FX-class®
High-Flux Dialysis for Improved Survival
Haemodialysis
No Copy can Match the Original
2
aFreseniusPolysulfone®
High-Flux Membranes Improve Patient Outcome
3
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
Pro
po
rtio
n o
f P
atie
nts
Sur
vivi
ng
Year
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).
4
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.
5
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.
6
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.
7
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)
8
9
0 100 200 300 400 500 600
0.6
1.0
1.4
1.8
2.2
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)
10
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.
11
“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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