대사증후군과만성신질환과의연관성 Effects of Metabolic Syndrome on Chronic Kidney Disease In-Chang Cho, Young-Won Kim, Yunbyung Chae, Tong-Wook Kim 1, Seok Joong Yun, Sang-Cheol Lee, Wun-Jae Kim, Yong-June Kim From the Department of Urology, Chungbuk National University College of Medicine, Cheongju, 1 Konkuk University College of Medicine, Chungju, Korea Purpose: Metabolic syndrome (MS) has been identified as a causal risk factor for cardiovascular disease, stroke, and cardiovascular mortality. Recent studies have suggested a possible relation between MS and renal function. The aim of this study was to evaluate the influence of MS on renal function. Materials and Methods: We analyzed 12,348 healthy Koreans who underwent a general health checkup. MS was defined as 3 or more of the criteria according to the National Cholesterol Education Program Adult Treatment Panel guidelines III (NCEP ATP III). The glomerular filtration rate (GFR) was estimated by the redefined Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was categorized into 3 categories according to the Kidney Disease: Improving Global Outcomes guidelines; I: GFR 90 ml/min, II: 60-89 ml/min, III: 30-59 ml/min. Results: The overall proportion with MS was 19.3%. Compared with populations without MS, those with MS showed a significantly decreased GFR. The prevalence of CKD increased with the number of MS components, and it was prominent in the group of males over 40 years of age. In multivariate analyses using age, sex, and individual MS components, age (odds ratio [OR]=20.40; 95% CI: 10.81-38.49), sex (OR=1.98; 95% CI: 1.51-2.60), and obesity (OR=1.48; 95% CI: 1.13-1.93) were strongly associated with CKD. Conclusions: This study showed that MS is a significant determinant of CKD. Handling of correctable factors such as obesity may be considered one of the preventive modalities against the development of CKD. (Korean J Urol 2009;50:261-266) Key Words: Metabolic syndrome, Obesity, Chronic renal insufficiency Korean Journal of Urology Vol. 50 No. 3: 261-266, March 2009 DOI: 10.4111/kju.2009.50.3.261 충북대학교, 1 건국대학교의과대학비뇨기과학교실 조인창ㆍ김영원ㆍ채윤병김동욱 1 ㆍ윤석중ㆍ이상철김원재ㆍ김용준 Received:September 24, 2008 Accepted:October 21, 2008 Correspondence to: Yong-June Kim Department of Urology, Chungbuk National University College of Medicine, 62, Gaesin-dong, Heungdeok-gu, Cheongju 361-711, Korea TEL: 043-269-6134 FAX: 043-269-6129 E-mail: urokyj@cbnu.ac.kr This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (PT-ERC). C The Korean Urological Association, 2009 서론만성신질환은말기신부전과심혈관질환, 조기사망의중요한위험인자일뿐만아니라그유병률의중가추세로인해세계적으로공중보건의심각한문제로대두되고있다. 1 최근역학조사에서만성신질환을가진환자는대개신부전으로인한사망보다신기능저하에따른심혈관질환의조기발병으로인해사망하는경우가대부분임이밝혀졌다. 2,3 심혈관질환의위험인자및이로인한사망률증가라는측면에서, 만성신질환의조기발견은매우중요 하다. 최근만성신질환의발병인자와말기신부전으로의진행요소에대한연구가활발해지면서심혈관질환의위험인자인대사증후군에대한관심이증가되고있다. 4-6 최근세계적으로대사증후군의유병률증가와함께만성신질환및말기신부전의유병률이동시에증가하고있다는점은이들의밀접한관련성에대한가능성을보여주고있다. 7,8 대사증후군은고혈압, 당뇨, 이상지방혈증, 비만등관상동맥질환의위험요인이되는질환들이군집되어나타나는것으로정의된다. 기본적인병태생리는인슐린매개성포도당흡수장애로인한인슐린저항성에따른 2차적고인슐린혈증및교감신경계의과활성에의하여발생하는임상적 261
262 Korean Journal of Urology vol. 50, 261-266, March 2009 특성을보이고있다. 대사증후군은세계적으로 20-25% 의유병률을보이고있으며, 연령이증가할수록흔히발병되는것으로알려져있다. 7 최근우리나라에도식습관및생활방식의서구화로인해연령의증가에따라대사증후군으로인한관상동맥질환및그위험인자의유병률이급속히증가하는추세를보이고있다. 9,10 대사증후군은신장뿐아니라방광, 전립선등의비뇨기계장기에악영향을미치는것으로알려져있다. 11-13 이중특히대사증후군은만성신질환발생의위험요소로의심되고있으나, 이러한두질병군사이에직접적인인과관계를규명하기에는어려움이있다. 또한대사증후군의구성요소중당뇨병, 고혈압, 비만, 이상지방혈증등은만성신질환의발병과악화에관여하는중요한위험요소로생각되나, 각각의인자들이만성신질환의발생에영향을주는역할은다를것으로추정되고있다. 14,15 이에본연구에서는대사증후군과이들의각각의위험인자들이만성신질환의발생에미치는영향에대하여알아보고자하였다. 대상및방법 1. 연구대상 2002년 1월부터 2006년 5월까지 1일건강검진프로그램을통하여검진을시행받은환자들을대상으로하였다. 총환자는 12,348명으로평균연령 46.4±10.3세 (20-79) 였고, 이중남자는 7,818명 (63.3%), 여자는 4,530명 (36.7%) 이었다. 대상군을연령대별로세분화하면 20-30대가 3,411명 (27.6%), 40-50대가 7,373명 (59.7%), 60대이상이 1,564명 (12.7%) 이었다. 2. 평가항목및진단기준대사증후군은개정된 Adult Treatment Panel guidelines III (ATP-III) 를이용하여 5가지의구성요소중 3가지이상의요소를가진경우진단하였다. 16 5가지구성요소는 (1) 비만 : body mass index (BMI) 가 25 kg/m 2 이상인경우, (2) 고중성지방혈증 : 중성지방농도가 150 mg/dl 이상인경우, (3) 저고밀도지단백콜레스테롤혈증 : 고밀도지단백콜레스테롤의농도가남자의경우 40 mg/dl 미만, 여자의경우 50 mg/dl 미만인경우, (4) 고혈압 : 수축기혈압과이완기혈압이각각 130 mmhg 이상이거나 85 mmhg 이상인경우혹은항고혈압약물을복용중인경우, (5) 고혈당 : 공복혈당이 110 mg/dl 이상인경우로정의하였다. 비만의정도를객관화하기위해환자의신장과체중을측정하고수정된 WHO criterion for the Asia Pacific Region was substituted as the measure of obesity (WPRO) 의기준에따라체질량지수 (BMI=weight/ height 2 x100) 를구하여체질량지수가 25 이상인경우를비만으로정의하였다. 17 또한이상지방혈증유무를알기위해최소 8시간금식후에혈중에서공복혈당 (fasting blood sugar; FBS), 혈중고밀도지단백콜레스테롤 (high density lipoprotein; HDL), 중성지방 (triglyceride; TG) 을측정하였으며, 혈압은적어도 5분이상안정을취한상태에서 3번측정하여평균을기록하였다. 사구체여과율 (glomerular filtration rate; GFR) 은 Modified Modification of Diet in Renal Disease (MDRD) 연구수식 [186.3x(serum creatinine 1.154 )x(age 0.203 )x0.742 (if, female)] 을이용하여계산하였다. 만성신질환은 kidney disease: improving global outcomes (KDIGO) 의분류에따라세군으로나누어사구체여과율이 90 ml/min인경우제i군, 60-89 ml/min인경우를제ii군, 30-59 ml/min인경우를제iii군으로정하고, 이중 III 군을만성신질환으로정하였다. 18 3. 통계학적분석대상군에서대사증후군과만성신질환의유병률을조사하였고, 대사증후군의유무또는보유위험인자수에따른신기능변화에대한분석을시행하였다. 대상군을연령, 성별에따라분류하여대사증후군의유무및개별인자의유무에따른신기능을평가하였다. 또한연령, 성별및대사증후군의위험인자들을포함하여단변량및다변량분석을시행하여이들인자들이만성신질환에미치는영향에대한조사를시행하였다. 모든통계분석은 SPSS (ver.12.0) 를이용하였으며, p값이 0.05 미만인경우를유의한차이가있는것으로간주하였다. 결과 1. 대사증후군과만성신질환의유병률대사증후군과만성신질환은각각 19.3% 와 2.1% 의유병률을보였다. 자세히살펴보면전체연구대상군에서대사증후군의위험인자를 3개이상가진대사증후군환자는 19.3% (2,388/12,348) 였다. 그밖에 1개또는 2개의대사증후군의위험인자를가진환자는 49.2% (6,072/12,348), 대사증후군의위험인자를가지고있지않은환자는 31.5% (3,888/12,348) 였다 (Fig. 1). 대사증후군의위험인자별로비만은 3,973명 (32.2%), 고혈압은 4,686명 (37.8%), 고중성지방혈증은 4,224명 (34.2%), 저고밀도지단백콜레스테롤혈증은 2,761명 (22.4%), 내당능장애는 983명 (8%) 의유병률을보였다 (Fig. 2). 사구체여과율에따른신기능은제III군인만성신질환자가 257명 (2.1%) 이었다. 그외제II군에해당하는환자가 8,874명 (71.9%), 제I군은 3,217명 (26.1%) 이
In-Chang Cho, et al:metabolic Syndrome and Chronic Kidney Disease 263 Fig. 1. The prevalence of metabolic syndrome by number of components. Fig. 3. The prevalence of chronic kidney disease (CKD). CKD was categorized according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. I: GFR 90 ml/min, II: 60-89 ml/min, III: 30-59 ml/min. Table 1. Baseline characteristics of the study population (n=12,348) by presence of metabolic syndrome Variables p-value Fig. 2. The prevalence of individual metabolic components. TG: triglyceride, HDL: high-density lipoprotein. 었다 (Fig. 3). 대사증후군이없는사람들에비하여대사증후군이있는사람들의연령대가높았고, 더비만하였다 (p). 대사증후군이있는사람들이보다높은혈압, 혈당, 혈중중성지방농도와낮은고밀도지단백콜레스테롤농도를보였다 (p). 사구체여과율의경우대사증후군이있는사람들이약간더낮은경향을보였다 (84.3 ml/min/1.73m 2 vs. 81.6 ml/min/1.73 m 2, p)(table 1). 2. 대사증후군과신기능의관계 대사증후군이있으면만성신질환의유병률은증가하였다. 대사증후군의유무에따른만성신질환의유병률은각각 1.7% (171명) 와 3.6% (86명) 였다. 대사증후군의구성요소의수와만성신질환의유병률의연관정도에대해분석 No. of patients (%) Age (years) Height (cm) Weight (kg) BMI (kg/m 2 ) Systolic BP (mmhg) Diastolic BP (mmhg) Triglycerides (mg/dl) HDL-c (mg/dl) Fasting glucose (mg/dl) GFR (ml/min per 1.73 m 2 ) 9,953 (80.7) 45.5±10.0 165.1±8.4 62.8±10.0 22.9±2.7 119.9±15.0 75.4±10.0 121.6±73.6 55.0±12.7 90.2±14.7 84.3±16.7 2,395 (19.3) 50.1±10.8 164.8±9.1 0.091 72.6±10.8 26.6±2.6 136.6±16.0 85.5±10.4 244.1±131.3 43.7±9.7 105.1±30.8 81.6±18.4 BMI: body mass index, BP: blood pressure, HDL-c: high density lipoprotein cholesterol, GFR: glomerular filtration rate 한결과, 대사증후군의구성요소의수가증가할수록만성신질환의유병률은증가하였다. 구성요소가없는군에서의유병률은 1.1% (41명) 인데비해 1개또는 2개의구성요소가있는군과 3개이상의구성요소가있는군의유병률은각각 2.1% (130명), 3.6% (86명) 로나타났다 (p) (Table 2). 3. 성별, 연령에따른대사증후군과신기능의관계 대사증후군의구성요소와만성신질환의상관관계가성별과연령에따라다른양상을보이는지알아보기위하여대상군을성별과연령대별로 20-30대, 40-50대, 60대이상의세군으로분류하여분석하였다. 대상군을연령, 성별에따라세분화하였을때, 대사증후군은 40세이상의남성
264 Korean Journal of Urology vol. 50, 261-266, March 2009 에서신기능저하와높은연관성을보였다 (p<0.05)(table 3). 40세이상의여성에서대사증후군의빈도와신기능저 Table 2. Glomerular filtration rate by number of metabolic syndrome components No. of MS risk factor 0 1-2 3-5 I II III p-value 1,103 (28.4) 1,600 (26.4) 514 (21.5) 2,744 (70.6) 4,342 (71.5) 1,788 (74.9) 41 (1.1) 130 (2.1) 86 (3.6) Total 3,217 (26.1) 8,874 (71.9) 257 (2.1) MS: metabolic syndrome, CKD: chronic kidney disease. Data is number (percentage). The CKD was categorized into the 3 categories (I: GFR 90 ml/min, II: 60-89 ml/min, III: 30-59 ml/ min) according to the Kidney Disease: Improving Global Outcomes (KDIGO) Table 3. Prevalence of chronic kidney disease by age, sex, and metabolic syndrome Sex Age MS I II III p-value Male (%) Female (%) 20-30 40-50 >60 20-30 40-50 >60 568 (33.8) 122 (36.4) 670 (17.0) 156 (14.5) 132 (22.5) 27 (13.7) 538 (40.5) 20 (29.9) 700 (35.8) 145 (36.2) 95 (20.3) 44 (14.1) 1,109 (66.0) 3 (2.0) 213 (63.6) 0 (0.0) 3,220 (81.7) 52 (1.3) 898 (83.8) 23 (2.1) 432 (73.6) 23 (3.9) 161 (81.7) 9 (4.6) 784 (59.0) 7 (0.5) 46 (68.7) 1 (1.5) 0.495 0.026 0.029 0.146 1,216 (62.3) 37 (1.9) 0.067 241 (60.1) 15 (3.7) 325 (69.3) 49 (10.4) 0.085 229 (73.6) 38 (12.2) MS: metabolic syndrome, CKD: chronic kidney disease. The CKD was categorized into the 3 categories (I: GFR 90 ml/min, II: 60-89 ml/min, III: 30-59 ml/ min) according to the Kidney Disease: Improving Global Outcomes (KDIGO) 하가증가하는것으로관찰되었으나, 통계학적유의성은관찰되지않았다. 전체대상군에서만성신질환의유병률에영향을주는연령, 성별과대사증후군의각구성요소들의비교위험도를단변량분석과다변량분석을통해살펴보았다. 단변량분석결과, 만성신질환발생은연령, 성별, 비만, 고혈압, 고중성지방혈증, 저고밀도지단백콜레스테롤혈증, 내당능장애등의예후인자에의해영향을받았다. 이에대한다변량분석결과에서연령 (OR=20.40, 95% CI: 10.81-38.49, p=0.004) 과성별 (OR=1.98, 95% CI: 1.51-2.60, p), 비만 (OR=1.48, 95% CI: 1.13-1.93, p=0.004) 만이만성신질환의발생을예측할수있는독립적예후인자였다 (Table 4). 고찰본연구결과대사증후군은만성신질환의유병률과연관이있으며이들의위험인자가증가할수록신기능저하와관련됨을확인하였다. 또한다변량분석결과대사증후군의위험인자중비만이만성신질환의발생을예측할수있는독립적인예후인자였다. 최근만성신질환과심혈관계질환의위험인자에관한연구가활발하다. 현재까지알려진만성신질환발생의위험인자는고령, 흡연, 당뇨, 고혈압, 이상지방혈증등인데, 이러한위험인자들에대한공통된견해는성립되어있지않은실정이다. 만성신질환은흔히조기에발견되지않고, 시간이지나면서진행하여심혈관계질환등의합병증에이르게되는경우가많다. 이에심혈관계질환의위험인자로알려진대사증후군등의조기발견의중요성이강조된다. 1,4,5,18 대사증후군이란인슐린저항성, 내당능장애, 고혈압, 고지혈증, 비만이군집해서발병및진행하고만성적인경과를보이는대사장애를지칭한다. 7 기존의연구를통해대사증후군이있는환자들에서는당뇨병과심혈관질환의발생 Table 4. Univariate and multivariate analyses for prediction of chronic kidney disease Variables Age Sex Obesity a Hypertension a High TG a Low HDL a Impaired fasting glucose a Univariate Multivariate OR 95% CI p-value OR 95% CI p-value 25.46 2.35 1.81 1.83 1.43 2.14 1.67 13.68-47.35 1.83-3.02 1.41-2.32 1.43-2.35 1.11-1.83 1.66-2.77 1.14-2.43 0.005 20.40 1.98 1.48 1.08 1.11 1.26 1.00 10.81-38.49 1.51-2.60 1.13-1.93 0.83-1.41 0.84-1.47 0.95-1.67 0.67-1.48 OR: odd ratio, CI: confidence interval, TG: triglyceride, HDL: high density lipoprotein, a : component is absent or present 0.004 0.004 0.561 0.445 0.108 0.999
In-Chang Cho, et al:metabolic Syndrome and Chronic Kidney Disease 265 률이높아지고결국그로인한합병증이증가하는것으로알려져왔다. 19,20 그러나대사증후군의만성신질환에대한영향은현재많은연구에의해서여러가설이제시되고있으나아직까지일치된결론에는도달하지못하였다. Chen 등 1 의연구결과대사증후군과만성신질환은상관관계가있으며, 다변량분석에서고혈압, 고중성지방혈증, 저고밀도지단백콜레스테롤혈증, 복부비만모두가만성신질환과관련되는독립적인예후인자였다. 또한동남아시아코호트연구에서는내당능장애, 고혈압및고중성지방혈증의위험인자를가진경우나내당능장애, 고중성지방혈증및비만의위험인자를가진경우만성신질환이새롭게발생할수있는가능성이증가하였다고보고하였다. 5 상기의연구들에서대사증후군의각위험인자이외에도연령, 성별등이만성신질환의강력한위험인자일것으로추측되었지만, 어떠한위험인자를조절하여신질환의발생과진행을억제할수있을지에대한이론적근거는부족하며국내에서도뚜렷한연구성과는없는실정이다. 대사증후군의진단기준으로보면 5개의요소들이증후군의진단에서동일한비중을차지하는것으로되어있지만, 만성신질환에미치는영향력은진단기준과달리같지않을가능성이있음을여러논문에서제시하고있다. Kurella 등 4 은대사증후군은만성신질환발병에관여함은물론또한환자가보유한대사증후군의인자는만성신질환의발병와일정한비율로비례하며, 내당능장애를가진환자를제외한경우에도각위험인자는만성신질환의증가된발병률과관련이있었다고하였다. 최근까지비만등을비롯한대사증후군의위험인자와신기능손상의연관관계에대해서는정확히밝혀진바는없지만, 비만한남녀성인모두신장의구조적인변화와기능적변화를나타냈으며, 여성의경우대사증후군을유발하는중요한인자는복부비만이라는점은강조된바있었다. 21 또한일본의경우, Tanaka 등 6 은 60세이상의남성에서대사증후군은만성신질환발생에있어중요한예후인자였음을주장하였다. 본연구의경우, 만성신질환에대한연령, 성별등의영향을배제하기위해세분화하여분석하였을때, 대사증후군은특정연령과특정성별에서비교적다른영향을미친다는사실을발견할수있었고, 다변량분석에서연령과성별이외에가장중요한인자는비만이었다. 이러한사실은각위험인자이외에도식생활습관이나지역, 인종적차이나사회경제학적상황등이각국의증가된만성신질환의유병률에영향을미치고있을것으로생각하게하는점이다. 몇몇논문에서일반적으로비만한남녀성인모두에서신장은구조적인변화를일으키며, 단백뇨와신질환을유발한다는보고들이있었다. 22,23 일본에서 Iseki 등 24 은일본남 성에서고혈압이나단백뇨등의기타만성신질환에영향을미칠수있는인자들을보정하여시행한연구에서비만은말기신부전의중요한위험인자임을주장하였다. 또한신장에대한대규모병리검사에서비만은국소부분적모세관토리굳음증과모세관토리확장등과연관이있었으나, 당뇨등의기타위험인자에의해유발되는신병증과는다른비만환자특유의병리학적소견이발견되었다. 25 이러한사실은대사증후군의각위험인자들이관상동맥질환이나뇌졸중등에서미치는영향과만성신질환에미치는영향과기전은다를수있다는가능성을보여주며, 그중비만은큰비중을점하고있다는사실을뒷받침한다. 본연구결과에서도역시대사증후군의위험인자의개수가증가할수록신기능저하가관찰되었고, 연령과성별등의인자는중요한영향을미치고있으며, 교정가능한인자중에서는비만이유일한독립적인예후인자였다. 그러나본연구는몇가지제한점을가지는데, 첫째, 연구대상자체가자의로진원한건강검진집단으로건강한근로자효과 (healthy worker effect) 에의한편향효과때문에대사증후군과만성신질환의유병률이일반인구를대상으로한연구에서보다낮았다는점이다. 26 둘째, 본연구에서인용된 MDRD 연구수식은대규모역학연구나실제임상에서널리쓰이고있으나한국인의적용에대해서는의견일치가이루어지지않았다. 셋째, 비만의정의를허리둘레대신 BMI를이용하여, 25 kg/m 2 기준으로나누어사용하였는데, 이는허리둘레에대한결측값이많았기때문이다. 넷째, 대사증후군유무를조사함과함께의학적병력이나약물복용력, 흡연유무등을설문하지않았다는점등이다. 본연구에서대상군의수가비교적충분하였기에한계점들이다소절충된면이있겠으나향후이러한한계점들이보완된다면더욱신뢰할수있는결과를도출할수있을것으로생각한다. 따라서비만을포함한각대사증후군의위험인자는만성신질환의위험인자로상호작용할것으로생각한다. 또한대사증후군과만성신질환간에상호작용에대한기전을밝혀보는연구가향후엄밀한기준아래진행되어야할것으로생각한다. 이러한연구의성과하에일반인구군에서대사증후군등의만성신질환의위험인자를발견하는것은심혈관계질환발생및말기신부전으로의진행을예방하는도움이될것으로생각한다. 결론대사증후군은신기능저하및만성신질환과밀접한관계를가지며, 교정가능한인자라는측면에서대사증후군
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