Utilizzo di nuove membrane in HDF on-line con alto volume di scambio

Size: px

Start display at page:

Download "Utilizzo di nuove membrane in HDF on-line con alto volume di scambio"

Alice Booth
6 years ago
Views:

1 Utilizzo di nuove membrane in HDF on-line con alto volume di scambio Antonio Bellasi, MD, PhD U.O.C. Nefrologia & Dialisi ASST-Lariana, Ospedale S. Anna, Como, Italy

2 Disclosures The views expressed in this presentation are the personal, professional views of Antonio Bellasi Disclosures: Amgen, Genzyme/Sanofi, Sanifit, Keryx, Vifor Fresenius This presentation is only to be used for educational reference purposes No slides of this presentation may be used without the specific written consent of the presenter, Dr Antonio Bellasi (

3 HD or HDF? More than 2 ml patients treated with hemodialysis worldwide Survival probability of ESRD on maintenance dialysis: - 81% at 1 year - 68% at 2 years - 39% at 5 years Data suggest that increasing urea clearance does not improve survival and survival depends also on middle-molecules clearance References ERA-EDTA-Registry. ERA-EDTA Registry Annual Report Eknoyan G, et aln Engl J Med 2002; 347: Cheung et al. J Am Soc Nephrol 2006; 17: Study Main Conclusion Post Hoc Analysis Grooteman et al NDT 2012; 24: No benefit associated with HDF 17 l/session Ok et al NDT 2013; 28: No benefit associated with HDF Maduell et al JASN 2013; 24: % risk reduction with HDF 23 l/session 22 l/session

4 Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials Peters Nephrol Dial Transplant 2016 Dec 26. pii: gfw381. doi: /ndt/gfw381 [Epub ahead of print] Study N Comparison Suggested target Reference Contrast 714 HD low flux 6 l/hour (24l/session) Grooteman et al. J Am Soc Nephrol 2012; 23: ESHOL 906 HD high flux At least 18 l/session Maduell et al. J Am Soc Nephrol 2013; 24: French HDF stuy 391 HD high flux No target Canaud et al Project supported by a French National Grant from Health Ministry (PHRC national), 2004 Turkish study 782 HD high flux At least 15 l/session Ok et al. Nephrol Dial Transplant 2013; 28:

Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials Peters Nephrol Dial Transplant 2016 Dec 26.

5 Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials Peters Nephrol Dial Transplant 2016 Dec 26. pii: gfw381. doi: /ndt/gfw381 [Epub ahead of print] The distribution of convection volume differed across studies because of differences in study methodology, clinical practice and patient characteristics.

6 Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials Peters Nephrol Dial Transplant 2016 Dec 26. pii: gfw381. doi: /ndt/gfw381 [Epub ahead of print]

7 Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials Peters Nephrol Dial Transplant 2016 Dec 26. pii: gfw381. doi: /ndt/gfw381 [Epub ahead of print] ü The dose response association between online HDF and clinical outcomes was examined in thirds of the actual (on-treatment) delivered, 1.73 m2 body surface area (BSA)-standardized, convection volume. ü BSA was estimated using the formula from Gehan and George as recommended by the European Best Practice Guidelines: BSA (m2 ) = X baseline height (cm) X baseline weight (kg) ü Standardization of delivered convection volume was done by dividing by patient BSA: 1.73 X (patient convection volume/patient BSA)

8 Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials Peters Nephrol Dial Transplant 2016 Dec 26. pii: gfw381. doi: /ndt/gfw381 [Epub ahead of print]

9 Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials Peters Nephrol Dial Transplant 2016 Dec 26. pii: gfw381. doi: /ndt/gfw381. [Epub ahead of print Figure 3 enables estimation of the convection volume required for a patient with a given height and weight to achieve a 1.73 m2 BSA-standardized sessional convection volume of 23 L. To achieve 23 BSA-standardized liters Body Weight 45 Kg, Height 150 cm = 18 l/session Body Weight 70 Kg, Height 180 cm = 25 l/session Patient convection volume=(23*patient BSA)/1.73m2

Dialysis and Patient Factors Which Determine Convective Volume Exchange in

2016 Dec;40(12):1121-1127 Aim: assess factors associated with amount of convective

volume Study design: Cross-sectional study Study cohort: N= 653 adult patients on

10 Dialysis and Patient Factors Which Determine Convective Volume Exchange in Patients Treated by Postdilution Online Hemodiafiltration Davenport Artif Organs 2016 Dec;40(12): Aim: assess factors associated with amount of convective clearance is the sum of the substitution fluid infused and the ultrafiltration volume Study design: Cross-sectional study Study cohort: N= 653 adult patients on maintenance dialysis assessed during the midweek dialysis Setting: outpatient clinics, London, UK

11 Dialysis and Patient Factors Which Determine Convective Volume Exchange in Patients Treated by Postdilution Online Hemodiafiltration Davenport Artif Organs 2016 Dec;40(12):

How can dialysis membrane modulate convective clearance (sobstitution volume + ultrafiltration) Dawn of hemodialysis ü 1914 canine dialysis membrane: colloidon + sodium salicylate; dialyser 40 cm

12 How can dialysis membrane modulate convective clearance (sobstitution volume + ultrafiltration) Dawn of hemodialysis ü 1914 canine dialysis membrane: colloidon + sodium salicylate; dialyser 40 cm diamter 8 mm ü 1943 human dialysis cellophane (low PERMEABILITY) ü 1956 development of cellulose dissolved in cuprammonium (Cuprophan) and regenerated cellulosic membranes (cast from cellulose or cotton fibers). These membrane were more permeable than dry cellulose membranes but extremely fragile (blood leakage) ü 1956 disposable coil dialyser become available ü 1960s Chemical modification to RCs to improve BIOCOMPATIBILITY (replacing of hydroxyl group(s) with acetate group(s)): cellulose acetate, cellulose diacetate and cellulose triacetate ü 1967 first cellulosic HOLLOW FIBER membrane was developed (compact with large surface area) ü 1969 first polymeric membrane was developed: acrylonitrile (AN-69). This was also the first dialyzer sterilized by the GAMMA-RAY irradiation (strong absorption characteristics still in use for AKI) ü 1980 first hollow synthetic fiber membrane: polymethyl methacrylate (PMMA) sterilized by the gamma-ray irradiation ü 1980s To improve SOLUTE AND HYDRAULIC PERMEABILITY as well as biocompatibility many synthetic polymeric membranes have been introduced: polysulfone (PSf) and the like polyethersulfone (PES), polyaryletherrsulphone (PAES) all derived by petroleum

13 Types of membranes Updates in Hemodialysis, edited by Hiromichi Suzuki, ISBN , Published: September 9, 2015 How can dialysis membrane modulate convective clearance (substitution volume + ultrafiltration)? ü Chemical structure synthetic vs natural polymers ü Hydrophilization and biocompatibility ü Physical structure: homogeneous vs asymmetry membrane ü Pore size and distribution physical structures ü Dialyser design:packing density of hollow fibers (minimize blood-dialysate miss-match) ü Smoothness of the membrane surface ü Protein adsorption

Types of membranes Updates in Hemodialysis, edited by Hiromichi Suzuki, ISBN 978-953-51-2162-6, Published: September 9, 2015 Hydrophylic nature Biocompatibility

14 Types of membranes Updates in Hemodialysis, edited by Hiromichi Suzuki, ISBN , Published: September 9, 2015 Hydrophylic nature Biocompatibility (replacing of hydroxyl group(s) with acetate group(s)) Hydrophobic in nature (originated from petroleum) Biocompatibility: blood coagulation PVP to increase hydrophilicity

15 Types of membranes Updates in Hemodialysis, edited by Hiromichi Suzuki, ISBN , Published: September 9, 2015 Cellulosic and synthetic membranes: Negatively charged syndrome (negatively charged membranes such AN69): induces factor XII activation bradickinin activation. Addition of positively charged substances (i.e DEAE or vitamin E) Cellulosic membranes: Transient leukopenia (occurs minutes after starting the treatment; due to complement activation and leukocytes accumulation in the blood vessels and in the lung) substitution of hydroxyl groups with acetate groups increases biocompatibility and permeability to solutes and water transport Synthetic membranes: Hydrophobic membrane induce coagulation activation: addition of substances such as Polyvinylpyrrolidone (PVP) to reduce blood clotting Polyvinylpyrrolidone (PVP) intollerance: added to hydrophobic membranes to increase hydrophilicity but may induce C3a and complement activation

Types of membranes: homogeneous vs asymmetry membranes Updates in Hemodialysis, edited by Hiromichi Suzuki,

Entire thickness contribute to the transport resistance for solutes Dense thin layer on inner surface (skin

and most cellulosic membranes) Skin layer contribute to the transport resistance for solutes High mechanical

16 Types of membranes: homogeneous vs asymmetry membranes Updates in Hemodialysis, edited by Hiromichi Suzuki, ISBN , Published: September 9, 2015 Homogeneous membrane: Asymmetric membrane: Dense membrane Entire thickness contribute to the transport resistance for solutes Dense thin layer on inner surface (skin layer) from which density is gradually decreasing in radial direction Thickness about 15 mcm (EVAL, PMMA, AN-69 and most cellulosic membranes) Skin layer contribute to the transport resistance for solutes High mechanical strength and little solutes resistance Thickness about 35 mcm (thickness skin layer mcm) (most synthetic membranes)

Types of membranes: homogeneous vs asymmetry membranes Updates in Hemodialysis, edited by Hiromichi Suzuki, ISBN 978-953-51-2162-6, Published:

characteristic determines the hydrophilicity and hydrophobicity of the material, whereas physical structure determines the pore sizes as well as

17 Types of membranes: homogeneous vs asymmetry membranes Updates in Hemodialysis, edited by Hiromichi Suzuki, ISBN , Published: September 9, 2015 Pores of the membrane Same porosity, however membrane B has almost 2 times higher solute permeability than membrane A Chemical characteristic determines the hydrophilicity and hydrophobicity of the material, whereas physical structure determines the pore sizes as well as the thickness that contributes to the transport resistance. Therefore, both chemical and physical features are important for designing dialysis membrane.

18 Blood and Dialysate Flow Distributions in Hollow-Fiber Hemodialyzers Analyzed by Computerized Helical Scanning Technique Ronco et al J Am Soc Nephrol 2002; 13:S53-S61

19 Fundamental Characteristics of the Newly Developed ATA TM Membrane Dialyzer Sunohara et al Contrib Nephrol. 2017, vol 189, pp

20 Proinflammatory mediators generated during bioincompatible dialytic treatment Cytokines: IL-1, TNFa, IL-6, Chemokines (MCP-1, IL-8) and their receptors, Growth factors (PDGF, TGF) Complement fragments: Coagulation factors: Adhesion molecules: C3a/C5a, C5b-9 Thrombin, FXa and their receptors CD15, CD11b/CD18, P-selectin, E-selectin, ICAM-1, VCAM-1 INFLAMMATION/OXIDATIVE STRESS

21 Proteomics characterization of protein adsorption onto hemodialysis membranes. Bonomini et al J Proteome Res 2006; 5(10):

Urbani et al Mol Biosyst 2012; 8(4):1029-39

22 Proteomic analysis of protein adsorption capacity of different haemodialysis membranes. Urbani et al Mol Biosyst 2012; 8(4): Cellulose Triacetate Helixone Albumin Removal Fibrinogen activation

23 Fundamental Characteristics of the Newly Developed ATA TM Membrane Dialyzer Sunohara et al Contrib Nephrol. 2017, vol 189, pp Membrane ATA CTA Asymmetric Triacetate Cellulose Triacetate Semi-natural Semi-natural Asymmetric Symmetric Inner diameter (µm) Wall thickness (µm) Oxygen free Gamma-Ray Oxygen free Gamma-Ray Yes Yes Housing Polypropylene Polypropylene Potting Polyurethane Polyurethane Membrane and housing Membrane and housing Membrane structure Sterilization Micro wave in the fibre Moiré structure BPA Free Considering the needs for hemodiafiltration a newer version of cellulose triacetate membrane was developed: ü Asymmetric ü Low risk of hypersensitivity ü Decreased platelet count decrease ü high permeability and filtration perfomance

24 Fundamental Characteristics of the Newly Developed ATA TM Membrane Dialyzer Sunohara et al Contrib Nephrol. 2017, vol 189, pp Filtration properties These data confirmed that with the ATA membrane the pressure-induced increase or decrease in the diameter of the pores through which albumin permeates is smaller and there was less temporal variation during blood filtration compared with the conventional CTA membrane or polysulfone membrane. In vivo (n=5): Qb:350ml/min, Qd:600ml/min, Qs:85ml/min In vitro: Qb:400ml/min, Qs:100ml/min

25 Fundamental Characteristics of the Newly Developed ATA TM Membrane Dialyzer Sunohara et al Contrib Nephrol. 2017, vol 189, pp Fix250Eeco - Filtration properties B2-microglobulin removal A1-microglobulin removal Albumin leakage Qb 250 ml/min Qd 600 ml/min 4 hours 60 liters HDF pre-dilution g/session Qb 250 ml/min Qd 600 ml/min 4 hours 12 liters HDF post-dilution g/session Condition

26 ATA biocompatibility Curtesy of Nipro Complement Activation (C5a) - White Blood (WBC) count Platelet count In vivo : Qb:350 ml/min, Qd: 600 ml/min, Qs: 0 ml/min session 4 h, Germany, 2015

27 Acute reactions to polysulfone/polyethersulfone dialysers: literature review and management Boer et al Neth J Med. 2017; 75(1): 4-13

28 .one swallow does not a spring make. KW Body weight (Kg): 84 Height (cm): 178 BSA (m2): 2

HEMODIALFILTRATION LITERATURE REVIEW AND PRACTICE CONSIDERATIONS 1.0 PRACTICE CONSIDERATIONS 2.0 CURRENT LITERATURE REVIEW

HEMODIALFILTRATION LITERATURE REVIEW AND PRACTICE CONSIDERATIONS This document was prepared at the request of the BC Hemodialysis Committee to provide a brief overview of the literature and to identify