高通量血液透析的临床应用实践

1、高通量血液透析的临床应用实践,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

2、)改編 2005年EDTA開催時報告,透析器膜的历史,Membranes for Medical Applications,regenerated cellulose,modified cellulose,hydrophilized copolymers,hydrophobic/ hydrophilic blend,synthetic membranes,cellulosic membranes,AN69 (Hospal) PMMA (Toray) EVAL (Kuraray) PEPA (Nikkiso) SPAN (Akzo/Asahi),PA/PAES/PVP (Gambro) PAES

3、/PVP (Hospal) PSU/PVP(Fresenius/Minntech/Braun 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 Vlassara et al 1996; Miyate et al, 19

4、97,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,0,20,40,60,80,100,120,0,4,12,20,28,lipid concentration mg/dl,0,0.5,1.0,1.5,2.0,2.5,3.0

5、,3.5,4.0,ratio LDL/HDL,*,*,*,LDL,HDL,LDL/HDL,Pitone J et al, ISBP, 2003,Modified cellulose versus Polyflux S 43 patients Polyflux: 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,

6、8,9,10,11,12,HF80S,P170H,0,5,10,15,20,25,30,35,40,Ratio (%),b2m/Albumin,Patients,HF80S,P170H,Selectivity 2M / Albumin HDF Post-Dilution,Polyflux 170 H: 1.7 m PS (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 Dial Transplant 15:1399-1409, 2000,b2m MD=11,8

7、00D,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？,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

8、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 改善脂质代谢 延迟透析相关淀粉样变性 改善营养 降低住院率

9、,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 / min),High-flux 膜

10、 (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,PBo,Morp

11、hological Characteristics,Polyflux,Polysulfone based,Homogeneous Sponge-like-Structure,Novel 3-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

12、- low diffusive 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

13、,超纯透析液对细胞因子和2-微球蛋白的影响,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 ren

14、al osteopathy in ESRD,Comparison 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 Tr

15、ansplant, 2001,Effect of MHD on renal 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

16、dialyser(BLS627),Gong Dehua, et al. Bulletin 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. B

17、ulletin of Medical Postgraduate,2000,Changes of 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