Haemodialysis

FX-class
High-Flux Dialysis for Improved Survival

No Copy can Match the Original

a Fresenius Polysulfone

High-Flux Membranes Improve Patient Outcome

The Membrane Permeability Outcome (MPO) Study, a

for haemodialysis patients treated with High-Flux

clinical trial specifically designed to resolve the effect

compared to Low-Flux membranes.*

of High- and Low-Flux membranes on patient outcomes,

has recently been completed.

The MPO Study finally provides strong evidence in

favour of using biocompatible High-Flux membranes

The results, officially presented by Prof. Locatelli,

to improve the long-term outcome of patients with

principal investigator of the study group, at the XLIV

end-stage renal disease.

Congress of the ERA-EDTA, show a survival benefit

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)
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

Proportion of Patients Surviving

showing a beneficial effect of High-Flux membranes

1 Low-Flux Cellulosic
2 Low-Flux Semisynthetic
3 Low-Flux Synthetic
4 High-Flux Synthetic

membranes on patients outcome compared to

cellulosic membranes and Low-Flux membranes
was shown for patients with type 2 diabetes.

Year

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.

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

The higher packing density of the fibre bundle

blood flow-path, avoiding low velocity stagnation

together with the special wavy fibre structure regulates

zones in the header region. Furthermore, the risk

a homogeneous distribution of dialysate over the

of accidental twisting of bloodlines is virtually

whole cross-section of the dialyser. This is evident in

eliminated.

the superior clearance values of the FX-class(8).

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.
SC2m = 0.8) but with minimal leakage of useful
proteins like albumin (SCalbumin 0.001).

Radial dialysate flow

Fibres designed for High-Flux HD

The pinnacle structures at both ends of the polypro-

The reduced inner diameter and wall thickness of the

pylene housing together with the potting technology

fibre increase the internal filtration and minimise the

ensure an even, radial flow of the dialysate around the

diffusion resistance. A significant increase of both

individual fibres of the bundle.

the diffusive and convective clearances is therefore

achieved, allowing the efficient removal of a broad
spectrum of uremic toxins.
5

Superior Production Process Involving

INLINE Steam Sterilisation

The FX-class dialysers are sterilised by the unique

Every dialyser is then tested for fibre integrity. Fresenius

INLINE steam sterilisation process specifically

Medical Care carries out its 100% fibre leak testing

developed by Fresenius Medical Care.

procedures using a bubble-point test: Air pressure

is applied to the fibre bundle from one side while

During the INLINE steam sterilisation process, both

the other side contains sterile water. If there were

blood and dialysate compartment of the dialysers are

leakages in the membrane, air would pass the

rinsed continuously for 15 minutes with steam at a

membrane and create bubbles, which are then

temperature of 121 C. 42

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
sterile water

steam
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.
6

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

membrane as high-energy radiation produces ionisation

90

INLINE steam sterilisation

(Fresenius Medical Care)

and excitation in polymer molecules such as polysulfone.

80

Gamma-ray sterilisation
(different manufacturers)

This process may result in physical or chemical cross-

70

linking or degradation of the material and cytotoxic

substances may be generated(9,10).
Among others, it has been shown that 4,4'-methylendianilin, a substance of known carcinogenic potential,

DNA Synthesis Rate (%)

irradiation may physically and/or chemically alter the

Control

60
50
40
30

may be generated in the polyurethane potting material

20

of capillary dialysers during gamma-radiation(11).

10
0

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.

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)

Advantages of FX-class High-Flux Dialysers

Highly purified dialysers sterile and pyrogen-free

All production steps from the manufacturing of the

membrane to the finished dialyser are adjusted to

Excellent haemobiocompatibility, unaffected by

each other resulting in constant highest quality.

sterilisation
The FX-class of dialysers is like all other products
Dry packed, light-weight products

from Fresenius Medical Care produced with quality

foremost in mind. Production and quality control

Dialysers without pore-fillers or sterilising agent

systems are ISO 9001 and EN 45001 certified;

residues

the product specifications are also determined

and controlled according to the acknowledged EN

Safe and comfortable treatment for your patients

standards.

Environmentally friendly sterilisation method

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.
At low blood flow rates, large dialyser surface areas
are not exploited to their full extent.

Surface Area (m2)

2.2

FX 100

1.8

FX 80

1.4

FX 60
FX 50

1.0

FX 40

0.6
0

100

200

300

400

500

600

Blood Flow (mL/min)

In-vitro performance data

FX 40
Ultrafiltration coefficient
Clearances: QB 200 (mL/min)




Clearances: QB 300 (mL/min)




Clearances: QB 400 (mL/min)

(mL/h x mmHg)
Urea
Creatinine
Phosphate
Vitamin B12
Inulin
Urea
Creatinine
Phosphate
Vitamin B12
Inulin
Urea
Creatinine
Phosphate
Vitamin B12
Inulin

20
170
144
138
84
54
*




*

FX 50
33
189
170
165
115
76
250
210
201
130
81
*

FX 60

FX 80

FX 100

46
193
182
177
135
95
261
230
220
155
104
303
262
248
167
109

59
197
189
185
148
112
276
250
239
175
125
326
287
272
190
133

73
*

278
261
248
192
142
331
304
284
213
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 = 37C (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
2-microglobulin
Albumin

Effective surface area

KOAurea
Wall thickness/inner diameter
Blood filling volume
Membrane
Housing material
Potting compound
Sterilisation method
Treatment mode
Article number

(m2)

(m)
(mL)
Polypropylene
Polyurethane
INLINE steam
HD/HDF/HF

1
0.8
0.001
0.6
489

32

1.0
824

53

1.4
977
35/185
74

1.8
1292

2.2
1351

95

116

5008841

5008851

5008861

5008881

5008901

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 studys High-Flux group were
treated with our dialysers, said Dr. Emanuele Gatti,
Fresenius Medical Cares Chief Executive Officer for
Europe, Latin America, Middle East and Africa.

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

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

ESRD: design of a prospective randomised multicentre trial.
J Nephrol (1999); 12(2): 85-8.

2. Pisoni RL et al., Anemia management and outcomes from 12

countries in the Dialysis Outcomes and Practice Patterns
Study (DOPPS). Am J Kidney Dis. (2004); 44: 94-111.

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

concentration and interindividual variability. Kidney Int (2003);
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.

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

Nephrol Dial Transplant (2007); 22 Suppl 2: ii5-21.

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.

dianiline, from thermosetting polyurethane during sterilization.

J Anal Toxicol (1989); 13: 354-357.

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.

5. Chauveau P et al., Dialyzer membrane permeability and survival

in hemodialysis patients. Am J Kidney Dis (2005); 45: 565-571.

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-

dialysis patients: results of the HEMO study. Am J Kidney Dis
(2006); 47: 131-138.

16. Locatelli F et al., Comparison of mortality in ESRD patients

on convective and diffusive extracorporeal treatments. Kidney
Int (1999); 55: 286-293

7. Krane V et al., Dialyzer membrane characteristics and outcome

of patients with type 2 diabetes on maintenance hemodialysis.
Am J Kidney Dis (2007); 49: 267-275.

17. Lonnemann G et al., A switch to High-Flux helixone membranes

reverses suppressed interferon-gamma production in patients
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.

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.

9. Hemmerich KJ, Polymer Materials Selection for Radiation-

Sterilized Products, MDDI (2000); 2: 78-90.
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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732 701 1/4 GB (2,0 V&B 04.08) Copyright 2008 Fresenius Medical Care Deutschland GmbH

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