를나타내었다. 기존연구에서크레 아티닌과 egfr 의상관계수는 0.80 (Kim et al. 2007), 0.88 (Le Bricon et al. 2000) 과는차이를보였으나, Newman et al. (1995) 이보고한 0.81 과는유사한결과가본연구의환자의 조사에서산출되었다. 연구에대한기대효과는만성신부전에대한자료를축 적하여활용할수있고, 크레아티닌및 GFR 조사로임상에 서조영제부작용을예방하는연구기대효과가있다. 연구 의제한점으로는 CT 조영제주입에따른부작용이발생한 환자를대상으로하여정상대조군과의비교가없어추가적인연구가필요하고, 환자에대한다양한자료를추가적으로광범위하게후향적으로연구하여분석하여야필요성이제기된다. 결 CT검사에서환자에게사용되는조영제로인한부작용발생은 egfr 수치가낮을수록발생확률이높을수있다. 임상에서조영제부작용을예방하고안전한 CT 조영제사용을위하여검사전환자의 egfr 프로그램을이용을필수적으로고려하여야한다. 사 이논문은 2019년도국립암센터의지원을받아수행된연구임. 론 사 참고문헌 Cockcroft DW and Gault MH. 1976. Prediction of creatinine clearance from serum creatinine. Nephron. 16(1):31-41. Coresh J, Astor BC, Greene T, Eknoyan G and Levey AS. 2003. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am. J. Kidney Dis. 41(1): 1-12. Giles PD and Fitzmaurice DA. 2007. Formula estimation of glomerular filtration rate: have we gone wrong? BMJ. 334 (7605):1198-1200. Keith DS, Nichols GA, Gullion CM, Brown JB and Smith DH. 2004. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch. Intern. Med. 22(164):659-663. Kim EY, Lee OS and Lim SC. 2012. Evaluation of factors affecting glomerular filtration rate by contrast media in patients with coronary angiography. Korean J. Clin. Pharm. 22(2): 103-112. Kim YH, Min WK and Rhew JS. 2007. Assessment of the accuracy and precision of cystatin C-based GFR estimates and Cr-based GFR estimates in comparison with Cr51-EDTA GFR. Korean J. Lab. Med. 27(1):34-39. Kopp AF, Mortele KJ, Cho YD, Palkowitsch P, Bettmann MA and Claussen CD. 2008. Prevalence of acute reactions to iopromide: postmarketing surveillance study of 74,717 patients. Acta Radiol. 49(8):902-911. Le Bricon T, Thervet E, Froissart M, Benlakehal M, Bousquet B, Legendre C and Erlich D. 2000. Plasma cystatin C is superior to 24-h creatinine clearance and plasma creatinine for estimation of glomerular filtration rate 3 months after kidney transplantation. Clin. Chem. 46(8):1206-1207. Levey AS, Bosch JP, Lewis JB, Greene T, Rodgers N and Roth D. 1999. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann. Intern. Med. 130(6):461-470. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J and Eknoyan G. 2003. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann. Intern. Med. 139(2):137-147. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. 2006. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann. Intern. Med. 145(4):247-254. Levey AS, Greene T, Kusek I and Beck G. 2000. A simplified equation to predict glomerular filtration from serum creatinine. J. Am. Soc. Nephrol. 11(15):155A. Lysaght MJ. 2002. Maintenance dialysis population dynamics: current trends and long-term implications. J. Am. Soc. Nephrol. 13(Suppl 1):S37-40. McCullough PA. 2008. Contrast-induced acute kidney injury. J. Am. Coll. Cardiol. 51(15):1419-1428. Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, Dellavalle R, Danaei G, Ezzati M, Fahimi A, Flaxman D, Foreman, Gabriel S, Gakidou E, Kassebaum N, Khatibzadeh S, Lim S, Lipshultz SE, London S, Lopez, MacIntyre MF, Mokdad AH, Moran A, Moran AE, Mozaffarian D, Murphy T, Naghavi M, Pope C, Roberts T, Salomon J, Schwebel DC, Shahraz S, Sleet DA, Murray, Abraham J, Ali MK, Atkinson C, Bartels DH, Bhalla K, Birbeck G, Burstein R, Chen H, Criqui MH, Dahodwala, Jarlais, Ding EL, Dorsey ER, Ebel BE, Ezzati M, Fahami, Flaxman S, Flaxman AD, Gonzalez-Medina D, Grant B, Hagan H,
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