prof. bernard canaud

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



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85 98%

10 centers

One year follow-up11258 HDF sessions97 patients 3961 samples



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99

100 %



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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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C


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C



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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

prof. bernard canaud

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