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Korean J Gastroenterol Vol. 68 No. 5, 237-244 https://doi.org/10.4166/kjg.2016.68.5.237 pissn 1598-9992 eissn 2233-6869 REVIEW ARTICLE 문맥압항진증을동반한간경변증환자에서의급성신손상 김소미, 송일한 단국대학교의과대학내과학교실 Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension So Mi Kim and Il Han Song Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea Acute kidney injury (AKI) is one of the most common manifestations encountered in clinical practice. It is associated with high morbidity and mortality in cirrhotic pre- and post-transplantation patients. Hepatorenal syndrome (HRS), a special form of AKI in cirrhotic patients, was recognized as a consequence of renal vasoconstriction from systemic/renal hemodynamic alterations developed in advanced cirrhosis with portal hypertension. Recently, multiple factors such as infection/inflammation, underlying glomerulonephritis, bile cast, or increased abdominal pressure have been considered to contribute to renal dysfunction in cirrhotic patients, which were presumed to induce HRS. Moreover, in addition to changing the definition of AKI in the nephrologic guidelines, the new AKI definition for early diagnosis and intervention based on characteristics of liver cirrhosis has been proposed in an international meeting. This article provides a comprehensive and recent review of AKI definition, laying out the topics in accordance with the pathophysiologic mechanisms and therapeutic interventions of AKI in cirrhotic patients with portal hypertension. (Korean J Gastroenterol 2016;68:237-244) Key Words: Acute kidney injury; Hepatorenal syndrome; Liver cirrhosis; Portal hypertension 서론 급성신손상 (acute kidney injury) 이란신장기능이급격히저하되어대사성노폐물이체내에축적되는상태로, 환자의이환율과사망률을증가시킬뿐만아니라의료비용적측면에서사회적부담이큰중요한질병이다. 간경변환자에서급성신손상은흔하게발생하는합병증중하나로입원환자의약 20% 에서발생하는것으로알려져있고, 1-3 비대상성간경변뿐만아니라간이식에서도사망률에영향을미치는독립적인인자임이보고되었다. 4-6 간경변에서는신전 (prerenal), 신성 (intrarenal) 및신후 (postrenal) 등모든종류의신손상이발생할수있으나, 그중에서도심한간기능저하와문액압항진으로인한신장의혈역학적변화를특징으로하는독특한형 태의신손상인간신증후군 (hepatorenal syndrome) 이강조되어왔다. 7,8 하지만기존에간신증후군으로여겨지던신손상이최근단순한혈관운동성신손상 (vasomotor nephropathy) 이아닌감염 / 염증, 사구체 / 세뇨관이상, 담즙원주및복압상승등복합적인요소들이연관되어있음이밝혀지고있다. 9-11 그동안 Acute Dialysis Quality Initiative (ADQI) 그룹, 12 Acute Kidney Injury Network (AKIN) 13 및 Kidney Disease Improving Global Outcome (KDIGO) 14 등에서표준화된급성신손상진단기준을잇달아발표함에따라, 간경변환자에서도급성신손상을어떻게분류하고치료할것인가에대한논의가지속되었고, 2015년에간경변환자의급성신손상에대한수정된 International Club of Ascites의임상지침 (ICA-AKI) 15 이발표되었다. 이종설에서는최근에발표된표 CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2016. Korean Society of Gastroenterology. 교신저자 : 송일한, 31116, 천안시동남구망향로 201, 단국대학교병원내과 Correspondence to: Il Han Song, Department of Internal Medicine, Dankook University Hospital, 201 Manghyang-ro, Dongnam-gu, Cheonan 31116, Korea. Tel: +82-41-550-3924, Fax: +82-41-556-3256, E-mail: ihsong21@dankook.ac.kr Financial support: None. Conflict of interest: None. Korean J Gastroenterol, Vol. 68 No. 5, November 2016 www.kjg.or.kr

238 김소미, 송일한. 문맥압항진증을동반한간경변증환자에서의급성신손상 준화된급성신손상의진단기준을알아보고, 간경변환자에서논의된급성신손상의정의및임상지침을소개하고자한다. 또한문맥압항진증이동반된간경변환자에서급성신손상을일으키는고전적인원인이외의다른요인, 병태생리및치료법등을기술하고자한다. 본론 1. 급성신손상의정의급성신손상은지난수십년간급성신부전 (acute renal failure) 이라는명칭으로불려왔으나, 급성신부전이라는용어가정상신기능과대비되는신대체요법 (renal replacement therapy) 을필요로할만큼의중증신부전이라는이분법적인의미로쓰여지면서다양한단계의신기능저하를구분하는데한계가있었다. 또한약 40개이상의각기다른급성신부전에대한정의들로인해표준화된진단및치료체계를구축하는데어려움이있었다. 따라서 2004년 ADQI 그룹에서처음으로혈청크레아티닌, 사구체여과율및소변량등세가지지표를설정하고, 이들의변화에따라신손상정도를 Risk, Injury 및 Failure 등세단계로분류하였고, 신기능소실기간에따라 Loss, End-Stage Kidney Disease 로세분화하여첫글자를딴 RIFLE 진단기준을발표하였다. 12 RIFLE 진단기준에서는급성신손상을혈청크레아티닌이최근 7일이내에기저치의 1.5배이상상승한경우, 사구체여과율이 25% 이상감소한경우, 또는소변량이 6시간동안 0.5 ml/kg/hr 미만으로감소한경우등으로정의하였고, 이러한정의는간경변환자를포함하여중환자실입원환자나인공호흡기치료환자등여러중증의임상상황에서사망률과유의한상관관계가있음을보여주었다. 16-18 하지만이후 RIFLE 진단기준의민감도가낮다는주장이제기됨에따라, 2007년 AKIN 그룹에서 RIFLE 진단기준을수정한새로운진단기준을발표하였다. 13 AKIN 진단기준에서는급성신손상진단시충분한수분보충이이루어졌는지혹은요로폐색은없는지에대한원인평가가강조되었고, 급성신손상지표중사구체여과율은급성신손상시부정확성을이유로배제되었으며, 기저혈청크레아티닌이없는경우, 입원시 48시간이내에최소두차례혈청크레아티닌을측정하도록하였다. 또한급성신손상정의에 48시간이내 0.3 mg/dl 이상의혈청크레아티닌이상승한경우를추가하였고, Risk, Injury, Failure 세단계를각각 1, 2, 3단계 (stage) 로변경하였으며, 신대체요법이필요한모든상황을 3단계로명시해급성신손상의진단과분류를간편하고용이하게하였다. RIFLE이나 AKIN 두진단기준이사망과같은임상결과를예측하는좋은지표로널리받아들여지고있으나 19-21 실제임상분야나보건역학연구분 야에서통일된기준이필요하였고, 이후 2012년 KDIGO에서두진단기준을통합한새로운진단기준을제시하였다. 14 KDIGO 진단기준에서는 48시간이내에 0.3 mg/dl 이상의혈청크레아티닌증가, 기저혈청크레아티닌보다 1.5배이상증가, 혹은 6시간동안 0.5 ml/kg/hr 미만의소변량감소를급성신손상으로정의하였다. 현재다양한임상상황에서 KDIGO 진단기준의유용성이입증되고있으나, 22-24 아직간경변환자에서의대규모전향적연구는없는상황이다. 2. 간경변에서급성신손상평가시고려할사항위에서기술한급성신손상의정의를간경변환자에그대로적용하기에는몇가지문제점이있다. 첫째, 급성신손상정의의지표로사용되는혈청크레아티닌과소변량은간경변환자에서신기능을제대로반영하지못한다는점이다. 간경변환자의경우근감소증 (sarcopenia), 영양불량 (malnutrition), 그리고단백질식이제한등으로기본근육량이감소된경우가많고, 간기능저하로인하여크레아티닌의전구물질인크레아틴합성이감소되어있다. 반면에신세뇨관으로의크레아티닌배출은증가되고부종으로인한크레아티닌의혈청내희석이일어나, 혈청크레아티닌이낮게측정될수있다. 25,26 또한혈청크레아티닌을측정하는 Calorimetric Jaffe 분석법은빌리루빈과같은비크레아티닌색소에의해간섭을받기때문에, 27 간경변과같은만성간질환에서혈청크레아티닌을지표로한신장기능은과대평가 (overestimation) 되기쉽다. 그리고문맥압항진증이동반된간경변환자에서는복수나말초부종등체액분포이상이생기고이뇨제를복용하는경우도흔해소변량자체로전신체액량및신기능을정확히예측하는것은불가능하다. 둘째, 간경변에서발생하는급성간부전의대표적인형태인간신증후군의정의에따른딜레마이다. 간신증후군은신손상의임상양상과경과에따라두타입으로나뉜다. 1형간신증후군은 2주내에혈청크레아티닌이기저치의 2배이상이면서 2.5 mg/dl 이상상승한경우로정의되며, 대부분급격히악화되는임상경과를보인다. 반면에 2형간신증후군은혈청크레아티닌이 1.5-2.5 mg/dl 정도로상승하며, 1형과비교하여천천히진행하는임상경과를보인다. 28 따라서 RIFLE, AKIN 및 KDIGO 등의기준에의해급성신손상을진단받은간경변환자들의일부에서신기능저하가있다하더라도 1형간신증후군진단기준인혈청크레아티닌 2.5 mg/dl에도달하지못하는경우가있다. 또한만성신손상을동반한간경변환자에서신기능저하가발생한경우나 2형간신증후군발생후신기능저하가 3개월이상지속되는경우등은급성신손상으로서의간신증후군과만성신질환의정의가서로상충되어분류를어렵게한다. 29 The Korean Journal of Gastroenterology

Kim SM and Song IH. Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension 239 Table 1. A Comparison of the Diagnostic Criteria of AKI in General Population and Cirrhotic Patients RIFLE AKIN KDIGO ICA-AKI Definition scr 1.5 within 7 days or GFR >25% or Staging Risk scr 1.5 within 7 days or GFR >25% or Injury scr 2 or GFR >50% or UO <0.5 ml/kg/hr for 12 hr Failure scr 3 or GFR >75% or If baseline scr 353.6 mol/l (4.0 mg/dl) with scr 44.2 mol (0.5 mg/dl) or UO <0.3 ml/kg/hr for 24 hr or anuria for 12 hr Outcomes Loss of kidney function Complete loss >4 weeks End-stage kidney disease Complete loss >3 months scr 150-199% within Stage 1 scr 150-199% within Stage 2 scr 200-229% within UO <0.5 ml/kg/hr for 12 hr Stage 3 scr 300% or If baseline scr 353.6 mol/l (4.0 mg/dl) with scr 44.2 mol (0.5 mg/dl) or UO <0.3 ml/kg/hr for 24 hr or anuria for 12 hr or Initiation of RRT scr 1.5 time baseline to have occurred within 7 days or Stage 1 scr 1.5 baseline to have occurred within 7 days or Stage 2 scr 2 or UO <0.5 ml/kg/hr for 12 hr Stage 3 scr 3 or If baseline scr 353.6 mol/l (4.0 mg/dl) or UO <0.3 ml/kg/hr for 24 hr or anuria for 12 hr scr 1.5, baseline to have occurred within 7 days Stage 1 scr 1.5 baseline to have occurred within 7 days Stage 2 scr 2 Stage 3 scr 3 or If baseline scr 353.6 mol/l (4.0 mg/dl) with scr 44.2 mol (0.5 mg/dl) Initiation of RRT Response to treatment No response No regression of AKI Partial response Regression of AKI stage with reduction of scr 26.5 mol/l (0.3 mg/dl) Full response Return to scr to a value within 26.5 mol/l (0.3 mg/dl) of base-line value AKI, acute kidney injury; RIFLE, Risk, Injury, Failure, Loss, End-stage kidney disease; AKIN, Acute Kidney Injury Network; KDIGO, Kidney Disease Improving Global Outcome; ICA, International Club of Ascites; scr, serum creatinine; GFR, glomerular filtration rate; UO, urine output; RRT, renal replacement therapy. Vol. 68 No. 5, November 2016

240 김소미, 송일한. 문맥압항진증을동반한간경변증환자에서의급성신손상 3. 간경변에서급성신손상진단기준위에기술한문제점들을고려하여, 2012년 ADQI-ICA 그룹은간경변에서발생하는급성신손상의정의및분류에관한진단기준을발표하였다. ADQI-ICA 그룹은간경변환자에서도급성신손상, 만성신질환에서의급성신손상병발, 및만성신손상등으로단계를구분하여기술하였으며, 급성신손상진단시 AKIN 진단기준을적용하였다. 또한간신증후군대신간신질환 (hepato-renal disorders) 이라는보다포괄적인용어를사용하였다. 30 이후 2015년 ICA 그룹에서 KDIGO 진단기준을받아들여수정된임상지침을새로이발표하였다 (Table 1). ICA는급성신손상을혈청크레아티닌이 48시간이내에 0.3 mg/dl 이상으로증가하거나 7일이내에기저치의 50% 이상증가된경우로정의하였고, 각각의단계에따른치료알고리즘도추가하였다. 또한 2단계이상의급성신손상발생시, 기존의간신증후군의진단및치료지표로사용되던혈청크레아티닌의절대기준값에도달하지않았더라도조속히알부민과혈관수축제를투여할것을권고하였다. 이러한새로운 ICA 임상지침은진행성간경변환자에서조기에급성신손상을진단하고, 문맥압항진증으로부터발생하는혈관운동성신손상에대한조속한처치를가능하게하여, 향후신손상에따른이환율과사망률의임상결과를개선시킬것으로기대되고있다. 15 4. 간병변에서급성신손상의병태생리 (Fig. 1) 1) 신혈역학의변화신혈역학의변화는고전적인간신증후군의발생기전으로 설명되고있으나그병태생리가완전히규명된것은아니다. 간기능저하와문맥압항진에의한혈역학적변화가신손상을유발하는주요기전으로는 1) 문맥압항진에의한내장혈관의이완, 2) 유효혈장량의감소로인한심박출량저하, 3) 심박출량감소에따른보상작용으로신경호르몬계변화및신혈관수축인자의분비에따른신혈류량감소등으로요약할수있다. 7,31-33 비대상성간경변에서문맥압항진이진행되면산화질소 (nitric oxide), 일산화탄소 (carbon monoxide) 및글루카곤등혈관이완물질이분비되어내장동맥이이완된다. 이는유효혈장량의감소로이어지며심장은초기에는구축력을증가시켜심박출량을유지하지만, 신경호르몬계의활성화, 혈관수축인자분비및지속적인물리적압력등에의해간경변성심근병증이유발되어결국심박출량이저하된다. 31,33 이러한지속적인혈장량감소는레닌-안지오텐신-알도스테론시스템과교감신경계를활성화시키고, 바소프레신을포함한혈관수축인자들의분비로이어지게된다. 초기에는프로스타글란딘, 칼리크레인과같은혈관이완인자들이분비되어신혈류량이유지되지만, 궁극적으로는신혈관이수축되며신손상이발생하게된다. 이러한간경변환자의병태생리는간신증후군발생시혈관수축제를투여함으로써문맥압항진을개선시켜궁극적으로신혈류량을증가시키는치료의근간이되었다. 하지만, 비대상성간경변환자의약 40% 에서혈관수축제를통한치료에효과적으로반응하지않는다고보고되어있어, 이러한고전적인병태생리이외의신손상을유발하는다른요소들이연관되어있음을시사한다. 33,34 2) 감염및염증감염또는염증은간경변환자에서급성신손상을일으키 Fig. 1. Traditional and potential mechanisms of the development of acute kidney injury in cirrhotic patients with portal hypertension. NO, nitric oxide; CO, carbon monoxide; inos, inducible NO; TLR, toll like receptor; TNF, tumor necrosis factor; IL, interleukin; RAA, renin-angiotensinaldosterone; SNS, sympathetic nervous system; PGE2, prostaglandin E2; 6-keto PGF1, 6-keto-prostaglandin F1. The Korean Journal of Gastroenterology

Kim SM and Song IH. Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension 241 는가장흔한원인중의하나이다. 감염에의한신손상은주로신장허혈에의해발생하는급성세뇨관괴사 (acute tubular necrosis) 의형태로나타나며, 이는감염에의한전신및국소혈역학적변화와면역-매개세포독성기전이연관되어있다. 일반적으로세균은 toll-like receptor (TLR)-2, 4 등을통해단핵구에인식되며, 이러한수용체결합은 tumor necrosis factor-, interleukin 6 및 interleukin 1- 등과같은전염증성 (proinflammatory) 사이토카인분비를활성화시킨다. 이는전사인자 nuclear factor kappa-b를통해 nitric oxide synthase 합성을자극하는것으로이어지고, 심구축력을감소시키고혈관을이완시켜궁극적으로세뇨관의허혈성손상을야기한다. 35-37 또한실험연구에따르면간경변쥐모델에서감염이있는경우 TLR-4가상향조절되면서신세뇨관세포의세포자멸사를유도하는것으로보고되어있다. 37 Thabut 등 9 의임상연구에서도전신성염증반응증후군 (systemic inflammatory response syndrome) 이동반된간경변환자에서신손상이유의하게증가하였고, norfloxacin을예방적으로사용한환자에서신손상및사망률이개선됨을보고하였다. 이러한결과는감염이간경변환자에서급성신손상을일으키는주요요인임을시사하고있고, 이러한이유로최근발표된 ICA 지침에서도간경변환자에서자발성세균성복막염이나출혈이발생한경우항생제를통한적극적인감염조절을강조하고있다. 3) 사구체신질환간경변환자에서경미한단백뇨나혈뇨는종종볼수있는소견이나, 출혈과같은합병증발생가능성때문에적극적인신장조직검사를진행하는경우는흔하지않다. 간신증후군의병태생리에의하면신장의기본구조는정상이어야하며, 실제로몇몇간신증후군환자의부검에서사구체를포함한신장의구조적이상은없었다고보고된바있다. 하지만간경변환자의경우사구체신염을동반하는경우는드물지않다. B형간염의경우막성사구체신염과연관되어있는경우가흔하며, C형간염은막증식성사구체신염의원인으로알려져있다. 38,39 또한알코올성간경변은 IgA 신증, 윌슨병이나원발성담도성간경변에서는간질성신염이병발될가능성이높다고보고되어있다. 40 따라서간경변환자에서단백뇨나혈뇨등의소변검사이상이있는경우조직검사를통해확진하지못할지라도간경변의원인에따른사구체신염의동반가능성을생각해야하며, 간경변진행시신손상을가속화시키는원인중하나로고려되어야한다. 4) 담즙원주신손상 (bile cast nephropathy) 진행성간경변환자에서증가된빌리루빈또는답즙은신세뇨관세포에직접적인독성을나타내세뇨관손상을일으킬수있다. 또한세뇨관자체의낮은산도와담즙자체의불수용 성때문에결정이쉽게생길수있고, 이것이긴세뇨관을거치면서담즙원주를형성하여궁극적으로세뇨관폐쇄를유발하기도한다. van Slambrouck 등 10 의연구에따르면 40명의간경변환자를부검해본결과, 전체 55% 에서세뇨관에담즙원주가관찰되었으며, 그중간신증후군으로진단된환자에서는 85% 의높은담즙원주형성률을보였다. 또한담즙원주신손상발생에빌리루빈수치가유의한상관관계가있음을보고하였다. Nazar 등 33 의연구에따르면빌리루빈이높은경우, 간신증후군치료로 terlipressin을투여해도약물반응이효과적이지않음을보고한바있다. 이러한연구들은상승된빌리루빈또는담즙으로인해발생한담즙원주신손상이간경변환자의급성신손상의원인이될수있음을시사한다. 5) 복압상승복압상승이란간경변환자에서불응성복수에의해복압이 12 mmhg 이상증가하는경우로정의된다. 불응성복수를동반한간경변환자의경우약 11% 에서간신증후군이발생한다고알려져있다. Umgelter 등 41 은 19명의중환자실간신증후군환자를대상으로복수천자를시행하여, 복압을평균 22 mmhg에서 9 mmhg로낮추었을때사구체여과율이호전됨을보고하였다. 다른실험연구에서도 10 mmhg 이상의복압을보인쥐에서요소나크레아티닌등신기능의혈청지표들이악화되었고, 신장조직검사에서신혈관의울혈, 간질의부종및염증세포침윤등이확인되었다. 42 이러한결과들은간경변환자의복압상승시신정맥의압력증가로인한울혈, 간질및세뇨관의부종및염증등으로인하여신손상이초래될수있음을보여준다. 5. 간경변에서급성신손상의치료 1) 일반적인접근급성신손상이발생한경우, 우선원인을파악하여가역적인원인을교정하여야하며, 환자의개별적인임상상황에따라치료해야한다. 일반적으로급성신손상시에는원인인자교정외에수액보충, 전해질불균형교정, 동반된합병증의치료등보존적요법이우선하며, 필요시신대체요법을시행하게된다. 2) 치료가이드라인에의한접근 ICA-AKI 지침에따르면, 간경변환자에서급성신손상이발생한경우신손상 1단계에서는일차적으로신독성약제, 혈관이완제, 비스테로이드항염증제 (non-steroidal anti-inflammatory drug), 이뇨제등과같은약물을중단하고, 감염이있는경우즉시항생제를투여하도록하였다. 또한체액손실이있는경우정질 (crystalloid) 수액, 알부민, 혈액제제등을투여하여적극적으로혈장량을늘릴것을권고하였다. 이러한일차적치료후반응에따라신손상단계를재조정하고, 악화된경우 Vol. 68 No. 5, November 2016

242 김소미, 송일한. 문맥압항진증을동반한간경변증환자에서의급성신손상 2단계에준해치료하도록하였다. 급성신손상 2 단계이상의환자에서는 2일간연속적으로 1 g/kg/day ( 최대 100 g/day) 의알부민을정주하고, 반응이없는경우에는 terlipressin과같은혈관수축제투여를권고하였다. 15 이러한 ICA-AKI 임상지침은급성신손상진단시, 신전혹은신성신손상요소를교정하고혈관수축제를조기에투여하여문맥압항진에의한신손상을효과적으로감소시킬수있으리라기대되나, 아직전문가적견해에머물러있어앞으로대규모의전향적연구를통한입증이필요하다. 3) 신대체요법상기약물치료에도불구하고간경변환자가요독증상, 체액과다, 불응성고칼륨혈증및대사성산증등을보이게되면신대체요법이필요하다. 그러나이들환자들은유효혈장량의부족으로혈압저하가빈번하며, 혈소판감소, 프로트롬빈시간의증가에따른출혈위험및뇌압상승등으로효과적인혈액투석이어려운경우가종종있다. 지속적신대체요법 (continuous renal replacement therapy, CRRT) 은통상적인혈액투석이힘든만성간질환, 특히비대상성간경변환자에서고려해볼수있는신대체요법중하나이다. Wong 등 43 은급성신손상을동반한 102명의간이식대기자들에게 CRRT를포함한신대체요법을시행했을경우, 30% 에서간이식을받거나경과가호전되었음을보고하여비대상성간경변환자에서신대체요법의유용성을주장하였다. 하지만아직까지간이식대기자에서간신증후군동반시사망률이높으므로신대체요법의유용성에대해서는논란이있다. 인공간이라불리우는간보조장치로는 molecular adsorbent recirculating system (MARS), extracorporeal liver assist device, bio-artificial Liver, bio-artificial Liver Support System, modular extracorporeal liver support 등이있다. 그중 MARS는현재가장많이이용되는알부민을이용한투석보조장치로서, 실제로간이식대기자에 MARS를적용한후간성뇌증, 신기능및평균동맥압등이호전되었다는보고가있다. 44,45 몇몇소규모연구에서는환자의생존율향상에도움이된다는주장도있으나, 46,47 최근발표된메타분석에서는생존율을유의하게증가시키지는못하는것으로나타났다. 48 하지만 MARS는급성신손상을동반한비대상성간경변환자에서간이식까지의가교역할을할수있는대체요법으로시도해볼수있는선택이라할수있다. 결론 문맥압항진증을동반한간경변에서발생하는급성신손상은간이식전, 후모두에서환자의이환율과사망률을높이는심각한질환이다. 지금까지간신증후군으로일컬어져온비대 상성간경변의급성신손상은, 문맥압항진으로부터발생하는이차적인신혈역학변화에의한손상만이강조되면서감염 / 염증, 사구체신질환, 담즙원주신손상및복압항진등신기능저하에관여하는다른요인들에대해서는간과된측면이많다. 가능성있는다양한요인들에의한신손상의병태생리가규명되어야할것이다. 최근급성신손상에대한표준화된정의에따라새롭게수정된 ICA-AKI 임상지침은문맥압항진증-동반간경변환자의진단과치료에서좀더명확하고신속한접근을가능하게하였다. 향후이러한임상지침에근거한진단과치료가실질적으로환자의예후에얼마나영향을미치는지에대한전향적연구가진행되어야할것이다. REFERENCES 1. Wu CC, Yeung LK, Tsai WS, et al. Incidence and factors predictive of acute renal failure in patients with advanced liver cirrhosis. Clin Nephrol 2006;65:28-33. 2. Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology 2008;48:2064-2077. 3. Hampel H, Bynum GD, Zamora E, El-Serag HB. Risk factors for the development of renal dysfunction in hospitalized patients with cirrhosis. Am J Gastroenterol 2001;96:2206-2210. 4. Terra C, Guevara M, Torre A, et al. Renal failure in patients with cirrhosis and sepsis unrelated to spontaneous bacterial peritonitis: value of MELD score. Gastroenterology 2005;129:1944-1953. 5. Cholongitas E, Senzolo M, Patch D, Shaw S, O'Beirne J, Burroughs AK. Cirrhotics admitted to intensive care unit: the impact of acute renal failure on mortality. Eur J Gastroenterol Hepatol 2009;21:744-750. 6. Weismüller TJ, Negm A, Becker T, et al. The introduction of MELDbased organ allocation impacts 3-month survival after liver transplantation by influencing pretransplant patient characteristics. Transpl Int 2009;22:970-978. 7. Cárdenas A. Hepatorenal syndrome: a dreaded complication of end-stage liver disease. Am J Gastroenterol 2005;100:460-467. 8. Baraldi O, Valentini C, Donati G, et al. Hepatorenal syndrome: Update on diagnosis and treatment. World J Nephrol 2015;4: 511-520. 9. Thabut D, Massard J, Gangloff A, et al. Model for end-stage liver disease score and systemic inflammatory response are major prognostic factors in patients with cirrhosis and acute functional renal failure. Hepatology 2007;46:1872-1882. 10. van Slambrouck CM, Salem F, Meehan SM, Chang A. Bile cast nephropathy is a common pathologic finding for kidney injury associated with severe liver dysfunction. Kidney Int 2013;84:192-197. 11. Trawalé JM, Paradis V, Rautou PE, et al. The spectrum of renal lesions in patients with cirrhosis: a clinicopathological study. Liver Int 2010;30:725-732. 12. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure: definition, outcome measures, animal models, fluid therapy and in- The Korean Journal of Gastroenterology

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