FX-class - High Flux for Improved Survival

7/23/2019 FX-class - High Flux for Improved Survival

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FX-class

High-Flux Dialysis for Improved Survival

Haemodialysis


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No Copy can Match the Original

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a Fresenius Polysulfone


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High-Flux Membranes Improve Patient Outcome

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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.

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. Locatel li,

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 MPO Study is supported by other studies(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

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

was shown for patients with type 2 diabetes.41: Evaluation of outcome in patients with type 2 diabetes on maintenancehemodialysis treatment influenced by biocompatibility and flux characteristicsof the dialysis membrane (post hoc analysis of a randomised, double-blindmulticentre study). Data taken from Krane et al., 2007

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).

* 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-classDialyser Design

Several state-of-the-art technologies have been

combined to create the distinctive functional features

of the FX-classdialysers:

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.

Optimised fibre array

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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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.


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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

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.

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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steam

steam

steam

sterile air

sterile water

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

This extensive rinsing of FX-classdialysers with hot

steam and without chemicals results in extremely lowlevels of residuals.

Superior Production Process InvolvingINLINE Steam Sterilisation

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

The dialysers failing the integrity test are discarded.

Finally, the dialysers are dried with warm, sterile air.

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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.

steam

sterile water

sterile air

42 43


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The INLINE steam sterilisation process leads to:

Highly purified dialysers

Dialysers free of any toxic chemicals or sterilisation

by-products

Low rinsing volumes

In contrast to INLINE steam sterilisation, gamma-

irradiation may physically and/or chemically alter the

membrane as high-energy radiation produces ionisation

and excitation in polymer molecules such as polysulfone.

This process may result in physical or chemical cross-

linking or degradation of the material and cytotoxic

substances may be generated (9, 10).

Among others, it has been shown that 4,4'-methylen-

dianilin, a substance of known carcinogenic potential,

may be generated in the polyurethane potting material

of capillary dialysers during gamma-radiation (11).

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.

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A recent study carried out by the Fraunhofer Institute,

Germany, shows the effects of test extracts obtained

from dialysers after undergoing different sterilisation

procedures on the viability of cells in culture:

Samples from different irradiated dialysers inhibited

metabolic activity (determined with a cell proliferation

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.

Advantages of INLINE Steam Sterilised Dialysers

Control

INLINE steam sterilisation(Fresenius Medical Care)

Gamma-ray sterilisation(different manufacturers)

DNASyn

thesisRate(%)

Extracts from Dialysers

0

10

20

30

40

50

60

70

80

90

100

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-classHigh-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

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-classof 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)

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0 100 200 300 400 500 600

0.6

1.0

1.4

1.8

2.2

In-VitroPerformance 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

flow rate.

At low blood flow rates, large dialyser surface areas

are not exploited to their full extent.

Optimal application for the FX-classdialysers

Ultrafiltration coefficient (mL/hxmmHg) 20 33 46 59 73Clearances: Q

B200

(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: QB300

(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: QB400

(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-vitroperformance data were obtained with QD= 500 mL/min, Q

F= 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, Q

F= 60 mL/min Inulin 1

2-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 (m) 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

In-vitroperformance data

FX 40 FX 50 FX 60 FX 80 FX 100

FX 100

FX 80

FX 60

FX 50

FX 40

SurfaceArea(m2)

Blood Flow (mL /min)


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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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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.

High-Flux Dialysis Powered by Fresenius Helixone

Literature

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.

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.

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.

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.

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.

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.

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

dianiline, from thermosetting polyurethane during sterilization.

J Anal Toxicol (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.

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

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

on convective and diffusive extracorporeal treatments. Kidney

Int (1999); 55: 286-293

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.

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.


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FX-class - High Flux for Improved Survival