86 J Korean Soc Pediatr Nephrol Vol. 18, No. 2, 85-91, 2014 은신반흔의위험이높기때문에신속한진단과적절한치료에대해강조하고있고 [3-5], 특히상부요로감염은만성신부전과신성고혈압등의중요한원인인신반흔의위험인자이고그위험도는방광요관역류

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1 Original article J Korean Soc Pediatr Nephrol 2014;18:85-91 DOI: ISSN (print) ISSN (online) 요로감염소아에서혈청 Cystatin C 측정의임상적적용고려대학교의과대학소아과학교실 심지현 ᆞ 임형은 ᆞ 유기환 Ji Hyun Sim, M.D., Hyung Eun Yim, M.D., Ph.D., and Kee Hwan Yoo, M.D., Ph.D. Department of Pediatrics, College of Medicine, Korea University, Seoul, Korea Corresponding Author: Hyung Eun Yim Department of Pediatrics, College of Medicine, Korea University, Seoul, Korea Tel: , Fax: he-yim@hanmail.net Received: 11 September 2014 Revised: 23 September 2014 Accepted: 26 September 2014 Correlation between Serum Cystatin C Levels and Clinical Parameters in Children with Urinary Tract Infections Purpose: We aimed to investigate the correlation between serum cystatin C and clinical manifestations in pediatric patients with urinary tract infections (UTIs). Methods: We studied 137 patients admitted with UTIs from June 2012 to May Depending on the presence of renal cortical defects on 99m Tc-dimercaptosuccinic acid scintigraphy, we classified patients into non-renal and renal defect groups. Laboratory and clinical parameters were analyzed, including the levels of serum cystatin C. The correlation between cystatin C and other variables was assessed. Results: Serum cystatin C levels did not differ between the non-renal and renal defect groups. In both groups, serum cystatin C levels increased after 4-5 days of treatment, compared with the level at admission (P<0.001). However, mean levels were within normal ranges. The concentration of serum cystatin C positively correlated with serum creatinine and negatively correlated with age (P<0.05). In contrast, there was no correlation between serum cystatin C and other variables. Conclusion: Serum cystatin C does not appear to be a useful biomarker for renal defects in pediatric patients with UTIs. Further studies are necessary to conclude whether serum cystatin C is helpful in predicting deterioration in renal function in pediatric patients with UTIs. Key words: Cystatin C, Urinary tract infection, Pyelonephritis 서론 This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( creativecom mons.org/licenses/bync/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 소아연령에서의요로감염은가장흔한세균성질환중의하나로특히영 ᆞ 유아에서요로감염은세균성뇌수막염, 세균성폐렴, 패혈증보다높은유병률 을보인다 [1]. 여아에서약 1-3%, 남아에서약 1% 가이환되며, 설명되지않는 발열이있는영유아의 4-20% 정도에서요로감염으로진단된다 [2]. 미국소아 과학회는소아요로감염의가이드라인에서 2 세이전의첫발열성요로감염 Copyright 2014 The Korean Society of Pediatric Nephrology

2 86 J Korean Soc Pediatr Nephrol Vol. 18, No. 2, 85-91, 2014 은신반흔의위험이높기때문에신속한진단과적절한치료에대해강조하고있고 [3-5], 특히상부요로감염은만성신부전과신성고혈압등의중요한원인인신반흔의위험인자이고그위험도는방광요관역류가있을때, 적절한항생제치료의지연, 그리고신우신염의재발이있을때증가하게된다 [5, 7-8]. 요로감염은신실질의침범유무에따라하부요로감염과상부요로감염 ( 이하, 급성신우신염 ) 으로분류하고, 급성신우신염과하부요로감염을감별하기위해발열기간, 신장초음파및혈청백혈구, C- 반응단백등의염증표지자등이이용된다 [6, 7]. 최근의연구들에따르면 procalcitonin 이심한세균감염에서증가하며, 특히상부요로감염과하부요로감염의감별에유용한것으로보고되었으며 [8], Neutrophil gelatinase-associated lipocalin (NGAL) 은급성신우신염과신부전의조기진단에유용함이보고된바있다 [9]. 신반흔을진단하는여러방법중 Technetium-99m dimercaptosuccinate (Tc-99m DMSA) scan 검사는급성신우신염을진단하고이후신반흔을진단하는데가장민감한검사로알려져있으나방사선조사뿐아니라숙련된의료진이필요하다는단점이있다 [10, 11]. Cystatin C는최근대두되고있는새로운신기능지표중하나로, 혈청크레아티닌과달리세뇨관세포에서의변형이없고근육, 성별, 나이등에의해영향을받지않아사구체여과율과상관관계가높은것으로알려져있으며 [12], 급성신손상의조기진단에있어서모두혈청크레아티닌보다우월한것으로보고된바있으며, 또한만성신부전환자뿐아니라정상사구체여과율을가지고있는환자에있어심혈관계질환의예측인자로도알려져있다 [13, 14]. Cystatin C는혈중농도가염증성질환의영향을받지않는다고알려져있는데, 최근 Yim 등에의한소아요로감염환자를대상으로한전향적연구에서급성신우신염군에서하부요로감염군에비하여혈청 Cystatin C가의미있게증가하였고, 소변 NGAL/Cr, KIM-1/Cr 과도상관성이있음을보고하였다 [15]. 따라서, 만성신질환진행의위험요소인소아연령의요로감염에있어 Cystatin C의임상적적용에대하여체계적인연구의필요성이있으며, 이에저자들은앞선연구에치료기간과연구범위를확장하였고증상이있는소아요로감염환자에서치료반응을포함한임상증상과의연관성, 신기능의예측인자로서의혈청 Cystatin C측정의유용성에대하여알아보고자하였다. 대상및방법 1. 환자군 2012 년 6월부터 2014 년 5월까지 24 개월동안 38 이상의발열또는육안적혈뇨가있거나배뇨통, 빈뇨등의증상을주소로내원하여요로감염진단하고려대학교소아청소년과에서입원치료를시행한환자를대상으로하였으며입원시시행한소변침사현미경검사에서농뇨가확인되고소변배양검사상양성소견을보인환아중요로감염의기왕력이있는경우와선천수신증, 신우요관이행부폐색, 신저형성등의요로계기형이있는경우는대상에서제외하였고, 연구내용에대하여모든보호자에게동의서를시행하였다. 발열은고막체온계로 38 이상인경우로정의하였고, 소변및혈액검체는내원후즉시채취되었으며, 항생제투여는소변검체채취이후에시작되었다. 소변은치골상부방광천자및도뇨관채뇨에의해, 소변을가릴수있는경우에는청결중간뇨로채취되었다. 농뇨는소변침사현미경검사에서백혈구수가고배율시야당 5개이상인경우로정의하였으며배양검사결과 10 5 colony forming unit (CFU)/mL 이상의단일균집락이배양될때소변배양검사양성으로판단하였다. 2. 검사실소견및영상검사모든환아는입원당시정맥항생제투여전혈청 Cystatin C를포함한말초혈액내백혈구수, 혈청 C- 반응단백, 혈청크레아티닌을측정하였고, 정맥항생제투여 4-5 일후혈청 Cystatin C의변화를재측정하였다. 혈청 Cystatin C 의정량측정은 particle-enhanced turbidimetric immunoassay (Gentian, Moss, Norway) 를이용하였다. 복부초음파검사와 Tc-99m DMSA 신스캔검사는입원당일에시행되었으며, 복부초음파결과 Society for fetal urology grade 가 1 이상시에수신증으로진단하였고 [16], 신스캔검사에서신장피질의결손의유무에따라비신결손군 (non-renal defect group) 과신결손군 (renal defect group) 으로분류하였다. 초기신결손을보였던소아에서 5-6 개월후신스캔을재시행하여결손이보이는경우를신반흔으로정의하였으며 [17], 추적검사를시행하기까지의기간동안에요로감염이재발된소아는연구에서제외하였다. 2 세미만소아에서퇴원전배뇨중방광요도조영술을시행하였다. 각검사의이상여부는총두명이상의소아신장전문의와영상의학전문의또는핵의학전문의에의해판

3 Sim JH, et al.: Correlation between Serum Cystatin C Levels and Clinical Parameters in Children with UTIs 87 독되었다. 비신결손군 (non-renal defect group) 과신결손군 (renal defect group) 에서환아의성별과연령, 입원전발열기간, 항생제사용후발열기간, 총입원기간, 혈청 Cystatin C, 말초혈액내백혈구수, 혈청 C- 반응단백, 혈청크레아티닌, 수신증, 방광요관역류, 신반흔형성의항목들에대하여두군간비교분석을시행하였으며, 혈청 Cystatin C와각변수들간의상관관계를분석하였고, 입원당시와입원치료후혈청 Cystatin C의변화추이를비교하였다. 3. 통계분석 SPSS for Windows (version 18, SPSS, Chicago. IL, USA) 를사용하여통계처리및자료분석을하였으며, 결과값은평균 ± 표준편차로기술되었다. 신결손군과비신결손군에서연령의차이는 Mann-Whitney U test, 성별의차이는 Pearson chi-square test 를이용하여분석하였으며, 혼란변수인연령과성별을보정하기위하여연령이외의연속형변수는공분산분석 (analysis of covariance, ANCOVA) 으로분석하였고, 표본중정규성을만족하지않는변수는로그변환후분석을시행하였다. 명목형변수인신결손, 수신증과방광요관역류유무는로지스틱회귀분석 (logistic regression analysis) 을시행하였다. 혈청 Cystatin C와변수들간의상관관계는연령을보정하여편상관분석 (partial correlation analysis) 을이용하였으며, 치료전후혈청 Cystatin C 수치의비교는연령, 성별영향을보정하기위하여로지스틱회귀분석을이용하였다. P-value 가 0.05 미만인경우를통계적으로유의한것으로판정하였다. 결과 1. 연령및성별 2012 년 6월부터 2014 년 5월까지고려대학교병원소아청소년과에입원하여증상이있는첫요로감염으로치료받은소아중연구기준을만족하는소아는 137 명으로남아는 86명 (62.8%), 여아는 51 명 (37.2%), 남녀성비는 1.7:1 이었고, 평균연령은 9.73±17.62 개월이었다. 신스캔결과에따라비신결손군은 79 명으로남아가 54 명 (68.4%), 평균연령은 9.45±15.58 개월이었고, 신결손군은 58 명으로남아가 32 명 (55.2%), 평균연령은 9.04±15.16 개월로두군간에성별과연령은유의한차이가없었다 (Table 1). 2. 신결손유무에따른대상자들의임상적특성 모든변수는연령과성별을보정하여분석하였으며, 비신 결손군과신결손군에서입원전평균발열기간은각각 1.72 ±1.45 일 vs. 2.50±1.54 일로두군간에유의한차이가있었 으나 (P<0.05), 항생제사용후발열기간은각각 0.59±0.76 일 vs. 0.76±1.17 일, 평균재원기간은각각 8.47±1.74 일 vs. 8.60±2.13 일로통계적으로두군간에유의한차이가없었 다. 말초혈액백혈구수, 혈청 C- 반응단백과혈청크레아 티닌은비신결손군과신결손군에서통계학적으로유의한 차이를보였고 (P<0.001), 혈청 Cystatin C 는두군간에유의 한차이는없었다 (P=0.52). 비신결손군과신결손군에서수 신증유무는유의한차이가없었으며, 방광요관역류의유무 도각군간차이가없었다 (Table 1). 3. 혈청 Cystatin C 와다른변수들간의상관관계 혈청 Cystatin C 와환자군의연령은뚜렷한음의상관 관계를보였으며 (r=-0.409, P<0.05), 혈청크레아티닌과는 뚜렷한양의상관관계를보였다 (r=0.305, P=0.001). 혈청 Cystatin C 는입원전발열일수, 항생제사용후발열일수, 총입원기간, 총백혈구수, 혈청 C- 반응단백과상관성이 없었다 (Table 2). Table 1. Patient Characteristics between Non-Renal Defect Group and Renal Defect Group Variables Non-renal Renal P- defect group defect group Value Total, No. (%, n=137) 79 (57.7) 58 (42.3) Gender, Male, No. (%)* 54 (68.4) 32 (55.2) Age (months) 9.45± ± Fever duration (days) 1) 1.72± ±1.54 <0.05 Fever duration (days) 2) 0.59± ± Hospital day (days) 8.47± ± Leukocyte Count 14,333±3,987 18,701±8,008 <0.001 (count/mm 3 ) CRP (mg/dl) 3.69± ±7.27 <0.001 Creatinine (mg/dl) 0.29± ±0.15 <0.001 Serum Cystatin C 1.01± ± Hydronephrosis, No. (%) 27 (19.7) 27 (19.7) VUR, No. (%, n=112) 16/67 (14.3) 10/45 (8.9) Renal scar, No. (%, n=14) - 6 (42) - Values are presented as means±sd or numbers (proportions). 1) Fever duration before admission. 2) Fever duration after antibiotics administration. *Chi-square test, Mann-Whitney U test, ANCOVA adjusted for age and gender after log transformation, logistic regression analysis adjusted for age, gender.

4 88 J Korean Soc Pediatr Nephrol Vol. 18, No. 2, 85-91, 항생제투여전과후혈청 Cystatin C 수치변화 전체환자중 56 명에서항생제투여 4-5 일후혈청 Cystatin C 를다시측정하였고, 입원당시에비하여치료후 유의하게증가하였다 (1.02±0.21 mg/l vs. 1.07±0.21 mg/ L, P<0.001). 비신결손군 (n=29) 과신결손군 (n=27) 각각에 서도혈청 Cystatin C 가치료전에비해치료후통계적으 로유의하게증가함을확인하였다 ( 비신결손군, 1.00±0.25 Table 2. Correlation of Serum Cystatin C with Variables Variables Serum Cystatin C (mg/l) Correlation coefficient (r) P-value Age (months) <0.05 Fever duration (days) 1) Fever duration (days) 2) Hospital stay (days) Leukocyte count (cell/mm 3 ) CRP (mg/dl) Creatinine (mg/dl) <0.05 r=partial correlation coefficient adjusted by age, gender and serum creatinine. 1) Fever duration before admission. 2) Fever duration after antibiotics administration. A B Fig. 1. Comparison of the levels of serum cystatin C at admission and after 4-5 days of treatment. (A) Non-renal defect group (n= 29), (B) Renal defect group (n=27), *P<0.001, vs. pre-treatment. mg/l vs. 1.04±0.25 mg/l; 신결손군, 1.05±0.16 mg/l vs. 1.10±0.20 mg/l, P<0.001) (Fig 1A, B). 치료후두군간혈청 Cystatin C 수치는차이를보이지않았다 (P=0.83). 고찰 Cystatin C는 1961 년뇌척수액에서처음발견된 cystein protease inhibitor 의한종류로, 1985 년 Simonsen 등 [18] 에의해 1/cystatin C와 51Cr-EDTA 제거율간의상관관계가있음이처음으로보고되었다. Cystatin C는모든유핵세포에서일정한속도로생성되는 13.3 kd의저분자량단백질로, 사구체기저막에서자유롭게여과되며근위세뇨관에서전량재흡수되고완전히분해되어체내에서의농도가사구체여과율에의해서만결정되는특성을가지고있기때문에사구체여과율을반영하는표지자로제안되었다. Dharnidharka 등 [19] 에의한대규모메타분석에서혈청 Cystatin C가사구체여과율을측정함에있어크레아티닌에비해진단적가치가높음을증명하였고, 2004 년에는신기능을평가하는지표로미국식품의약국의승인을받았다. 또한, Cystatin C는다양한연구를통해기존의방법들에비해장점을가지고있음이알려졌는데, 초기신기능감소를확인함에있어크레아티닌보다민감하고, 근육량, 성별, 나이, 식품섭취또는약물등에의해혈중농도가변하는크레아티닌과달리성별, 연령, 근육량및영양상태에의한개인차가없기때문에소아나노인의신기능평가에유용하며 [20-22], β2-microglobulin 과달리혈중농도가염증성질환의영향을받지않는다고보고되었다 [23, 24]. 발열을포함하여악성질환, 당뇨, 간경변등에영향을받지않으며 [25, 26], 급성신부전과만성신부전환자에서신기능의감소를예민하게반영한다고알려져있다 [27, 28]. 반면, 갑상선호르몬에의해 Cystatin C의생성이조절되기때문에갑상선질환시수치가변할수있으며, 신이식환자에서스테로이드호르몬투여시에증가하였다는보고가있고, 방광암, 결장직장암, 백혈병에서수치가증가하였다는보고도있어, 결과치의해석에주의가요구되며, 1세미만에서정상치가확립되어있지않다는제한점이있다 [29-32]. 저자들은이전연구에서 12 개월간요로감염으로입원한 73 명의소아환아를대상으로혈청 Cystatin C가하부요로감염환아에비하여급성신우신염환아에서유의하게농도가증가하여염증지표로서의가능성이있음을확인하였다 [15]. 이에본연구에서는연구기간과대상을확대하

5 Sim JH, et al.: Correlation between Serum Cystatin C Levels and Clinical Parameters in Children with UTIs 89 고, 혈청 Cystatin C와소아요로감염의임상소견과의연관성을확장시켜소아요로감염에서혈청 Cystatin C 측정의의의에대하여알아보고자하였다. 염증지표로서의 Cystatin C의유용성을확인하기위한연구로 Randers 등 [24] 에의하면심각한급성염증상태에있는 21 명의성인환자에서 C- 반응단백과혈청 Cystatin C를측정하였으며, 대부분의환자에서높은 C- 반응단백수치를보이는반면 Cystatin C 수치는상승되지않았고, 치료후추적검사에서 C- 반응단백은통계적으로유의하게감소하였으나, Cystatin C는유의한차이가없다고보고하였다. 소아발열성요로감염환자를대상으로본원에서시행한이전연구결과또한 Cystatin C와혈청 C- 반응단백은상관성이없었으나, 신결손의유무에따라급성신우신염과하부요로감염으로분류하였을때혈청 Cystatin C 는각군간통계적으로의미있는차이를보였다 [15]. 그러나연구기간을연장하고발열이없는증상성요로감염환자를포함한본연구에서는혈청 Cystatin C는비신결손군과신결손군에서차이를보이지않았다. 본연구에서의평균연령이각각 9.04±15.16 과 9.45±15.58 개월임에반해이전연구에서는급성신우신우신염군 (n=46) 과하부요로감염군 (n=27) 의평균연령이각각 21.3±41.0 개월과 19.9±30.1 개월로본연구와연령의차이가있었으며환자군에도비발열군이포함되어있었기때문에결과의차이가있었던것으로생각된다. 대개의요로감염의발생이생후 12 개월이내라는점에서본연구의강점이있고, 발열유무에따른추가분석의필요성이있었으나본연구에서는비발열군의대상환자가상대적으로적어발열의유무와 Cystatin C와의관련성은비교하지못하였다. 향후더많은환아를대상으로발열과혈청 Cystatin C의상관성에대한연구가필요할것으로사료된다. 본연구에서는치료전에비해치료 4-5 일후 Cystatin C 의혈중농도가통계적으로유의하게증가하였고, 또한비신결손군과신결손군각각에서도치료전에비해치료후의 Cystatin C는유의하게증가하였으나각군간치료후혈청 Cystatin C는의미있는차이가없었다. 혈청 Cystatin C 는사구체여과율의작은변화에도반응하기때문에크레아티닌에비하여경도의신기능감소도반영하며 [19, 33], 또한정상범위가약 0.5 에서 1까지거의 2배에가깝고, cho 등에의하면혈청 Cystatin C는크레아티닌에비해약 3배까지증폭되어상대적으로큰변동폭으로변화하기때문에사구체여과율의변화를발견하는데보다용이하다고보고하였다 [34]. 심장수술을받은소아환자를대상으로한 Vandevoorde 등 [35] 의연구에서수술후급성신손상 의발생을예측하는데있어 NGAL의혈중농도는 2시간후증가한반면 Cystatin C는 12 시간이소요되었다고보고하였다. 위의연구결과들을고려하였을때본연구결과치료후 Cystatin C의증가는경미한신기능의저하를시사할수있으나하부요로감염군에서도의미있게증가하였고, Cystatin C의참고범위인 1.10 mg/l 를초과하지않은점으로미루어신기능저하와의관련성은명확하지않으며, 따라서요로감염에의한직접적인상승효과또는염증반응과혈청 Cystatin C와의관련성을고려해야할것으로생각된다. Cystatin C는혈청과소변모두에서검사가가능하여측정방법이용이하고, 소아와성인모두에서사구체여과율을크레아티닌보다민감하게반영한다고알려져있어, 현재유망한신기능지표로생각되고있다. 또한생후 1년이후로는연령과는무관하게일정한값을유지하고, 성인과거의같은값을보여크레아티닌과달리연령에따라다른정상범위를적용할필요가없다는장점이있고, 재현성이좋으므로지속적인추적관찰에사용하기좋은지표이나, 일부연구에서는상반되는결과를제시하기도하였다 [36]. 영아를대상으로한 Armangil 등 [37] 에의하면생후 1일부터첫 1년간 Cystatin C는높은혈중농도를보이고, 출생직후에가장높으며, 이후 4개월간사구체여과율의성숙에따라급격히감소된다고보고하였다. 본연구에서혈청 Cystatin C는혈청크레아티닌과양의상관관계가있었으며, 연령이증가함에따라뚜렷이감소하는추세를보였는데, 이는본연구의연령범위가 1세에서 5세사이이지만, 3개월미만이 42.5%, 4-12 개월이 48.7% 로상대적으로 1세미만의영아가많았기때문으로생각되며, 요로감염환아의약반수가주로 1세미만임을고려할때 [1, 2], 임상에활용할수있는정상치의확립이중요할것이며, 향후전연령의소아를대상으로한연구가계획되어야할것이다. 앞서언급하였듯이소아기의요로감염은신기능저하를유발할수있으므로정확한진단뿐아니라지속적인추적관찰이중요하며, 따라서본연구에서저자들은소아요로감염에있어혈청 Cystatin C의의의에대하여고찰하고자하였다. 혈청 Cystatin C는신결손유무를진단하는데의미가없었으나, 치료후의미있게상승함으로써지연염증표지자로의가능성을시사하였다. 그러나, 크레아티닌을제외한다른변수들과의상관성이없고연령에대해변화하는값을가지므로이상적인지표라고보기어렵다. 본연구에서는대상자의수와연구범위를확대하였다는점에서의의가있으나정상소아의대조군이없었다는점에서한계가있다. 또한, Cystatin C의추적검사가평균적으로 4-5

6 90 J Korean Soc Pediatr Nephrol Vol. 18, No. 2, 85-91, 2014 일후에이루어졌기때문에 Cystatin C의상승의원인을단정짓기어렵다는제한점이있으며, 이를위해연속적인 Cystatin C 농도변화및연령에따른 Cystatin C의차이를확인해야할것으로생각되고, 정상소아와요로감염을제외한감염이있는소아에대한비교연구및신생아를제외한 1세미만의소아에서참고치의정리가필요할것으로보인다. 이미 Cystatin C는그유용성에대하여많은연구가이루어지고있고, 여러센터에서신속한검사가가능하지만성인에비하여소아에서사용이제한적이었다. 그러나크레아티닌등의다른지표와비교하여유리한점을많이가지고있다는점을고려하였을때향후소아요로감염영역에서단지염증지표로서의역할뿐아니라신기능의저하를예견하고지속적인추적관찰을하는데유용성이있을것이라생각되며이를위해대규모전향적인연구가필요할것이라사료된다. 요약목적 : 만성신질환진행의위험요소중하나인소아요로감염에서 Cystatin C의관련성에대해서는알려진바가없으며, 본연구는소아요로감염에서혈청 Cystatin C 측정의임상적유용성에대하여알아보고자하였다. 방법 : 2012 년 6월부터 2014 년 5월까지요로감염으로입원한소아 137 명을대상으로하였다. 신결손유무에따라비신결손군과신결손군으로나누어각군에서혈청 Cystatin C를포함한다른변수들의평균치를비교분석하였으며, Cystatin C와혈청및임상변수들간의상관분석을시행하였고, 입원당시와치료후혈청 Cystatin C의변화를분석하였다. 결과 : 비신결손군과신결손군에서혈청 Cystatin C는유의한차이가없었다. 혈청 Cystatin C는연령이증가함에따라감소하는경향을보였고 (P<0.05), 혈청크레아티닌과는뚜렷한양의상관관계를보였으며 (P<0.05), 이외의변수들과는상관성이없었다. 항생제투여 4-5 일후재시행한혈청 Cystatin C는입원당시에비하여치료후비신결손군과신결손군에서유의하게증가하였다 (P<0.001). 결론 : 혈청 Cystatin C는소아요로감염에서신결손유무를감별하는데있어유용하지않을것으로사료되며, 향후혈청 Cystatin C가소아요로감염에서신기능의저하를예견하고지속적인추적관찰을하는데유용할수있을지에대한추가연구가필요할것으로생각된다. References 1) Winberg J, Andersen HJ, Bergstrom T, Jacobsson B, Larson H, Lincoln K. Epidemiology of symptomatic urinary tract infection in childhood. Acta Paediatr Scand Suppl 1974: ) Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: a meta-analysis. Pediatr Infect Dis J 2008;27: ) Practice parameter: the diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics 1999;103(4 Pt 1): ) Jacobson SH, Eklof O, Eriksson CG, Lins LE, Tidgren B, Winberg J. Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up. BMJ 1989;299: ) Newman TB. The new American Academy of Pediatrics urinary tract infection guideline. Pediatrics 2011;128: ) Morgan MG, McKenzie H. Controversies in the laboratory diagnosis of community-acquired urinary tract infection. Eur J Clin Microbiol Infect Dis 1993;12: ) Jaye DL, Waites KB. Clinical applications of C-reactive protein in pediatrics. Pediatr Infect Dis J 1997;16:735-46; quiz ) Smolkin V, Koren A, Raz R, Colodner R, Sakran W, Halevy R. Procalcitonin as a marker of acute pyelonephritis in infants and children. Pediatr Nephrol 2002;17: ) Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis 2008; 52: ) Stokland E, Hellstrom M, Jacobsson B, Jodal U, Lundgren P, Sixt R. Early 99mTc dimercaptosuccinic acid (DMSA) scintigraphy in symptomatic first-time urinary tract infection. Acta Paediatr 1996;85: ) Majd M, Nussbaum Blask AR, Markle BM, Shalaby-Rana E, Pohl HG, Park JS, et al. Acute pyelonephritis: comparison of diagnosis with 99mTc-DMSA, SPECT, spiral CT, MR imaging, and power Doppler US in an experimental pig model. Radiology 2001;218: ) Ahlstrom A, Tallgren M, Peltonen S, Pettila V. Evolution and predictive power of serum cystatin C in acute renal failure. Clin Nephrol 2004;62: ) Nejat M, Pickering JW, Walker RJ, Westhuyzen J, Shaw GM, Frampton CM, et al. Urinary cystatin C is diagnostic of acute kidney injury and sepsis, and predicts mortality in the intensive care unit. Crit Care 2010;14:R85. 14) Ristikankare A, Poyhia R, Kuitunen A, Skrifvars M, Hammainen P, Salmenpera M, et al. Serum cystatin C in elderly cardiac surgery patients. Ann Thorac Surg 2010;89: ) Yim HE, Yim HS, Bae ES, Woo SU, Yoo KH. Predictive value of

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386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon