Kim SH Kim YK Yang CW Table 1. Classification of uremic toxin Molecules Small watersoluble compounds Protein-bound solutes Middle molecules 이외에도수분상태,

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1 pissn: eissn: Focused Issue of This Month 말기신부전의현황과문제점 투석적절도의효율성 김수현 1 김용균 2 양철우 2* 1 중앙대학교, 2 가톨릭대학교의과대학내과학교실 The efficacy of dialysis adequacy Su-Hyun Kim, MD 1 Yong Kyun Kim, MD 2 Chul Woo Yang, MD 2* Department of Internal Medicine, 1 Chung-Ang University, 2 The Catholic University of Korea, Seoul, Korea *Corresponding author: Chul Woo Yang, yangch@catholic.ac.kr Received April 2, 2013 Accepted April 16, 2013 Adequate dialysis is essential for improving dialysis therapies and reducing all-cause mortality in end-stage renal disease (ESRD) patients. Efficient removal of the uremic toxins in the blood remains the fundamental role of dialysis therapies. Therefore, urea clearance as assessed by urea kinetic modeling (Kt/V urea ) is a surrogate marker for dialysis adequacy in ESRD patients undergoing dialysis, and the NKF-DOQI recommends a Kt/V urea of no less than 1.2. The current status of dialysis adequacy in Korea has not been fully investigated. Our Clinical Research Center for End Stage Renal Disease revealed that the mean Kt/V urea in maintenance hemodialysis patients was 1.49±0.28, and 91.5% of patients satisfied the target level of Kt/V urea. In addition to Kt/V urea, clinical parameters such as the volume status, residual renal function, blood pressure, acid-base disorders, anemia, nutrition, inflammation, mineral metabolism, and middle molecule clearance are important for determining adequate dialysis treatment. Further evaluation of clinical parameters is needed to improve dialysis adequacy. Keywords: Dialysis; Renal insufficiency; Survival; Uremia 서 론 말기신부전환자는신장의기능이저하되면서다양한노폐물과대사산물이체내에축적되어수분및전해 질의불균형과요독증상이발생하게된다. 생명유지및연 장을위해신장이식, 혈액투석혹은복막투석등의신대체 요법이필요하다. 전세계적으로말기신부전으로투석치료 를받고있는환자는백만명이넘으며, 미국은 40 만명이고, 우리나라는대한신장학회의등록사업발표에의하면 2009 년 을기준으로혈액투석환자가 37,391 명, 복막투석 7,618 명 으로총투석환자는 45,009 명이다 [1]. 이는 2000 년의 20,524 명에비해약 10 년간 2 배이상증가한것으로, 인구의 고령화와당뇨병및고혈압과같은만성질환의유병률증가로추후지속적으로증가할것으로보인다. 게다가투석환자는일반인구에비해 4-10배가넘는심혈관질환의유병률과사망률을나타내므로의료재정의부담뿐아니라사회적문제가되고있다 [2-4]. 투석환자의생존율을높이기위한많은시도가이루어지고있는데, 기본적으로투석치료를적절히시행할필요가있다. 적절한투석의정의를명확히내리기는어렵지만투석의적절도를나타내는다양한지표들이있으며, 혈액투석에서는요소의동력학모델을이용하여계산한 Kt/V urea, 요소감소율 (urea reduction ratio) 을, 복막투석에는주당 Kt/V urea, 크레아티닌청소율등이투석적절도의주요한지표로활용되고있다. c Korean Medical Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 대한의사협회지 583

2 Kim SH Kim YK Yang CW Table 1. Classification of uremic toxin Molecules Small watersoluble compounds Protein-bound solutes Middle molecules 이외에도수분상태, 혈압, 산염기균형, 빈혈, 영양상태, 염 증, 칼슘 인등의무기질대사, 중분자물질청소율등이생 존율에영향을미치므로인자들을모두고려하여투석의적 절도를정해야한다. 따라서투석적절도의지표들을정리해 보고그효율성과투석환자의생존율의관련성을정리해보 고자한다. Molecular weight Example <500 Da Urea, asymmetric dimethylarginine, creatine, creatinine, guanidine, hypoxanthine, uric acid, and oxalate Variable p-cresol, phenol, 3-deoxyglucosone, hippuric acid, indoxyl sulfate, melatonin, leptin, retinolbinding protein, and homocysteine >500 Da β 2 -microglobulin, parathyroid hormone, and advanced glycosylation end products 요독증과요독물질이란? 투석적절도에대해설명하기앞서, 투석을통해제거해야 할물질들이무엇인지에대한정의가필요하다. 흔히말기신 부전환자에서요독증이라는표현을쓰는데, 이는신장기능의 저하로배출되어야할다양한노폐물들이체내에축적되어일 어나는임상증후군을의미한다. 말기신부전환자는사구체여 과율이 15 ml/min/1.73 m 2 이하로떨어져도상당기간소변 량을정상적으로유지한다. 따라서환자나환자의가족뿐아 니라의료진도소변량이정상적으로유지되는데도신장에서 노폐물을배출하지못한다는개념을이해하지못하는경우가 있다. 사구체여과율이감소하면신장에서배출할수있는노 폐물의양이줄어들어일정량의노폐물이체내에축적되어요 독증을일으키게된다. 증상으로는심한피로, 불면증, 허약 감, 가려움증등이나타날수있고지속될경우입맛이감소하 고체중이줄수있다. 혹은요독성뇌병증을일으키거나심낭 염, 흉막염을유발할수있고고칼륨혈증이나대사성산혈증 과같은산 염기, 전해질이상이발생할수도있다. 체내에축적되는이러한다양한증상을유발하는노폐물을요독물질 (uremic toxin) 이라고부르며 European Uremic Toxin Work Group에서는 2003년에 90개이상의요독물질을분류하여발표하였으며다음과같이세가지종류로분류하였다 (Table 1) [5]. 분자량과단백질결합여부에따라, 1) 수용성의소분자물질 (small water-soluble compounds), 2) 단백질결합물질 (protein-bound solutes), 3) 중분자물질 (middle molecules) 로나누었다. 소분자물질의대표격으로는요소 (blood urea nitrogen, BUN) 와크레아티닌이가장잘알려져있으며, 투석에의해제거가용이하다. 투석적절도의지표로요소청소율을많이사용하는반면, 크레아티닌은근육량이나섭취하는음식의영향을많이받아서최근에는잘사용하지않는다. 반면단백질결합물질과중분자물질은투석에의해효과적으로제거가되지않아현재투석치료에서는한계가존재한다. 예를들어중분자물질로가장잘알려져있는 β 2 -마이크로글로블린은투석치료에도불구하고정상인에비해투석환자에서유의하게증가한다는것은이미잘알려져있다 [6]. 혈액투석환자의투석적절도 혈액투석은팔에동맥과정맥을연결하여만든동정맥루에바늘을천자하여투석기에연결하여몸안의노폐물을제거하는신대치요법이다. 혈액투석환자의투석치료를적절히하는것은사망률과이환율을감소시키기위해필요한기본요건이다 [7]. 우선소분자물질청소율의주요지표인 Kt/V urea 에대해알아보겠다. 1. Kt/V urea 와생존율에대한임상연구투석적절도의지표로흔히사용되는 Kt/V urea 가사망률에미치는영향에대한주요연구들을 Table 2에정리하였다. 1981년에발표한 National Cooperative Dialysis Study는혈액투석환자를시간평균혈액요소질소를 50 mg/dl로유지한군과 100 mg/dl로유지한군으로나누었는데, 3년추적을목표로했으나 24주에중간분석한결과에서혈액요소질 584 투석적절도의효율성

3 The efficacy of dialysis adequacy 특 집 Table 2. Clinical studies examining the influence of the dose of hemodialysis Reference (study) Study design No. of patients Description and results Eknoyan et al., 2002 [8] (HEMO) Depner et al., 2004 [9] (HEMO) Termorshuizen et al., 2004 [10] (NECOSAD)-2 Port et al., 2004 [11] Lowrie et al., 1981 [12] (NCDS) RCT 1,846 Standard-dose group (spkt/v urea =1.32±0.09) vs. high-dose group (1.71±0.11) 소가높은군이입원율이증가하는등이환율이유의하게상 승하여조기종료하였다 [12]. 추후이연구를바탕으로 1985 년 Gotch 와 Sargent [13] 가자료를재분석하여 Kt/V urea 라는 요소동력학모델 (urea kinetic model) 을발표하였는데, 이 연구이후로 Kt/V urea 는투석적절도의임상지표로써가능한 높게유지하도록권고해왔다. 또한 Port 등 [11] 은남성과여 성을분리하여분석하였을때남성은고투석량군투석과저투 석량군투석이생존율에큰영향을미치지못했으나여성의 경우고투석량군투석이생존율향상과유의한관련성이있다 고보고하였다. Netherlands Cooperative Study on the Adequacy of Dialysis 에서역시 Kt/V urea 가상승할수록사 망가능성이 0.44 감소한다는유사한결과를발표하였다. RR of death = 0.96 (95 % CI, 0.84 to 1.10; P=0.53) RCT 1,846 Women: high dose group had a lower mortality rate (RR=0.81, P=0.02) Men: nonsignificant trend (RR=1.16, P=0.16) Prospective 740 RenalKt/V(urea) and dialysatekt/v urea were associated with a better survival 1/wk in renal Kt/V urea : RR of death=0.44 (P<0.0001) Dialysate Kt/V urea, RR of death=0.76 (P<0.01) Prospective 10,816 High dose group (URR 70%-to- 75%) vs. standard-dose group (65%-to-70%) For men: RR=0.9 (P<0.0001) For women: RR=0.81 (P<0.0001) RCT 151 High-BUN groups vs. low-bun groups; hospitalization and withdrawal of patients were greater in the high-bun groups HEMO, Hemodialysis study; RCT, randomized controlled study; spkt/v urea, single-pool Kt/V urea ; RR, relative risk; CI, confidence interval; NECOSAD, Netherlands Cooperative Study on the Adequacy of Dialysis; URR, urea reduction ratio; NCDS, National Cooperative Dialysis Study; BUN, blood urea nitrogen. 념이다. 계산식은다음과같다. 하지만, 이러한결론은 2002 년발표 한대규모임상연구인 Hemodialysis (HEMO) 연구에서고투석량투석이 생존율에큰영향을주지않는다고보 고함으로써 Kt/V urea 일정이상증가시 키는것이사망률에큰영향을미치지 않는것으로결론이지어졌다 [8,10]. 따라서말기신부전환자에서의투석적 절도에관한미국신장재단 (National Kidney Foundation, NKF) 의임상실 행지침 (Dialysis Outcomes Quality Initiative [DOQI] Clinical Practice Guidelines) 에의하면요소동력학모 델에의한 Kt/V urea 가가장추천되는적 절도의지표이며, 주 3 회혈액투석을 받는환자의 Kt/V urea 는최소량인 1.2 이 상유지할것을권장하고있다 [14]. 2. Kt/V urea 의계산법과목표치는? 1985 년 Gotch 와 Sargent [13] 가개 발한요소청소율을이용한요소동력학 모델인 Kt/V urea 는요소청소율인 K 와 투석시간인 t 를체내의 urea 의분포배 치 (volume of distribution) 로나눈개 Single pool Kt/V= -ln (R-0.008xt)+(4-3.5R)xUF/W R: 투석후혈중요소치 / 투석전혈중요소치 (post dialysis/ predialysis BUN ratio) t: 치료시간 (treatment time in hour) UF: 한외여과량 (ultrafiltration volume in liters) W: 투석후체중 (postdialysis weight in kilograms) 이것을더욱간소화한것이요소감소율이며, 계산식은다 음과같다. 요소감소율 =1- 투석후혈중요소치 / 투석전혈중요소치 대한의사협회지 585

4 Kim SH Kim YK Yang CW 요소감소율은투석전후에요소가감소한정도를알려주는개념이다. 요소동력학모델을이용한투석량측정은요소의농도측정을위해서채혈이필요한데, 최근소개된이온치환투석제거율 (ionic dialysance) 은투석에의해제거되는요소를포함한투석된양만큼의물질이나트륨으로치환된다는이론을기초로한것으로 [15], 이온확산속도변화율에의한투석량을측정함으로써채혈없이투석량측정이가능한새로운시도이다. Kt/V urea 를늘리기위한시도로써투석방법의변화를시도하는연구가많이발표되고있다. 투석시간을주 3회 4시간하는표준치료가아니라야간투석을하면서매일혹은주 5-6회투석을하거나시간을 6시간으로늘리거나혹은혈액여과법, 혈액투석여과법등의다양한시도를시행하고있으며소분자물질청소율뿐아니라이외의요독물질의제거를늘리려는시도가되고있다 [16]. 그러나현재까지대규모임상연구를통해투석환자의생존율을증가시킨다는증명이되지는않았는데, 이는 Kt/V urea 는주로소분자물질청소율을의미하는지표로써중분자물질이나단백결합물질의제거에대한고려도추후필요할것으로보인다. 따라서, 환자개개인의상태나임상양상에따라필요하면투석치료처방을조절하는시도가필요할것으로사료된다. 복막투석환자의투석적절도 복막투석은환자자신의복막을이용한투석방법으로도관을복강으로삽입한후투석액을복강으로투입하여노폐물을제거하는방법이다. 지속성외래복막투석환자 (continuous ambulatory peritoneal dialysis) 에서투석적절도는환자의생존율뿐만아니라삶의질에영향을미치는중요한인자이다. 1회투석시의 Kt/V urea 를지표로삼는혈액투석과달리복막투석은주당 Kt/V urea 를기준으로투석량을정하고있으며주당크레아티닌청소율도흔히사용하고있다. 1. 투석적절도와생존율에관한임상연구 Canada-USA Peritoneal Dialysis Study (CANUSA 연구 ) 는 1990년대초반에시행된것으로캐나다와미국에서 복막투석을새롭게시작하는 680명의환자를대상으로이루어진관찰적연구로써, 주당 Kt/ Vurea 가 0.1 감소할때마다사망위험이 5% 가량증가한다고발표하였다 [17]. 따라서 1997년에발표된미국의 NKF-DOQI 진료지침에서는복막투석환자에서최소한주당 Kt/V urea 가 2.0 이상유지해야한다고권고를했었다. 그러나멕시코에서발표한 ADEMEX 연구에의하면 2 L X 4 회의표준투석을한환자와크레아티닌청소율을 60 L/wk 이상으로유지한고투석량투석군의생존율의차이를보이지않았다 (Table 3) [18]. 또한홍콩에서시행한연구도유사한결과를보였는데, 주당 Kt/V urea 를 , , 2.0 이상의세군으로나누어비교하였는데사망률의차이는없었다 [19]. 국내에서도역시 Park 등 [20] 이주당 Kt/V urea 가 2.1 이상인군과 2.1 이하인군을비교했을때사망률의통계학적차이는보이지않는다고보고한바있다. 또한 CANUSA 연구를재분석하여보고한결과에의하면잔여신기능을제외한주당 Kt/V urea 가생존율에큰영향을미치지않는다고보고하였다 [21]. 이런연구결과를바탕으로최근에는미국의 NKF-DOQI 와유럽의신장학단체등에서복막투석환자에서총주당 Kt/V urea 를최소한 1.7 이상은넘도록권고하고있다 [22,23]. ADEMEX (ADEquacy of PD in MEXico) 연구에서생존율의차이를보이지는않았으나주당 Kt/V urea 가 1.7 미만으로유지된군에서심부전으로사망한환자가더많았으며, 요독증상, 고칼륨혈증및산혈증등의다양한합병증의비율이더높았기때문이다. 또한대조군에서더많은환자가중도탈락하였기때문에주당 Kt/V urea 의최소량을지키도록권고하지만개인별, 임상양상에따라서요독증상이나다른합병증이발생하는경우 Kt/V urea 의양을늘릴필요가있을수도있다. 2. 잔여신기능이란? 복막투석환자는혈액투석과달리투석시작후의잔여신기능이더잘보전되는것으로알려져있다. 잔여신기능은 24시간소변을모아서크레아티닌청소율및요소청소율을구한후그평균으로계산한다. 재분석한 CANUSA 연구에의하면잔여신기능이유지되는환자의경우복막투 586 투석적절도의효율성

5 The efficacy of dialysis adequacy 특 집 Table 3. Clinical studies examining the influence of the dose of peritoneal dialysis Reference (study) Study design No. of patients Description and results Churchill et al., 1996 [17] (CANUSA study) Paniagua et al., 2002 [18] (ADEMEX) Termorshuizen et al., 2003 [24] (NECOSAD) Lo et al., 2003 [19] (HongKong) Prospective unit Kt/V urea /wk was associated with a 5% in the RR of death. of 5 L/1.73 m 2 CrCl /wk was associated with a 7% in the RR of death. RCT 965 Control group (2 L x 4 exchange) vs. intervention group (peritoneal CrCl of 60 L/wk per 1.73 m). RR of death of 1.00 (95% CI, ); patient survival was similar. Prospective 413 No significant effect of peritoneal CrCl on patient survival was established (RR=0.91, P=0.47). For each ml/min/1.73 m 2 increase in residual glomerular filtration rate, a 12% reduction in mortality rate was found (RR=0.88, P=0.039). RCT 320 Three Kt/V urea targets: group A, 1.5 to 1.7; group B, 1.7 to 2.0; group C,>2.0 Kt/V urea. No statistical difference in patient survival But, group A had more clinical problems and severe anemia. 의하면잔여신기능이사망률에미치 는영향이크지않다는연구결과도있 다 [25]. 따라서잔여신기능이가지는 의미에대해서는논란의여지가있긴 하지만, 잔여신기능이남아있을경우, 체액량조절과혈압조절이더양호하 고, 수분섭취량이늘어나므로삶의질 을높을수있어서생존율이향상에도 움이될것으로사료된다. 특히안지오 텐신전화효소억제제나안지오텐신수 용체차단제와이뇨제는혈압조절과는 독립적으로잔여신기능유지에도움이 된다는연구결과가있어잔여신기능이 유지되는환자에서투약을고려해야한 다 [26,27]. 말기신부전임상연구센터의현황 : 혈액투석환자의 Kt/V urea CANUSA study, Canada-USA Peritoneal Dialysis Study; RR, relative risk; CrCl, creatinine clea rance; CI, confidence interval; NECOSAD, Netherlands Cooperative Study on the Adequacy of Dialysis; RCT, randomized controlled study. No. of patients Kt/V urea 석에의한요독의제거보다잔여신기능이환자생존율에 더큰영향을미친다 [21]. 하지만국내의후향적연구보고에 A Figure 1. Distribution of Kt/V urea in prevalent (A) and incident (B) hemodilalysis patients from Clinical Research Center for End Stage Renal Disease Registry (unpublished data). No. of patients Kt/V urea B 전국에 34 개참여병원으로구성된 말기신부전임상연구센터 (Clinical Re- search Center for End Stage Renal Disease) 에서전향적코호트를구성하 여혈액투석환자의적절도를구하였 다 년 11 월까지등록되어혈액투 석중인환자를대상으로등록초기 3 개월이내의 Kt/V urea 를분석한결과를 Figure 1 에표시하였다 (unpublished data). 혈액투석환자는투석중인구환 에서 1,295 명이, 투석을처음시작하면 서코호트에등록된환자중 473 명에서 Kt/V urea 를 3 개월내에측정하였다. 구 환의평균 Kt/V urea 는 1.49±0.28 이였 고, NKF-DOQI 진료지침에서제시한최소목표치인 1.2 에미치는못하는환자는 8.5% 였다. 반면신환에서는평균 대한의사협회지 587

6 Kim SH Kim YK Yang CW Table 4. Other parameters of dialysis adequacy Parameters Volume hemeostatis Blood pressure Acid-base disorders Anemia Nutrition Inflammation Mineral metabolism (calcium/phosphate/intact-parathyroid hormone) Middle molecule clearance Kt/V urea 는 1.3±0.4 이였고, 최소목표치인 1.2 에미치는못 하는환자는 28.9% 에달했다. 투석후초기환자들은적응 기간중투석량을천천히늘리는과정이어서목표치에미달 하지못한것으로사료되며, 추후지속적인코호트연구를통 해적절도에대한분석을시행할예정이다. 투석적절도의다른지표들 미국의경우 Kt/V urea 에대한목표치에 95% 이상의환자 가도달함에도불구하고일반인구에비해심혈관질환의사 망률이 10 배이상을보인다. 따라서투석의지표인 Kt/V urea 만으로는적절한투석의지표로삼기는어려울것으로보인 다. 우선소분자물질청소율을기반으로 Kt/V urea 를적절히 유지해야하고, 환자개개인의임상양상과함께수분상태, 혈압, 산염기균형, 빈혈, 영양상태, 염증, 칼슘 인등의무 기질대사, 중분자물질청소율등의여러인자를모두합해 서투석적절도의지표로이용하여야한다 (Table 4) [28]. 이 지표들중특히수분상태와중분자물질청소율에대해이야 기해보고자한다. 1. 수분상태와혈압 복막투석환자에서체액과다는흔히관찰되는데, 특히 2006 년에발표된 International Society for Peritoneal Dialysis 에서는투석적절도와연관된진료지침의제목을 용질과수분의제거라고명명하였다 [29]. 비록무작위대조 연구에서는수분조절이이환율과사망률를낮추지는못하 였지만 EAPOS (European Automated Peritoneal Dialysis Outcomes Study European Automated Peritoneal Dialysis Outcomes Study) 연구에의하면무뇨의자동복막투석환자에게복막초여과량은생존의유의한예측인자로초여과량이 750 ml/day 이하인경우사망률이증가하였다 [30,31]. 복막투석환자에게서체액과다상태는심박출량을증가시키고전신혈관저항성을증가시켜혈압을올리고좌심실비대나울혈성심부전등의결과를일으킬수있다. 많은염분과수분의제거는적절한수분상태를보다더잘조절할수있고혈압조절을더용이하게할수있게도와준다. 따라서, 모든복막투석환자는일정한간격으로수분상태를평가해야하며, 그주기는환자상태를고려하여정해야하겠지만, 적어도 1-3개월에한번은평가해야한다. 혈액투석환자들은건체중을정해서체중을유지하게되는데투석후환자가견딜수있는가장낮은체중을의미하게된다 [32]. 따라서고혈압약물의처방없이혈압이정상적으로유지되는체중을말하는데, HEMO 연구에의하면고혈압약물치료에도불구하고 72% 환자가고혈압을보인다 [33]. 따라서적절한체액균형상태를유지하는것은복막투석, 혈액투석환자에게공히필요한것으로환자의혈압을적절히유지하고심장기능을유지하여생존율을높일것으로생각된다. 2. 중분자물질청소율소분자물질청소율만이용하여투석적절도를구하면분자량이큰중분자물질이나단백결합물질에대한평가가어렵다. 흔히 β 2 -마이크로글로블린은중분자물질의주요표지자로알려져있다. 분자량이크기때문에기존의혈액투석으로는중분자물질과단백결합물질의제거가용이하지않아서투석액의속도를늘리거나고유량혈액투석혹은대류를이용한혈액여과투석법등의다양한시도가이루어지고있다 [34]. 고유량혈액투석은고유량투석기를사용하는방법으로분자량이적은요소청소율뿐아니라분자량이큰 β 2 -마이크로글로블린청소율도증가하게된다. 고유량투석을이용한 Membrane Permeability Outcome 연구에서 β 2 -마이크로글로블린의농도가낮을수록생존율의향상 588 투석적절도의효율성

7 The efficacy of dialysis adequacy 특 집 을기대할수있다는결과가있다 [35]. 또한 Cystatin C 등과 같은물질을이용하여중분자량요독물질의제거를측정하 려는시도도있었다 [36]. 하지만대규모연구에서아직까지 이런긍정적효과를확인하지못하였으므로추가적인연구 결과를필요로한다. 요약및결론 투석치료가필요한말기신부전환자의유병률은지속적 으로증가하고있지만사망률은일반인구에비해의미있게 높아적절한투석치료를반드시필요로한다. 역사적으로 요소는신부전증의중요한요독소로여겨져왔으며임상적 으로요독증이라는용어도요소에서유래하였다. 현재요소 는중요한독성요독물질은아니어도측정이용이하고임상 양상을잘반영하므로말기신부전환자에서투석적절도의 대리지표인 Kt/V urea 를계산하는데주로사용된다. 그러나 단순히요소를기반으로한 Kt/V urea 로만투석적절도를평가 할수는없으며임상적인양상과함께수분상태, 혈압, 산염 기균형, 빈혈, 영양상태, 염증, 칼슘 인등의무기질대사, 중분자물질청소율에의한종합적인평가를필요로한다. 또한복막투석환자에서는잔여신기능을유지하기위한노 력이필요할것이며환자의삶의질을적절히유지시켜주는 것이생존율을높이고이환율을줄이는중요한요인이될것 이다. 따라서적절한투석을통해환자의장기생존율과삶 의질이더욱향상되기를기대하며투석적절도에대한지속 적인연구가필요할것으로생각된다. Acknowledgement This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). 핵심용어 : 투석 ; 말기신부전 ; 생존율 ; 요독증 REFERENCES 1. Jin DC. Current status of dialysis therapy in Korea. Korean J Intern Med 2011;26: Foley RN, Hakim RM. Why is the mortality of dialysis patients in the United States much higher than the rest of the world? J Am Soc Nephrol 2009;20: Seok SJ, Kim JH, Gil HW, Yang JO, Lee EY, Hong SY. Comparison of patients starting hemodialysis with those underwent hemodialysis 15 years ago at the same dialysis center in Korea. Korean J Intern Med 2010;25: Chin HJ. The chronic kidney disease in elderly population. J Korean Med Assoc 2007;50: Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T, Jorres A, Lemke HD, Massy ZA, Passlick-Deetjen J, Rodriguez M, Stegmayr B, Stenvinkel P, Tetta C, Wanner C, Zidek W; European Uremic Toxin Work Group (EUTox). Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int 2003;63: Choe TS, Kim SS, Kwon YJ, Cho WY, Kim HK, Woo DJ. Effect of continuous ambulatory peritoneal dialysis on beta-2-microglobulin in the patients with diabetic renal failure. Korean J Intern Med 1991;41: Kang SH, Park CW. Adequacy of dialysis: beyond Kt/V. Korean J Nephrol 2010;29: Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto R; Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002;347: Depner T, Daugirdas J, Greene T, Allon M, Beck G, Chumlea C, Delmez J, Gotch F, Kusek J, Levin N, Macon E, Milford E, Owen W, Star R, Toto R, Eknoyan G; Hemodialysis Study Group. Dialysis dose and the effect of gender and body size on outcome in the HEMO Study. Kidney Int 2004;65: Termorshuizen F, Dekker FW, van Manen JG, Korevaar JC, Boeschoten EW, Krediet RT; NECOSAD Study Group. Relative contribution of residual renal function and different measures of adequacy to survival in hemodialysis patients: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol 2004;15: Port FK, Wolfe RA, Hulbert-Shearon TE, McCullough KP, Ashby VB, Held PJ. High dialysis dose is associated with lower mortality among women but not among men. Am J Kidney Dis 2004;43: Lowrie EG, Laird NM, Parker TF, Sargent JA. Effect of the hemodialysis prescription of patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med 1981; 305: 대한의사협회지 589

8 Kim SH Kim YK Yang CW 13. Gotch FA, Sargent JA. A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int 1985;28: Hemodialysis Adequacy 2006 Work Group. Clinical practice guidelines for hemodialysis adequacy, update Am J Kidney Dis 2006;48 Suppl 1:S2-S Oh JS, Kim SM, Sin YH, Kim JK, Son YK, An WS, Kim SE, Kim KH. Reliability of hemodialysis adequacy measured by ionic dialysance. Korean J Nephrol 2011;30: Locatelli F, Canaud B. Dialysis adequacy today: a European perspective. Nephrol Dial Transplant 2012;27: Adequacy of dialysis and nutrition in continuous peritoneal dialysis: association with clinical outcomes. Canada-USA (CANUSA) Peritoneal Dialysis Study Group. J Am Soc Nephrol 1996;7: Paniagua R, Amato D, Vonesh E, Correa-Rotter R, Ramos A, Moran J, Mujais S; Mexican Nephrology Collaborative Study Group. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol 2002;13: Lo WK, Ho YW, Li CS, Wong KS, Chan TM, Yu AW, Ng FS, Cheng IK. Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study. Kidney Int 2003;64: Park HC, Kang SW, Choi KH, Ha SK, Han DS, Lee HY. Clinical outcome in continuous ambulatory peritoneal dialysis patients is not influenced by high peritoneal transport status. Perit Dial Int 2001;21 Suppl 3:S8 0-S Bargman JM, Thorpe KE, Churchill DN; CANUSA Peritoneal Dialysis Study Group. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol 2001;12: Dombros N, Dratwa M, Feriani M, Gokal R, Heimbürger O, Krediet R, Plum J, Rodrigues A, Selgas R, Struijk D, Verger C; EBPG Expert Group on Peritoneal Dialysis. European best practice guidelines for peritoneal dialysis. 7 Adequacy of peritoneal dialysis. Nephrol Dial Transplant 2005;20 Suppl 9:ix24- ix Clinical practice recommendations for peritoneal dialysis adequacy. Am J Kidney Dis 2006;48 Suppl 1:S130-S Termorshuizen F, Korevaar JC, Dekker FW, van Manen JG, Boeschoten EW, Krediet RT; NECOSAD Study Group. The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD )-2. Am J Kidney Dis 2003;41: Kim SG, Kim NH. The effect of residual renal function at the initiation of dialysis on patient survival. Korean J Intern Med 2009;24: Medcalf JF, Harris KP, Walls J. Role of diuretics in the preservation of residual renal function in patients on continuous ambulatory peritoneal dialysis. Kidney Int 2001;59: Suzuki H, Kanno Y, Sugahara S, Okada H, Nakamoto H. Effects of an angiotensin II receptor blocker, valsartan, on residual renal function in patients on CAPD. Am J Kidney Dis 2004;43: Goldberg R, Yalavarthy R, Teitelbaum I. Adequacy of peritoneal dialysis: beyond small solute clearance. Contrib Nephrol 2009; 163: Lo WK, Bargman JM, Burkart J, Krediet RT, Pollock C, Kawanishi H, Blake PG; ISPD Adequacy of Peritoneal Dialysis Working Group. Guideline on targets for solute and fluid removal in adult patients on chronic peritoneal dialysis. Perit Dial Int 2006;26: Ates K, Nergizoglu G, Keven K, Sen A, Kutlay S, Erturk S, Duman N, Karatan O, Ertug AE. Effect of fluid and sodium removal on mortality in peritoneal dialysis patients. Kidney Int 2001;60: Brown EA, Davies SJ, Rutherford P, Meeus F, Borras M, Riegel W, Divino Filho JC, Vonesh E, van Bree M; EAPOS Group. Survival of functionally anuric patients on automated peritoneal dialysis: the European APD Outcome Study. J Am Soc Nephrol 2003;14: Charra B, Laurent G, Chazot C, Calemard E, Terrat JC, Vanel T, Jean G, Ruffet M. Clinical assessment of dry weight. Nephrol Dial Transplant 1996;11 Suppl 2: Rocco MV, Yan G, Heyka RJ, Benz R, Cheung AK; HEMO Study Group. Risk factors for hypertension in chronic hemodialysis patients: baseline data from the HEMO study. Am J Nephrol 2001;21: Eloot S, Van Biesen W, Vanholder R. A sad but forgotten truth: the story of slow-moving solutes in fast hemodialysis. Semin Dial 2012;25: Locatelli F, Martin-Malo A, Hannedouche T, Loureiro A, Papadimitriou M, Wizemann V, Jacobson SH, Czekalski S, Ronco C, Vanholder R; Membrane Permeability Outcome (MPO) Study Group. Effect of membrane permeability on survival of hemodialysis patients. J Am Soc Nephrol 2009;20: Park JS, Kim GH, Kang CM, Lee CH. Application of cystatin C reduction ratio to high-flux hemodialysis as an alternative indicator of the clearance of middle molecules. Korean J Intern Med 2010;25: 투석적절도의효율성

9 The efficacy of dialysis adequacy 특 집 Peer Reviewers Commentary 본논문은투석환자가적절한투석을받고있는지의지표, 즉투석적절도의지표들의개념을정리하였고그것의효율성과투석환자의생존율과의관련성을기술한논문이다. 우리가흔히사용하는요소역동모델을비롯한여러지표들의계산방법, 투석환자에서의목표치, 유용성, 제한점등에대해정리하였다. 또한투석적절도와생존율과의관계를살펴본연구들을근거로진료지침들에서투석적절도의기준치가정해진근거를잘설명하였다. 예비결과이긴하지만말기신부전임상연구센터에등록된국내자료들을분석하여우리나라환자들의투석적절도의현황을보고하였다는점도의의가있다고생각된다. 추후지속적인코호트연구를통해더많은국내환자들을대상으로한투석적절도의보고를기대한다. [ 정리 : 편집위원회 ] 자율학습 2013 년 6 월호정답 ( 수혈요법의최신지견 ) 대한의사협회지 591

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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