FX-class®

High-Flux Dialysis for Improved Survival

Haemodialysis

No Copy can Match the Original

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aFreseniusPolysulfone®

High-Flux Membranes Improve Patient Outcome

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The benefits of High-Flux membranes – the essence of the MPO Study:

•A37%reductionoftherelativeriskofdeathwasobserved

forpatientshavingaserumalbuminlevel≤4.0g/dL.

•Significantlyimprovedsurvivalfordiabetespatients.

TheMembranePermeabilityOutcome(MPO)Study,a

clinical trialspecificallydesignedtoresolvetheeffect

ofHigh-andLow-Fluxmembranesonpatientoutcomes,

hasrecentlybeencompleted.

The results, officially presented by Prof. Locatelli,

principal investigatorof thestudygroup,at theXLIV

Congress of the ERA-EDTA, show a survival benefit

for haemodialysis patients treated with High-Flux

comparedtoLow-Fluxmembranes.*

The MPO Study finally provides strong evidence in

favourofusingbiocompatibleHigh-Fluxmembranes

to improve the long-term outcome of patients with

end-stagerenaldisease.

TheMPOStudyissupportedbyotherstudies(3,4,5,6)

showing a beneficial effect of High-Flux membranes

for dialysis patients like the recently published data

by Krane et al. (2007) from the database of the

GermanDiabetesandDialysis(4D)Study(7):

•A beneficial effect of biocompatible High-Flux

membranes on patients’ outcome compared to

cellulosic membranes and Low-Flux membranes

wasshownforpatientswithtype2diabetes.41:Evaluationofoutcomeinpatientswithtype2diabetesonmaintenance hemodialysistreatmentinfluencedbybiocompatibilityandfluxcharacteristics ofthedialysismembrane(posthocanalysisofarandomised,double-blind multicentrestudy).Data taken from Krane et al., 2007

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1 Low-Flux Cellulosic2 Low-Flux Semisynthetic3 Low-Flux Synthetic4 High-Flux Synthetic

As between 56% and 86% of dialysis patients

worldwide have a serum albumin level < 4.0 g/dL,

themajorityofpatientsondialysiswouldbenefitfrom

High-Fluxdialysis(2).

*Inclusioncriteria(1): •Incident(onHDfor≤2months) •Age18–80years •Atrisk(serumalbumin≤4.0g/dL)

Duringthestudy,additionalenrolmentofpatientswithserumalbumin>4.0g/dLwasallowed.

FX-class® Dialyser Design

Several state-of-the-art technologies have been

combinedtocreatethedistinctivefunctionalfeatures

oftheFX-class®dialysers:

Thefibrebundlegeometry,themembranenanostruc-

ture, theflowportandthehousingdesignallprovide

advantagesintermsofperformance,haemodynamics,

dialysateflowaswellassafetyandhandling.

Optimised fibre array

The higher packing density of the fibre bundle

togetherwiththespecialwavyfibrestructureregulates

a homogeneous distribution of dialysate over the

wholecross-sectionofthedialyser.Thisisevidentin

thesuperiorclearancevaluesoftheFX-class®(8).

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Refined haemodynamics

The lateral blood-inlet port defines a homogeneous

blood flow-path, avoiding low velocity stagnation

zones in the header region. Furthermore, the risk

of accidental twisting of bloodlines is virtually

eliminated.

The membrane

Helixone® is the advanced High-Flux polysulfone

membrane of the FX-class® dialysers. Helixone®has

beendesignedspecifically tomeet thepresent-day

demandsofHigh-Fluxdialysisandconvectivetherapies:

• Largeraverageporesize(3.3nm)

• Moreevendistributionofpores

• High membrane porosity for enhanced hydraulic

permeability

Theresultof thesestructural refinements is thesmooth

andunrestrictedtransportoflargeruremictoxinsacross

themembranewall, as exemplifiedby the significantly

increased sieving coefficient for larger solutes (e.g.

SCß2m = 0.8) – but with minimal leakage of useful

proteinslikealbumin(SCalbumin≤ 0.001).

Radial dialysate flow

The pinnacle structures at both ends of the polypro-

pylene housing together with the potting technology

ensureaneven,radialflowofthedialysatearoundthe

individualfibresofthebundle.

Fibres designed for High-Flux HD

Thereducedinnerdiameterandwallthicknessofthe

fibre increase the internal filtration and minimise the

diffusion resistance. A significant increase of both

the diffusive and convective clearances is therefore

achieved, allowing the efficient removal of a broad

spectrumofuremictoxins.

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steam

steam

steam

sterile air

sterile water

The FX-class® dialysers are sterilised by the unique

INLINE steam sterilisation process specifically

developedbyFreseniusMedicalCare.

During the INLINE steam sterilisation process, both

bloodanddialysatecompartmentofthedialysersare

rinsed continuously for 15 minutes with steam at a

temperatureof121°C.42

ThisextensiverinsingofFX-class®dialyserswithhot

steamandwithoutchemicalsresultsinextremelylow

levelsofresiduals.

Superior Production Process Involving INLINE Steam Sterilisation

Everydialyseristhentestedforfibreintegrity.Fresenius

Medical Care carries out its 100% fibre leak testing

procedures using a bubble-point test: Air pressure

is applied to the fibre bundle from one side while

the other side contains sterile water. If there were

leakages in the membrane, air would pass the

membrane and create bubbles, which are then

detectedbyautomatedcamerasystems.43

Thedialysers failing the integrity testarediscarded.

Finally,thedialysersaredriedwithwarm,sterileair.

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After INLINE steam sterilisation the dry dialysers

get labeled, are visually inspected and finally fully

automaticallypacked.

During every production step, all Fresenius Medical

Care dialysers are undergoing various automated

in-processcontrols.

steam

sterile water

sterile air

42 43

The INLINE steam sterilisation process leads to:

•Highlypurifieddialysers

•Dialysersfreeofanytoxicchemicalsorsterilisation

by-products

•Lowrinsingvolumes

In contrast to INLINE steam sterilisation, gamma-

irradiationmayphysically and/orchemically alter the

membraneashigh-energy radiationproduces ionisation

andexcitationinpolymermoleculessuchaspolysulfone.

Thisprocessmayresultinphysicalorchemicalcross-

linking or degradation of the material and cytotoxic

substancesmaybegenerated(9,10).

Amongothers,ithasbeenshownthat4,4'-methylen-

dianilin,asubstanceofknowncarcinogenicpotential,

maybegeneratedinthepolyurethanepottingmaterial

ofcapillarydialysersduringgamma-radiation(11).

Furthermore,chemicallyactiveorpyrogenicsubstances

and residuals from sterilisation or production may

remainwithin the fibre. Intensiveprimingand rinsing

proceduresareneededwithirradiatedfilters.

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ArecentstudycarriedoutbytheFraunhoferInstitute,

Germany,showstheeffectsoftestextractsobtained

from dialysers after undergoing different sterilisation

proceduresontheviabilityofcellsinculture:

•Samplesfromdifferentirradiateddialysersinhibited

metabolicactivity(determinedwithacellproliferation

assay) of cells by 70% to 97%. The samples of

INLINEsteamsterilisedFX80dialysersshowedonly

anegligibleinfluence.

•DNAsynthesiswasdeterminedafterincorporationof

the base analogue BrdU (5-bromo-2'-deoxyuridine):

Theextracts fromFMEdialysersaffected thecells

only inanon-significantmanner,whereas irradiated

dialyserscontaincytotoxicresidualskillingamajority

ofthecells.44

Therefore, highly intensive rinsing is recommended

beforeuseofirradiateddialysers.

Advantages of INLINE Steam Sterilised Dialysers

Control

INLINE steam sterilisation (Fresenius Medical Care)

Gamma-ray sterilisation (different manufacturers)

DN

A S

ynth

esis

Rat

e (%

)

Extracts from Dialysers0

10

20

30

40

50

60

70

80

90

100

44: In vitro cytotoxicity testing of eight dialysers acc. to ISO 10993: Effectofthesamples(testextracts)fromthedialysersonDNAsynthesis (BrdU-Test) on L929 cells. (Fraunhofer Institute, St. Ingbert, Germany; unpublisheddata)

Advantages of FX-class® High-Flux Dialysers

•Highlypurifieddialysers–sterileandpyrogen-free

•Excellenthaemobiocompatibility,unaffectedby

sterilisation

•Drypacked,“light-weight”products

•Dialyserswithoutpore-fillersorsterilisingagent

residues

•Safeandcomfortabletreatmentforyourpatients

•Environmentallyfriendlysterilisationmethod

All production steps from the manufacturing of the

membrane to the finished dialyser are adjusted to

eachotherresultinginconstanthighestquality.

TheFX-class®ofdialysers is– likeallotherproducts

fromFreseniusMedicalCare–producedwithquality

foremost in mind. Production and quality control

systems are ISO 9001 and EN 45001 certified;

the product specifications are also determined

and controlled according to the acknowledged EN

standards.

There has been an increasing interest in the

development of more efficient haemodialysis

treatment modalities in recent years. The main

objectiveoftheseeffortshasbeenprimarilytoremove

awiderangeofuremicretentionsolutes–particularly

the middle molecules – in the most efficient way(12).

The FX-class® possesses outstanding clearances

for both low-molecular weight solutes but also for

largeruremictoxins.

An extended clinical experience worldwide has

establishedthattheefficientremovalofawiderange

of toxins by High-Flux is a significant contributing

factor for improved long-term results for dialysis

patients(EBPG2.2)(13),forexampleintermsof

•bettercontrolofrenalanemia.(14)

•delayedonsetofamyloidosis.(15,16)

• reducedinflammation.(14)

• improvedimmuneresponse.(17)

•prolongedpreservationofresidualrenalfuntion.(18)

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In-Vitro Performance Data

To utilise a dialyser to its full capacity and achieve

optimal blood flow conditions in the dialyser, it is

important to consider the relationship between its

effective surface area and the achievable blood

flowrate.

At lowbloodflow rates, largedialyser surfaceareas

arenotexploitedtotheirfullextent.

Optimal application for the FX-class® dialysers

Ultrafiltration coefficient (mL/h x mmHg) 20 33 46 59 73

Clearances:QB200

(mL/min) Urea 170 189 193 197 *

Creatinine 144 170 182 189

Phosphate 138 165 177 185

VitaminB12

84 115 135 148

Inulin 54 76 95 112

Clearances:QB300

(mL/min) Urea * 250 261 276 278

Creatinine 210 230 250 261

Phosphate 201 220 239 248

VitaminB12

130 155 175 192

Inulin 81 104 125 142

Clearances:QB400

(mL/min) Urea * * 303 326 331

Creatinine 262 287 304

Phosphate 248 272 284

VitaminB12

167 190 213

Inulin 109 133 152

*Refertorecommendedbloodflowrange.

Thein-vitroperformancedatawereobtainedwithQD=500mL/min,Q

F=0mL/minandT=37°C(EN1283,ISO8637).

Theultrafiltrationcoefficientsweremeasuredusinghumanblood,Hct32%,proteincontent6%.

Sieving coefficient QB = 300 mL/min, QF = 60 mL/min Inulin 1 ß2-microglobulin 0.8 Albumin 0.001

Effectivesurfacearea (m2) 0.6 1.0 1.4 1.8 2.2

KOAurea

489 824 977 1292 1351

Wallthickness/innerdiameter (µm) 35/185

Bloodfillingvolume (mL) 32 53 74 95 116

Membrane

Housingmaterial Polypropylene

Pottingcompound Polyurethane

Sterilisationmethod INLINEsteam

Treatmentmode HD/HDF/HF

Articlenumber 5008841 5008851 5008861 5008881 5008901

In-vitro performance dataFX 40 FX 50 FX 60 FX 80 FX 100

FX 100

FX 80

FX 60

FX 50

FX 40

Sur

face

Are

a (m

2 )Blood Flow (mL /min)

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Ever since the conceptionof haemodialysis therapy,

nephrologistsworldwidehaveaddressed the factors

contributing towards thepoor long-termoutcomeof

dialysispatients.

The task has been complicated by the fact that

manydialysispatientssufferfrommultipleco-morbid

conditions, particularly hypertension, diabetes and

malnutrition – all of which contribute to the high

incidenceofcardiovasculardiseaseinthispopulation

group.

Thecentral functionofhaemodialysis therapies is to

removeabroad rangeof ’uremic toxins’efficiently–

likethenaturalkidney.

Overthe lastyearstherehasbeenan increasingbody

of evidence pointing towards a reduced death risk

in patients undergoing High-Flux dialysis as well

as advanced treatments such as haemodiafiltration

(HDF)(13).

Both High-Flux dialysis and HDF require dialysis

membranesthatarehighlypermeabletolargetoxins

and water. In addition, such membranes must be

biocompatible and have a high endotoxin retention

capacity.

Fresenius Polysulfone® and Helixone® membranes –

themostwidelyuseddialysismembranesworldwide

–havespeciallybeendesignedtofulfiltheseessential

criteria.

Together with nephrologists and nurses, Fresenius

Medical Care continues to contribute towards the

improvedqualityoflifeofHDpatients,andultimately

theirsurvival.

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“The positive results of the MPO Study validate our

efforts to offer innovative dialysis products such as

our High-Flux dialysers with Helixone® membranes

sothatdialysispatientscanlooktowardthefuturewith

moreconfidence.Andweareproudthat themajority

of the patients in the study’s High-Flux group were

treated with our dialysers,” said Dr. Emanuele Gatti,

Fresenius Medical Care’s Chief Executive Officer for

Europe,LatinAmerica,MiddleEastandAfrica.

High-Flux Dialysis – Powered by Fresenius Helixone®

Literature

1. Locatelli F et al., The effect of membrane permeability on

ESRD:designof aprospective randomisedmulticentre trial.

JNephrol(1999);12(2):85-8.

2. PisoniRLetal.,Anemiamanagementandoutcomesfrom12

countries in the Dialysis Outcomes and Practice Patterns

Study(DOPPS).AmJKidneyDis.(2004);44:94-111.

3. HornbergerJCetal.,Amultivariateanalysisofmortalityand

hospitaladmissionswithHigh-Fluxdialysis.JAmSocNephrol

(1992);3:1227-1237.

4. WoodsHFandNandakumarM,Improvedoutcomeforhaemo-

dialysispatients treatedwithHigh-Fluxmembranes.Nephrol

DialTransplant(2000);15(S1):36-42.

5. ChauveauPetal.,Dialyzermembranepermeabilityandsurvival

inhemodialysispatients.AmJKidneyDis(2005);45:565-571.

6. DelmezJAetal.,Cerebrovasculardiseaseinmaintenancehemo-

dialysispatients:resultsoftheHEMOstudy.AmJKidneyDis

(2006);47:131-138.

7. KraneVetal.,Dialyzermembranecharacteristicsandoutcome

ofpatientswithtype2diabetesonmaintenancehemodialysis.

AmJKidneyDis(2007);49:267-275.

8. WizemannVetal.,Efficacyofhaemodiafiltration.NephrolDial

Transplant(2001);16Suppl4:27-30.

9. Hemmerich KJ, Polymer Materials Selection for Radiation-

SterilizedProducts,MDDI(2000);2:78-90.

10.Takesawa S et al., Varying methods of sterilisation, and their

effectsonthestructureandpermeabilityofdialysismembranes.

TransAmSocArtifInternOrgans(1987);33:584-587.

11.Shintani H et al., Analysis of a carcinogen, 4,4'-methylene-

dianiline, from thermosetting polyurethane during sterilization.

JAnalToxicol(1989);13:354-357.

12.Vanholder R et al., Review on uremic toxins: classification,

concentration and interindividual variability. Kidney Int (2003);

63:1934-1943.

13.Tattersall, J et al., EBPG guideline on dialysis strategies.

NephrolDialTransplant(2007);22Suppl2:ii5-21.

14.MerelloGodinoJIetal.,ResultsfromEuCliD(EuropeanClinical

Dialysis Database): impact of shifting treatment modality. Int

JArtifOrgans.(2002);25(11):1049-60.

15.KodaYetal.,SwitchfromconventionaltoHigh-Fluxmembrane

reduces the risk of carpal tunnel syndrome and mortality of

hemodialysispatients.KidneyInt(1997);52:1096-1101

16.LocatelliFetal.,Comparisonofmortality inESRDpatients

onconvectiveanddiffusiveextracorporeal treatments.Kidney

Int(1999);55:286-293

17.LonnemannGetal.,AswitchtoHigh-Fluxhelixonemembranes

reversessuppressed interferon-gammaproduction inpatients

onLow-Fluxdialysis.BloodPurif.(2003);21(3):225-31.

18.McKane, W et al., Identical decline of residual renal function

inHigh-FluxbiocompatiblehemodialysisandCAPD.KidneyInt.

(2002);61(1):256-65.

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FreseniusMedicalCareDeutschlandGmbH·61346BadHomburgv.d.H.·Germany·Phone:+49(0)6172-609-0·Fax:+49(0)6172-609-2191Headoffice:Else-Kröner-Straße1·61352BadHomburgv.d.H.

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