원저접수번호 :09-036 만성콩팥병이급성뇌경색후사망률에미치는영향 순천향대학교의과대학신경과학교실 Influence of Chronic Kidney Disease on Mortality After Acute Ischemic Stroke Il Mi Jang, MD, Kyung Bok Lee, MD, Hakjae Roh, MD, Moo Young Ahn, MD Department of Neurology, College of Medicine, Soonchunhyang University, Seoul, Korea Background: Chronic kidney disease (CKD) is known to be associated with atherosclerosis and silent small-vessel occlusion, but there is scant information regarding the association between CKD and acute stroke. The aim of this study was to establish whether CKD influences the outcome and mortality rate after acute ischemic stroke. Methods: From January 2005 to June 2008, patients with CKD and with normal kidney function were identified from the entire population of patients presenting with acute ischemic strokes at Soonchunhyang university hospital. We analyzed the baseline demographics, risk factors, stroke severity, functional outcome, mortality rate, and the prognostic factors affecting mortality in the two groups, and investigated the causes of death. Results: Totals of 541 patients with normal kidney function (age 67.0±12.6 years; mean±sd) and 66 patients with CKD (age 70.8±11.9 years) were recruited. Hypertension and diabetes were more prevalent in the CKD group. National Institutes of Health Stroke Survey scores at admission (8.3±8.5 vs 5.5±6.0, p=0.001) and Modified Rankin Scale (mrs) scores at discharge (2.32±1.5 vs 1.92±1.5, p=0.067) were higher in the CKD group than in that with normal kidney function. Patients with CKD had a higher case-fatality rate (median survival time 13.9±13.6 months) than those without CKD (median survival time 19.2±13.2 months) and CKD was an independent prognostic factor for mortality after acute ischemic stroke. Cox proportional hazard analysis leukocytosis (hazard ratio, HR=4.46; 95% confidence interval, CI=1.28 15.52), high cardioembolic risk (HR=7.68; 95% CI=1.59 37.08), and poor (mrs 3) functional outcome at discharge (HR=8.67, 95% CI=2.19 34.33) were significant influencing factors on mortality in the CKD group. Conclusions: Compared with the normal kidney function condition, CKD is associated with a higher mortality after acute ischemic stroke. Leukocytosis, high cardioembolic risk, and poor functional outcome may be important prognostic factors of mortality from acute ischemic stroke with CKD. J Korean Neurol Assoc 27(3):229-236, 2009 Key Words: Chronic kidney disease, Ischemic stroke, Mortality, Prognostic factors 서론 만성콩팥병 (chronic kidney disease, CKD) 은콩팥손상 (kidney damage) 에상관없이 3개월이상사구체여과율 (glomerular filtration rate, GFR) 이 60 ml/min/1.73m 2 미만인경우로정의하며, 1 최근뇌졸중분야에서소동맥질환 (small vessel disease) 과 Received March 27, 2009 Revised May 13, 2009 Accepted May 13, 2009 *Kyung Bok Lee, MD Department of Neurology, Soonchunhyang University Hospital 22 Daesakwan-gil, Yongsan-gu, Seoul, 140-743, Korea Tel: +82-2-709-9026 Fax: +82-2-709-9226 E-mail: kblee@hosp.sch.ac.kr 무증상뇌경색 (asymptomatic infarction) 의발생과연관이있다고보고되었다. 2,3 이에대한정확한기전은알려져있지않지만, 아마도뇌와콩팥혈관은공통적으로높은박동성과압력을가진혈류가낮은저항을가진소동맥에노출이되는유사한혈관구조를형성하고있어서, 콩팥기능저하환자들이뇌경색이나무증상백질병변이동반되는빈도가높을것이라는가설이유력하다. 더욱이, CKD 의콩팥기능저하는동맥경화를일으키는다른위험인자와는독립적으로동맥경직 (arterial stiffness) 과내피세포기능저하를유발시켜소동맥뿐만아니라큰동맥에도영향을미친다고알려져있어, 4 뇌졸중과 CKD 에대한관심이높아지고있다. 한편, CKD 는심근경색 (myocardial infarction, MI) 등심혈 J Korean Neurol Assoc Volume 27 No. 3, 2009 229
관질환 (cardiovascular disease) 의발생을높이는독립적인위험인자이며, 5,6 CKD 환자들은콩팥부전 (kidney failure) 에의한사망보다는심혈관질환으로사망하는경향이더높다. 7 CKD 는심혈관질환후사망을예측하는예후인자로도알려져있는데, 8-11 일반인과비교할때, 콩팥투석환자의심혈관질환에의한사망률이 10~30 배높다는보고도있다. 5 하지만, 콩팥기능의저하가허혈심장질환 (ischemic heart disease) 발생의위험인자이며사망률을높인다는사실에비하여, 콩팥기능과허혈뇌졸중 (ischemic stroke) 과의연관성에대해서는아직논란의여지가많다. 일반인구중콩팥기능의저하가있었던군에서허혈뇌졸중의발생이높았다는보고가있었으나, 12 다른연구에서는콩팥기능의저하가허혈뇌졸중을제외한출혈뇌졸중의발생만을증가시킨다고보고하였다. 13 급성뇌졸중후사망과관련있다고알려진예후인자중혈액검사로알수있는것들에는백혈구수치, 입원시혈당, C반응단백 (C-reactive protein, CRP), 섬유소원 (fibrinogen) 등이있다. 14-16 콩팥기능이뇌졸중이후사망에미치는영향에대한대규모연구가아직까지많지는않지만, 한연구에서급성뇌졸중으로입원했을당시의혈청크레아티닌 (creatinine) 이높았던환자들은 18개월후사망률이높은것으로보고되었다. 17 그러나, 뇌영상검사시행비율이매우낮아뇌졸중의진단이정확하지않았고, 입원당시 1회측정한크레아티닌수치를사용하였으므로지속적인콩팥기능이저하되어있는환자군이라고볼수는없었다. 다른연구에서는급성뇌졸중발생당시사구체여과율이낮았던환자군에서 7년후사망률이높았다고하였으나, 18 투석을받았던환자들을모두제외하였고, 출혈뇌졸중까지도포함하여 CKD 와뇌경색의관계를단정짓기는어려웠다. 최근급성뇌졸중환자를평균 10년간추적관찰한결과, 내원당시사구체여과율이낮았던환자군에서사망률과심근경색등새로운심혈관계질환의발생률이높았다는연구가있었으나, 19 이전다른연구들처럼사망원인에대한언급이없었으며, 그기전에대한뚜렷한가설을제시하지는못했다. 아직까지국내에콩팥기능의저하와뇌졸중, 특히뇌졸중후사망의연관성에대한연구는전무하다. 이에본연구는급성허혈뇌졸중이발생한환자들중에서만성콩팥병을가진환자들의임상적특징과뇌졸중후사망률, 그리고사망원인및사망에영향을미치는인자가무엇인지를알아보고자하였다. 대상과방법 본연구는전향적관찰연구 (prospective observational study) 로한국뇌졸중환자등록 (Korean Stroke Registry, KSR) 20 의 자료를토대로 2005 년 1월부터 2008 년 6월까지순천향대학교병원에서급성허혈뇌졸중으로입원치료받은환자를대상으로하였고, 입원당시측정한사구체여과율 (estimated glomerular filtration rate, egfr) 이 60 ml/min/1.73m 2 미만인환자중에서사구체여과율검사가 1회이거나 2회이상이더라도 3개월이상의간격을가진수치가없는환자는제외하였다. 본연구는순천향대학교의과대학임상시험심사위원회 (Institutional Review Board) 로부터뇌졸중환자의자료분석및예후관찰에대한승인을받았으며, 제시된기준을준수하였다. 만성콩팥병의진단은 2002 년 NKF (National Kidney Foundation) 의임상적기준에따라콩팥손상 (kidney damage) 이있거나또는없더라도 3개월이상 GFR 이 60 ml/min/1.73 m 2 미만인경우이며, egfr 값이 30 이상 60 미만으로감소된경우 3기 (stage), 15 이상 30 미만으로감소된경우 4기, 15 미만인경우는콩팥부전 (kidney failure, 5기 ) 으로분류한다. 1 만성콩팥병의정의에서그기준을 60으로정의하는이유는이수치가젊은성인의정상범위에서반이상이감소된수치이기때문이다. 5 본연구에서 GFR 의측정은환자들의혈중크레아티닌과나이, 성별을이용한 abbreviated Modification of Diet in Renal Disease (MDRD) 공식을사용하였다. 21 Abbreviated MDRD Study equation GFR (ml/min/1.73 m 2 )=186 (serum creatinine) -1.154 Age -0.203 (0.742 if female) (1.21 if black) 내원당시에 egfr 이 60 미만이었던환자중반복측정하여 3개월이내에 60 이상으로회복된환자들은정상콩팥기능환자군 (normal kidney function group) 으로재분류하였고, 3개월이상 egfr 이 60 미만인환자들만을만성콩팥병환자군 (CKD group) 에포함하였다. 급성뇌경색의진단은 7일이내의급성허혈뇌졸중증상을가진환자중 MRI 에서증상과연관된뇌경색병변이발견되었을때로정의하였고, 뇌경색의아형은 TOAST 분류 22 를따랐으며, 일과성허혈발작 (transient ischemic attack, TIA) 환자는제외하였다. 모든환자에게 MRI 를하였고, 확산강조영상 (diffusion weighted imaging, DWI) 의시행률은 99% 였다. 정상환자군과 CKD 환자군에서기본정보와함께고혈압, 당뇨병, 흡연등혈관위험인자들의유무를비교하였다. 고혈압은이전병력이있거나, 심전도상좌심실의비대소견, 또는안정시반복혈압측정에서수축기혈압이 140 mmhg 이상이며, 확장기혈압이 90 mmhg 이상인경우로정의하였다. 23 당뇨병은기왕력이있거나, 공복시측정한혈당이 140 mg/dl 이상이거나, 75 g의혈당을경구투여하여 2시간이내에측정한혈당이 200 mg/dl 이상인경우로정의하였다. 24 흡연은현재흡연상태이 230 대한신경과학회지제 27 권제 3 호, 2009
만성콩팥병이급성뇌경색후사망률에미치는영향 거나, 발병전 2년이내에금연한경우로정의하였고, 고심장색전위험 (high cardioembolic risk) 에포함되는심장질환은 sss- TOAST 25 를따랐다. 내원당시백혈구, 공복혈당, 헤모글로빈, 총콜레스테롤, HDL 콜레스테롤등을측정하였다. 신경학적결손상태를평가하기위해서미국국립보건연구소뇌졸중점수 (National Institutes of Health Stroke Scale, NIHSS) 를입원및퇴원시측정하여비교하였는데, NIHSS 1~4 점을경도 (mild), 5~16 점을중등도 (moderate), 17점이상을중증 (severe) 신경학적결손 (neurological deficit) 으로정의하였다. 기능적회복상태를평가하기위해서 modified Rankin Scale (mrs) 를퇴원시에측정하였고, mrs 0~2 점을양호한회복, 3~5 점을불량한회복으로분류하였다. 예후분석에서양군의입원중사망 (in-hospital mortality), 뇌졸중발생후 3개월과 1년이되는시점에서 mrs 와사망유무를조사하였는데, 외래에내원하지않았던환자는연구시작시미리정해진기능적수준의평가항목으로전화설문을통해조사하였다. 사망률에영향을미치는예후인자를알아보기위하여우선단변량분석을하였고, 이후단변량분석에서유의한변수와임상적으로사망에중요할것으로사료되는변수를추가하여사망예측모델을추정하였다. 입원중사망한모든환자에서사망원인을조사하였는데, 뇌경색직접사망 (direct cause) 은뇌경색으로인한뇌탈출 (herniation) 이나치명적뇌출혈 (fatal cerebral hemorrhage) 등에의한경우로하였고, 뇌혈관질환이외의심혈관질환, 예를들어급성심근경색이나심부전, 대동맥류파열, 폐색전증등에의한사망은혈관성사망 (vascular death) 으로, 폐렴이나급성콩팥부전, 위장관출혈등에의한사망은뇌경색합병증 (complications) 으로분류하였다. 통계분석은 SPSS 15.0을이용하여범주형변수는 Chisquare 검정을이용하였고, 연속변수는 student t-검정으로분석하였다. 환자군의생존에대한분석은 Kaplan-Meier 법후 Cox proportional hazard analysis 를하였다. 모든분석에서 p-value 가 0.05 미만인경우에통계적으로유의한것으로판정하였다. 결과 본연구의환자등록기간에내원한 659 명중일과성허혈발작으로진단된 43명을제외한급성뇌경색환자는 616 명이었다. 정상환자군은입원시 GFR 이정상인환자 487명과, 입원시 GFR 이 60 ml/min/1.73m 2 미만이었으나 3개월이내에정상화된환자 54명을합하여총 541 명 (89.1%) 이었고, CKD 환자군은입원시측정된 GFR 이 60 ml/min/1.73m 2 미만이었던환자중단 1회만측정하였거나, 3개월이상의간격을두고측정된수치가없는 9명은제외하여 66명 (10.9%) 명이었다 (Fig. 1). CKD 환자군의평균연령은정상환자군보다많았고 (70.8± 11.9세 VS 67.0±12.6세 ), 고혈압 (84.8% VS 65.2%, p=.001), 당뇨병 (57.6% VS 34.9%, p=.000) 과정맥내혈전용해술 (intravenous thrombolysis; 15.2% VS 7.2%, p=.036) 시행률이높았다. CKD환자군에서내원시공복혈당 (fasting serum glucose; 169.5±82.2 mg/dl VS 138.8±65.9 mg/dl, p= Figure 1. Patients selection. GFR; glomerular filtration rate, egfr; estimated GFR, TIA; transient ischemic attack Figure 2. Kaplan-Meier analysis on mortality of any cause in normal kidney function group and chronic kidney disease group. J Korean Neurol Assoc Volume 27 No. 3, 2009 231
.001) 이높았으나, HbA1c 의차이는없었고, 내원시백혈구수치 (8495.9±3205.8 VS 9862.1±4641.9, p=.002) 가높았으며, HDL 콜레스테롤 (39.3±10.1 VS 44.3±11.2, p=.001) 은유의하게낮았다. 양군에서성별, 심방세동을포함하는고심장색전위험 (high cardioembolic risk), 흡연율, 평균혈압과총콜레스테롤의차이는없었다. 내원시 NIHSS 는 CKD 환자군에서통계적으로유의하게높았다 (8.3±8.5 VS 5.5±6.0, p=.001) (Table 1). 본연구에서전체환자의평균추적기간 (median survival time) 은 18.6±13.3 개월 ( 정상환자군 19.2±13.2 개월 VS CKD 환자군 13.9±13.6 개월 ) 이었고, 입원기간중사망은총 37명이었는데 CKD 환자군이 14명 (21.2%), 정상환자군이 23명 (4.3%) 으로 CKD 환자군에서약 5배높았다. 급성뇌경색이후 3개월째사망 (33.3% VS 7.7%) 과 1년째사망률 (43.9% VS 14.4%) 도 CKD 환자군에서높았고통계적으로유의한차이가있었다 (Fig. 2). 하지만, 퇴원시점, 3개월, 1년의 mrs 는 CKD 환자군에서높은경향을보였으나통계학적으로유의하지는않았다 (Table 2). Table 1. Baseline demographics and risk factors between normal kidney function group and chronic kidney disease (CKD) group Normal group CKD group p value Patients (607 persons) 541 (89.1%) 66 (10.9%) Age (years) 67.0±12.6 70.8±11.9.021* Male 303 (56.2%) 32 (48.5%).246 Hypertension 353 (65.2%) 56 (84.8%).001* Diabetes mellitus 189 (34.9%) 38 (57.6%).000* High cardioembolic risk 140 (25.9%) 24 (36.4%).070 Smoking 162 (29.9%) 14 (21.2%).140 Intravenous thrombolysis 41 (7.2%) 10 (15.2%).036* Fasting serum glucose 138.8±65.9 169.5±82.2.001* HbA1c 6.82±1.80 7.20±1.75.118 Total cholesterol 178.9±43.0 175.6±51.9.571 HDL cholesterol 44.3±11.2 39.3±10.1.001* WBC count 8495.9±3205.8 9862.1±4641.9.002* Systolic blood pressure 148.3±26.0 146.3±28.2.573 Diastolic blood pressure 88.9±13.4 87.9±15.6.593 NIHSS at admission 5.5±6.0 8.3±8.5.001* HbA1c; Hemoglobin A1c, HDL cholesterol; High density lipoprotein cholesterol, NIHSS; National Institutes of Health Stroke Scale, WBC; white blood cells, *p<0.05 Table 2. Comparison of stroke functional outcomes and mortalities between normal kidney function group and CKD group Normal group CKD group p value mrs at discharge 1.92±1.5 2.32±1.5.067 3-month mrs 1.78±1.5 2.14±1.5.118 1-year mrs 1.56±1.5 1.72±1.5.575 In hospital mortality (persons) 23 (4.3%) 14 (21.2%).000* 3-month mortality 39 (7.7%) 21 (33.3%).000* 1-year mortality 61 (14.4%) 25 (43.9%).000* CKD; chronic kidney disease, mrs; modified Rankin Scale, *p<0.05 Table 3. Multivariate Cox proportional hazard analysis of prognostic factors on mortality in all patients Mortality HR 95% CI p value Age 65 years 2.34 1.42-3.85.001* CKD 2.89 1.89-4.41.000* High cardioembolic risk 1.44.96-2.15.081 Intravenous thrombolysis 1.17.64-2.12.617 Leukocytosis 2.13 1.39-3.29.001* Hyperglycemia 1.09.73-1.63.665 Mild neurologic deficit.000* Moderate neurologic deficit 2.04 1.29-3.24.003* Severe neurologic deficit 4.28 2.32-7.90.000* CI; confidence interval, CKD; chronic kidney disease, HR; Hazard ratio, *p<0.05 232 대한신경과학회지제 27 권제 3 호, 2009
만성콩팥병이급성뇌경색후사망률에미치는영향 Table 4. The significant prognostic factors on mortality in normal kidney function group and CKD group Mortality HR 95% CI p value Normal group Age 65 years 5.27 2.20-12.67.000* Leukocytosis 1.88 1.00-3.55.060 Mild neurologic deficit.00 Moderate neurologic deficit 2.19.69-2.82.004* Severe neurologic deficit 5.89.92-6.75.000* CKD group Age 65 years.15.04-.630.009* High cardioembolic risk 7.68 1.59-37.08.011* Leukocytosis 4.46 1.28-15.52.019* Poor outcome (mrs 3) 8.67 2.19-34.33.002* CI; confidence interval, CKD; chronic kidney disease, HR; Hazard ratio, *p<0.05 Table 5. Comparison of the causes of in-hospital death between normal kidney function group and CKD group Total deaths (n=37) Normal group (23) CKD group (14) Stroke direct causes (19) 12 (52.2%) 7 (50%) Vascular deaths (7) 4 (17.4%) 3 (21.4%) Complications (9) 6 (26.1%) 4 (28.6%) Others (1) 1 (4.3%) 0 (0%) CKD; chronic kidney disease 뇌경색후사망률은정상환자군보다 CKD 환자군에서약 2.9 배높았으며, 이후 CKD 가뇌졸중후사망에미치는독립적인인자인지를확인하기위하여전체뇌경색환자를대상으로 Coxproportional hazard 분석을하였다. 과거여러대규모코호트연구를통해알려진뇌경색후사망예측인자들, 즉나이, 초기중증도 (NIHSS), 심방세동, 고혈압, 입원시고혈당등과, 26-28 Kaplan-Meier 법에서통계적으로유의하게나온변수들을예측모델분석에사용하였고, 고연령, CKD, 내원시백혈구증가증, 내원시 NIHSS 가환자의사망에영향을미치는독립적인예후인자로나타났다 (Table 3). 이후 CKD 환자의사망률이높은원인을알아보기위해, CKD 환자와정상환자를나누어각군에서사망원인과사망에영향을미치는예후인자를조사하였다. Cox proportional hazard 분석결과, 정상환자군에서는고연령 (HR 5.27, 95% CI 2.20-12.67) 과입원시신경학적결손 (moderate deficit: HR 2.19, 95% CI 0.69-2.82; severe deficit: HR 5.89, 95% CI 0.92-6.75) 이유의한인자였던반면, CKD 환자군은고심장색전위험 (HR 7.68, 95% CI 1.59-37.08), 백혈구증가증 (HR 4.46, 95% CI 1.28-15.52), 퇴원시불량한기능적회복 (HR 8.67, 95% CI 2.19-34.33) 이사망에영향을미치는독립적인예후인자로나타났다. 정상환자군의결과와달리입원시신경학적결손 (HR 0.51, 95% CI 0.07-3.52) 은 CKD 환자군에서유의하지않았으며, 연령 (HR 0.15, 95% CI 0.04-0.63) 은오히려 CKD 환자군의사망률의감소와연관이있었다 (Table 4). 입원중사망은 37명에서발생하였는데, 그중 14명이 CKD 환자군, 23명이정상환자군이었다. 뇌경색에의한직접적사망은 CKD 환자군이 12명 (52.1%), 정상환자군이 7명 (50%) 으로비율의큰차이는없었다. 심근경색을포함한혈관계사망은 CKD 환자군이 3명 (21,4%) 으로급성심근경색이 2명, 대동맥류파열이 1명이었고, 정상환자군이 4명 (17.4%) 으로급성심근경색 3명과폐색전증이 1명이었다. 뇌경색후유증에의한사망은 CKD 환자군 4명 (28.4%) 중, 폐렴 2명, 급성콩팥부전 1명, 상부위장관출혈 1명이었으며, 정상환자군은 6명 (26.1%) 중, 폐렴 5명, 상부위장관출혈 1명이었다 (Table 5). 고찰 본연구에서급성뇌경색으로입원한환자중 CKD 로진단된환자는약 10.9% 로, 다른연구 19,29 에서보고된 28.08%, 36% 보다는낮은비율을차지하였다. 이전연구에서는본연구와달리 CKD 기준을사용하지않았고뇌졸중급성기탈수, 약제등의원인에의해일시적크레아티닌이상승된환자까지포함되었던반면에, 본연구에서는사구체여과율이 3개월이내에정상화가된 54명 (8.8%) 을정상환자군으로재분류하여정상환자군이많아졌던것으로보인다. 하지만, 급성뇌경색으로입원한 CKD 환자들이정상환자군보다입원시의신경학적손상정도가심하고, 퇴원시의기능적회복정도가낮았던것은이전연구들의결과와일치하였다. 19,29 다른연구에서는나이, 관상동맥질환, 심방세동, 입원당시의고혈당, 심한신경학적손상, 낮은사구체여과율이뇌졸중후 J Korean Neurol Assoc Volume 27 No. 3, 2009 233
사망률을의미있게높였으며, 19 본연구결과전체뇌졸중환자의사망에영향을미치는독립적예후인자로는 65세이상의고연령 (HR=2.34), 내원시백혈구증가증 (HR=2.13), 내원시중증신경학적결손 (HR=4.28) 과 CKD (HR=2.89) 이었다. 두연구모두에서 CKD 가기존에잘알려진여러사망예측인자 26-28 를보정한후에도통계적으로유의하게뇌졸중후사망률을높이고, 다른인자에못지않은비교적강력한예측력이있다고볼수있겠다. 비록최근일부연구에서콩팥기능저하가뇌졸중후사망률을높인다는결과는있었으나, 그원인과기전에대한분석은이루어지지않았다. 이에본연구에서는정상환자군과 CKD 환자군에서각각사망률에영향을미치는예후인자들을알아보았는데, 정상환자군에서사망에영향을주는인자는나이, 신경학적중증도였다. CKD 환자군에서는고심장색전위험, 입원시백혈구증가증, 퇴원당시의기능적회복정도이었고, 정상환자군에서유의한결과를보였던급성뇌경색의신경학적결손정도나고연령은사망률에영향을미치지못했다. 즉, CKD 환자군의사망은정상환자군과는다르게연령이많거나급성뇌경색에의한신경학적결손에의해영향을받기보다는, 심방세동등고심장색전위험, 감염및염증상태, 퇴원시기능회복정도에의해결정될가능성이높다는의미로볼수있다. 더욱이최근한연구에서 CKD 는심방세동의혈전형성을촉진시킬수있다는보고가있어, 30,31 이는본연구의결과를뒷받침하는근거가될수있을것으로생각한다. 또한 CKD 환자에서는다른기왕력의동반이많고, 면역력이저하되어있다고알려져있어 32-34 전신적인염증 (systemic inflammation) 의선행인자 (predisposing factor) 로서역할을하게되며, 이는높은사망률의원인이될수있을것으로보인다. 신경학적결손자체보다는퇴원시기능적회복이사망에더중요하게나타났는데, 이는급성기의뇌졸중자체또는합병증에의한사망보다는아급성기이후기능적의존성에의해발생하는내과적또는외과적합병증이 CKD 환자의사망에더큰영향을주는것으로추정하였다. 사망원인분석에서뇌탈출에의한사망을제외하면정상환자군과 CKD 환자군에서폐렴등에의한뇌경색후유증이나다른혈관성사망의비율은비슷했다. 하지만, 입원중사망만을조사했기때문에, 각군의사망환자수가매우적어정확한의미를부여하는것은어렵다. 다만, 이미언급한바와같이 CKD 환자의사망은입원중보다퇴원후정상환자군에비해차이를보일가능성이있으나, 향후더많은연구가필요할것으로생각한다. CKD 나콩팥기능저하에대한정의도중요할수있는데, 본연구와비교할수있는기존의연구에서는입원당시의크레아 티닌수치만을콩팥기능의지표로삼았고, 17 근육량에영향을받는계산법인 Cockcroft-Gault equation 35 으로 1회측정한자료만을사용하였으며, 급성콩팥기능저하이나내원당시의탈수로인한경우를제외하지않았다. 18 최근한연구에서는사구체여과율을 MDRD equation 과 Mayo Clinic equation 두가지방법을모두사용하여구하였는데, MDRD equation 으로구한결과는뇌졸중후 1년사망률을예측한반면에, Mayo Clinic equation 으로구한결과에서는약간의통계적경향만이있는것으로나와, 29 사구체여과율을구하는방법에따라서예후에대한예측은다소차이가날수도있겠다. 일반적으로 MDRD 로계산하는사구체여과율은콩팥기능이좋은단계에서는과측정되는경향과나이에따라서영향을받는다는단점이있지만, 나이와성별만을알면 24 시간소변수집과같은번거로운노력없이도, 매우쉽게크레아티닌수치만으로 GFR 을측정할수있어임상에서널리사용할수있다는장점이있다. CKD 가심장혈관질환의사망률을높인다는사실은, 8-11 CKD 환자에서뇌졸중후사망률이높은또다른원인이될수있다. 최근 CKD 와뇌경색의연구결과 17-19,29 에서유추할수있는것처럼, 뇌혈관과관상동맥혈관, 콩팥혈관은동맥경화생성의생물학적인기전을공유하고있을것으로생각되며, 각질환에서고혈압이나당뇨병등기존의혈관위험인자의분포도비슷할것으로보인다. 즉, CKD 와뇌경색을함께가지고있는환자일수록관상동맥질환등의심장질환빈도가더높아질수있으므로높은사망률을보일수있을것으로생각된다. 또한이전부검연구에서도뇌졸중이있었던환자들에서콩팥동맥의동맥경화가많다는보고가있다. 36,37 본연구의장점은 DWI 촬영비율이 99% 로기존의연구와달리비교적순수한뇌경색환자군을대상으로하였으며, 일시적콩팥기능저하환자를배제한만성콩팥병환자에서뇌졸중예후및사망원인을분석하고자하였다. 하지만일개 3차대학병원에서진행된연구로, 대상군의환자수가적어전체뇌졸중환자를대표하기에는한계가있고, 입원중사망의원인파악은가능하였으나추후 3개월과 1년째의사망원인은파악하지못하였으며사망여부만을확인하였다. 또한콩팥조직검사나콩팥손상 (kidney damage) 을나타내는알부민뇨 (albuminuria) 등의검사를통해서진단할수있는만성콩팥병환자들이누락되었을가능성이있고, cystatin C 38 와같은콩팥특이적인인자들을분석하지못했다는한계점이있다. 본연구는콩팥기능의저하, 특히만성콩팥병환자들의사망과원인분석에대한국내의유일한연구로, 만성콩팥병이급성뇌경색이후의사망의독립적인예후인자임을보였다. 특히만성콩팥병을가진뇌경색환자의사망에백혈구증가증, 고심장 234 대한신경과학회지제 27 권제 3 호, 2009
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