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1 대한내과학회지 : 제 74 권제 5 호 28 p-anca 연관신염의임상적고찰 : 단일임상기관연구 경북대학교의과대학내과학교실, 동국대학교의과대학내과학교실 2 강혁주 2 박선희 박자용 신용봉 김찬덕 탁우택 2 이정호 2 김용림 Clinical characteristics of p-anca (anti-neutrophil cytoplasmic antibody)-related nephritis: a single center experience Hyeock-Joo Kang, M.D. 2, Sun-Hee Park, M.D., Ja-Yong Park, M.D., Yong-Bong Shin, M.D., Chan-Duck Kim, M.D., Woo-Taek Tak, M.D. 2, Jeong-Ho Lee, M.D. 2 and Yong-Lim Kim, M.D. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea ; Department of Internal Medicine, Dongguk University College of Medicine, Kyongju, Korea 2 Background/Aims : We evaluated the clinical characteristics and prognostic value of the clinical, laboratory, pathologic features, at time of diagnosis, and the renal survival of patients with ANCA (anti-neutrophil cytoplasmic antibody)-related nephritis. Method : We retrospectively analyzed 7 patients who were diagnosed with ANCA-related nephritis at a single center. The risks of progression to ESRD or death according to the clinical parameters, the ANCA pattern and the renal pathologic findings were evaluated. Results : The major symptoms were hematuria (%), proteinuria (%), uremic symptoms (4.2%), edema (35.5%), upper respiratory symptoms (29.4%) and oliguria (23.5%), which were not correlated with renal survival. All the patients showed a p-anca pattern. The BUN level (p=.32) and GFR (p=.23) at the time of diagnosis were different between the improved and the progressed patients in terms of renal function. The pathology indices were not predictive factors of both renal and patient survival. Eight patients (47.%) were treated with steroid IV pulse, 4 (23.5%) with steroid IV pulse and cyclophosphamide IV pulse, 2 (.8%) with steroid IV pulse, cyclophosphamide IV pulse and plasma exchange, and 2 (.8%) with steroid IV pulse and plasma exchange. Fourteen patients (82.4%) needed hemodialysis. There were 3 (7.6%) disease-related deaths, 3 patients (76.5%) reached ESRD and 4 (23.5%) showed recovery of renal function. The mean percent of patients who survived was 8.2% and the mean percent of renal survival was 33.3% at the st and 3rd year, respectively. Conclusions : Poor renal function at presentation was associated with a high risk for disease progression, but age, gender, the clinical patterns of presentation and the pathologic findings were not associated with the prognosis. Early diagnosis and treatment seems to be essential to improve the renal outcomes. (Korean J Med 74:523-53, 28) Key Words : ANCA; Nephritis Received : Accepted : Correspondence to : Yong-Lim Kim, M.D., Division of Nephrology, Department of Internal Medicine Kyungpook University Hospital, 5 Samduck-dong, Jung-gu, Daegu 7-72, Korea ylkim@knu.ac.kr

2 - The Korean Journal of Medicine : Vol. 74, No. 5, 28 - 서 론 할수없는환자들을 ANCA-related nephritis 로진단하였다 ). 급속진행성사구체신염 (rapidly progressive glomerulonephritis, RPGN) 은요독증, 핍뇨등의임상상이빠르게진행되는사구체신염으로일반적으로신장기능의감소가회복되지않고진행하여발병후수주또는수개월내에요독증에빠지게된다 ). 신생검에서사구체들의 5~7% 이상에서반월 (crescent) 형성이확인되는경우반월상사구체신염 (cresentic glomerulonephritis, Crescentic GN) 으로진단할수있다. 반월상사구체신염의병리소견을보이는대부분의경우에원인질환에관계없이 RPGN의임상양상을보이는것으로알려져있다 2). 반월상사구체신염의원인질환은면역학적병인에따라항-사구체기저막반월상사구체신염 (anti GBM crescentic GN), 면역복합체반월상사구체신염 (immune-complex crescentic GN) 그리고무면역침착반월상사구체신염 (pauciimmune crescentic GN) 으로분류될수있다. 무면역침착반월상사구체신염은약 8% 의환자에서항-중성구세포질항체 (anti-neutrophil cytoplasmic antibody, ANCA) 양성을보이므로 ANCA 연관반월체사구체신염이라고도하며 Wegener 씨육아종증 (Wegener's granulomatosis, WG), 미세다발성혈관염 (Microscopic polyangitis, MPA), Churg-Strauss 증후군등과같은전신적소혈관혈관염에병발하여발생할수도있다 3, 4). 조기진단에의해초기에적극적인치료를시작하면약 7% 에서신기능이호전된다 5, 6). 그러나본질환의발생빈도는매우낮아서국내에서는 RPGN 에대한소수의증례또는임상적경험등만보고되어있고 ANCA연관반월상사구체신염에대한보고는없다 7, 8). 이에연구자들은 ANCA 연관신염 (ANCA-related nephritis) 에대한한국인에서의국내임상경험과예후와관련있으리라생각되는인자들을분석보고하고자한다. 대상및방법. 대상 2년 월부터 26년 7월까지경북대학교병원내과에입원하여후향적조사에서 ANCA-related nephritis로진단된 7명의환자의임상소견및검사실소견을분석하였다. 급격한신기능저하, 혈청 ANCA 양성소견을보이고신장조직검사에서 Crescentic GN의양상이나면역형광현미경검사에서는면역글로불린, 보체의침착이경미또는관찰 2. 검사실검사모든환자들은신조직검사시말초혈액검사, 일반뇨검사, 간기능검사, BUN, 혈청크레아티닌, 혈청총콜레스테롤, 24시간요단백량, estimated GFR (by MDRD equation), anti-nuclear antibody, anti-dna antibody, ANCA, ASO, CRP, rheumatoid factor, VDRL, cryoglobulin, 혈청 IgG, IgA, C3, C4 등을실시또는측정하였다. ANCA 측정은 indirect immunoflorescence assay 원리를이용하여환자의혈청또는희석된혈청을 slide well과반응시켜검체내에존재하는 ANCA와 slide에 ethanol 고정된 human granulocytes가결합되면이를세척한후 anti-human IgG conjugated to fluorescein isothiocyanate를넣고 incubation한뒤결합되지않은 conjugates를세척후현광현미경을이용하여 c-anca 혹은 p-anca로판독하였으며, 이배수희석을하여역가산출을하였다. ANCA 의 titer와 anti-mpo 항체는일부의환자에서확인되지않아기술하지않았다. 3. 신생검신생검은초음파유도하에실시하였으며신조직은광학현미경, 면역현광현미경및전자현미경으로관찰하였다. Crescentic GN의진단기준은광학현미경표본에서 8개이상의사구체가관찰가능하고관찰된사구체의 5% 이상에서반월체 (crescent) 가관찰되는것으로하였다. 각환자에서반월상, 사구체경화 (glomerular sclerosis) 를동반하는비율을평가하였으며, 간질성염증세포침윤 (interstitial inflammatory cell infiltration) 과섬유화 (interstitial fibrosis) 는정도에따라반정량적 scoring system으로나누어평가하였다 (=none, =mild, 2=moderate, 3=severe). 4. 치료방법각환자들에게임상소견에따른대증요법을실시하였고면역억제요법으로는 cyclophosphamide 2~3 mg/kg/day와 prednisone mg/kg/day를매일경구로투여하였으며, 신장외장기의침범이있는경우 methylprednisone 충격요법 ( g/day, 3일 ) 이나혈장교환법을추가로시행하였다 9). 5. 통계신생존에영향을미치는인자를알아보고자신기능이회복되어장기적인유지투석이필요하지않았던호전된환

3 - Hyeock-Joo Kang, et al : Clinical characteristics of p-anca-related nephritis - Table. Age and gender distribution age (year) male female Total (%) -9 (5.9) 2-29 () (.8) 4-49 (5.9) (.8) (29.4) (35.3) Total () Table 2. Clinical findings Number of patients progressed (n=3) improved (n=4) Total (%) p value hypertension (76.9) 3 (75) 3 (76.5). uremic symptoms 6 (46.2) (25) 7 (4.2).63 Edema 5 (38.5) (25) 6 (35.3). URI symptoms 3 (23.) 2 (5) 5 (29.4).583 Oliguria 3 (23.) (25) 4 (23.5). hemoptysis 3 (23.) (25) 4 (23.5). proteinuria 3 () 4 () 7 () - hematuria 3 () 4 () 7 () - URI, Upper Respiratory Infection 자 (improved group, n=4) 와최종적으로장기적인유지투석이필요했던악화된환자 (progressed group, n=3) 로나누어 Fisher's exact test, Mann-Whitney U test를사용하여비교분석하였으며, 신생존율과환자생존율을보기위하여 Kaplan- Meier 방법을이용하였다. 신생존율분석시치료중질환과관계되어환자가사망한경우 event case 로, 질환과관계없이환자가사망한경우는 `censored case`로간주하여생존율을분석하였다. 결과치는 SPSS for Windows 3. 을이용하여통계처리하였다. p 값이.5 미만일때통계적으로의의가있다고판단하였다. 결과 RPGN으로진단된 39예중 ANCA 연관신염으로분류된경우는 7예로 43.6% 를차지하였으며, 예가 microscopic polyarteritis의소견을보였고, 나머지 6예에서는전신혈관염소견을보이지않고신장에만국한된소견을보였다. 환 자의평균연령은 6.5±8.세 (5~79세) 였고, 성별분포는남자가 9예, 여자가 8예였으며연령별분포는 6~79세사이가 예로전체환자의 65% 를차지하였다 ( 표 ). 호전된환자군과악화된환자군에서나이, 성별에따른생존율및신생존율의차이는없었다 ( 표 3). 내원당시의중요임상증상은혈뇨, 단백뇨가모든환자 (7예, %) 에서관찰되었으며고혈압 3예 (76.5%), 요독증상 7예 (4.2%), 부종 6예 (35.3%), 상기도감염증상 5예 (29.4%), 핍뇨 4예 (23.5%), 객혈 3예 (23.5%) 의소견을보였으나, 두군사이에빈도의차이는없었다 ( 표 2). 진단당시의면역혈청학적소견은 7예모두에서 p-anca 양성이었으며, anti-nuclear antibody, anti-dna antibody 는모든환자에서음성소견을보였다. 중요검사실소견은혈색소 8.±.7 g/dl, 24시간뇨단백량 2.24±2.2 g/day, 혈중요소질소 72.6±3.3 mg/dl, 혈청크레아티닌 8.2±3.8 mg/dl, 혈청알부민 2.94±.46 g/dl, 혈청총콜레스

4 - 대한내과학회지 : 제 74 권제 5 호통권제 573 호 28 - Table 3. Patients characteristics and laboratory findings Number of patients progressed (n=3) improved (n=4) Total (n=7) p value Gender (male/female) 7/6 2/2 9/8. Age (year) 6.92± ± ± Hemoglobin (g/dl) 7.69±.7 9.7±. 8.± hr urine protein (g/day) BUN (mg/dl) 2.23±2.5 8.± ± ± ± ± * creatinine (mg/dl) 9.2± ± ±3.8.6 albumin (mg/dl) 2.93± ± ± total cholesterol 59.2± ± ±4..87 C3 4.6± ±5.2 3.± C4 estimated GFR (MDRD, ml/min per.73m 2 ) 36.3± ± ±3. 4.4± ± ± * BUN, Blood Urea Nitrogen; GFR, Glomerular Filtration Rate Table 4. Pathologic findings progressed (n=3) improved (n=4) Total (n=7) p value crescent (%) 44.62± ± ± glomerular sclerosis (%) interstitial infiltration * 32.2± ± ±34. 2.± ±3.8.88± interstitial fibrosis *.3±.8.25±.5.29± * the scoring of interstitial infiltration and interstitial fibrosis; =none, = mild, 2=moderate, 3=severe Table 5. Modality of therapy Number of patients (%) SP 8 (47.) SP + CP 4 (23.5) SP + CP + plasma exchange 2 (.8) SP + plasma exchange 2 (.8) no treatment (5.9) Hemodialysis 4 (82.4%) SP, steroid pulse; CP, cyclophosphamide pulse 테롤 6.7±4. mg/dl, estimated GFR (MDRD, ml/min per.73m 2 ) 8.4±5.36 이었다. 신생존과관련하여호전된환자군과악화된환자군에서의미있는차이점을보인인자는진단당시의혈중요소질소 (p=.32) 와사구체여과율 (estimated GFR) (p=.23) 로확인되었다 ( 표 3). 진단시의신생검소견은전예의면역형광현미경검사에서사구체내에면역글로불린과보체의침착이경미하거나 관찰할수없었고, 반월상의동반율은 48.8±3.9%, 사구체경화의동반율은 32.6±3.8% 였다. 실제로 7명의환자중 crescent의개수로만 5% 를넘는환자는 명이었고, 나머지는 33%, 6%, 4.3%, 6.7%, %, 3.8%, 33.3% 로확인되었으며, glomerulo-sclerosis를 crescent로포함하였을때는 환자 ( 상기의 microscopic polyangitis 환자 ) 를제외하고는모두 5% 이상을넘었다. 간질성염증세포침윤과섬유화정도는 scoring system에따라각각.88±.8과.29±.7 소견을보여 mild에서 moderate 의소견을보였다. 이중신생존과관련하여호전된환자군과악화된환자군에서의미있는차이점을보인인자는없었다 ( 표 4). 환자들에대한치료는 4예 (82.4%) 에서내원당시투석치료가필요하였으며, 스테로이드충격요법이 8예 (47.%), 스테로이드충격요법과싸이클로포스파마이드 (cyclophosphamide) 병합요법을시행한예가 4예 (23.5%), 스테로이드충격요법과싸이클로포스파마이드및혈장교환술을시행한예가 2예 (.8%), 스테로이드충격요법과혈장교환술을시

5 - 강혁주외 7 인 : p-anca 연관신염의임상적고찰 - Table 6. Outcomes Number of patients (%). Survival Function Censored recovery 4 (23.5) ESRD 3 (76.5) expired 3 (7.6) Total 7 () ESRD, end-stage renal disease 행한예가 2예 (.8%) 였다 ( 표 5). 평균 5개월의추적기간동안 3예 (76.5%) 에서말기신부전으로진행하여유지신대치요법이필요하였고, 4예 (23.5%) 에서신기능이회복되었으며경과중사망한경우는 3예 (7.6%) 였다 ( 표 6). 사망한환자들은모두악화된군에속했으며질환과관련하여사망하였다. 환자생존율은 년및 3년에서 8.2% 였고, 신생존율은 년및 3년에서 33.3% 였다 ( 그림, 2). Cumulative survival probability Follow-up period (month) Figure. Patient survival: There were 3 (7.6%) diseaserelated deaths and the patient survival rate were 8.2% at the st and 3rd year. 6 7 고찰 WG, MPA, 그리고신장국한성혈관염 (renal limited vasculitis) 등은 ANCA와관련된자가면역질환으로여러장기들을침범하여열, 체중감소, 빈혈, 기력감소등비특이적전신적염증소견들을보인다. 고령의환자 (65~74세) 에서대부분발생하고, WG와 MPA의경우신장에서도공통된조직학적소견을관찰할수있어 ANCA 연관신염 (ANCA related nephritis) 라고통칭한다, ). ANCA 연관신염은병세가급격히진행하고예후도좋지않으며치료방법들도본질적으로위험하기때문에의료진들은 ANCA 특이성, 나이, 신장기능, 신장병리소견, 신장이외장기에서의혈관염등예후에관련있으리라생각되는여러인자들에관심을가져왔다 2-5). ANCA 연관신염에서는 ANCA가중요한병인으로기여한다. 호중구의 serin protease (proteinase-3) 에대한항체인 cytoplasmic ANCA (c-anca) 는주로 WG와관련이크고, 호중구의 myeloperoxidase에대한항체인 perinuclear-anca (p-anca) 는주로일차성 crescentic GN과 MPA와관련있다. c-anca와관련이된경우신병변이더심하고신기능의감소가더빠르게나타나며 p-anca와관련이있는경우는이와대조적으로만성병변을보이는경우가많다는보고가있어, 두 ANCA type에따른기전의차이가있을것으로생각되나아직확실하지않다 6). Cumulative survival probability Follow-up period (month) 4 5 Survival Function Censored Figure 2. Renal survival: There were 3 patients (76.5%) who reached ESRD and 4 (23.5%) showed recovery of renal function and the renal survival rate were 33.3% at the st and 3rd year. ANCA 연관신염은고령 (65~74세) 의환자에서대부분발생하며, c-anca 는남자, p-anca 는여자에서더흔히관찰되는것으로보고되었으나 7), 본연구에서는 6세이상 (64.7%) 의고령환자에서대부분발생하였으며남녀차이없이모든환자에서 p-anca 양성소견을보였기때문에 ANCA type에따른경과나예후의차이는확인할수없었다. 또한고령일수록나쁜예후를보인다는보고가있었으

6 - The Korean Journal of Medicine : Vol. 74, No. 5, 28 - 나 4-6) 본연구에서는성별, 나이에따른신생존률또는사망률의차이가없었다. RPGN의임상양상은원인신질환을감별하기에는비전형적이나선행하는상기도감염이반수정도에서보이고핍뇨, 부종, 호흡곤란등이갑작스럽게진행된다. 또한육안적혈뇨와뇨검사에서전형적인이형적혈구및적혈구원주혹은다양한원주들을볼수있다 7, 8). 본연구에서는혈뇨와단백뇨가모든환자에서관찰되었고, 고혈압이 3예 (76.5%), 요독증상 (4.2%), 부종 (35.3%) 상기도감염증상 (29.4%), 핍뇨 (23.5%) 의순서로관찰되었다. 급격한신기능의감소로인한신증후군의발생, 수분조절부전으로인한핍뇨와부종, 사구체모세혈관파열에의한혈뇨등이임상양상의원인으로생각된다. 진단당시핍뇨, 기관지증상이있는경우예후가불량하다는연구들이있으나 6, 9) 본연구에서는임상양상들과신생존률은관련이없었다. ANCA 연관신염에서예후를예측할수있는인자로는진단또는치료시작시의신장기능감소정도라는연구들이다수있다 9, 2-22). Hogan 등 6) 은 ANCA 연관신염에서장기간의신생존에관여하는강력한예후인자의하나로진단당시의혈청크레아티닌을들고있다. Morgan 등 ) 은진단당시신부전이심할수록예후가나쁘다고보고하였고, Hauer 등 23) 도 ANCA 연관신염에서 8개월후의 GFR을예측할수있는가장좋은인자는치료시작시의 GFR 수치라고보고하였다. 본연구에서는신생존과관련하여악화된환자군에비해호전된환자군에서의미있는차이를보인인자는진단당시의혈중요소질소 (p=.32) 와사구체여과율 (p=.23) 로나타나상기연구들과유사한결과를보였다. 진단당시의신생검소견과예후와의연관성을보고하는연구도다수있었다. Hauer 등 23) 은 8개월후의 GFR과관련있는인자들로 interstitial fibrosis, glomerulosclerosis, tubular atrophy, crescents, fibrinoid necrosis 를언급하였으나이들인자들과재발또는사망과의연관성은증명할수없었다고보고하였다. Hogan 등 6) 은장기간의신생존과 arterial sclerosis의연관성을보고하였고, Gans 등 3) 은신생검성적으로면역억제치료에대한반응을예측할수있었다고보고하였다. 또한만성적인병변, 특히 interstitial fibrosis 가있는경우불량한신생존율과연관성이있다는보고들도있다 9, 24). 본연구에서저자들은사구체경화나간질염증세포침윤, 반월상등을예후인자로기대하였으나신생존과관련하여호전된환자군과악화된환자군에서의미있는차이점을보인인자는없었으며, 이는대부분의환자들에서이 미심한사구체손상이진행되어예후를결정지을정도의손상의차이를볼수없었기때문이라고생각된다. ANCA 연관신염의치료는스테로이드, 퓨린대사길항제 (purine anti-metabolites), 알킬화제 (alkylating agents) 를이용한광범위한면역억제에기초를두고있다. 치료초기에는적극적인면역억제를통한염증조절을통해더진행되는장기의손상을막음으로써관해를유도한다. 초기치료후치료제의부작용을줄일수있는범위의덜집중적인면역억제를통하여관해유지요법을시행한다. 치료하지않을경우 8% 이상에서사망하거나말기신부전으로진행하며, 잦은재발때문에면역억제치료는저용량으로 2~24개월동한지속한다. 싸이클로포스파마이드와스테로이드를사용함으로써재발을줄이고생존율을크게향상시켰으나, 약제의독성, 치료자체와관련된유병률, 사망률을고려해야한다. 최근에는싸이클로포스파마이드대신에관해유도나유지요법으로아자시오프린 (azathioprine) 이나 mycophenolate mofetil을사용하기도한다 9, 22). 혈장교환술은치료당시투석의존성이있는환자에서만예후에부가적인도움이된다는보고가있다 25). 혈청크레아티닌수치가 5.6 mg/dl 이상인환자에서는부가적으로혈장교환술을사용하는것이메틸프레드니솔론을사용하는것보다신장기능의회복에더좋다는보고도있다 26). 본연구에서는진단후강력한면역억제치료, 혈장교환술, 투석치료에도불구하고말기신부전으로의진행이 76.5% 로많았으며, 이는진단시이미신사구체손상이심한신부전상태에서치료가시작되었기때문이라고생각된다. 증례의부족으로치료방법의차이에따른통계학적분석은불가능하였다. 결론적으로 ANCA 연관신염은진단당시이미신기능의감소가심한경우신생존율의악화를보이므로진단과치료는가능한빨리시작하여사구체염증과신부전을감소시키는것이중요하겠으며, ANCA 연관신염의임상양상을보이면서 ANCA 양성소견을보이면신생검으로확진되기이전이라도조기에스테로이드충격요법과같은강력한면역억제제치료를시작해보는것이신생존율향상에도움을줄수도있을것으로판단되다. 요약목적 : 급속진행성사구체신염은전체사구체신염의약 2~% 를차지하며, 그중에서무면역침착질환 (pauciimmune disease) 은항호중구세포질항체 (ANCA) 와연관있

7 - Hyeock-Joo Kang, et al : Clinical characteristics of p-anca-related nephritis - 는염증질환으로, 본원에서 ANCA 연관신염 (ANCA associated nephritis) 으로진단된예를대상으로한임상경험과예후과관련이있으리라생각되는인자들을분석보고하고자한다. 방법 : 2년 월부터 26년 7월까지경북대학교병원내과에입원하여후향적조사에서 RPGN, crescentic GN으로진단된 39예중혈청ANCA 양성인 7예를대상으로하였다. 결과 : 환자의평균연령은 6.5±8.세 (5~79세) 였으며성별분포는남자가 9예, 여자가 8예로남녀성별비는.3: 였으며, 6세이상의환자가전체의 64.7% 를차지하였다. 중요임상증상은혈뇨, 단백뇨가모든환자 (7예, %) 에서관찰되었으며고혈압, 요독증상, 부종, 상기도감염증상, 핍뇨, 객혈의순이었으며, 이중신생존과연관을보이는인자는없었다. 면역혈청학적소견은 7예모두에서 p-anca 양성이었으며, 중요검사실소견에서신생존과관련하여호전된환자군과악화된환자군에서의미있는차이점을보인인자는진단당시의혈중요소질소 (p=.32) 와사구체여과율 (estimated GFR) (p=.23) 이었다. 진단시의신생검소견은환자모두에서사구체내에면역글로불린과보체의침착이경미하거나관찰할수없었고반월상의동반율은 48.8±3.9%, 사구체경화의동반율은 32.6±3.8% 였으며, 간질성침윤과섬유화정도는경증에서중등증의소견을보였으며이중신생존과관련하여두군사이에의미있는차이점을보인인자는없었다. 치료는 4예 (82.4%) 에서내원당시투석치료가필요하였으며, 스테로이드충격요법이 8예 (47.%), 스테로이드충격요법과싸이클로포스파마이드 (cyclophosphamide) 병합요법을시행한예가 4예 (23.5%), 스테로이드충격요법과싸이클로포스파마이드및혈장교환술을시행한예가 2예 (.8%), 스테로이드충격요법과혈장교환술을시행한예가 2예 (.8%) 였다. 평균 5개월의추적기간동안 3예 (76.5%) 에서말기신부전으로진행하여유지신대치요법이필요하였고, 4예 (23.5%) 에서신기능이회복되었으며경과중사망한경우는 3예 (7.6%) 였다. 환자생존율은 년및 3년에서 8.2% 였고, 신생존율은 년및 3년에서 33.3% 였다. 결론 : 진단당시신기능이예후와가장관계가있었으며환자의나이, 성별, 임상양상이나병리학적소견은신생존과관계가없었다. 따라서조기진단과치료가신생존율향상에도움을줄수있을것으로판단된다. 중심단어 : ANCA; 신염 REFERENCES ) 대한신장학회. 임상신장학. 초판. p. 2-22, 광문출판사, 2 2) Couser WG. Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy. Am J Kidney Dis : , 988 3) Jennette J, Olson J, Schwartz M, Silva F. Crescentic glomerulonephritis. In: Heptinstall's pathology of the kidney. 5th ed. p , Philadelphia, Lippincott-Raven press, 998 4) Jennette J, Falk R. Antineutrophil cytoplasmic autoantibodies and associated diseases. Am J Kidney Dis 5:57-529, 99 5) Booth A, Almond M, Burns A, Ellis P, Gaskin G, Neild G, Plaisance M, Pusey C, Jayne D. Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis 4: , 23 6) Hogan SL, Nachman PH, Wilkman AS, Jennette JC, Falk RJ. Prognostic markers in patients with antineutrophil cytoplasmic autoantibody-associated microscopic polyangitis and glomerulonephritis. J Am Soc Nephrol 7:23-32, 996 7) 권진경, 이상수, 서상혁, 박성배, 김현철, 박관규. 급속진행성사구체신염의임상적고찰. 대한신장학회지 8:4-48, 999 8) 김구, 남현경, 고병성, 허정훈, 주희린, 손승현, 안원석, 김성은, 김기현. 급속진행성사구체신염의임상상. 대한내과학회지 67:76-84, 24 9) Jayne D. Update on the European Vasculitis Study Group trials. Curr Opin Rheumatol 3:48-55, 2 ) Watts RA, Lane SE, Bentham G, Scott DG. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom. Arthritis Rheum 43:44 49, 2 ) Morgan MD, Haper L, Williams J, Savage C. Anti-neutrophil cytoplasm-associated glomerulonephritis. J Am Soc Nephrol 7: , 26 2) Keller F, Oehlenberg B, Kunzendorf U, Schwartz A, Offermann G. Long-term treatment and prognosis of rapidly progressive glomerulonephritis. Clin Nephrol 3:9-97, 989 3) Gans RO, Kuizinga MC, Goldschmeding R, Assmann K, Huysmans FT, Gerlag PG, Donkey AJ, Hoorntje SJ. Clinical features and outcome in patients with glomerulonephritis and antineutrophil cytoplasmic autoantibodies. Nephron 64:82-88, 993 4) Andrassy K, Kuster S. Waldherr R, Ritz E. Rapidly progressive glomerulonephritis: analysis of prevalence and clinical course. Nephron 59:26-22, 99 5) Briedigkeit L, Kettritz R, Gobel U, Natusch R. Prognostic factors in Wegener s granulomatosis. Postgrad Med J

8 - 대한내과학회지 : 제 74 권제 5 호통권제 573 호 28-69:856-86, 993 6) 노정우. 반월상사구체신염의발생과정및발생기전. 대한신장학회지 2: , 2 7) Geffriaud-Ricouard C, Noel L, Chauveau D, Houhou S, Grunfeld J, Lesavre P. Clinical spectrum associated with ANCA of defined antigen specificities in 98 selected patients. Clin Nephrol 39:25-36, 993 8) Morrin P, Hinglais N, Nabarra B, Kreis H. Rapidly progressive glomerulonephritis: a clinical and pathologic study. Am J Med 65:446-46, 978 9) Heilman R, Offord K, Holley K, Velosa J. Analysis of risk factors for patient and renal survival in crescentic glomerulonephritis. Am J Kidney Dis 9:98-7, 987 2) Savage CO. ANCA-associated renal vasculitis. Kidney Int 6:64-627, 2 2) Hamidou MA, Derenne S, Audrain MA, Berthelot JM, Boumalassa A, Grolleau JY. Prevalence of rheumatic manifestations and antineutrophil cytoplasmic antibodies in haematological malignancies: a prospective study. Rheumatology 39:47-42, 2 22) Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term outcome of anti-glomerular basement membrane antibody disease treated with plasma exchange and immunosupression. Ann Intern Med 34:33-42, 2 23) Hauer H, Bajema I, Houwelingen H, Ferrario F, Noel L, Waldherr R, Jayne DR, Rasmussen N, Bruijn JA, Hagen EC. Determinants of outcome in ANCA-associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients. Kidney Int 62: , 22 24) Vergunst C, van Gurp E, Hagen E, van Houwelingen H, Hauer H, Noel L, Waldherr R, Ferrario F, van der Woude F, Bruijn J, Bajema I. An index for renal outcome in ANCAassociated glomerulonephritis. Am J Kidney Dis 4: , 23 25) Pusey CD, Rees AJ, Evans DJ, Peters DK, Lockwood CM. Plasma exchange in focal necrotizing glomerulonephritis without anti-gbm antibodies. Kidney Int 4: , 99 26) Gaskin G, Jayne D, Group EV. Adjunctive plasma exchange is superior to methylprednisolone in acute renal failure due to ANCA-associated glomerulonephritis [Abstract]. J Am Soc Nephrol 3:2A,

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