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1、提要,高通量透析器历史为什么应用高通量透析器高通量透析技术要求临床实践中的高通量透析,EU,USA,巴西,中国,日本,世界人口与透析患者,人口：约亿人透析患者：约万人,出典（Table4)改編2005年EDTA開催時報告,USA,24%（HD22%,PD2%）,EU,18%,日本,18%（HD17%,PD1%）,其他,40%,世界整体透析患者约137万人,世界透析患者的比例,出典（Table4)改編2005年EDTA開催時報告,透析患者所占的人口比例,出典（Table4)改編2005年EDTA開催時報告,世界人口与透析患者,出典（Table4)改編2005年EDTA開催時報告,透析器膜的历史,
2、Membranes for Medical Applications,regeneratedcellulose,modifiedcellulose,hydrophilized copolymers,hydrophobic/hydrophilicblend,syntheticmembranes,cellulosicmembranes,AN69(Hospal)PMMA(Toray)EVAL(Kuraray)PEPA(Nikkiso)SPAN(Akzo/Asahi),PA/PAES/PVP(Gambro)PAES/PVP(Hospal)PSU/PVP(Fresenius/Minntech/Braun
3、 Kawasumi,Toray,Asahi)PES/PVP(Membrana-Bellco-Baxter Nipro),Cuprophan(Membrana)RC(Asahi)RG(Tejin,Terumo),Hemophan(Membrana)CA,CTA(Membrana/Toyobo)SMC(Membrana)PEG(Asahi)SCE(Membrana/Tejin),Membrane&Filter Technology of ASAHI KASEI MEDICAL,Cellulose Hollow Fiber,Polysulfone Hollow Fiber,Polyacryronit
4、rile Hollow Fiber,Hemodialyser,Plasma Therapy Products,Leukocyte Reduction Filter,(Materials),Polyethylene Hollow Fiber,Cellulose diacetate Hollow Fiber,Amino acids immobilized PVA,Styrene divinyl benzene Column,Activated charcoal Column,Polyethylene Hollow Fiber,Non-woven polyester sheet,Market Sha
5、re of Dialyzers in Japan(Asashis estimation),1996,2004,Worldwide Dialyzer Market,Modules2001-2009,(Figures in millions of modules),Worldwide Dialyzer Market Share by Competitor2003,Source:Kalorama Information,透析器膜应用情况,High-flux and high-efficiency dialysis,High-flux defined as dialyzer ultrafiltrati
6、on coefficient20ml/hr/mmHgHigh-efficiency defined as dialyzer ultrafiltration 1019ml/hr/mmHg,Low-flux HD High-flux HDHDF HF,不同透析方式的清除率,透析器/膜的筛系数,In vitro performance of REXEED-15Aand other polysulfone dialyzers,提要,高通量透析器历史为什么应用高通量透析器高通量透析技术要求临床实践中的高通量透析,为什么应用高通量血液透析？,保存残余肾功能减少炎症反应减少血管性病变改善脂质代谢延迟透析相关
7、淀粉样变性改善营养降低住院率,并发症和死亡率,高通量透析:保存RRF,Hartmann et al,1997,高通量透析:保存RRF,为什么应用高通量血液透析？,保存残余肾功能减少炎症反应减少血管性病变改善脂质代谢延迟透析相关淀粉样变性改善营养降低住院率,并发症和死亡率,Inflammationthe total war against invaders,BioINcompatibility reactions,Inflammatory factors in dialysis patients,CRP levels and mortality German HD patients(n=280)
8、,Ref:Wanner et al,KI 2002,Inflammatory markers and dialysis membrane,randomized cross-over study in 18 patients,3 x 8 weeks,Ref:Schindler et al,2000,高通量透析:减少炎症反应,生物不相容,激活 IL-1,IL-6,TNF,氧化应激,A G Es,白蛋白合成,CRP,修饰蛋白,修饰脂蛋白,2-M产生,心血管疾病,血管病变,淀粉样变性,死 亡 率,补体激活,InflammationOxidative Stress,ESRD,释放活性炎症介质,单核细胞激
9、活,细胞因子,慢性刺激,免疫反应,炎症,炎症,急性期反应性蛋白,急性炎症反应,并发症,1,2,3,内毒素,高通量透析对Leptin的影响(HEMO study),纤维素,Leptin:16 kDa 血浆蛋白由脂肪细胞产生认为它抑制食欲参与体重的调节高水平可致营养不良和厌食细胞因子的升高可导致LEPTIN产生的增加,Coyne et al.Am J Kidney Dis 32:1031-1035,1998,为什么应用高通量血液透析？,保存残余肾功能减少炎症反应减少血管性病变改善脂质代谢延迟透析相关淀粉样变性改善营养降低住院率,并发症和死亡率,高通量透析:减少血管性病变,从血-膜反应到蛋白修饰的过
10、程临床上影响透析病人长期生存质量的反面证据,Makita et al,1995;Vlassara et al 1996;Miyate et al,1997,高通量透析:降低LMW AGEs,Makita et al,1994,为什么应用高通量血液透析？,保存残余肾功能减少炎症反应减少血管性病变改善脂质代谢延迟透析相关淀粉样变性改善营养降低住院率,并发症和死亡率,Improvement of lipid profile,*p0.05 vs time 0 and 4 weeks,time weeks,Modified Cellulose,Polyflux S,0,20,40,60,80,100,1
11、20,0,4,12,20,28,lipid concentration mg/dl,0,0.5,1.0,1.5,2.0,2.5,3.0,3.5,4.0,ratio LDL/HDL,*,*,*,LDL,HDL,LDL/HDL,Pitone J et al,ISBP,2003,Modified cellulose versus Polyflux S 43 patientsPolyflux:Improvements in lipid profile may help to reduce the lipid lowering medications,为什么应用高通量血液透析？,保存残余肾功能减少炎症反
12、应减少血管性病变改善脂质代谢延迟透析相关淀粉样变性改善营养降低住院率,并发症和死亡率,1,2,3,4,5,6,7,8,9,10,11,12,HF80S,P170H,0,5,10,15,20,25,30,35,40,Ratio(%),b2m/Albumin,Patients,HF80S,P170H,Selectivity 2M/AlbuminHDF Post-Dilution,Polyflux 170 H:1.7 mPS(HF 80 S):1.8 m,Souid et al.ISBP 2003,膜通量和膜材料对淀粉样变性的影响(Hemo Study),Schiffl et al.Nephrol
13、Dial Transplant 15:1399-1409,2000,b2m MD=11,800D,Prevention of b2m-related amyloidosis by high-flux therapies,0,0,2,0,4,0,6,0,8,1,Relative amyloidosis risk,Low-flux HD,High-flux HD,HDF,Risk of a worse therapeutic effect,Japanese Dialysis Patient Registry(N=1196)Ref:Nakai et al AJKD 2001,为什么应用高通量血液透析
14、？,保存残余肾功能减少炎症反应减少血管性病变改善脂质代谢延迟透析相关淀粉样变性改善营养降低住院率,并发症和死亡率,高通量透析对血清白蛋白的影响(HEMO study),Marcus et al.Am J Kidney Dis 31:491-494,1998,Increased loss of vital solutes not confined to high flux treatments,营养不良患者的治疗策略,充分透析避免或尽量减少急慢性的炎症反应选用血液生物相容性好的膜排除任何外源性的潜在刺激，诸如透析液的污染,为什么应用高通量血液透析？,保存残余肾功能减少炎症反应减少血管性病变改善脂
15、质代谢延迟透析相关淀粉样变性改善营养降低住院率,并发症和死亡率,透析膜和死亡率,(Woods et al.),提要,高通量透析器历史为什么应用高通量透析器高通量透析技术要求临床实践中的高通量透析,0,1000,2000,3000,4000,5000,0,1,2,3,4,细菌计数(CFU/ml),内毒素(IU/ml),软化后,滤芯后,未净化的水,1st滤器后,0,1,2,3,4,5,6,7,8,9,10,碳缸后,反渗后,机器入口,透析液,透析液滤器后,水处理和透析液制备的细菌污染情况,100,1.000,10.000,0,50,100,150,200,Mol weight,D,清除率(ml/mi
16、n),High-flux 膜(反向滤过),Low-flux 膜(反向弥散),内毒素片断,尿素,肌酐,磷,Vit.B,12,菊酚,2-m,白蛋白,清除率:双向,5200 dal.,1355 dal.,11800 dal.,60 dal.,113 dal.,高通量透析需要高质量的透析液,Weber et al.1996,High-flux dialyzers and backfiltration,压力,反向弥散,反向滤过,High-flux,Low-flux,Length along Dialyser,血液,透析液,Dialysate,血液,膜,透析液,血液,滤过,反向滤过,PDo,PBi,PDi
17、,PBo,Morphological Characteristics,Polyflux,Polysulfone based,HomogeneousSponge-like-Structure,Novel3-layer-Structure,3-Layer Structure,Inner Selective Layer(Skin)-narrow pore size-separation layer-0.1-0.5 m Stabilization layer-support function-2 5 m Finger Type Structure-high void fraction-low diff
18、usive resistance-40 45 m,Most effective and stable removal characteristics Endotoxins retention,透析膜对提高清除率的2个重要原因,Less materiel high permeability,Tri-dimensional configuration of the hollow fiber bundle,透析液侧,血侧,从透析液侧到血侧无内毒素的转移:透析液侧泡沫状膜，血液侧膜光滑、表面大吸附能力强 仅有 1/百万单位的内毒素能跨过膜!,高通量聚砜膜:内毒素截留能力,超纯透析液对细胞因子和2-微球
19、蛋白的影响,提要,高通量透析器历史为什么应用高通量透析器高通量透析技术要求临床实践中的高通量透析,Removal of uremic toxins,*P0.01,Gong Dehua,et al.J Nephrol Dialy Transplant,2002,Removal of uremic toxins,*,P0.05,*,P0.01,Gong Dehua,et al.J Nephrol Dialy Transplant,2002,Reduction rate post-dialysis(%),Effect of MHD on renal osteopathy in ESRD,Compar
20、ison between HFHD and LFHD in serum PTH,Ca and P,Gong Dehua,et al.J Nephrol Dialy Transplant,2001,Effect of MHD on renal osteopathy in ESRD,Serum iPTH levels in patients between HFHD and LFHD*,P0.01,Maitainence time on HD(years),Gong Dehua,et al.J Nephrol Dialy Transplant,2001,Effect of MHD on renal
21、 osteopathy in ESRD,Clinical and bone biopsy data from patients treated by LFHD and HFHD,Gong Dehua,et al.J Nephrol Dialy Transplant,2001,Effect of reusing of HFHD on the performance,Use number of dialyser,Solutes clearance changes during reuse of a high flux dialyser(BLS627),Gong Dehua,et al.Bullet
22、in of Medical Postgraduate,2000,Effect of reusing of HFHD on the performance,Use number of dialyser,Reduction rate of MMS and beta2-M after HD during reuse of a high flux dialyser(BLS627),*,*,*,Compared with first use,*,P0.05,*,P0.01,Gong Dehua,et al.Bulletin of Medical Postgraduate,2000,Changes of
23、endotoxins during MHD,Serum endotoxins level change during HFHD and LFHD,HD time(min),Gong Dehua,et al.Chinese Critical Care Medicine,2001,Serum IL-1 level change during HFHD and LFHD,HD time(min),Gong Dehua,et al.Chinese Critical Care Medicine,2001,Changes of cytokines during MHD,Changes of cytokines during HFHD,Serum TNF-level change during HFHD and LFHD,HD time(min),Gong Dehua,et al.Chinese Critical Care Medicine,2001,Survival rate of MHD in 1254patients,Ji daxi.CJN 2005,High-Flux,趋势.,HD,HFHD,HDF,Low-Flux,谢谢,谢谢!,
