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1 Korean J Fam Pract. 2011;1: 정상신기능가진성인에서 Cystatin C 와 Visceral Fat 과의연관성 Original Article 홍정아, 이광미, 손유나, 이지원 * 연세대학교의과대학가정의학교실 Association between Serum Cystatin C Level and Visceral Fat in Healthy Individuals with Normal Kidney Function Jeong-Ah Hong, Kwang-Mee Lee, You-Na Son, Ji-Won Lee* Department of Family Medicine, Yonsei University College of Medicine, Seoul, Korea Background: Visceral abdominal fat is a known risk factor for the kidney diseases and cystatin C which is a better marker for kidney function is increased in obese patients. The aim of this study is to evaluate the correlation between the visceral adiposity measured by computed tomography (CT) of the abdomen and serum cystatin C level in healthy individuals with normal kidney function. Methods: 318 Healthy individuals with glomerular filtration rate (GFR) greater than 60 ml/min/1.73 m 2 were included in the study. The questionnaire, physical measurements, blood testing, and CT for visceral fat measurement were carried out. The association between visceral fat and serum cystatin C level or kidney function was investigated by using Pearson s correlation and multiple regression analysis. Results: Significant positive correlation was found between visceral fat and cystatin C (r = 0.284, P < 0.001) where as negative correlation was observed between visceral fat and egfrcys (r = 0.820, P < 0.001). After adjustment for confounding variants, the multiple regression analysis demonstrated significant positive correlation between the visceral fat area and serum cystatin C level (P = 0.013) and significant negative correlation between visceral fat and egfrcys. Conclusion: In healthy individuals with normal kidney function, the visceral fat was independently associated with the cystatin C level, a marker for early detection of renal dysfunction, which indicates the possible relationship between the visceral fat and renal dysfunction prior to development of the kidney disease. Keywords: Cystatin C; Visceral Fat; Kidney Disease 서론 Received: August 31, 2010, Accepted: May 6, 2011 *Corresponding Author: Ji-Won Lee Tel: , Fax: indi5645@yuhs.ac This study was supported by a faculty research grant from the Yonsei University College of Medicine in Korean Journal of Family Practice Copyright 2011 by The Korean Academy of Family Medicine 비만은당뇨병, 고지혈증, 심혈관질환뿐아니라최근만성신장질환의위험인자로알려져있다. 1-3) 또한비만뿐아니라지방분포가신장기능에영향을미치는주요인자로제시되면서 4-6) 만성신질환이있는사람에서복부비만이사구체여과율 (egfrcys) 감소와연관되어있다고알려져있다. 5,6) 하지만현재까지만성신질환이발생하기이전정상신기능에서비만및지방분포와신기능에관련된연구는거의없는실정이다. 94 Vol. 1, No. 2 Aug 2011 Korean J Fam Pract

2 홍정아외 : 정상신기능가진성인에서 Cystatin C 와 Visceral Fat 과의연관성 Cystatin C는모든유핵세포에서생성되는저분자단백질로사구체에서여과된후세뇨관세포로재흡수되는특성을가지고있어신기능을측정하는지표로사용되며혈청크레아틴과달리나이, 성별, 근육량과무관하고그혈중농도가여러생리학적인자에의해영향을받지않아초기신손상에의한사구체여과율감소를혈청크레아틴에비해더민감하게반영한다고알려져있다. 7) 또한 Muntner 등 8) 은 cystatin C 가허리둘레와독립적인관련성이있다고보고하였다. 9,10) 하지만기존연구들의대부분은내장지방과피하지방을정확히측정할수없기때문에신장기능과복부지방의구성요소사이의관계를알수없는한계를보였다. 11) 컴퓨터단층촬영 (computed tomography, CT) 으로측정된복부지방은지방의분포를정확히측정할수있으며 CT로측정된내장지방은체질량지수나허리둘레보다대사증후군및당뇨병, 심혈관질환과더밀접한관련이있고보다나은예측인자로알려져있다 ) 이에본연구에서는만성신질환발생이전정상신기능을가진성인에서 CT를통해정확하게복부내장지방을측정후 cystatin C와의관련성을알아보고자하였다. 방법 2) 신체계측및혈압검사가벼운옷을입고신을벗고체중과키를킬로그램과센티미터단위로각각소수점한자리까지측정하였으며, 체질량지수는체중 (kg)/ 키 (cm 2 ) 으로계산하였다. 혈압은앉은자세에서 5분간의휴식후에우측팔에서기계혈압계를이용하여수축기 / 이완기혈압을측정하였다. 3) CT 복부내장지방과피하지방단면적을컴퓨터단층촬영을이용하여측정하였다. 대상자가누운상태에서 2-5번째요추를횡단하는부위에서 Hounsfield unit -150에서 -50에속하는부위를측정하여복부지방면적을구하였으며복막을경계로바깥쪽의피하지방면적, 안쪽의내장지방면적을구하였다. 4) 혈액검사 8시간이상금식한후총콜레스테롤, 중성지방, 고밀도지단백콜레스테롤, 공복혈당을측정하였다. 혈청크레아티닌은 Jaffe법으로자동분석기에서측정하였고, 혈청 cystatin C는 particle enhanced immunophelometry를이용하여측정하였다. Cystatin C 를이용한사구체여과율은기존의연구에서제시된 [egfrcys = 76.7 Scys 1.18 ] 공식 13) 을이용하였다. 1. 연구대상 2008년 9월부터 2010년 3월까지일개대학병원외래를내원한사람을대상으로문진및신체계측, 혈액검사, CT를통한지방측정을실시한만 20세이상의성인을대상으로하였다. 문진을통해인구학적정보, 질병의과거력, 현병력을조사하였으며신체계측및혈액검사, CT를이용하여복부내장지방분포를측정하였다. 정상신기능을가진사람을대상으로하기위해 modification of diet in renal disease (MDRD) 공식 [ 사구체여과율 (ml/min/1.73 m 2 ) = 1.86 ( 혈청크레아티닌 ) ( 연령 ) ( 여성인경우 0.742)] 에의한사구체여과율 60 ml/min/1.73 m 2 미만인사람을제외하였다. 전체 344명중제외기준을적용한후연구대상자는총 318명이었으며본연구는해당병원의윤리위원회 (Institutional Review Board) 의승인을받았다. 2. 연구방법 1) 문진연령, 흡연력 (pack year), 폐경여부, 고혈압약복용여부, 고지혈증약복용여부, 당뇨약복용여부를확인하였다. 폐경은마지막월경이후 12개월이상무월경이지속된경우로정의하였다. 3. 통계분석 SPSS ver (SPSS Inc., Chicago, IL, USA) 를사용하였고 P-value는 0.05 미만일때통계적으로유의다고하였다. 조사대상자의일반적특성을살펴보기위하여연속변수인경우평균 ± 표준편차로기술하였고명목변수인경우백분율로기술하였다. 복부지방분포와 cystatin C 및신장기능 (egfrcys) 의관련성을알아보기위해피어슨상관관계분석하였으며, 연령, 성별, 수축기혈압, HDL, 고혈압약복용여부, 당뇨병약복용여부, 고지혈증약복용여부, 흡연, 폐경여부등의혼란변수를보정한뒤복부지방분포와 cystatin C 및신장기능의독립적인관련성을알아보기위해다중회귀분석을실시하였다. 결과 1. 연구대상자의일반적특성연구대상자의신체계측및일반적인특성은 Table 1에나타내었다. 연구대상자 318명의연령은평균 38.4±12, 성별은남성 83명 (26.1%), 여성 235명 (73.9%) 이었으며복부내장지방 가정의학회지 Vol. 1, No. 2 Aug

3 Jeong-Ah Hong, et al: Association between Serum Cystatin C Level and Visceral Fat in Healthy Individuals with Normal Kidney Function 면적은평균 376.4±194.7 cm 2, cystatin C는 0.7±0.1 mg/l, 사구체여과율은평균 125.4±44.7 ml/min/1.73 m 2 를나타내었다. 2. Cystatin C와복부지방분포및심혈관위험인자와의관련성 Cystatin C는연령 (r=0.216, P<0.001), 수축기혈압 (r=0.127, P=0.028), 복부내장지방 (r=0.284, P<0.001) 과양의상관관계가있었고 HDL 콜레스테롤 (r=-0.203, P<0.001) 과는음의상관관계가있었다. 또한, 남성이여성에비해유의하게 cystatin C 가높았으며 (r=-0.173, P=0.002), 폐경후여성이폐경전여성 Table 1. Clinical characteristics of subjects. Characteristics Mean ± SD or n (%) Age (y) 38.4 ± 12.0 Gender 318 (100.0) Men 83 (26.1) Women 235 (73.9) Systolic blood pressure (mm Hg) ± 15.3 Diastolic blood pressure (mm Hg) 75.6 ± 10.2 High-density lipoprotein cholesterol (mg/dl) 51.0 ± 11.9 Body mass index (kg/m 2 ) 28.0 ± 4.8 Hypertension treatment 311 (97.8) Yes 284 (89.3) No 27 (8.5) Diabetes mellitus treatment 309 (97.2) Yes 298 (93.7) No 11 (3.5) Lipid treatment 318 (100.0) Yes 305 (95.9) No 13 (4.1) Smoking (pack y) 2.0 ± 6.5 Menopause 311 (97.8) Men 83 (26.1) Women-No 190 (59.2) Women-Yes 38 (11.9) Visceral fat area (cm 2 ) ± Subcutaneous fat area (cm 2 ) ± Cystatin C (mg/l) 0.7 ± 0.1 egfrcys (ml/min/1.73 m 2 ) ± 44.7 egfr: estimated glomerular filtration rate. 에비해 cystatin C가유의하게높은것으로나타났다 (r=0.200, P=0.002). 사구체여과율은 HDL 콜레스테롤 (r=0.129, P=0.022) 과양의상관관계가있었고, 연령 (r=-0.124, P=0.028), 흡연 (r=-0.117, P=0.040), 복부내장지방 (r=-0.156, P=0.005) 과는음의상관관계가있었다. 또한폐경전여성이폐경후여성에비해사구체여과율이유의하게높은것으로나타났다 (r= , P<0.001) (Table 2, Figures 1, 2). 3. 복부내장지방과 cystatin C와의독립적인연관성복부내장지방과 cystatin C와의고유한관계를알아보기위하여나이, 성별, 수축기혈압, 고혈압약복용여부, 고지혈증치료여부, 당뇨치료여부, 고밀도지단백콜레스테롤, 흡연력, 폐경여부를보정한후다중회귀분석을실시하였다. 컴퓨터단층촬영에의해측정된복부내장지방면적과 cystatin C는독립적으로유의한양의연관성이있었다 (P=0.013) (Table 3). 또한복부내장지방과신기능과의관계를보기위하여시행한다중회귀분석에서는복부내장지방이증가할수록사구체여과율이감소함을알수있었다 (P=0.045) (Table 3). 고찰 본연구에서는정상신기능을가진성인을대상으로하였을때혼란변수를보정한후에도 CT를이용하여측정한복부내장지방은 cystatin C와독립적인양의관련성이있었고사구체여과율과독립적인음의관련성이있었다. 이는복부내장비만이당뇨, 고혈압, 심혈관위험인자일뿐아니라정상신기능을가진성인일지라도신기능저하와관련될수있음을의미한다. 이전연구들에서허리-엉덩이비가증가할수록신기능이저하되고 4) 체질량지수가증가할수록말기신부전위험이증가함이알려졌으며 2) Framingham Heart Study에서는 18.5년추적관찰하였을때체질량지수가증가할수록신장질환발생이 23% 높게나타났다. 15) 기존의만성신장질환환자와비만또는복부비만과의관계에대한연구들은대부분간접적으로허리둘레혹은허리-엉덩이둘레비로비만및복부비만을측정하였으며컴퓨터단층촬영을이용하여정확히복부지방분포를측정한연구는거의없었다. 또한정상신기능가진사람을대상으로한대규모연구에서심혈관계질병에대한위험률이사구체여과율이낮은군이높은군에비해더높음을보여주는연구는있지만 16) 만성신장질환발생이전정상신기능환자를대상으로 cystatin C와복부내장비만과의관계에 96 Vol. 1, No. 2 Aug 2011 Korean J Fam Pract

4 홍정아외 : 정상신기능가진성인에서 Cystatin C 와 Visceral Fat 과의연관성 Table 2. Correllation of cystatin C and variabls. Variable Cystatin C egfrcys r P-value r P-value Age (y) < Gender Systolic blood pressure (mm Hg) HDL cholesterol (mg/dl) < Hypertension treatment DM treatment Lipid treatment Smoking (pack y) Menopause (women) <0.001 Visceral fat area (cm 2 ) < Cystatin C (mg/l) <0.001 egfrcys (ml/min/1.73 m 2 ) < Coefficients (r) and P-values are calculated by Pearson correlation analysis. egfr: estimated glomerular filtration rate, HDL: high density lipoprotein, DM: diabetes mellitus. Figure 1. Correlation between visceral abdominal fat and cystatin C. Coefficients (r = 0.284) and P-values (P < 0.001) were calculated by Pearson correlation analysis. Cystatin: cystatin C, Visce sum: visceral fat area. Figure 2. Correlation between visceral abdominal fat and egfrcys. Coefficients (r = ) and P-values (P = 0.005) were calculated by Pearson correlation analysis. Visce sum: visceral fat area, egfr: estimated glomerular filtration rate. 대한연구는거의없었다. Cystatin C는기존의연구에서비만과허리둘레와독립적으로연관되어있음이보여졌으며 8-10) 지방세포가 cystatin C를분비함을보였다. 17) The Health ABC 연구에서는 cystatin C는체질량지수와제지방과연관성을보여 cystatin C가대사과정에연관되어있음을제시하였다. 18) 이에본연구에서는급격한신기능변화혹은초기신손상에의한사구체여과율감소를혈청크레아틴에비해더민감하게반영한다고알려진 cystatin C와사구체여과율을구해정상신기능가진성인을대상으로복부내장비만과의관련성을알아보았다. 복부내장지방과 cystatin C사이의관련성에대한메커 가정의학회지 Vol. 1, No. 2 Aug

5 Jeong-Ah Hong, et al: Association between Serum Cystatin C Level and Visceral Fat in Healthy Individuals with Normal Kidney Function Table 3. Multiple regression analysis of visceral abdominal fat and cystatin C, and renal function (egfrcys). Variables Cystatin C (mg/l) egfrcys (ml/min/1.73 m 2 ) B SE P-value B SE P-value Visceral fat area (cm 2 ) ( 1/1000) ( 1/10000) F = 4.124, R 2 = F = 3.645, R 2 = Calculated by multiple regression model using each cystatin C and egfrcys as the dependent variable. Each model (cystatin C and egfrcys) is adjusted for age, sex (male, o; pre-menopause women, 1; post-menopause women, 2), systolic blood pressure, high-density lipoprotein cholesterol, hypertension treatment, diabetes mellitus treatment, lipid treatment, and smoking. egfr: estimated glomerular filtration rate. 니즘은현재까지정확히알려져있지는않지만복부내장지방으로부터분비되는염증인자및싸이토카인, 인슐린저항성, 복부비만이있을때혈관내피기능장애및레닌-안지오텐신계의활성화등이이들의관련성을설명할수있을것으로생각한다 ) 복부내장지방은렙틴 (leptin), 아디포넥틴 (adiponectin), 레지스틴 (resistin) 을포함하는수많은아디포카인 (adipokine) 과 TNF-a 및 IL-2,6 등의염증관련사이토카인 (cytokine) 을분비하며 24) 이는고인슐린혈증 (hyperinsulinemia), 증가된 cortisol생산같은내분비장애와도연관되어있어인슐린저항성과대상증후군, 당뇨와도연관되어있다 ) 이런모든생리학적인과정은신장기능저하를일으키는요인과도연관되어있다. 본연구의한계점은단면연구이기때문에복부내장지방과 cystatin C와의인과관계를정확히알수없고다른혼란변수를배제하지못하였을가능성이있다. 앞으로전향적인연구가필요하며, 내장지방의감소가 cystatin C의증가와신기능저하에유용한영향을미칠수있을지에대한연구가필요할것으로생각한다. 결론적으로본연구에서는정상신기능을가진성인에서도복부내장지방은신기능감소의조기지표인 cystatin C와독립적인연관성이있음을알수있었으며복부내장지방은기존의심혈관위험인자로주의를요할뿐아리나신질환발생이전신기능저하와도관련될수있음을고려하여야한다. 는정상신기능을가진성인을대상으로컴퓨터단층촬영으로측정한내장지방과 cystatin C와의연관성을알아보고자하였다. 방법 : 사구체여과율 60 ml/min/1.73 m 2 이상인 318명을대상으로문진및신체계측, 혈액검사, 컴퓨터단층촬영을통한지방측정을실시하였다. 내장지방과 cystatin C 및신장기능과의상관성을피어슨상관분석과다중회귀분석법으로분석하였다. 결과 : 내장지방과 cystatin C는양의상관관계가있었으며 (r=0.284, P<0.001) 내장지방과사구체여과율 (egfrcys) (r= , P<0.001) 은음의상관관계를보였다. 혼란변수를보정한후다중회귀분석결과내장지방면적과 cystatin C는독립적으로유의한양의연관성이있었으며 (P=0.013) 내장지방과사구체여과율은독립적으로유의한음의상관관계를보였다. 결론 : 정상신기능가진성인을대상으로내장지방은신기능감소의조기지표인 cystatin C와독립적인연관성이있음을알수있었으며이를통해내장지방이신질환발생이전신기능저하와의관련성이있음을알수있었다. 중심단어 : Cystatin C; 내장지방 ; 신장질환 REFERENCES 요약 연구배경 : 복부내장지방은신장질환의위험인자로알려져있으며 cystatin C는 creatine보다신기능저하의더예민한지표로비만환자에서증가하는것으로알려져있다. 이에본연구 1. Gelber RP, Kurth T, Kausz AT, Manson JE, Buring JE, Levey AS, et al. Association between body mass index and CKD in apparently healthy men. Am J Kidney Dis 2005;46: Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med 2006;144: Vol. 1, No. 2 Aug 2011 Korean J Fam Pract

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7 Jeong-Ah Hong, et al: Association between Serum Cystatin C Level and Visceral Fat in Healthy Individuals with Normal Kidney Function adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 2003;26: Marasinghe JP, Amarasinghe AA. Visceral fat mass as a marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome. BJOG 2007;114: Vol. 1, No. 2 Aug 2011 Korean J Fam Pract

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