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7/21/2019 prof. Bernard Canaud
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H: ?
Controversies conference on Novel techniquesand innovation in blood purification: How can we
improve clinical outcomes in hemodialysis ?Paris 14-15 October 2011
Prof. Bernard Canaud
Nphrologie, Dialyse et Soins IntensifsHpital Lapeyronie CHRU Montpellier - France
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Cardiac StunningCardiac StunningCardiac Stunning
Maltolerance of dialysis sessions
StrokeStrokeStrok
e
IntradialyticHypotensionIntradialyticHypotensionIntradialyticHypotension
Gut ischemia - TranslocationGut ischemia - TranslocationPoor Quality of LifePoor Quality of Life
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Dialysis-related pathology
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DD
EEFF HDF HDF
EE
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DD
EEFF HDF HDF
EE
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HDF ,
Inlet Blood Flow Outlet D+UF
1. Ultrafiltration2. Diffusion3. Adsorption
1
3
SubstitutionFluid (SF)
Ultrafilter
100
Outlet BloodFlow
Inlet D+SF
2
2
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H
HD Low Flux HD High Flux HDF HF
DiffusionConvection
Adsorption
Middle molecules removal
Low molecules removal
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HDF
D C
= D+ 0.43 F+ 8.3.103 2F + ?
Jaffrin M et al. Artif Organs1995; 19:1162
= D+ + A
= D+ 0.50 F
CD A
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2-Microglobulin, Reduction Rate (%)
C
On-line HDF substitution volume (ml/min)
15 l15 l 25 l25 l5 l5 l 31 l31 l
Lornoy W et al, Nephrol Dial Transplant. 2000: 15: 49-54Postdilution HDF
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DD
EEFF HDF HDF
EE
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HDF E 2010
0.67
0.550.60
0.70
0.80
0.90
1.00HD : 294400 HDF : 50800 B HDF : 3550
Percent of HDF treated patients, %
0.130.16 0.18
0.13 0.140.18
0.48
0.29 0.30
0.19
0.42
0.33
0.26 0.27 0.28
0.20
0.00
0.10
0.20
0.30
0.40
0.50
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H C
D 14 * (19962010)
BE
SW
UK
30%
40%
% of Patients
ANZJP
FR
GE
GE
IT
SP
SP
UK
0%
10%
20%
1(1996-2000)
2(2002-2004)
3(2005-2008)
4(2009-Present)
Study Phase (years)
*Initial prevalent cross-sections who dialyzed 3 times/wk with vintage 3 months; DOPPS 4 data are preliminary; ANZ, BE andSW did not participate in DOPPS phase 1
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F % HDF, C
60%
70%
80%
90%
100%
Facility % of Patients
0%
10%
20%
30%
40%
50%
2 3 4 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4 2 3 4 1 2 3 4 3 4 1 2 3 4
Initial prevalent cross-sections who dialyzed 3 times/wk with vintage 3 months* p-value
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DD
EEFF HDF HDF
EE
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H/ I
ConcentrateWater
Water treatment system
mac ne
Patient
Dialysate
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Recirculating Loop
DialysisStation
ActivatedCharcoal RO RO
Filter
Filter
0.1+
Softener Filter
Filter
0.1+Pump
Tap Water
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Nephrol Dial Transplant 2002; 17 [Suppl 7]
2002
2009
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I I 2009
2009
ISO/FDIS 2009-11663
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ISO/FDIS 2009-11663
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ISO/FDIS 2009-11663
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International standards of water
and dialysis fluid
Maximum levelsRegularWater
UltrapureWater
UltrapureDialysis Fluid
Microbial contamination(CFU/ml)
Sensitized methods
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, C
H
.
A
C
HDF
FF
F
F
C
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B
()
D
F (H, C)
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Online HDF, Modalities of substitution
Dialysate outlet+ Ultrafiltrate
Fluid
lancing
odule
Dialysate outlet+ Ultrafiltrate
id cing
ule
Infusionpump
- Infusate B
SterilizingultrafiltersInfusion
pump
HDF
HDF
Dialysate inlet
- Infusate
Fl
Bala
M
o
Sterilizing
ultrafilters
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HDF
CE
Nikkiso DBB-05
Gambro AK 200S/ UltraB.Braun Dialog+
Bellco Formula
FMC 5008FMC 4008 Gambro Innova
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DD
EEFF HDF HDF
EE
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(1994
1997)
Canaud B et al, Nephrol Dial Transplant 2000; 15[S1]:60-67
19200 HDF sessions
Total production of substitution fluid 533 594 liters
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I (19941997)
Canaud B et al, Nephrol Dial Transplant 2000; 15[S1]:60-67
19200 HDF sessions Mean volume filtrate 24 liters
Total production of substitution fluid 533 594 liters
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HDF
Subgroup analysis after enrolment
- y w-u
97 patients - 11258 HDF sessions
3961 samples
Penne EL et al, Kidney Int. 2009 ; 76: 665-672CONTRAST Dutch Convective Transport Study
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C
One year follow-up
97 atients
11258 HDF sessions
No febrile reactions
No clinical adverse events
Penne EL et al, Kidney Int. 2009 ; 76: 665-672CONTRAST Dutch Convective Transport Study
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85 98%
10 centers
One year follow-up11258 HDF sessions97 patients 3961 samples
Penne EL et al, Kidney Int. 2009 ; 76: 665-672CONTRAST Dutch Convective Transport Study
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99
100 %
Penne EL et al, Kidney Int. 2009 ; 76: 665-672CONTRAST Dutch Convective Transport Study
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Effects of OL-HDF & r-HDF on inflammatory &nutritional markers
Cross-over, randomized multicentre trial
Panichi V et al, Nephrol Dial Transplant2006; 21: 756-762
25 HD patients
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Effects of OL-HDF and r-HDF on inflammatory andnutritional markers
Cross-over, randomized multicentre trial
Panichi V et al, Nephrol Dial Transplant2006; 21: 756-762
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HF-HD OL-HDF HF-HD OL-HDF HFHD
Effect of HD and HDF on CD14+CD16+ monocytes,
TNF, IL6 and inflammatory markers
Cross-over, randomized study (31 HD patients)
CD14+ CD16+
TNF - IL6
Telomere length
Polysulfone membrane
Ultrapure dialysate
Same dialysis conditions
Carracedo J et al, J Am Soc Nephrol. 2006; 17: 2315
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HDF CD14+CD16+
Carracedo J et al, J Am Soc Nephrol. 2006; 17: 2315
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DD
EEFF HDF HDF
EE
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Treatment schedule
3 sessions of 4 hours weekly (minimum)
Longer or more frequent (possible)
Highly permeable synthetic membrane
Large surface area > 1.8 m2
High-Efficiency on-line HDF. What does it means?
Ultrapure bicarbonate dialysis fluid High blood flow (effective QB: 350 - 400 ml/min)
High dialysate flow (500-700 ml/min) diffusive dose
Large volume of substitution
convective dose Post-dilution (Qsub : 100 ml/min, 24 l / session)
Pre-dilution (Qsub : 200 ml/min, 48 l / session)
Mixed dilution (Qsub : 150ml/min, 36 l/session)
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D F
HDF, C
30
35
40
45
50 Percentile
95th
75th
50th
25th
5th
Volume of replacement fluid (Liters)
0
5
10
15
20
25
ANZ50
BE86
FR184
GE142
IT270
JP73
SP56
SW129
UK69
All1059
Country across phase 1 - 3
Initial prevalent cross-sections who dialyzed 3 times/wk with vintage 3 months;
HDF not used in the US and Canada
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HDF FHD HFHD
69,1 70
54,2
60,6
72,1
63,5
75,4
62,7
80,981,6
82,7
60
80
100
LF-HD HF-HD Ol-HDF
HDF post 26.8l/sPercent reduction per session (%)
4,3
24,5
0
20
40
Urea, 60d Creat, 113d Osteoc,5.8kd B2M, 11.8kd Myogl, 16kd
Maduell F et al, Am J Kidney Dis 2002; 40: 582-589
C HDF
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C HDF
Canaud B et al, Am J Kidney Dis 1998; 31:74-80Urea Monitoring, BioStat 1000
HDF HFHD /
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HDF HFHD: /
2
ol-HDF
Movilli E et al, Nephro Dial Transplant. 2011; 0:1-6 ePub May2011
LFHD
2
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2
HFHD HDF
Tiranathanagul K et al. Ther Apher Dial 2009; 13: 56-62
Hi h ffi i HDF i th
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High efficiency HDF increases the
erythropoietic response to ESA
Vaslaki L et al, Blood Purif2006; 24: 163-173
70 HD patsHD
HDFHDF
HD24wks 24wks
H HDF
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H HDF
Lornoy W et al, J Ren Nut2006; 16: 47-53
22 HD patsHD
HDFHDF
HD
4hrs x 3wk
HF80 - QD800Direct dialysate quantification
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Hemodynamic tolerance is improved in HDFHemodynamic tolerance is improved in HDF
Tiranathanagul K et al. Ther Apher Dial 2009; 13: 56-62
ol-HDF in Southeast Asia: 3 years experience22 HD patients HFHD ol-HDF
Convective therapies (HF HDF) reduce intradialytic
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Convective therapies (HF, HDF) reduce intradialytic
symptomatic hypotension (ISH)
Total incidence of ISH 7.5% 28950 sessions
Locatelli F et al, J Am Soc Nephrol2010; 21:1798-1807Italian Multicentric Study RCT
LFHD, HF, HDF Ratio 2/1/1
9.8 to 8.0%
18.4%
10.6 to 5.2%
50.9%
7.1 to 7.9%
9.9%
Daily online HDF promotes catch up growth in
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Daily online HDF promotes catch-up growth in
CKD children
Fischbach M et al, Nephrol Dial Transplant. 2009;
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HDF
mean
Fischbach M et al, Nephrol Dial Transplant2004; 19: 2360-2367
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, ,
Time & FrequencyVolume substitution
Maduell F et al, Nephro Dial Transplant. 2011; 0:1-13 ePub 13Sep2011
Intracorporeal
resistance
Convective
dose
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Maduell F et al, Nephro Dial Transplant. 2011; 0:1-13 ePub 13Sep2011
C
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C
Maduell F et al, Nephro Dial Transplant. 2011; 0:1-13 ePub 13Sep2011
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Maduell F et al, Nephro Dial Transplant. 2011; 0:1-13 ePub 13Sep2011
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DD
EEFF HDF HDF
EE
Outcomes of HDF versus HD
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Outcomes of HDF versus HD
Author, Year HDF vs Comparator Type of study Grading
Wizemann V et al, 2000 HDF vs LFHD RCT Ia
Bosch JP et al, 2006 HDF vs LFHD vs HFHD Historical prospectivecohort IIb
Canaud B et al 2006 HDF vs LFHD vs HFHD Historical prospective cohort IIa
Jirka et al, 2006 HDF vs LFHD vs HFHD Historical ros ective cohort IIa
Schiffl H et al, 2007 HDF vs HFHD + UPD RCT Ia
Vinhas J et al, 2007 HDF vs HFHD Prospective controlled study IIb
Panichi V et al. 2008 HDF+/- vs LFHD Prospective controlled study IIa
Santoro A et al, 2008 HF vs HFHD RCT Ia
Tiranathanagul K 2009 HDF vs HFHD Prospective controlled study IIa
Vilar E et al, 2009 HDF vs HFHDHistorical prospective
cohortIIb
Locatelli F et al, 2010 HDF vs HD vs LFHD RCT Ia
Distribution of dialysis modality for prevalent
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y y ppatients
Canaud B et al, Kidney Int 2006; 69: 2087-2093
Mortality risk for patients receiving high
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efficiency HDF vs. HD is reduced
European Results from DOPPS
35% hs
7% ns
Canaud B et al, Kidney Int 2006; 69: 2087-2093
Cardiovascular mortality is reduced in ol HDF
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Cardiovascular mortality is reduced in ol-HDF
Panichi V et al. Nephrol Dial Transplant. 2008; 23:2337-2343RISCAVID Study
Survival is significantly higher in HDF treated
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g y g
patients
RR 0.66 vs 1.0 for HDF
Vilar E et al, Clin J Am Soc Nephrol 2009, ePub
Outcomes of HDF versus HD up to 2011
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Outcomes of HDF versus HD up to 2011
Author, Year HDF vs Comparator Type of study 2-MAnnual
MortalityHD/HDF
SurvivalGain
Wizemann V et al, 2000 HDF vs LFHD RCT 9.5/4.3 =
Bosch JP et al, 2006 HDF vs LFHD vsHFHD Historical prospectivecohort ? 45%
Canaud B et al 2006 HDF+/- vs LFHD vsHFHD
Historical prospectivecohort
? 12.7/8.9 35%
Jirka et al, 2006HDF vs LFHD vs Historical prospective
? 14.8/8.2 36%
Schiffl H et al, 2007HDF vs HFHD
+ UPD RCT 4.1/4.2 =
Vinhas J et al, 2007 HDF vs HFHDProspective controlled
study ? 19.9/8.9 50%
Panichi V et al. 2008 HDF+/- vs LFHD Prospective controlledstudy
13.2/10 15%
Santoro A et al, 2008 HF vs HFHD RCT 13.3/12 18%
Tiranathanagul K 2009 HDF vs HFHDProspective controlled
study =
Vilar E et al, 2009 HDF vs HFHDHistorical prospective
cohort 9/6 34%
Locatelli F et al, 2010 HDF vs HD vs LFHDProspective randomized
controlled study ? =
E
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HDF HD
Dutch TrialCONTRAST
French TrialHFHD vs HDF
Catalonian Trial
Turkish TrialHFHD vs HDF
Italian TrialLFHD vs HF/HDF
LFHD vs HDF
350/350CV eventsMortality
36 months
300/300
ToleranceCV eventsMortality
24 months
300/300
CV eventsMortality
24 months
300/300
CV eventsMortality
24 months
150/75/75
ToleranceMorbidityMortality
24 months
Reported & PublishedCompletedReported at ERA-EDTA
Ongoing Ongoing CompletedReported at ERA-EDTA
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DD
EEFF HDF HDF
EE
F C
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Small water soluble solutes Protein-bound solutes Middle moleculesAsymmetric dimethylarginine 3-Deoxyglucosone AdrenomedullinBenzylalcohol CMPF* Atrial natriuretic peptide-Guanidinopropionic acid Fructoselysine 2-Microglobulin-Lipotropin Glyoxal -EndorphinCreatinine Hippuric acid CholecystokininCytidine Homocysteine Clara cell proteinGuanidine Hydroquinone Complement factor DGuanidinoacetic acid Indole-3-acetic acid Cystatin C
Middle moleculesHypoxanthine Kinurenine Delta-sleep-inducing peptideMalondialdehyde Kynurenic acid EndothelinMethylguanidine Methylglyoxal Hyaluronic acidMyoinositol N-carboxymethyllysine Interleukin 1Orotic acid P-cresol Interleukin 6Orotidine Pentosidine Kappa-Ig light chainOxalate Phenol Lambda-Ig light chainPseudouridine P-OHhippuric acid LeptinSymmetric dimethylarginine Quinolinic acid Methionine-enkepahlin
Urea Spermidine Neuropeptide YUric acid Spermine Parathyroid hormoneXanthine Retinol binding protein*CMPF is carboxy-methyl-propyl-furanpropionic acid Tumor necrosis factor alpha
Vanholder R. et al New insights in uremic toxins. Kidney Int, 2003, 63; 84: S6S10
2 - Microglobulin
HDF D HDF 2
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HDF D HDF, 2
Maduell F et al, Kidney Int. 2003; 64:3058 patients (6M, 2F)
4-5 hrs x 3 to 2-2,5 hrs x 6 per week for 6 months
HDF
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Automated
dialysis
procedure
CleansingPriming
Blood volumecontrolled
machine
Manual
Flexible HDF
Rinsing
Suppressingsaline
requirementReducing
manualhandling
Save money
Biofeedbacksystem
Self Care or Home therapy
Internal HDF
I
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@.
European Dialysis Working Group dedicatedto improve dialysis outcomes focusing on
online convective therapies