Clinical and Experimental Study of Maintenance Hemodialysis Vascular Access Failure

vascular access is the line of life for long-term maintenance hemodialysis patients.With the development of blood purification technology,with prevention and cure kinds of complication in time,the life span of hemodialysis patients are longer and longer,how to protect and prolong the access use becomes an important clinical issue.Native arteriovenous fistula is the best,majorest access style,it account for more than 90%,its failure is one of main reasons for insufficiency dialysis,death,high hospitalization.Between 1991 and 2001,the incidence of vascular access events in patients undergoing hemodialysis rose by 22%,Vascular access-related complications account for 15-20% of hospitalizations among end-stage renal disease patients undergoing hemodialysis,Vascular access-related complications accounted for 24% of all hospital admissions.Access failure always induce to low dialysis prescription and catheter use,Every 0.1 decrease in Kt/V was independently and signifi cantly associated with 11%more hospitalizations,12%more hospital days,and a USD 940 increase in Medicare inpatient expenditures,clinic data show 20%-25%AVF did not mature adequately to support hemodialysis,a primary patency of 85%for AVF at 1 yr and 75%at 2 yr,This difference was greatest in women,patients with diabetes,and patients who were older than 65yr,it is a draconic challenge to physician.The National Kidney Foundation Kidney Disease Outcomes Quality Initiative update in 2006 propose techniques may be used in surveillance for stenosis in grafts include Physical findings,Directly measured or derived static venous dialysis pressure,Recirculation, Intra-access flow,Duplex ultrasound.In AVF propose to surveillance above index,but prefer Direct flow measurements,Recirculation or Duplex ultrasound may be beneficial,access flow surveillance can prediscover the stenosis and thrombus of grafts or AVF,effective intervention prolong the span life of access.Clinical practice guidelines for vascular access of Canadian Society of Nephrology propose to monitor access flow and evaluation every two month,flow＜500ml/min or decrease 20%than base line should prefer contrast examination.The mothods of access flow surveillance include ultrasonic dilution(UD),glucose pump test(GPT),Duplex ultrasound(DU), transcutaneous access flow rate(TQA),conductometry,ultrafiltration and so on.But there is not gold standard.Now ultrasonic dilution technology has been extensively used in clinic.In 1995 professor Krivitski invented and developed the technology of UD,its basic theory as follows:the spread velocity of ultrasonic connect with the protein density of blood,injecting saline changes protein density and spread velocity,the sensor linked with dialysis line can detect the change,by means of the software we calculate the recirculation rate,access flow and cardiac output.the transonic company make the HD01,HD02monitor and extensively used in the foreign dialysis center,but in our country the report about access surveillance is rare and the viewpoint is retardation.So we chosed 90 prevalent chronic hemodialysis patients with AVF in our dialysis center,using the HD02 hemodialysis monitor detects recirculation,access flow and cardiac output of during the period of dialysis and analysing the related factors of access blood flow.4 patients(3.33%) occure access recirculation(AR) and AR＞5%,21 patients(23.33%) have Qa(blood flow)＜500ml/min,3 patiens(3.33%) have Qa＞2000ml/min,the logistic regress analysis the factors including age,sex,time of hemodialysis,time of fistula creation,MAP are no significantly associated with access flow,but low cardiac output and diabetes are significantly associated with access flow decrease.33 patients(36.67%) have CO(cardiac output)＜4 L/min,it show the part of patients maybe have low cardiac output situation during hemodialysis. the result of cardiac color Doppler in 8 patients show they all have change of cardiac function and structure such as interventricular septum pachynsis,cardiac valve calcification and back-streaming,left ventricle diastolic pachysis.We think that ultrasound dilution is a simple noninvasion access surveillance method.The recirculation rate of AVF obtaining enough blood flow is rare,mulvariation analysis shows the low cardiac output and diabetes are significantly associated with access flow decrease.Moreover,the group of Magnasco A invented the method of Glucose pump test because UD need special and expensive equipment,validated in vitro and vivo and the result showed lower false positive rate and similary sensitivity compared with UD.so we chosed thirty-nine hemodialysis patients with arteriovenous fistula determined fistula flow rate with GPT and ultrasound dilution during hemodialysis.Color Doppler Ultrasonography(CDU) was carried out in patients with QA＜500ml within two weeks.The Results show that The Qa of 2 patients can't be measured by GPT and UD,4 patients were difficult to calculate Qa in GPT because of little change of glucose concentration in two blood samples.By analysing 33 patients data,we found that the average Qa of GPT higher than that of UD,which has statistically difference.The regression analysis showed a good correlation between GPT and UD results(r=0.8480,R~2=0.7191).The fistulas of patients with QA＜500ml had arteriovenous stoma stenosis or venous stenosis near stoma.Both methods of GPT and UD are feasible in arteriovenous fistula blood flow surveillance and can predict vascular access failure.The factors,such as the internal environment change of ESRD patients,neointimal hyperplasia,abnormity vascular remodeling,local hemodynamics change and so on,induce to AVF mature failure and lated dysfunction,Kinds of factors,including multiple cells,cytokines, mediators of inflammation,Signal Transduction paths and so on, participated vein-arterialization and neointimal hyperplasia,but molecular mechanism is complex and dimness,now lack of valid drugs and other intervention method.there are reports in recent years about outvascualr stent and local drugs delivery,for example Paclitaxel and Sirolimus,which restrained VSMC and myofibroblast proliferation, prolonged access use.To study pathogenesis and intervention,we found an simple rat AVF model.30 Wister rats,divided to 5 groups(include 5 rats in control group and ensure 5 rats succeed anastomoses in every time point),10%hydral intravenous anesthesia,intraoperative heparinize,carotid artery-internal carotid vein end-to-end anastomosis with 10-0 stitch by means of surgery microscope.sacrifice in postoperative 7,14,28 day and obtain artery and vein tissue near anastomotic stoma.Make HE and elastic fibers-collagen fiber double staining,calculate neointimal thickness and area,calculate VSMC proliferation rate,observe the change of TGF-β1,NF-κB protein expression.the result show that artery near anastomotic stoma have not obvious pathological change in postoperative,vein tissue near anastomotic stoma occue generous VSMC and collagen fiber proliferation,neointimal hyperplasia on 7th day postoperative,on 14th day intracavity occur sarcomyces maked up VSMC and collagen fiber,the neointimal hyperplasia rate among groups have obvious variance,specific stain occur interio elastic layer continuity interruption,collagen fiber proliferation. Immunohistochemisty result show that TGF-β1,NF-κB protein expression increase.myocardium pathology have not obvious heart failure pathological change such as cardiac muscle fibers chaotic Courser vacuolar degeneration and interstitial fibrosis.we propose that this model simulate focal hemodynamic influence,in short-term occur typical pathological change,initial show TGF-β1,NF-κB may participate the neointimal hyperplasia pathological process,available to study the pathogenesis and intervention.To sum up,our study show that UD and GPT are a simple noninvasion access surveillance method.The recirculation rate of AVF obtaining enough blood flow is rare,mulvariation analysis shows the low cardiac output and diabetes are significantly associated with access flow decrease this model simulate focal hemodynamic influence,in short-term occur typical pathological change,initial show TGF-β1, NF-κB may participate the neointimal hyperplasia pathological process, available to study the pathogenesis and intervention.