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1 Korean J Urol Oncol 2012;10(3): 현미경적혈뇨의평가 연세대학교원주의과대학비뇨기과학교실 정현철 Evaluation of Microscopic Hematuria Hyun Chul Chung Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea Microscopic hematuria is common cause for referral to urology, nephrology or both. However, the definition and evaluation of microscopic hematuria is not established. The most common urologic causes are benign hyperplasia, urinary calculi and infection. But urologic malignancy is found about 2.6% to 4% in patients with microscopic hematuria. The assessment of microscopic hematuria patient is include a history, physical examination and a radiologic evaluation such as multi-phasic computed tomography. Especially in high risk patient (35 years and older, smoking history, male gender, chemical exposure), malignancy rate is more increased, cystoscopy and cytology should be performed. (Korean J Urol Oncol 2012;10: ) Key Words: Microscopic hematuria, Urologic malignancy 서 현미경적인혈뇨는임상적으로가장흔하게보는증상으로과도한운동, 염증, 결석등의양성질환부터신장종양, 방광종양에이르는악성질환등의다양한원인에의해서발생한다. 하지만임상에서환자에대한접근은병원마다임상의사마다다양한방식으로진행되고이는현미경적혈뇨에대한정의및검사에대한방식및검사를필요로하는환자, 추적관찰의방법에대한명확한기준이선행되지않음에기인한다. 특히재발성혈뇨환자및항응고제복용환자의경우진단계획및검사방식에많은혼선이있어불필요한검사로인한환자의진료비증가, 진료혼선을야기한다. 논문접수일 :2012 년 11 월 21 일, 수정일 :2012 년 12 월 6 일, 채택일 :2012 년 12 월 8 일교신저자 : 정현철, 연세대학교원주의과대학비뇨기과학교실강원도원주시일산동 162, Tel: , Fax: chc7174@yonsei.ac.kr 론 여기서는최근에나온논문및진료지침을근거로현미경적인혈뇨의정의및원인을찾기위한방법, 이후추적검사에대해서이야기하고자한다. 현미경적혈뇨의정의현미경적혈뇨는말그대로적정한방법을이용한검체를채취한소변을이용하여고배율시야에서적혈구가발견되는것으로정의할수있다. 하지만임상적으로의미있고보다정밀한검사를요하는현미경적혈뇨인지여부에대해서는아직많은논란이있다. 가장널리이용되며최근미국비뇨기과학회현미경적인혈뇨기준 1-5 은고배율시야에서 3개이상의적혈구가발견되는것을기준으로하지만캐나다비뇨기과학회 6 에서는 2개이상의현미경적혈뇨를의미있는것으로보고하고있으며국내 7 의연구에서도고배율시야당 5개이상을정의하는등아직현미경적혈뇨의정의에대해서는이견이많이있다 (Table 1). 또한현미경적혈뇨의경우검사시기및운동, 생리등의일상적인상태에서도유발되고이에따른개개인의편차도존재하기때문에진단기준을명확히하 101

2 102 대한비뇨기종양학술지 : 제 10 권제 3 호 2012 Table 1. Degree of hematuria versus diagnostic yield 2 RBCs/HPF >50 Total no Significant lesion (%) 2(16.7) 8(11.6) 100 (19.7) 31 (30.1) Life-threatening (%) 2 (2.9) 16 (3.2) 9 (8.7) RBCs: red blood cells, HPF: high power field. p-value <0.05 <0.05 <0.05 는데많은어려움이있으며이러한혼재로인해논문간의결과의해석에많은편차가존재한다. 국내현미경적혈뇨에대한기준은아직명확하지않으며특히병원마다검사실마다검사방법및참고치에대한기준이상이하여임상에서환자를진료하는데많은애로점이있으며앞으로국내에서도많은환자를대상으로하는장기간연구를통해진단및치료에대한명확한기준이설정되어야할것이다. 소변검사의방법과시기 현미경적혈뇨를진단하는데가장기본이되는것은정확한검체를얻는것이다. 일반적으로중간뇨를깨끗한방법 (mid stream clean catch collection) 으로채취하는것을권장하고있으며초기약 10ml의소변을버린후채취하게된다. 보다정확한검사를위해농뇨, 세균뇨및오염이일어난경우는제외하며과도한운동, 생리, 바이러스질환및손상, 감염의증상이있는경우에는제외한다. 만약검체에서의미있는편평세포가관찰되는경우에는검체가오염된것으로간주하고도뇨관을이용하거나소변검사를다시시행하는것을권장한다. 검체의채취는남성의경우스스로소변을보는경우중간뇨를채취하며포경이되어있지않은경우에는음경포피를뒤로제친후오염이되지않은상태로채취한다. 여성의경우대음순과소음순주위를소독된거즈를이용하여깨끗하게한후중간뇨를채취하며배뇨가불가능할경우에는도뇨관을이용하여채취한다. 현미경적혈뇨검사기준 현미경적혈뇨는전통적으로 2회이상의검사에서연속적으로혈뇨가보이는경우검사를진행하는것을권장했지만 2012년미국비뇨기과학회 1 에서는보다기준을강화하여 1회라도의미있는현미경적혈뇨가나타나는경우에 추가검사를진행하는것을권장한다. 이러한근거로첫째위중한질환즉종양의경우재검사로인한진단이늦어짐으로써치료시기를놓칠수가있다. 여러보고에의하면현미경적혈뇨환자의 % 8-12 에서악성종양이관찰되며이를메타분석한결과전립선암의발생율 3.6% 와비슷한 3.3% 가능성을보인다고이야기하고있다. 1 둘째로현미경적혈뇨환자의검사방법이심각한수준의건강에위협이되지않으며검사시행후악성종양, 요로결석등의질환발견시얻는이득이매우크다는점을들수있다. 현미경적혈뇨환자의메타분석연구 1 에서환자중요로결석이있을확률은 6.0%, 전립선비대증은 12.9%, 요도협착은 1.4% 로많은수의환자에서질병이발견되고이를치료함으로서얻는이득이검사로인한손실보다크다고볼수있다. 즉소변검사에서현미경적혈뇨가관찰된경우원인을찿기위한검사로종양및다른양성질환의진단을높임으로써시간이지체되면서생길수있는여러문제를예방하는것이중요하다. 현미경적혈뇨의역학및원인현미경적혈뇨의역학은앞에서언급한바와같이현미경적혈뇨의정의에따라다양하게보고가된다. 또한연구대상환자의연령, 성별, 검사시기및기간, 검체의채취방식, 위험인자의유무등으로인해많은차이를보인다. 최근일반인 8만명을대상으로한대규모연구에의하면 % 의유병률을가지며특히 60세이상의흡연력이있는남성에서높게나타나는것으로보고하고있으며 13,14 국내에연구에서는 13,678명을대상으로한연구에의하면약 1.38% 의유병률을나타내는것으로보고하고있다. 15 현미경적혈뇨는많은경우에서원인을찾지못하는경우도있지만내과적질환및양성질환, 악성종양등의다양한원인에의해발생하며가장흔한비뇨기과적인원인은양성전립선비대증, 방광염, 요로결석등의질환이있다. 보고자마다차이를보이지만메타분석을통한연구를보면비뇨기계악성종양의경우약 2.6% 에서비뇨기계암을포함한악성종양은약 4% 에서관찰된다 (Table 2, 3). 7,16-21 이러한비뇨기계암을고려해야하는위험인자는나이성별및흡연력, 화학물질등의노출정도가중요하며환자에대한문진이이러한위험요소가있는경우에는보다정밀한추가검사를시행하여야한다 (Table 4). 내과적인질환을예측할수있는인자로는 urine cast, 단백뇨, 비정형적혈구가관찰되는경우전통적으로감염및면역, 약물등에의한신장염및신장병을고려해야하며

3 정현철 : 현미경적혈뇨의평가 103 Table 2. Lesions found at evaluation of asymptomatic microscopic hematuria 7 Highly significant lesions (n=33) Moderately significant lesions (n=127) Insignificant lesions (n=61) Ureteral stone (29) Bladder carcinoma (2)* Renal cell carcinoma (1)* Renal pelvic carcinoma (1)* Renal parenchymal disease (34) Renal stone (33) Cystitis (31) Prostatitis (21) Polycystic kidney (4) Papillary necrosis (3) Atrophic kidney (1) Renal cyst (26) Exercise hematuria (10) Duplicated collecting sys. (9) Asymptomatic BPH (6) Verumontanitis (5) Nephroptosis (3) Calyceal diverticulum (2) *Urologic malignancy (4), BPH: benign prostatic hyperplasia. Table 3. Likelihood of finding cancer for each gender and age group in the presence of microscopic hematuria 21 Total no. females Age Total no. males Age No. patients No. cancer (%) (3.5) 3 (2.9) 2 (1.9) 5 (4.5) 4 (4.5) 3(15.8) 34 (6.8) 1 (1.7) 1 (1.3) 2 (1.9) 9 (7.9) 16 (17.4) 4(21.1) 1(33.3) 특히 40세이하의젊은환자에서현미경적혈뇨의경우신장병에대한세심한관찰이요구된다. 하지만신장병을의심하는경우에도흡연및지속적인방광자극증상등의종양의위험요소가동반된경우에는비뇨기과질환에대한검사가같이시행하는것을권장하고있다 항응고제환자 최근심장혈관, 뇌혈관질환의증가로항응고제를투여하는환자가증가하고이러한환자들은검사의제한성으로인해진단이늦어지는경우가많다. Culclasure 등 26 은항응 Table 4. Common risk factors for urinary tract malignancy in patients with microhematuria 1 Male gender Age (>35 years) Past or current smoking Occupational or other exposure to chemicals or dyes (benzenes or aromatic amines) Analgesic abuse History of gross hematuria History of urologic disorder or disease History of irritative voiding symptoms History of pelvic irradiation History of chronic urinary tract infection History of exposure to known carcinogenic agents or chemotherapy such as alkylating agents History of chronic indwelling foreign body 고제복용환자와일반인을대상으로현미경적혈뇨및원인에대한연구에서현미경적혈뇨가보이는경우는양군에서차이가없었으며특히항응고제복용환자중 2명에서악성종양이관찰되어항응고제를복용하고있는경우에현미경적인혈뇨가보이는경우비뇨기과및내과적인검사를시행하여야한다고보고하였으며항응고제의종류와현미경적혈뇨와는상관이없는것으로이야기하고있다. 즉항응고제를복용하는환자의현미경적혈뇨의발생률및원인에는일반적인경우와차이가없으며항응고제를복용하는이유만으로검사의진행을늦추는경우는없어야한다. 현미경적혈뇨의검사 현미경적혈뇨환자에서검사는일반적인검사외에영상검사및비뇨기계검사로나눌수있다. 일차적으로환자가내원시과거력, 수술력등을검사해야하며특히앞에언급한위험인자유무에대한세심한청취가요구된다. 특히위

4 104 대한비뇨기종양학술지 : 제 10 권제 3 호 2012 험인자가있는환자의경우영상의학검사를시행하기전에신장기능평가를시행하여이후조영제사용으로인한신장손상을예방하여야하며고위험군에서는방광내시경검사를통한방광내종물에대한세심한관찰이요구된다. 현미경적혈뇨환자의영상의학적인검사는전통적으로경정맥신우조영술 (Intravenous Urograpy) 및복부초음파검사법이이용되어왔다. 경정맥신우조영술은소변을배출부위를따라신우, 요관방광종물의유무에대한유용한검사법이지만작은종물및신장의종물의발견에는제한점을가직있으며복부초음파의경우신장종물의관찰에는유용하지만 Carlos 등 27 의연구에의하면 3cm 이하의작은신종물의경우복부전산화단층촬영에비해많은제한점을가진다. 복부전산화단층촬영은가장널리쓰이는영상의학검사방식으로최근에는조영제를이용하여신우, 요관, 방광부위를검사할수있는다상전산화요로조영술 (Multi phasic Computed Tomography Urography) 을이용하게된다. 이방식을이용하면조영전단계 (Preenhancement phase) 에서는결석및지방을함유하는종양의구분이가능하며동맥기 (Aterial phase) 에는조영제조영을통해종물및염증으 로인한신생혈관의진단이용이하고신실질기 (Parechymal phase) 에는신실질의변화및손상을배설기 (Excreatory phase) 에신우요관등의부위이상유무를감별가능하다. 28,29 최근연구를보면 359명의 40세이하젊은혈뇨환자의약 22.1% (83명) 에서임상적으로유의한병변을진단할수있었으며이들중 75.3% (73명) 의경우에는신장및요관결석이관찰되었고약 4명에서는종양이관찰되었다. 30 방광내시경은현미경적혈뇨환자에서방광내병변을진단할수있는가장중요한검사이지만검사의침습성및환자가느끼는불편감등으로인해주저하게되는검사다. 98개개별연구를분석한결과에따르면 409명의현미경적혈뇨환자중 99.3% 에서 35세이상에서악성종양이관찰되고있기때문에방광내시경은 35세이상의현미경적혈뇨환자에서추천되며 1 특히고위험군 (35세이상, 남성, 흡연력등 ) 에서는나이와상관없이방광내시경검사가이루어져야하는것으로보고하고있다. 요세포검사는방광내시경과동시에혹은소변을이용하여할수있는중요한검사지만검사의특이도및민감도에대해서는아직많은논란이있다. 이에미국비뇨기과학회에서는 1 환자의위험요소유무, 임상증상및신체검사를 Fig. 1. Evaluation of Microscopic hematuria; AUA Guideline

5 정현철 : 현미경적혈뇨의평가 105 고려하여종합적으로판단할것을권장하고있다. 특히지속적인방광자극증상, 흡연력, 유기용제등의화학품에노출이가능한환자에서현미경적혈뇨가관찰될경우검사를고려할수있다. 이외에현재많이시행되고잇는방광암표지인자 (NMP 22, BTA test, UroVysion FISH) 및 Blue Light 방광내시경은일반적인검사로는민감도및특이도에대한보다많은데이터가나올때까지권장하고있지않다. 현미경적혈뇨환자의추적검사현미경적혈뇨환자의추적검사방식및시기에따라서는보고자마다차이가있으나일반적으로다음과같이요약할수있다. 현미경적혈뇨가나타난환자중검사상특이한소견이없으며연속 2년간소변검사에서음성으로보이는경우추가적인혈뇨검사는필요하지않다. Jaffe 등 20 은현미경적혈뇨환자의 % 에서는원인을찾지못하며 Madeb 등 31 은 214명의현미경적혈뇨환자를 14년간추적관찰을한연구에서 2명의환자에서방광암이관찰되었으며처음검사에서병변이관찰되지않은경우추적관찰시악성종양의발생율은 1% 미만으로보고하였다. 현미경적혈뇨환자중비뇨기과검사에서특이사항은없으나지속적또는재발성의현미경적혈뇨가보이는경우매년소변검사를시행하며 3-5년간격으로비뇨기과검사를시행하는것을권장한다. 이는현미경적혈뇨는악성종양이외에요로결석및요관협착증등의건강에중요한문제를일으키는원인및신장염등의내과적질환으로나타날수있으며지속적인관찰로조기에병을진단하는것이중요하다. 특히 35세이상의흡연력이있는남자, 방사선및유기용제를접하는환자등의위험인자를가지고있는경우상대적으로종양의발생률이높기때문에반드시지속적인추적관찰이필요하다. 결론현미경적혈뇨는임상에서흔히접하는검사실소견이지만이에대한진단기준및검사에대한지침은아직명확하지않다. 현재많은연구를통해밝혀진것처럼현미경적혈뇨환자에서도삶에중요한문제를일으킬수있는비뇨기계악성종양, 요관결석, 요로협착, 전립선비대증의하나의검사실소견임을유념해야할것이며특히고위험군환자에서는보다면밀하고세심한검사가진행되어야할것이다. 최근미국비뇨기과학회에서발표된현미경적혈 뇨환자의진료지침 (Fig. 1) 과더불어국내에서도많은인원을대상으로하는장기간의연구를통해국내실정에부합되는지침이만들어져야할것이다. REFERENCES 1. Davis R, Jones JS, Barocas DA, Castle EP, Lang EK, Leveillee RJ, et al. Diagnosis, evaluation and follow-up of Asymtomatic microscopic hematuria in adults: AUA Guideline Mariani AJ, Mariani MC, Macchioni C, Stams UK, Hariharan A, Moriera A. The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. J Urol 1989;141: Sutton JM. Evaluation of hematuria in adults. JAMA 1990;263: Copley JB. Isolated asymptomatic hematuria in the adult. Am J MED Sci 1986;291: Grossfeld GD, Litwin MS, Wolf JS Jr, Hricak H, Shuler CL, Agerter DC, et al. Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy-part I: definition, detection, prevalence, and etiology. Urology 2001;57: Wollin T, Laroche B, Psooy K. Canadian guidelines for the management of asymptomatic microscopic hematuria in adults. Can Urol Asso J 2009;3: Lee GG, Cheon SH, Park RJ. Clinical features and efficacy of diagnostic methods in adults with asymptomatic microscopic hematuria. Korean J Urol 2005;46: Messing EM, Young TB, Hunt VB, Emoto SE, Wehbie JM. Urinary tract cancers found by homescreening with hematuria dipsticks in healthy men over 50 years of age. Cancer 1989;64: Messing EM, Young TB, Hunt VB, Roecker EB, Vaillancourt AM, Hisgen WJ, et al. Home screening for hematuria: results of a multiclinic study. J Urol 1992;148: Messing EM, Young TB, Hunt VB, Newton MA, Bram LL, Vaillancourt AM, et al. Hematuria home screening: repeat testing results. J Urol 1995;154: Britton JP, Dowell AC, Whelan P, Harris CM. A community study of bladder cancer screening by the detection of occult urinary bleeding. J Urol 1992;148: Huussen J, Koene RA, Meuleman EJ, Hilbrands LB. Diagnostic approach in patients with asymptomatic microscopic hematuria: efficient or not? Int J Clin Pract 2006;60: Steiner H, Bergmeister M, Verdorfer I, Granig T, Mikuz G, Bartsch G, et al. Early results of bladder-cancer screening in a high-risk population of heavy smokers. BJU Int 2008;102: Suzuki Y, Sasagawa I, Abe Y, Suzuki H, Kubota Y, Nakada T, et al. Indication of cystoscopy in patients with asympto-

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슬라이드 1

슬라이드 1 Proposed Korean guideline for the diagnosis of BPH Hyun Woo Kim The Catholic University of Korea BPH Guideline AHCPR guideline on BPH (1994) AUA guideline on BPH (2003) EAU guideline on BPH (2004) International