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1 대한내과학회지 : 제 76 권제 5 호 2009 특집 (Special Review) - 만성콩팥병, 적극적치료가필요하다. 말기만성콩팥병환자에서새로운투석치료 가톨릭대학교의과대학내과학교실 윤혜은 김용수 New dialysis treatment options for patients with end-stage chronic kidney disease Hye Eun Yoon, M.D. and Yongsoo Kim, M.D. Department of Internal Medicine, College of Medicine, The Catholic University of Korea Medical College, Seoul, Korea Since the first hemodialysis and peritoneal dialysis were performed in humans in the early 1900s, the survival rates of patients with end-stage renal disease have increased. The number of patients in need of renal replacement therapy (RRT) is increasing, and there have been substantial advances in RRT modalities and technologies. To improve the patient outcomes requiring RRT, progress has been made to improve the efficiency and biocompatibility of dialysis in both hemodialysis and peritoneal dialysis. This review covers the basic principles of dialysis and the history of technological advances in hemodialysis and peritoneal dialysis. In addition, it includes the benefits of hemodiafiltration, new peritoneal dialysis solutions and automated peritoneal dialysis. (Korean J Med 76: , 2009) Key Words: Hemodialysis; Hemodiafiltration; Peritoneal dialysis; Automated peritoneal dialysis; Chronic kidney disease 서론대한신장학회보고에의하면우리나라에서말기만성신부전으로신대체요법을받고있는환자수는 2007년 12월말기준으로 48,675명으로인구 100만명당 973명에해당된다. 이중혈액투석 30,907명 (63.5%), 복막투석 7,649명 (15.7%), 신장이식 10,119명 (20.8%) 으로투석환자가약 80% 를차지하고있다. 투석환자에서말기신부전의흔한원인신장질환은당뇨병신장병증 (45%), 고혈압신장경화증 (17%) 및만성사구체신염 (12%) 의순서이다. 국외보고에의하면 1980년대말부터투석치료를받고있는말기신부전환자의사망률이감소하고장기생존율이향상되었다 1). 이같은생존율향상에는혈액투석막, 복막투 석액, 투석치료방법, 의료기관확대및투석치료관련의료비확대등복합적요인들이관여하였을것으로생각된다. 본글에서는투석환자생존율향상에기여한새로운투석방법에대하여정리하고자한다. 혈액투석기 (dialyzer) 의개발투석의개념은 1854년 Thomas Graham이라는화학자에의해서최초로사용되었는데, 그는소의방광을이용하여용질이반투과성막을통하여이동하는것을설명하면서투석 (dialysis) 라는용어를사용하였다 2). 1900년대초체액에서투석에의해용질을제거하는실험적혈액투석이개에서시도된이후사람에서첫혈액투석은 1924년 George Hass에의해서시도되었고, 1928년부터항응고제로헤파린을투석에이

2 - Hye Eun Yoon, et al. New dialysis treatment options for ESRD patients - 용하였다. 1937년 Wilhelm Thalheimer는소시지포장용으로사용하는셀로판 (cellophane) 이반투과성막으로용질제거에사용될수있음을발견하였고, 1943년 Willem Kolff에의해셀로판막을이용한회전드럼투석기 (rotating drum dialyzer) 가개발되면서혈액투석이임상의학으로정착되었다 년 Nils Alwall에의해최초의초여과조절투석기 (ultrafiltration-controlled dialyzer) 가소개되었고, 드럼을움직이지않고투석액이주위로흐르도록한수직드럼투석기 (vertical drum dialyzer) 를개발하였다. 1948년 Kolff의회전드럼투석기를사용하기편리하게개조한콜프- 브리그함투석기 (Kolff- Brigham dialyzer) 가개발되면서이후전세계에서사용되었다 2). 1947년 Leonards와 Skeggs는최초의평형판투석기 (parallel plate dialyzer) 를개발하였는데, 이는투석기내의혈액양과저항이적은것이특징이다. 1954년 Kolff 는 1회용투석기인코일형투석기 (coil dialyzer) 를개발하였고, 세탁기의원리를기초로 100 L의투석액을담으면서혈액펌프를부착한투석기를고안하였다. 1950년대말 Leonards, Skeggs가고안한평행판투석기를 Fredrik Kiil이셀루로즈 (cellulose) 막인큐프로판 (cuprophane) 을나사로조여개선시켰는데, 이는코일형투석기보다값이싸고혈액펌프가필요없어많이사용되었다. 1960년 Richard Stewart에의해서속이빈섬유형투석기 (hollow fiber dialyzer) 가고안되었다. 이속이빈섬유 (hollow fiber) 는내경이 250~350 μ 정도로가늘고섬유의두께가 10 μm 정도로매우얇은데, 투석기의표면적은 1 m 3 정도였다. 이러한구조로인하여투석기의표면적에대한혈류량이적고, 표면적이크고, 혈류에대한저항이낮으면서초여과율을조정할수있었다. 이후오늘날까지속이빈섬유형투석기가사용되고있다 2). 1950년대에처음인간에게혈액투석기를사용하면서투석초기에말초혈액의백혈구와혈소판수의감소가있다는것이발견되었다 3). 1970년대후반혈액투석초기 15~30분동안일시적으로백혈구수가감소하는것은셀루로즈막 (cellulose membrane) 에의하여보체계가활성화되어폐혈관계의백혈구정체현상 (leukostasis) 이발생하기때문으로밝혀졌다 4,5). 이시기에일어나는보체, 염증세포및혈소판의활성화는염증성매개물질과사이토카인의분비를발생시켜폐내피계의누출 (pulmonary endothelial leak) 과저산소증을유발함이알려졌다. 이후변형된셀룰로즈투석막 (modified cellulosic membrane) 과합성투석막 (synthetic membrane) 이개발되면서이같은염증세포의활성화가투석막의구성성분과관련있음이밝혀졌고, 이는투석기의생체적합성 (biocompatibility) 의문제를제기시켰다 6). 그러나투석기의생체적합성은투석막의구성성분뿐만아니라, 소독제, 투석액의구성, 봉합물질, 혈류와투석액관류의특성및제품의생산과정등여러인자가영향을준다. 초창기의혈액투석기에사용된투석막은셀룰로즈막의일종인큐프로판으로만들어졌다. 큐프로판은막두께가얇아서 (10 μm) 확산에의한저분자량의용질제거에는효과적이지만, 친수성이있어서대류에의한용질제거에는비효율적이었다. 또한막표면에붙어있는수산기 (hydroxyl group) 가보체계를활성화시켜백혈구감소증이나저산소증을유발하는등생체적합성이떨어졌다. 이후에셀루로즈막의수산기에아세테이트나아미노기를부착시켜보체활성을제한시킴으로써생체비적합성을개선시킨셀루로즈막 (modified cellulose and cellulose synthetic membrane) 이개발되었다. 합성중합체 (synthetic polymer; polysulphone, polyacrylonitrile, polymethamethylacrylate) 로만들어진합성막 (synthetic membrane) 은막표면의수산기를제거시켜생체적합성을높였다. 또한확산과대류에의한용질제거율을높여서 β2-microglobulin 과같은중분자크기의물질제거에도효율적이다 7). 투석막은 β2-microglobulin의청소율에따라서 10 ml/min 이하의저유량 (low-flux) 투석막, 10~20 ml/min 의중유량 (mid-flux) 투석막, 20 ml/min 이상의고유량 (high-flux) 투석막으로나뉜다. 최근에이러한고유량합성투석막의임상적이점을보여준연구결과가발표되었는데고유량합성막이저유량셀루로즈투석막이나저유량반합성투석막 (semisynthetic membrane) 에비하여심혈관질환발생위험이적고 8), 환자생존율이높으며 9), 체내축적된 β2-microglobulin의농도에따라사망률이증가한다고 10) 알려졌다. 확산투석 (diffusion dialysis) 과대류투석 (convection dialysis) 투석과정에서용질제거는확산 (diffusion) 과대류 (convection) 에의해발생한다. 확산은반투과성막을중앙에두고양편의용질의농도경사에따른이동을말하며혈액투석에서주된용질제거기전이다. 확산에의한용질제거는용질의농도경사와용질의크기에따라결정되며, 작은크기의용질 (<500 Da) 제거에빠르고효과적이다 6). 반면, β2-microglobulin과같이큰용질 (>500 Da) 의제거에는대류가효과적이다. 대류는혈장내수분이한외여과 (ultrafiltration) 과정에서발생하는용매끌기 (solvent drag) 에의하여용질이제거되는기전으로, 용질의크기와투석막의구멍크기에따라결

3 - 대한내과학회지 : 제 76 권제 5 호통권제 585 호 정된다 6). 혈액투석치료방법의개발 혈액투석치료에는현재고식적인혈액투석 (hemodialysis, HD), 혈액여과 (hemofiltration, HF) 와혈액투석여과 (hemodiafiltraton, HDF) 의세가지방법이이용되고있다 ( 그림 1) 11). 기존의혈액투석은앞에서언급한대로 10 KDa 이상의용질을제거하지못하여장기투석환자에서 β2-microglobulin 의축적에의한아밀로이드증의발생이문제되었다 12). 고유량투석막이개발되면서저유량투석막에비하여 β2-microglobulin의청소율은높였으나이또한제한적이고분자량이더큰용질제거에는충분하지못하여새로운투석방법의개발이필요하였다 13). 1975년 Henderson 등은투과성이높은투석막을사용하고많은양의대류에의하여고분자물질의제거율을증가시킬수있는혈액여과법을제시하였다 14). 혈액여과법은많은양의한외여과를유발하여대류에의한용질제거를늘려확산에의한용질제거에비해크기가큰물질을제거하는방법으로한외여과양만큼수액을보충해주어야한다. 이때많은양의수액을보충하기때문에투석액을정맥수액수준으로정화하여보충액으로사용하며이를위해추가적인필터가필요하다. 보충액은혈액의동맥부에서주입하여혈액이투석막을통과하기이전단계에서혈액을희석시키는방법 (pre-dilutional HF) 과혈액의정맥부에서주입하여혈액이투석막을통과한이후단계에서혈액을희석시키는방법 (post-dilutional HF) 이있다. 혈액여과의이점은고분자물질제거뿐만아니라심혈관계의안정성이혈액투석보다우월하다는것이다. 혈액여과는혈액투석에비하여저혈압과근육경련이적게발생하고 15), 심혈관계안정성을유지할수있으며 16), 사망률이적다 17) 는보고들이이를뒷받침한다. 이는혈액여과의요소청소율이혈액투석의요소청소율의반이하로낮기때문에 ( 약 100 ml/min) 혈액에서요소가제거되는속도로인한세포내로의수분이동이적어서삼투압변동으로인한저혈압이적게발생하기때문이다. 그러나혈액여과는혈액투석에비해저분자용질의제거에는효율이낮았다 18). 이러한결점을보완하여주로확산에의해용질을제거하는혈액투석과대류에의해용질을제거하는혈액여과의장점을모두이용한혈액투석여과방법이개발되었다. 초기에는많은양의무균용액을투여하는점과투과성이우수한값비싼투석막을사용하는비용때문에사용이제한적이었다 19). 그러나혈액투석중에사용하고있는정수된투석액을세균학적으로초정제하여온라인 (on- Figure 1. Comparison of hemodialysis, hemofiltration and hemodiafiltration. (A) In conventional hemodialysis (HD), the dialysate passess through the dialyzer in an opposite direction to the blood flow. (B) In hemofiltration (HF), the infusate can be added to the blood flow in two ways, pre-dilutional method or post-dilutional method. In pre-dilutional HF, the infusate is given to the arterial side of the hemofilter, diluting the blood before it is filtered. In post-dilutional HF, the infusate is given to the venous side of the hemofilter, diluting the blood after filtration has taken place. (C) In hemodiafiltration (HDF), both the dialysate and infusate is used. line) 으로혈액내로주입하는온라인혈액투석여과방법 (online hemodiafiltration) 이소개되면서 1990년대중반이후부터사용이확대되었다 20). 혈액투석여과의임상적장점 혈액투석여과방법이혈액투석에비하여갖는장점은크게세가지이다. 첫째, 저분자용질뿐만아니라중분자용질의제거에효과적이고둘째, 투석동안심혈관계안정성을유지할수있으며셋째, 초순수투석액과보충액을사용함으로써생체적합성이더우수하다는점이다. 혈액투석여과에의한저분자량의용질제거율은혈액투

4 - 윤혜은외 1 인. 말기만성콩팥병환자에서새로운투석치료 - 석에비해 10~15% 더높다 21). 특이인의제거가우수하여일회치료에 30~35 mmol 더제거된다 22-24). 또한 β2-microglobulin을포함한중 / 고분자용질제거에효과적이다 24-26). 이처럼투석전 β2-microglobulin의농도를감소시킴으로써아밀로이드증의발생시기를지연시키고, 수근관증후군의증상을경감시키며, 수근관증후군의수술및사망률의상대위험도를감소시킬것이다 17). 이외혈액투석여과에의하여제거될수있는중분자용질로렙틴 (leptin, 16 KDa) 27), 사이토카인 28), 마이오글로빈 (myoglobin, 16 KDa) 29) 및보체요소 D (complement factor D) 30) 등이있다. 그러나이용질들의제거가갖는임상적이점에대해서는아직확실하지않다. 혈액투석여과의심혈관계안정성은투석중저혈압의발생빈도가혈액투석에비하여감소하였다는결과들에서증명되었다 31,32). 이와같은저혈압감소의다양한원인중투석동안체온의변화가관련될것으로추정된다. 혈액투석과정에서체액이제거되면말초혈관의수축이일어나피부에서의열손실을방지하는데, 체온정도로온도를맞춘투석액이체온을상승시켜말초혈관확장을일으켜저혈압이일어난다. 혈액투석여과중사용하는보충액은혈액으로들어가면서식어서체온을낮춰말초혈관확장이일어나지않기때문에저혈압발생이감소하는것으로생각된다 11). 투석환자에서의만성염증은영양결핍과심혈관질환으로연결되는악순환을형성하는데, 이를일컬어 malnutrition, inflammation, and atherosclerosis (MIA) 증후군이라고한다 33). 투석액중세균성부산물들이투석막을통과하여면역계를활성화시킴으로써다양한염증성매개물질과내독소가분비되는것이이와관련된다 34-38). 혈액투석여과에서는투석액을정화하여보충액을만들고보충액이바로혈관계로주입되기때문에혈액투석의투석액에비해엄격히무균상태를유지해야한다. 초순수투석액이나보충액은세균이 0.1 colony forming unit/ml 미만이고, 내독소가 0.03 unit/ml 미만인상태를의미한다 39). 따라서모든혈액투석여과기계에는세균필터가장착되어투석액과보충액모두를무균상태와내독소가없는상태로유지하게된다. 혈액투석여과로투석시감소하였다는염증성매개물질로는 interleukin (IL)-1 수용체길항제 37), IL ), C-반응성단백질 (C-reactive protein) 34,37,38,40-46) 등이있으며, pentosidine과같은후기당화산물 (advanced glycation end product) 의감소도보고되었다 40,47-49). 복막투석액의개발복막투석의개념은 Wegner에의해서제시되었는데, 그는 1876년에복막을경계로용질의확산이일어남을관찰하였다 2). 1895년에 Orlow 나 Putnam 은복막을이용하여혈액내독소를제거할수있음을보여주었고, 1918년 Ganter 는신부전환자의요독증을복막투석으로조절할수있음을실험적으로증명하였다. 1945년 Frank, Seligman, Fine은급성신부전환자의복강내로무균의용액을주입하여요독증을치료함으로써실제적으로복막투석을신부전환자의치료에적용시켰다 2). 생리식염수를시작으로사용된복막투석액은현재물, 삼투물질, 전해질, 완충제및미네랄로구성되는데한외여과를유발하기위한삼투물질로포도당, 젤라틴, 자이리톨, 솔비톨, 만니톨, 포도당중합체, 아미노산등이연구되었으며, 현재포도당이주성분으로된복막투석액이보편적으로사용된다. 1. 복막투석액의비생체적합성복막투석환자가복막투석을하지못하게되는원인중복막기능의변화에따른한외여과부전 (ultrafiltration failure) 을들수있다 50,51). 장기간의복막투석후에발생하는복막의변화로는중피세포층의탈락, 중피하층세포외물질의축적및섬유화, 광범위한신생혈관의생성등이있는데 52), 이러한변화로복막기능이변하여한외여과부전이발생한다고생각된다. 따라서기존의복막투석액이인체에안전하다고는하나비생체적합성 (bioincompatibility) 이있음을알수있다. 복막투석액의비생체적합성으로는고포도당농도와고삼투농도, 포도당분해산물 (glucose degradation product, GDP) 의생성및산성산도와고농도락테이트의함유등이다. 이러한생체에부적합한특성들이앞서말한복막의변화를유발함이여러연구들에서증명되었고 53-63), 이러한특성을해결하기위하여 GDP의생성농도를감소시키거나, 락테이트대신다른물질을완충제로사용하여산도를낮추고, 포도당대신아미노산이나포도당중합체 (glucose polymer) 로구성된복막투석액들이개발되었다. 2. GDP 농도가낮은투석액포도당함유투석액의열소독과정및보관중발생하는포도당분해산물은복막중피세포에직접적인독성을나타내고후기당화산물의생성을촉진시킨다 59-63). 이러한문제를해결하기위하여포도당용액을아주낮은 ph에서열소독하여 GDP의생성을현저히줄일수있는 dual-chamber bag system이개발되어출시되고있다. 이러한투석액을사용하여무작위배정대조시험의공통된결과는 GDP가적은투석

5 - The Korean Journal of Medicine: Vol. 76, No. 5, 액을사용하였을때복막중피세포의부피와대사의정도를나타내는 CA125가증가하고염증을나타내는 hyaluronic acid가감소하여복막중피세포또는중피세포하간질의손상을줄일수있다는것이다 64-67). 투석액의주입시통증이감소되고영양상태가호전되며한외여과가증가된다는보고도있으나 65) 다른연구에서는주입시통증의차이가없거나 66) 한외여과가감소된다고 64) 보고하였다. 또한복강내대식세포의기능을향상시키고투석액내후기당화산물과 IL-6의생성이감소되었다는보고도있다 68). GDP가적은투석액의사용이환자생존율의향상을가져온다는결과는국내에서시행한연구가유일하다 69). 그러나이연구는무작위배정대조연구가아니고더젊은연령층의환자들이 GDP가적은투석액을사용하였기때문에 GDP의농도와환자생존율의향상과의상관성을증명하기위해서는추가연구가필요하다. 3. 정상산도의투석액인체와생리적으로가장가까운완충제는중탄산염 (bicarbonate) 이다. 그러나투석액에서중탄산염은열소독이나저장과정에서칼슘탄산염 (calcium carbonate) 으로침전되어사용할수없다. 그러나 dual-chamber bag system에서중탄산염과칼슘을분리하여열소독을할수있게되어순수한중탄산염, 혹은중탄산염 / 락테이트혼합투석액이사용가능하게되었다 70). 무작위배정대조시험연구들에서중탄산염혹은중탄산염 / 락테이트혼합용액이만성신부전환자의대사성산증조절에락테이트완충액보다효과적임이증명되었다 65,71-73). 또한중탄산염완충액이대사성산증교정뿐만아니라 CA125의증가소견을보여복막중피세포의보존에더효과적이고 74), 복강내대식세포의기능을향상시키고투석액내후기당화산물과 IL-6의생성을감소시킨다는보고도있다 68). 그러나일부무작위배정대조연구에서중탄산염완충액이락테이트완충액에비하여크레아티닌과인의제거율이떨어지고대사성산증의교정에효과가없다고하였다 75,76). 그외중탄산염혹은중탄산염 / 락테이트혼합용액이투석액주입시통증의감소및잔여신기능보존이나한외여과에더효과적인지는상반되는결과들이보고되고있어분명하지않다. 중탄산염완충액이환자생존율의향상을가져온다는보고역시국내에서시행한두연구가유일한데 69,77), 무작위대조연구가아니고환자군의연령이유사하지않은제한점을갖고있다. 4. Icodextrin 투석액투석액내의포도당은분자량이작기때문에복강에서혈액으로흡수되어투석액을장시간저류했을때한외여과량이적고비만, 포도당불내성, 고인슐린혈증및고지혈증등의대사성부작용을일으킨다. Icodextrin은평균분자량이 16,500 Da인포도당중합체로장시간저류시켜도 20~35% 만흡수되어최고 16시간까지지속적인한외여과가가능하다 78). Icodextrin은교질삼투 (colloid osmosis) 를일으키고주로림프계를통하여이동하여 3.86% 포도당투석액보다느리지만오래지속되는한외여과특성을갖고있기때문에복막투과성이증가된환자 (high-transporter) 에서도효과적으로사용할수있다 79). 또한한외여과를증가시키면서저분자용질의제거도증가시키기때문에 79-81), 3.86% 포도당투석액사용시한외여과부전을보이거나소변이나오지않는환자에사용하기적합하다. 포도당중합체는혈중의 α-amylase에의해 maltose, maltotriose, maltotetraose 로분해되고최종적으로조직의 maltase에의해분해되어포도당이되거나소변혹은복강으로배설된다 78). 이러한분해산물로인하여혈중나트륨농도가적게감소하며 80-82), 혈중의과도한포도당중합체와 maltose의축적을피하기위하여하루 1회만사용하도록되어있다 83,84). Icodextrin을사용한무작위배정대조연구들에서 icodextrin이일반포도당투석액에비하여한외여과량을증가시키고세포외수분을감소시켜체중조절에효과적임이입증되었다 85-87). 그외고지혈증 88) 과인슐린저항성을개선시켰다는보고들이있으나 89-91), 모두무작위대조연구가아니어서지질과포도당대사에대한효과는아직불명확하다. 자동복막투석의개발 1980년에자동으로교환기를사용해서야간에행할수있는복막투석방법인자동복막투석 (automated peritoneal dialysis, APD) 이도입되었다. 우리나라에서는 1995년 APD 환자가 14명으로시작하여 1998년 108명, 2003년에는총복막투석환자 6,919명중 425명 (6.2%) 로증가하였으며최근지속적인증가추세를보이고있다 92,93). 자동복막투석은투석액의교환을환자가직접하는대신미리조정된복막투석교환기 (cycler) 에의해서투석액교환이이루어지며, 지속성교환기복막투석 (continuous cyclic peritoneal dialysis, CCPD) 과야간복막투석 (nightly peritoneal dialysis, NPD) 의두가지종류가있다. CCPD는야간에기계가 4회투석액을교환하고, 낮에는필요할경우일회손으로교환하는지속적복막투석

6 - Hye Eun Yoon, et al. New dialysis treatment options for ESRD patients - 방법이다. 반면, NPD는야간에만투석을시행하는데, 교환방법에따라야간간헐성복막투석 (nightly intermittent peritoneal dialysis, NIPD) 과야간조류성복막투석 (nightly tidal peritoneal dialysis, NTPD) 으로구분된다 93). 자동복막투석의장점은무엇보다도고투과성복막을가진환자이면서 (high transporter) 한외여과량이감소한환자 95) 와잔여신기능이거의없어진환자에서적합하다 96). 고투과성복막을가진환자에서는짧은교환주기로한외여과를개선시키고대신포도당의흡수를감소시키고, 잔여신기능이거의없어진환자에서는투석용액의부피를증가시킬수있기때문이다. 또한사회적, 경제적활동에제한이적다는것도큰장점이다 94). 투석시간을환자편의에따라조절할수있고, 투석처방도다양하게선택할수있기때문이다. 반복적인탈장이발생하는환자에서도자동복막투석이도움이되는데, 자동복막투석이주로밤에누워있는상태에서투석액이교환되므로, 복압의상승이없어탈장의위험이감소하기때문이다 93). 자동복막투석은지속성복막투석에비하여복막염의빈도가낮은데 92,97,98), 그이유로는연결관의연결및분리횟수감소로인한접촉감염기회의감소, 적은출구손상으로도관감염기회의감소, 연결작업을편안하고동일한장소에서하는것으로인한안전성, 주간에복강내투석액주입을하지않음으로인한복강내방어기전의향상 93,97,99) 등을들수있다. 요약말기만성콩팥병으로신대체요법을받는환자의사망률과유병률을줄이고생존율을향상시키기위한노력이지속되어왔으며, 이에투석의효율성과생체적합성을높이기위한많은기술적인개발과발전이있었다. 혈액투석에서는기존의저유량혈액투석에서고유량혈액투석및혈액투석여과방법이개발, 시행되고있으며, 복막투석에서는기존의포도당투석액에서 GDP 생성이적고중성 ph를유지하는투석액및 icodextrin과같은새로운투석액과자동복막투석법이개발되었다. 이러한투석치료방법의발전으로투석환자의생존율과삶의질은향상되고있으며향후새로운투석치료방법이지속적으로개발될것으로기대된다. 중심단어 : 혈액투석 ; 혈액투석여과 ; 복막투석 ; 자동복막투석 ; 만성콩팥병 REFERENCES 1) Foley RN, Collins AJ. End-stage renal disease in the United States: an update from the United States Renal Data System. J Am Soc Nephrol 18: , ) Nissenson AR, Fine RN. Clinical dialysis. 4th ed. p. 1, New York, The McGraw-Hill, ) Kaplow LS, Goffinet JA. Profound neutropenia during the early phase of hemodialysis. JAMA 203: , ) Craddock PR, Fehr J, Brigham KL, Kronenberg RS, Jacob HS. Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N Engl J Med 296: , ) Craddock PR, Fehr J, Dalmasso AP, Brighan KL, Jacob HS. Hemodialysis leukopenia. Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes. J Clin Invest 59: , ) Davenport A. The role of dialyzer membrane flux in bioincompatibility. Hemodial Int 12(Suppl 2):S29-33, ) Misra M. Basic mechanisms governing solute and fluid transport in hemodialysis. Hemodial Int 12(Suppl 2):S25-28, ) Krane V, Krieter DH, Olschewski M, März W, Mann JF, Ritz E, Wanner C. Dialyzer membrane characteristics and outcome of patients with type 2 diabetes on maintenance hemodialysis. Am J Kidney Dis 49: , ) Delmez JA, Yan G, Bailey J, Beck GJ, Beddhu S, Cheung AK, Kaysen GA, Levey AS, Sarnak MJ, Schwab SJ. Hemodialysis (HEMO) Study Group. Cerebrovascular disease in maintenance hemodialysis patients: results of the HEMO Study. Am J Kidney Dis 47: , ) Cheung AK, Rocco MV, Yan G, Leypoldt JK, Levin NW, Greene T, Agodoa L, Bailey J, Beck GJ, Clark W, Levey AS, Ornt DB, Schulman G, Schwab S, Teehan B, Eknoyan G. Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study. J Am Soc Nephrol 17: , ) Petrie JJ, Ng TG, Hawley CM. Review Article: is it time to embrace haemodiafiltration for centre-based haemodialysis? Nephrology 13: , ) Gejyo F, Narita I. Current clinical and pathogenetic understanding of beta2-m amyloidosis in long-term haemodialysis patients. Nephrology (Carlton) 8(Suppl):S45-49, ) Ahrenholz PG, Winkler RE, Michelsen A, Lang DA, Bowry SK. Dialysis membrane-dependent removal of middle molecules during hemodiafiltration: the beta2-microglobulin/albumin relationship. Clin Nephrol 62:21-28, ) Henderson LW, Colton CK, Ford CA. Kinetics of hemodiafiltration. II. Clinical characterization of a new blood cleansing modality. J Lab Clin Med 85: , ) Schaefer K, Asmus G, Quellhorst E, Pauls A, von Herrath D, Jahnke J. Optimum dialysis treatment for patients over 60 years with primary renal disease. Survival data and clinical results from 242 patients treated either by haemodialysis or haemofiltration. Proc Eur Dial Transplant Assoc Eur Ren Assoc 21: ,

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