원저 ISSN 일산병원학술지 2017;16(2): 혈액투석용동정맥루조성술의결과와동정맥루개존율의위험인자 국민건강보험일산병원외과 1, 영상의학과 2, 신장내과 3 이진호 1, 남수민 1, 김태환 2, 이용규 3, 강이화 3, 신석균 3, 이형

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1 원저 ISSN 일산병원학술지 2017;16(2): 혈액투석용동정맥루조성술의결과와동정맥루개존율의위험인자 국민건강보험일산병원외과 1, 영상의학과 2, 신장내과 3 이진호 1, 남수민 1, 김태환 2, 이용규 3, 강이화 3, 신석균 3, 이형순 1 Surgical Outcomes and Risk Factors on Patency Rates of Arteriovenous Fistula for Hemodialysis Jin Ho Lee 1, Soomin Nam 1, Taehwan Kim 2, Yong Kyu Lee 3, Ea Wha Kang 3, Sug Kyun Shin 3, Hyung Soon Lee 1 Departments of 1 Surgery, 2 Radiology and 3 Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Korea Background: The objective of this study was to report the surgical outcomes of arteriovenous fistula (AVF) for hemodialysis and to identify the risk factors that may influence the patency rates of AVF. Methods: From May 2016 to August 2017, the patients who underwent AVF surgery for hemodialysis were reviewed. Patency rates were analyzed using the Kaplan-meier method. To identify risk factors for patency rates of AVF, clinical and surgical variables were assessed by Cox-regression analysis. Results: A total of 38 patients received AVF surgery for hemodialysis. Artificial vessels were used in 6 cases (15.8%). Pre-operative venography was performed in 37 patients (97.4%) and the mean diameter of the veins measured at the pre-operative venogram was 3.87 mm. However, the mean diameter of the veins measured at the time of surgery was 2.93 mm. The overall patency rates of 6 months and 1 year were 90.8% and 72.1%, respectively. By univariate analysis, percutaneous transluminal angioplasty after surgery, diabetes as a primary renal disease and presence of comorbidity was analyzed as risk factors of patency rates. However, multivariate analysis showed that diabetes as a primary renal disease was the only risk factor for patency rates of AVF (p=0.020, hazard ratio=7.467). Conclusion: We demonstrated comparable surgical outcomes for vascular access surgery compared to previous reports. And diabetes as a primary renal disease was the only significant risk factor affecting the patency rates of AVF. Therefore, the patients with diabetes as a primary renal disease may need detailed pre-operative evaluation, meticulous surgery and post-operative care. Key Words: Hemodialysis, Arteriovenous fistula, Treatment outcome, Vascular patency 서론 말기신부전환자의증가로인해혈액투석치료에의존하여삶을유지해야하는환자가증가하고있다. 1 또한말기신부전의주원인인당뇨병성신증의발생이계속적으로증가하고있고, 고령환자의비율이증가하는현시점에서혈액 책임저자 : 이형순 경기도고양시일산동구일산로 100 국민건강보험일산병원외과전화 : (031) , 팩스 : (031) soon0925@nhimc.or.kr. 투석동정맥루의개통을유지하는것은단순히환자의치료뿐만아니라, 생존과직결된문제로대두되고있다. 2 이상적인혈액투석용동정맥루는효과적인혈액투석을시행하기위한혈류속도를유지할수있으며, 오래사용할수있어야하고, 사용중합병증이적어야한다. 현재자가혈관동정맥루가이러한조건에가장근접하며, 특히요골동맥- 요측부정맥동정맥루는일단정맥성숙이성공적으로이루어지면개존율이높고, 합병증이낮기때문에가장이상적인혈액투석용동정맥루로알려져있다. 3 그러나당뇨병등여러가지이유로말초혈관의상태가좋지않을경우나, 말초정맥천자를여러번시행받은경우에는요측부정맥의손상이생겨수술하기어려운경우도많다. 이러한경우인조혈관을 Volume 16 Number 2 December

2 JH Lee, et al. Surgical Outcomes and Risk Factors on Patency Rates of Arteriovenous Fistula for Hemodialysis 이용한동정맥루가시행되고있는데, 인조혈관동정맥루는자가혈관동정맥루에비해낮은개존율, 높은합병증의발생이문제가되고있다. 4 동정맥루의종류이외에동정맥루의개존율을예견할수있는인자로알려진것들에는동정맥루수술을시행하는외과의의기술, 여성, 고령자, 환자의혈중알부민농도, 당뇨병의여부등이다. 5-7 그러나혈액투석동정맥루의개존율에대해수많은국외의보고들이나오고있는반면, 국내환자들을대상으로한혈액투석동정맥루의개존율과그에관련된위험인자들에대한연구는미미한상태이다. 이에저자들은본원에서동정맥루수술을받은환자들을대상으로동정맥루조성술의결과에대해살펴보고, 혈액투석용동정맥루의개존율에영향을미치는위험인자들을규명하고자한다. 대상및방법 1. 대상 2016년 5월부터 2017년 8월까지국민건강보험일산병원에서동정맥루수술을받은환자를대상으로하였으며, 자료는의무기록을바탕으로후향적으로분석하였다. 수술은동일한수술자에의해동일한수술방법과원칙하에시행되었다. 2. 방법수술방법의선택은정맥과동맥의상태에따라 ; (1) 비우성측 (nondominant) 손목관절부에서의요골동맥-요측피정맥동정맥루 (radiocephalic fistula), (2) 비우성측상완의상완동맥-요측피정맥동정맥루 (brachiocephalic fistula), (3) 우성측손목관절부에서의요골동맥- 요측피정맥동정맥루, (4) 우성측상완의상완동맥 -요측피정맥동정맥루, (5) 상완동맥-상완정맥간인조혈관을이용한동정맥루 [brachiobrachial fistula with polytetrafluoroethylene (PTFE)], (6) 액와동맥-액와정맥간인조혈관을이용한동정맥루 (axillo-axillary fistula with PTFE), (7) 대퇴동맥- 복재정맥간인조혈관을이용한동정맥루 (femoral-saphenous fistula with PTFE) 의순서를기준으로순차적으로결정하였다. 자가혈관을이용한동정맥루수술시에는동맥측- 정맥단의문합법을사용하였고인조혈관을이용한경우에는고리형 (loop configulation) 으로인조혈관을배치하고, 혈관과는동맥측- 정맥측또는단문합하였다. 인조혈관은 GORE-TEX 사의제품을사용하였으며, 모든경우에서내경 4mm에서 6mm로동맥쪽으로가늘어지는, 길이 40 cm 이상의인조혈관을사용하였다. 동정맥루를시행한환자에대해서는성별, 수술당시의연령, 체질량지수, 말기신부전의원인질환, 동반질환여부, 과거의투석경력, 수술전헤모글로빈, 수술전혈소판, 수술전크레아티닌청소율, 수술전 C-반응단백수치, 과거의동정맥루수술경력, 수술전정맥조영술에서정맥직경, 수술당시정맥직경과동맥직경, 수술당시동맥경화여부, 사용된혈관의종류, 동정맥루의위치를조사하였다. 수술결과를분석하기위해수술후합병증발생여부, 재수술여부, 수술후경피경관혈관성형술 (percutaneous transluminal angioplasty) 여부, 동정맥루의개존여부, 환자의사망여부등은본원에서투석중인환자들은직접적인문진을하였고, 타병원에서투석중인환자는투석중인의료기관의주치의또는환자와의전화상담으로조사하였다. 동정맥루조성술후한번도사용하지못하였거나, 동정맥루를유지할수없는합병증이발생하여수술적으로동정맥루를폐쇄시킨경우를동정맥루의실패로간주하였으며, 동정맥루가개존된상태에서환자가사망한경우에는그시점까지만동정맥루가개존된것으로처리하였다. 3. 통계분석개존율은 Kaplan-Meier 방법으로산출하였고, 통계적유의성은 Log-rank 방법을이용하여 p값이 0.05 미만인경우에통계적으로의의가있는것으로간주하였다. 위험인자에대한분석은 Cox-regression 분석을시행하여상대적위험도 (Hazard ratio) 로표시하였으며, 유의수준 0.05 이하로검증하였다. 결과 1. 수술당시의환자의임상적인양상 대상기간동안총 38명의환자에서동정맥루수술을시행하였으며, 수술당시의평균연령은 68.9세였고, 당뇨병이말기신부전의원인질환인경우가 24예 (63.2%) 이었다. 수술당시투석을시작하지않은환자는 4예 (10.5%) 였으며, 중심정맥도관으로혈액투석을시행중인환자는 26예 (28.9%), 복막투석을시행중인환자는 8예 (10.5%) 였다. 이전에동정맥루수술을받았던과거력이있는환자는 5예 (13.2%) 였다 (Table 1). 자가혈관으로손목관절부에요골동맥- 요측피정맥동정맥루를시행한경우가 16예 (42.1%), 상완부에상완동맥 - 요측피정맥동정맥루시행한경우가 16예 (42.1%) 였으며, 인조혈관을사용하여전완에고리형으로동정맥루를시행한경우는 4예 (10.5%), 인조혈관으로상완부에직선형으로동정 150 Korean Journal of National Health Insurance Service Ilsan Hospital

3 이진호외. 혈액투석용동정맥루조성술의결과와개존율의위험인자 맥루를시행한경우는 2예 (5.3%) 였다 (Table 2). 수술전정맥조영술 (venogram) 에서측정한정맥의직경은평균 3.87 mm 였으며, 수술당시측정한정맥의평균직경은 2.93 mm 였다. 2. 수술결과 평균 260 일간의추적조사결과, 3예 (7.9%) 의환자사망과 5예 (13.2%) 의동정맥루소실을확인하였다. 동정맥루소실의원인을살펴보면혈전증 (thrombosis) 4예 (10.5%), 정맥의미성숙에의한소실이 1예 (2.6%) 였다 (Table 3). 수술후동정맥루성숙에걸린평균기간은 75.6일이었으며, 수술후동정맥루성숙이지연되어동정맥루주위가지혈관결찰술 (branch ligation) 을시행한환자가 3예 (7.9%) 있었다. 수술후경피경관혈관성형술은 10예 (26.4%) 에서시행하였으며, 경피경관혈관성형술을시행한이유는정맥협착 5예 (13.2%), 혈전증 2예 (5.3%), 정맥의성숙지연 3예 (7.9%) 였다. 수술후경피경관혈관성형술시행까지평균기간은 113일이었고, 수술후합병증은동정맥루주위혈청종 (seroma) 4예 (10.5%), 출혈이 Table 1. Patient characteristics (n=38) Characteristic Age (years) Female gender [n (%)] * Body mass index(kg/m2) Primary disease Diabetes mellitus * Hypertension * Nephrotic syndrome * Polycystic kidney disease * IgA nephropathy * Unknown * Comorbidity Ischemic heart disease * Chronic heart failure * Arrhythmia * Renal replacement therapy before surgery Hemodialysis via central venous catheter * Peritoneal dialysis * No dialysis yet * Previous access operation history * Hemoglobin(g/dL) Platelet ( 100/μL) C-reactive protein (mg/dl) Albumin (g/dl) Creatinine clearance (ml/min) Values 68.9± (36.8%) 25.9± (63.2%) 6 (15.8%) 2(5.3%) 1(2.6%) 2(5.3%) 11 (28.9%) 26 (68.4%) 8 (21.1%) 5 (13.2%) 10.0± ±81 1.4± ± ±9.3 Values in parentheses are mean±standard deviation unless indicated otherwise.; * Values are number with percentages. 3 예 (7.9%) 였다. 3. 동정맥루의전체개존율 전체적인동정맥루의 6개월, 1년개존율 (patency rates) 은각각 90.8%, 72.1% 이었다 (Fig. 1). 4. 동정맥루개존율의위험인자 성별 ( 여자 ), 연령 (75세이상의고령자 ), 사용된혈관의종류 ( 인조혈관 ), 수술후경피경관혈관성형술여부, 수술후합병증발생여부, 말기신부전의일차질환 ( 당뇨 ), 동반질환여부, 동정맥루술의과거경력, 체질량지수 ( 25) 등을개존 Table 2. Characteristics of vascular access Characteristic Type of access AVF, radio-cephalic * AVF, brachio-cephalic * AVG, forearm loop * AVG, brachio-axillary * Measured vessel (pre-operative venogram, mm) Vein Measured vessel (at operation, mm) Artery Vein Presence of atherosclerosis (at operation) * Values 16 (42.1%) 16 (42.1%) 4(10.5%) 2 (5.3%) 3.87± ± ±0.49 5(13.2%) Values in parentheses are mean±standard deviation unless indicated otherwise.; * values are number with percentages. AVF, arteriovenous fistula; AVG, arteriovenous graft. Table 3. Surgical outcomes of vascular access surgery Duration of maturation (day) * Maturation failure Thrombosis Immaturity of vein Re-operation for branch ligation PTA Venous stenosis Thrombosis Delayed maturation Time to PTA after surgery (day) * Post-operative complication Seroma Bleeding Values 75.6±76.5 1(2.6%) 5 (13.2%) 2(5.3%) 113±72 7 (18.4%) Values in parentheses are number with percentages unless indicated otherwise.; * Values are mean±standard deviation. PTA, percutaneous transluminal angioplasty Volume 16 Number 2 December

4 JH Lee, et al. Surgical Outcomes and Risk Factors on Patency Rates of Arteriovenous Fistula for Hemodialysis 율에영향을미치는위험인자로설정하여단인자분석을시행하였다. 수술후경피경관혈관성형술을시행한경우, 동반질환이있는경우와말기신부전의일차질환이당뇨인경우가통계학적으로유의한위험인자였다. 하지만다인자분석에서말기신부전의일차질환이당뇨인경우만이동정맥루개존율에영향을미치는유의미한위험인자로분석되었다 (p=0.020, Hazard ratio=7.467, Table 4). Fig. 1. Kaplan-Meier analysis for patency rates of vascular access. 고찰 본연구에서대상기간동안총 38명의환자에서동정맥루수술을시행하였으며, 6예 (15.8%) 에서인조혈관을이용한동정맥루를시행하였다. 동정맥루의 6개월, 1년개존율은각각 90.8%, 72.1% 였으며, 수술후 5예 (13.2%) 의동정맥루소실이있었다. 그리고, 동정맥루의개존율에위험인자분석에서말기신부전의일차질환이당뇨인경우만이동정맥루개존율에영향을미치는유일한위험인자로분석되었다. 최근보고된연구에따르면수술후 1년동정맥루의일차개존율은자가혈관의경우 64-73% 정도로보고되고있다. 8 또한인조혈관을이용한동정맥루의 1년일차개통률은 50-60% 정도로자가혈관의일차개존율보다낮게보고되고있다. 4 본연구에서도수술후 1년째동정맥루의일차개존율은 72.1% 로관찰되었으며, 이전연구와비슷한개존율을보였다. 다만본연구에서는인조혈관을이용한동정맥루수술환자가적어 (6예, 15.8%) 자가혈관과인조혈관각각의일차개존율을비교할수없어아쉬운부분이있다. 따라서추후인조혈관수술환자가증가하면자가혈관과인조혈관의일차개존율및수술결과를비교해볼필요가있겠다. 동정맥루수술후개존율의위험인자에대한이전보고들에서이미여러위험인자에대해지적한바있다. 5,9 그중당뇨는대표적인동정맥루수술후개존율에대한위험인자중하나로, 비정상적인혈당의대사를유발하여혈관내피세포 Table 4. Univariate and multivariate Cox-regression analysis of risk factors for patency rate Variable Univariate analyses Age Sex Type of vascular access PTA after surgery Post-operative complication Primary disease of ESRD Comorbidity History of previous AVF operation Body mass index Multivariate analyses PTA after surgery Primary disease of ESRD Comorbidity Categories <75 years vs 75 years Male vs Female Autologous vs Prosthetics Non-DM vs DM <25 vs 25 Non-DM vs DM Disease-Free Survival Hazard ratio 95% Confidence interval p-value PTA, percutaneous transluminal angioplasty; ESRD, end-stage renal disease; DM, diabetes mellitus; AVF, arteriovenous fistula. 152 Korean Journal of National Health Insurance Service Ilsan Hospital

5 이진호외. 혈액투석용동정맥루조성술의결과와개존율의위험인자 의기능을떨어뜨리고, 산화스트레스 (oxidative stress) 를증가시키며, 세포의증식반응을변화시켜새로만들어진동정맥루의성숙과정중재형성과정에부정적인영향을미치는것으로알려져있다. 10 이와유사하게, 본연구에서도다인자분석에서말기신부전의일차질환이당뇨인경우가동정맥루개존율의유일한위험인자로분석이되었다. 따라서말기신부전의원인질환이당뇨인환자를수술하는경우에는수술전정밀한검사를통하여혈관상태를파악하고, 수술중세심한지혈및혈관문합을시행해야하겠다. 동정맥루수술전혈관상태를파악할수있는검사방법으로는대표적으로도플러초음파와정맥조영술두가지가있다. 11 하지만정맥조영술의경우조영제를사용함으로써조영제유발신병증 (contrast-induced nephropathy) 을유발할수있다는단점이있다. 특히, 아직투석을시작하지않은환자의경우조영제유발신병증을유발하여환자의신기능을떨어뜨릴수있어위험하다. 12 또한여러보고에서수술전시행한정맥조영술에서측정한정맥의직경과수술당시측정한정맥의직경보다크게측정이되는것을지적하고있다. 13,14 이와마찬가지로본연구에서도수술전정맥조영술에서측정한정맥의직경은평균 3.87 mm였으나, 수술당시측정한정맥의평균직경은 2.93 mm 로정맥조영술에서측정한정맥의평균직경이더크게측정되었다. 이는정맥조영술을시행할때조영제를주입하는과정에서정맥이확장되어원래정맥직경보다크게측정되는것으로판단된다. 따라서최근에는도플러초음파를이용하여수술전에혈관의상태를파악하는기관들이늘고있는데, 이는도플러초음파가보다정확한혈관크기의측정이가능하고비침습적이며, 혈관의구조적인측면이외에혈류량과같은기능적인측면도측정이가능하기때문이다. 15 그러므로, 동정맥루수술전에정맥조영술보다도플러초음파를시행하여혈관상태를평가한다면동정맥루수술의결과를향상시킬수있을것으로판단된다. 또한최근여러기관에서시행되고있는이산화탄소를이용한정맥조영술을시행한다면조영제유발신병증의확률을줄이면서혈관상태를보다정확히판단할수있을것으로생각된다. 16,17 본연구에서동정맥루의수술결과와수술후 1년일차개존율은이전보고된결과와큰차이가없는결과를보여주었다. 또한말기신부전의원인질환이당뇨인경우가동정맥루수술후개존율에영향을미치는유일한위험인자로분석되었다. 따라서말기신부전의원인질환이당뇨인환자를수술하는경우에는수술전정밀한검사를통하여혈관상태를 파악하고, 수술중세심한지혈및혈관문합을시행하여야하겠다. 또한수술후잦은추적관찰을통하여동정맥루상태를평가하여필요한경우에는조기에혈관조영술을시행하는것이동정맥루의개존율을향상시키는데도움이될것으로판단된다. REFERENCES 1. Lee YK, Kim K, Kim DJ. Current status and standards for establishment of hemodialysis units in Korea. Korean J Intern Med 2013;28(3): Allon M, Robbin ML. Hemodialysis vascular access monitoring: current concepts. Hemodial Int 2009;13(2): Thomas M, Nesbitt C, Ghouri M, Hansrani M. Maintenance of Hemodialysis Vascular Access and Prevention of Access Dysfunction: A Review. Ann Vasc Surg 2017;43: Allon M, Lok CE. Dialysis fistula or graft: the role for randomized clinical trials. Clin J Am Soc Nephrol 2010;5(12): Bashar K, Zafar A, Elsheikh S, Healy DA, Clarke-Moloney M, Casserly L, et al. Predictive parameters of arteriovenous fistula functional maturation in a population of patients with endstage renal disease. PLoS One 2015;10(3):e Peterson WJ, Barker J, Allon M. Disparities in fistula maturation persist despite preoperative vascular mapping. Clin J Am Soc Nephrol 2008;3(2): Rodriguez JA, Armadans L, Ferrer E, Olmos A, Codina S, Bartolome J, et al. The function of permanent vascular access. Nephrol Dial Transplant 2000;15(3): Bylsma LC, Gage SM, Reichert H, Dahl SLM, Lawson JH. Arteriovenous Fistulae for Haemodialysis: A Systematic Review and Meta-analysis of Efficacy and Safety Outcomes. Eur J Vasc Endovasc Surg 2017;54(4): Lamprou A, de Bruin C, van Roon A, Loonstra J, van der Laan M, Tielliu I, et al. Patient-related factors influencing patency of autogenous brachiocephalic haemodialysis fistulas. J Vasc Access 2017;18(Suppl. 1): Conte MS, Nugent HM, Gaccione P, Roy-Chaudhury P, Lawson JH. Influence of diabetes and perivascular allogeneic endothelial cell implants on arteriovenous fistula remodeling. J Vasc Surg 2011;54(5): Marques MG, Ponce P. Pre-operative Assessment for Arteriovenous Fistula Placement for Dialysis. Semin Dial 2017;30(1): Asif A, Ravani P, Roy-Chaudhury P, Spergel LM, Besarab A. Vascular mapping techniques: advantages and disadvantages. J Nephrol 2007;20(3): Won YD, Lee JY, Shin YS, Kim YS, Yoon SA, Kim YS, et al. Small dose contrast venography as venous mapping in predialysis patients. J Vasc Access 2010;11(2): McGrogan DG, Maxwell AP, Khawaja AZ, Inston NG. Current tools for prediction of arteriovenous fistula outcomes. Clin Kidney J 2015;8(3): Volume 16 Number 2 December

6 JH Lee, et al. Surgical Outcomes and Risk Factors on Patency Rates of Arteriovenous Fistula for Hemodialysis 15. Wilson NA, Shenoy S. Ultrasound in preoperative evaluation for dialysis-access placement. Semin Dial 2014;27(6): Heye S, Maleux G, Marchal GJ. Upper-extremity venography: CO 2 versus iodinated contrast material. Radiology 2006;241 (1): Sullivan KL, Bonn J, Shapiro MJ, Gardiner GA. Venography with carbon dioxide as a contrast agent. Cardiovasc Intervent Radiol 1995;18(3): Korean Journal of National Health Insurance Service Ilsan Hospital

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untitled Korean J Vasc Endovasc Surg 2012;28(4):202-206 http://dx.doi.org/10.5758/kjves.2012.28.4.202 우리나라 환자의 투석을 위한 혈관접근로 조성에서는 수술 전 일률적 초음파검사가 필요치 않다 계명대학교 동산병원 외과 현슬기ㆍ김형태ㆍ박의준ㆍ조원현 Careful Physical Examination