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State of the Art: On-line Hemodiafiltration

State of the Art: On-line Hemodiafiltration. Dr. Vaslaki Lajos. orvos-igazgató. Fresenius Dializis Centrum, Sopron. State of the Art On-line Hemodiafiltration. Vaslaki Lajos Fresenius MC Sopron. A hemodiafiltrácio az uremiás plazma epurációjának jelenleg leghatásosabb formája.

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State of the Art: On-line Hemodiafiltration

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  1. State of the Art: On-line Hemodiafiltration Dr. Vaslaki Lajos orvos-igazgató Fresenius Dializis Centrum, Sopron

  2. State of the Art On-line Hemodiafiltration Vaslaki Lajos Fresenius MC Sopron

  3. A hemodiafiltrácio az uremiás plazma epurációjának jelenleg leghatásosabb formája „ Amit sohasem vontak kétségbe, az nincs bebizonyítva „ Diderot

  4. Solute transport in different dialysis modalities DiffusionMembrane ConvectionMembrane Pressure Haemodialysis  Diffusive transport of solutesRelevant: - cut-off of membrane - weight of solutes Haemofiltration  Convective transport of solutes Relevant: - cut-off of membrane - flow across membrane Haemodiafiltration  Diffusive transport of small solutes Convective transport of large solutes

  5. A konvencionalis/diffuzión alapuló dializis limitjei/szövődményei • β-2 Mikroglubulin okozta amyloidozis • Accelerált arteriosclerozis • Bal kamra hypertrophia • Inflammációs folyamatok • Malnutrició/ gyorsult öregedés

  6. Miért hatékonyabb az OLHDF mint a hagyományos HD?! Az ol-HDF a nativ vese élettani működését próbálja utánozni ( intuitiv megközelítés) hemokompatibilis in vitro rendszerben • A glomerulus bazalis membránjához, annak müködésében, tehát áteresztőképességében hasonló, biokompatibilis membrán használata • A különböző molekula-súlyú uremiás toxinok konvektiv és diffuziv módon történő – jelenleg leghatékonyabb eltávolítása

  7. Konvencionális dializistől az On-line HemodiafiltrációigHemokompatibilis technikai rendszerekTechnikai feltételek • Nagyteljesítményű részben hydrophil „high-flux”dializis membránok megjelenése,klinikai eredmények • Zárt rendszerű, pontos ultrafiltrációs controllal működő dializis gépek – HDF-re alkalmas szoftverrel. • Ultratiszta/steril szubsztituciós oldat on-line előállítása korlátlan mennységben

  8. Szintetikus membránok biokompatibilis hemodiafilterekben.Kliniai eredmények • Okuno et al : beta – 2 MG szint a mortalitás önálló prediktora • Cheung et al : szignifikáns összefüggés a beta -2 MG plazma szint és az infekcio okozta mortalitás között • HEMO study : beta-2 MG – közép molsulyú toxinok markere High-flux filterek jelentősége • MPO ( Membrane Permeability OutcomeStudy ). A high-flux dializis klinikailag előnyös a rossz prognozisú betegek kezelésében( diabetes..)

  9. HD -, HF és On-line HDF kezelési eljárások müködési vázlata From: A Grassmann et al., Composition and Management of Hemodialysis Fluids; Pabst Publishers, 2000

  10. Substitution solution enters extracorporeal circuit before dialyser Improved membrane permeability- filtration from diluted blood! But … dilution also reduces efficiency lower diffusion gradient reduced clearance for small molecules blood (out) Filtrate (UF + HDF) HDF pump Substituate (pre) blood pump blood (in) Predilution On-Line HDF

  11. Substitution solution enters extracorporeal circuit after dialyser Best removal of small and middle size uremic toxins – filtration from undiluted blood! But … ultrafiltration limited by haemoconcentration high blood viscosity secondary protein layer membrane polarization and high blood flow rates are needed Substituate (post) HDF pump blood pump Postdilution On-Line HDF blood (out) Filtrate (UF + HDF) blood (in)

  12. Substitution solution enters extracorporeal circuit simultaneouslybefore and after the dialyser-regulated by feedback control system Improved water and solute permeability of the dialyser! Due to… individual dilution management and improved blood rheology high filtration rates → optimised convective flux → increased solute removal safe against albumin loss (occuring at high TMPs) Best of both worlds! Substituate (post) blood (out) HDF pump 2 feedbackcontrol Filtrate (UF + HDF) HDF pump 1 Substituate (pre) blood pump blood (in)

  13. Software: ON-LINE menu:H(D)F screen Automatic adaptation and control of infusion ratio and volume maintains the haemodynamic stability in the dialyser Total infusion volume is diverted between pre- and post-dilution at optimised ratio Initial phase: slow increase of post-dilution → minimises albumin loss Feedback control: TMP is kept constant in pre-set safe corridor → maintenance of hydraulic characteristics of the dialyser → maximal convection

  14. 2-m KDQ ml/min * ° 120 * 100 80 60 40 p< 0.05 * vs HD, ° vs post-HDF 20 0 low-flux HD post-HDF mixed HDF QB = 400ml/min QUFpost-HDF : 8.7 L/hour mixed HDF : 15L/hour

  15. Az On – line HDF alkalmazásának kritikaiszempontjai. SAFETY ISSUE • Lehetséges-e szubsztituciós oldat „hideg-sterilizálással” történő on-line előállítása ? • A dializáló oldatból történő un. back transfer-filtráció ( visszaáramlás) a high – flux filterekben / dia-filterekben elkerülhetetlen.Tehát, a steril szubsztituciós oldat itt is feltétlenül szükséges. • Az FMC hálózatban már hét éve,csak High-Flux dializist (On-line HDF-et)alkalmazunk

  16. Safety issue • Certified dialysis machines • Ultrapure dialysis water (CFU < 1 ; ET < 0.25 I.U) • Steril substitution fluid (CFU:steril ; ET<0.03 I.U) • Microbiological monitoring (monthly) • Regular (monthly) desinfection of the system • Biocompatible high-flux polysulphon/polyamid dialyzer with high adsorbtive capacity These measures _based on EBPG _ can prevent cytokine-inducing substances passing through dialysis membrane in daily,clinical routine

  17. A szubsztituciós oldat mínőségi mutatói az OLHDF és HF kezelési eljárásokban. Az Eropean Best Practice Guideline ajánlásai Raw water Water treatment system Highly purified water  100 CFU/ml  0.25 IU/ml Endotoxin filter/redundant Endotoxin filter Bicarbonate dialysis fluid  100 CFU/ml  0.5 IU/ml Ultrapure dialysis fluid < 1 CFU/ml  0.03 IU/ml Substitution fluid sterile pyrogenfree Recommendations for the quality of fluids used in the preparationof on-line Substitution Fluidfor HF and HDF( EBPG ) Pure bicarbonate concentrate

  18. Safety :Endotoxins and Cytokine(CIS)Activityin Substitution Fluids NDT Endotoxins (LAL reactivity, IU/ml) Cytokine inducing activity (pg IL-1Ra/106 WBC) Vaslaki L et al. Nephrol Dial Transplant (Suppl. 1): 74-78, 2000

  19. A High-efficiency ol-HDF klinikai előnyei ( Reduceed overall morbidity) • Reduced hypotenziv epizodes Altieri P., Sorba G. J.Nephrol 2004 • Better blood pressure control Stegmayer BG.Artif.Organs 2003 • Reduction of left ventricular hypertension Maduell F. 2005 • Longer and better preservation of residual kidney function McKane Kidney Int.2003 • Improved Hemocompatibilty& Reduced inflammation Canaud B Nephrol Dial Trasp 2001 • Improved anemia control Vaslaki L., Major L. Blood Purif.2006.24 • Pozitiv impact on nutritional state Basil C.,Nephrol Dial Transplant 2003 Nephrol Dial Transp 2007 • Improvement of lipid profil and reduce oxidativ stress Calo L. Artif Organs 2007 • Growth retardation correction by ol-HDF+growth hormon+ EPO Fischbach M. Pediatr Nephrol 2006 • Improved MORTALITY…………………

  20. Less Inflammation with On-line HDF Endotoxins IL-6 (pg/ml) Dialysis membrane Monocytes CD14+ & CD16+ UNPURE DYALYSATE IL - 1 Hepatocytes : acut phase reactans : CRP IL – 6 TNFalfa Soluble endothelial adheziv factors :sVCAM and sICAM ( Independent predictor of mortality in pre-dial patients (Stenwinkel ) Low-flux HDOn-line HDF Arteriosclerotic plaque Vaslaki L., Major.. 2006 Blood Purification

  21. DOPPS Study B.Canaud 35% lower mortality riskfor patients treated with HDF with a volume exchange of >15 L/ treatment vs. patients on low-flux HD. The need for high exchange rates

  22. Mortality risk for patients: epidemiological evaluation Study EuClid Database FMC Total Pts (No.) = 2564 Total Pts (No.) = 2567 Kidney Int 2006 Jirka at al

  23. ** Results: Odds Ratio Estimation 35,4 % RR ** Comorbids: Diabetes, Neoplasms, Heart Failure, Peripheral arterial disease, etc. Kidney Int. Jirka at al .

  24. Total HD and On-line HDF treatment number2008 – 2000 in FME Network

  25. The share of On-line HDF treatments in total HD treatments 2008 - 2000

  26. Conclusion … allows the premium therapy to become standard!

  27. „ Erős képzelet szüli az okokat ” Montaigne Köszönöm a figyelmet!

  28. A leghosszabb út is az első lépéssel kezdődik…..a konvektiv oldat transzport alkalmazása Brull L 1928 Realisation d’ultrafiltration Bluemle LW 1987 Early days of Hemodiafiltration Leber H. et all. 1978 Hemodiafiltration: a new alternative to hemofiltration and conventional hemodialysis Henderson LW 1978 Present status of Hemodiafiltration 1982 Historical review and principles of HDF 2003 The beginning of clinical hemodiafiltration : a personal account

  29. The modality’s is benefical effects on patient outcomes are not related to dialysis dose for small molecules (Kt/Vurea) but may be related to factors particular to HDF which combines enhanced removal of larger molecular weight substances with an improved biocompatible systemBernard Canaud

  30. A szubsztituciós oldat On-line előállításának vázlata Endotoxin filter Endotoxin filter Highly purified water Steril Substitution fluid Ultrapure dialysis fluid Dialysis fluid Predilution Bicarbonate concentrate Retentate Hemodiafilter Dialysis fluid Ultrafiltrate Dialysate Blood Post-dilution

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