Haemodialysis

FX-class®
High-Flux Dialysis for Improved Survival
 No Copy can Match the Original

a Fresenius Polysulfone ®

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High-Flux Membranes Improve Patient Outcome

The Membrane Permeability Outcome (MPO) Study, a
clinical trial specifically designed to resolve the effect
of High- and Low-Flux membranes on patient outcomes,
has recently been completed.
The results, officially presented by Prof. Locatelli,
principal investigator of the study group, at the XLIV
Congress of the ERA-EDTA, show a survival benefit
for haemodialysis patients treated with High-Flux
compared to Low-Flux membranes.*
The MPO Study finally provides strong evidence in
favour of using biocompatible High-Flux membranes
to improve the long-term outcome of patients with
end-stage renal disease.

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

• A 37 % reduction of the relative risk of death was observed

for patients having a serum albumin level ≤ 4.0 g/dL.
• Significantly improved survival for diabetes patients.

As between 56 % and 86 % of dialysis patients

worldwide have a serum albumin level < 4.0 g/dL,
the majority of patients on dialysis would benefit from
High-Flux dialysis (2).

The MPO Study is supported by other studies (3, 4, 5, 6) 1 Low-Flux Cellulosic

2 Low-Flux Semisynthetic
3 Low-Flux Synthetic
showing a beneficial effect of High-Flux membranes 4 High-Flux Synthetic
Proportion of Patients Surviving

for dialysis patients like the recently published data

by Krane et al. (2007) from the database of the
German Diabetes and Dialysis (4D) Study (7) :

• A beneficial effect of biocompatible High-Flux

membranes on patients’ outcome compared to
cellulosic membranes and Low-Flux membranes
Year
was shown for patients with type 2 diabetes.
41: Evaluation of outcome in patients with type 2 diabetes on maintenance
hemodialysis treatment influenced by biocompatibility and flux characteristics
of the dialysis membrane (post hoc analysis of a randomised, double-blind
multicentre study). Data taken from Krane et al., 2007

* Inclusion criteria (1):

• Incident (on HD for 2 months)
• Age 18 – 80 years
• At risk (serum albumin 4.0 g/dL)

During the study, additional enrolment of patients with serum albumin > 4.0 g/dL was allowed.

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 FX-class® Dialyser Design

Several state-of-the-art technologies have been

combined to create the distinctive functional features
of the FX-class® dialysers:

The fibre bundle geometry, the membrane nanostruc-

ture, the flow port and the housing design all provide
advantages in terms of performance, haemodynamics,
dialysate flow as well as safety and handling.

Refined haemodynamics Optimised fibre array

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 higher packing density of the fibre bundle
together with the special wavy fibre structure regulates
a homogeneous distribution of dialysate over the
whole cross-section of the dialyser. This is evident in
the superior clearance values of the FX-class® (8).

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Radial dialysate flow
The pinnacle structures at both ends of the polypro-
pylene housing together with the potting technology
ensure an even, radial flow of the dialysate around the
individual fibres of the bundle.
The membrane
Helixone® is the advanced High-Flux polysulfone
membrane of the FX-class® dialysers. Helixone® has
been designed specifically to meet the present-day
demands of High-Flux dialysis and convective therapies:
• Larger average pore size (3.3 nm)
• More even distribution of pores
• High membrane porosity for enhanced hydraulic
permeability
The result of these structural refinements is the smooth
and unrestricted transport of larger uremic toxins across
the membrane wall, as exemplified by the significantly
increased sieving coefficient for larger solutes (e. g.
SCß2m = 0.8) – but with minimal leakage of useful
proteins like albumin (SCalbumin ≤ 0.001).
Fibres designed for High-Flux HD
The reduced inner diameter and wall thickness of the
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
spectrum of uremic toxins.
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 Superior Production Process Involving
INLINE Steam Sterilisation

The FX-class® dialysers are sterilised by the unique
INLINE steam sterilisation process specifically
developed by Fresenius Medical Care.
During the INLINE steam sterilisation process, both
blood and dialysate compartment of the dialysers are
rinsed continuously for 15 minutes with steam at a
temperature of 121 °C. 42
Every dialyser is then tested for fibre integrity. 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
detected by automated camera systems. 43

This extensive rinsing of FX-class® dialysers with hot The dialysers failing the integrity test are discarded.
steam and without chemicals results in extremely low Finally, the dialysers are dried with warm, sterile air.
levels of residuals.

steam sterile water

steam sterile air

steam sterile air

steam sterile water

42 43

After INLINE steam sterilisation the dry dialysers

get labeled, are visually inspected and finally fully
automatically packed.

During every production step, all Fresenius Medical

Care dialysers are undergoing various automated
in-process controls.

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Advantages of INLINE Steam Sterilised Dialysers

The INLINE steam sterilisation process leads to: A recent study carried out by the Fraunhofer Institute,
Germany, shows the effects of test extracts obtained
• Highly purified dialysers from dialysers after undergoing different sterilisation
procedures on the viability of cells in culture:
• Dialysers free of any toxic chemicals or sterilisation
by-products • Samples from different irradiated dialysers inhibited
metabolic activity (determined with a cell proliferation
• Low rinsing volumes assay) of cells by 70 % to 97 %. The samples of
INLINE steam sterilised FX80 dialysers showed only
a negligible influence.

• DNA synthesis was determined after incorporation of

the base analogue BrdU (5-bromo-2'-deoxyuridine):
The extracts from FME dialysers affected the cells
only in a non-significant manner, whereas irradiated
dialysers contain cytotoxic residuals killing a majority
of the cells. 44

Therefore, highly intensive rinsing is recommended

before use of irradiated dialysers.

In contrast to INLINE steam sterilisation, gamma-

100
irradiation may physically and/or chemically alter the Control
90 INLINE steam sterilisation
membrane as high-energy radiation produces ionisation (Fresenius Medical Care)
Gamma-ray sterilisation
and excitation in polymer molecules such as polysulfone. 80 (different manufacturers)

This process may result in physical or chemical cross- 70

DNA Synthesis Rate (%)

linking or degradation of the material and cytotoxic 60

substances may be generated (9, 10). 50

40
Among others, it has been shown that 4,4'-methylen-
30
dianilin, a substance of known carcinogenic potential,
20
may be generated in the polyurethane potting material
of capillary dialysers during gamma-radiation (11). 10

Furthermore, chemically active or pyrogenic substances
and residuals from sterilisation or production may
remain within the fibre. Intensive priming and rinsing
procedures are needed with irradiated filters.
0
Extracts from Dialysers
44: In vitro cytotoxicity testing of eight dialysers acc. to ISO 10993:
Effect of the samples (test extracts) from the dialysers on DNA synthesis
(BrdU-Test) on L929 cells. (Fraunhofer Institute, St. Ingbert, Germany;
unpublished data)

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 Advantages of FX-class® High-Flux Dialysers
• Highly purified dialysers – sterile and pyrogen-free
• Excellent haemobiocompatibility, unaffected by
sterilisation
• Dry packed, “light-weight” products
• Dialysers without pore-fillers or sterilising agent
residues
• Safe and comfortable treatment for your patients
• Environmentally friendly sterilisation method
8
All production steps from the manufacturing of the
membrane to the finished dialyser are adjusted to
each other resulting in constant highest quality.
The FX-class® of dialysers is – like all other products
from Fresenius Medical Care – produced with quality
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
objective of these efforts has been primarily to remove
a wide range of uremic retention solutes – 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
larger uremic toxins.
An extended clinical experience worldwide has
established that the efficient removal of a wide range
of toxins by High-Flux is a significant contributing
factor for improved long-term results for dialysis
patients (EBPG 2.2) (13), for example in terms of
• better control of renal anemia. (14)
• delayed onset of amyloidosis. (15, 16)
• reduced inflammation. (14)
• improved immune response. (17)
• prolonged preservation of residual renal funtion. (18)
In-Vitro Performance Data

To utilise a dialyser to its full capacity and achieve Optimal application for the FX-class® dialysers
optimal blood flow conditions in the dialyser, it is
important to consider the relationship between its
effective surface area and the achievable blood
flow rate.
2.2 FX 100

Surface Area (m2)

At low blood flow rates, large dialyser surface areas 1.8 FX 80

are not exploited to their full extent. 1.4 FX 60

1.0 FX 50

0.6 FX 40

0 100 200 300 400 500 600

Blood Flow (mL /min)

In-vitro performance data

FX 40 FX 50 FX 60 FX 80 FX 100

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

Clearances: QB 200 (mL/min) Urea 170 189 193 197 *
Creatinine 144 170 182 189
Phosphate 138 165 177 185
Vitamin B12 84 115 135 148
Inulin 54 76 95 112
Clearances: QB 300 (mL/min) Urea * 250 261 276 278
Creatinine 210 230 250 261
Phosphate 201 220 239 248
Vitamin B12 130 155 175 192
Inulin 81 104 125 142
Clearances: QB 400 (mL/min) Urea * * 303 326 331
Creatinine 262 287 304
Phosphate 248 272 284
Vitamin B12 167 190 213
Inulin 109 133 152

* Refer to recommended blood flow range.

The in-vitro performance data were obtained with QD = 500 mL/min, QF = 0 mL/min and T = 37 °C (EN 1283, ISO 8637).
The ultrafiltration coefficients were measured using human blood, Hct 32 %, protein content 6 %.

Sieving coefficient QB = 300 mL/min, QF = 60 mL/min Inulin 1

ß2-microglobulin 0.8
Albumin 0.001
Effective surface area (m2) 0.6 1.0 1.4 1.8 2.2
KOAurea 489 824 977 1292 1351
Wall thickness/inner diameter (µm) 35/185
Blood filling volume (mL) 32 53 74 95 116
Membrane
Housing material Polypropylene
Potting compound Polyurethane
Sterilisation method INLINE steam
Treatment mode HD/HDF/HF
Article number 5008841 5008851 5008861 5008881 5008901

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 Ever since the conception of haemodialysis therapy,
nephrologists worldwide have addressed the factors
contributing towards the poor long-term outcome of
dialysis patients.

The task has been complicated by the fact that

many dialysis patients suffer from multiple co-morbid
conditions, particularly hypertension, diabetes and
malnutrition – all of which contribute to the high
incidence of cardiovascular disease in this population
group.

The central function of haemodialysis therapies is to

remove a broad range of ’uremic toxins’ efficiently –
like the natural kidney.

Over the last years there has been an increasing body

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

membranes that are highly permeable to large toxins
and water. In addition, such membranes must be
biocompatible and have a high endotoxin retention
capacity.

Fresenius Polysulfone® and Helixone® membranes –

the most widely used dialysis membranes worldwide
– have specially been designed to fulfil these essential
criteria.

Together with nephrologists and nurses, Fresenius

Medical Care continues to contribute towards the
improved quality of life of HD patients, and ultimately
their survival.

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High-Flux Dialysis – Powered by Fresenius Helixone®

“The positive results of the MPO Study validate our

efforts to offer innovative dialysis products such as
our High-Flux dialysers with Helixone® membranes
so that dialysis patients can look toward the future with
more confidence. And we are proud that the majority
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, Latin America, Middle East and Africa.

Literature
1. Locatelli F et al., The effect of membrane permeability on 11. Shintani H et al., Analysis of a carcinogen, 4,4'-methylene-
ESRD: design of a prospective randomised multicentre trial. dianiline, from thermosetting polyurethane during sterilization.
J Nephrol (1999); 12(2): 85-8. J Anal Toxicol (1989); 13: 354-357.

2. Pisoni RL et al., Anemia management and outcomes from 12 12. Vanholder R et al., Review on uremic toxins: classification,
countries in the Dialysis Outcomes and Practice Patterns concentration and interindividual variability. Kidney Int (2003);
Study (DOPPS). Am J Kidney Dis. (2004); 44: 94-111. 63: 1934-1943.

3. Hornberger JC et al., A multivariate analysis of mortality and
hospital admissions with High-Flux dialysis. J Am Soc Nephrol
(1992); 3: 1227-1237.
4. Woods HF and Nandakumar M, Improved outcome for haemo-
dialysis patients treated with High-Flux membranes. Nephrol
Dial Transplant (2000); 15 (S1): 36-42.
5. Chauveau P et al., Dialyzer membrane permeability and survival
in hemodialysis patients. Am J Kidney Dis (2005); 45: 565-571.
13. Tattersall, J et al., EBPG guideline on dialysis strategies.
Nephrol Dial Transplant (2007); 22 Suppl 2: ii5-21.
14. Merello Godino JI et al., Results from EuCliD (European Clinical
Dialysis Database): impact of shifting treatment modality. Int
J Artif Organs. (2002); 25(11): 1049-60.
15. Koda Y et al., Switch from conventional to High-Flux membrane
reduces the risk of carpal tunnel syndrome and mortality of
hemodialysis patients. Kidney Int (1997); 52: 1096-1101

6. Delmez JA et al., Cerebrovascular disease in maintenance hemo- 16. Locatelli F et al., Comparison of mortality in ESRD patients
dialysis patients: results of the HEMO study. Am J Kidney Dis on convective and diffusive extracorporeal treatments. Kidney
(2006); 47: 131-138. Int (1999); 55: 286-293

7. Krane V et al., Dialyzer membrane characteristics and outcome 17. Lonnemann G et al., A switch to High-Flux helixone membranes
of patients with type 2 diabetes on maintenance hemodialysis. reverses suppressed interferon-gamma production in patients
Am J Kidney Dis (2007); 49: 267-275. on Low-Flux dialysis. Blood Purif. (2003); 21(3): 225-31.

8. Wizemann V et al., Efficacy of haemodiafiltration. Nephrol Dial
Transplant (2001);16 Suppl 4: 27-30.
9. Hemmerich KJ, Polymer Materials Selection for Radiation-
Sterilized Products, MDDI (2000); 2: 78-90.
18. McKane, W et al., Identical decline of residual renal function
in High-Flux biocompatible hemodialysis and CAPD. Kidney Int.
(2002); 61(1): 256-65.

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

effects on the structure and permeability of dialysis membranes.
Trans Am Soc Artif Intern Organs (1987); 33: 584-587.

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