Nephrol Dial Transplant (2011) 26: 2624–2630
doi: 10.1093/ndt/gfq803
Advance Access publication 10 February 2011
Comparison of removal capacity of two consecutive generations of
high-flux dialysers during different treatment modalities
Natalie Meert1, Sunny Eloot1, Eva Schepers1, Horst-Dieter Lemke2, Annemieke Dhondt1,
Griet Glorieux1, Maria Van Landschoot1, Marie-Anne Waterloos1 and Raymond Vanholder1
1
Renal Division, University Hospital Gent, Gent, Belgium and 2EXcorLab GmbH, Obernburg, Germany
Correspondence and offprint requests to: Natalie Meert; E-mail: [email protected]
Abstract
Background. Innovative modifications have been introduced in several types of dialyser membranes to improve
adequacy and permselectivity. Which aspects of removal
are modified and how this relates to different diffusive
or convective strategies has, however, been insufficiently
investigated.
Methods. In a prospective cross-over study, 14 chronic
kidney disease (Stage 5D) patients were dialysed with a
second-generation high-flux dialyser (Polynephron) in
comparison to a first-generation type (DIAPES-HF800).
Both dialysers were assessed in haemodialysis, in online
pre-dilution and in post-dilution haemodiafiltration. Reduction ratio (RR, %) of small water-soluble compounds (urea
and uric acid), low-molecular weight proteins (LMWPs)
(b2-microglobulin, cystatin C, myoglobin and retinol-binding
protein) and protein-bound solutes (hippuric acid, indole
acetic acid, indoxylsulphate and p-cresylsulphate) was assessed, together with albumin losses into the dialysate.
Results. Comparing the two types of membranes, the second-generation dialyser demonstrated a higher RR for
LMWPs, whilst at the same time exhibiting lower albumin
losses but only during post-dilution haemodiafiltration. No
differences in RR were detected for both the small watersoluble and the protein-bound compounds. Comparing
dialysis strategies, convection removed the same amount
of solute or more as compared to diffusion.
Conclusions. The second-generation membrane resulted in
a higher removal of LMWPs compared to the first-generation
membrane, but for the other solutes, differences were less
prominent. Convection was superior in removal of a broad
range of uraemic retention solutes especially with the firstgeneration membrane.
Keywords: haemodiafiltration; haemodialysis; removal; uraemic toxins
Introduction
In end-stage renal failure [Stage 5D chronic kidney disease
(CKD)], high-flux dialysis strategies are used to mimic as
adequately as possible removal by the natural glomeruli,
which clear solutes approximately up to the molecular
weight (MW) range of albumin (67 kDa). Consequently,
only compounds with a MW smaller than albumin represent a target for direct elimination by non-selective extracorporeal renal replacement therapies. The removal of
low-molecular weight proteins (LMWPs) (peptides >500
Da but smaller than albumin, formerly named ‘middle molecules’) has become one of the targets of modern highefficacy dialysis strategies.
A current trend in dialysis membrane engineering is to
maximize the permeability for larger LMWPs while retaining albumin. Membranes that leak substantial amounts of
albumin do not meet these requirements. Particularly in
convective procedures, such as haemodiafiltration, their
albumin leakage is high [1].
The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
For Permissions, please e-mail: [email protected]
Removal study of new-generation high-flux dialyser
In function of this awareness, innovative approaches
have been introduced in the manufacturing of dialysis
membranes [2, 3], e.g. the application of advanced spinning
procedures, which enables that the innermost skin layer of
the membrane can be modulated at the nanoscale level,
resulting in uniformly sized, larger but homogenously distributed pores with a sharp cut-off. Their effect on solute
sieving is a steeper sieving curve for LMWPs in absence of
increased albumin leakage. Polynephron (Nipro Corp.,
Osaka, Japan), one of the membranes under evaluation in
the present study, is an example of such a new-generation
dialysis membrane manufactured based on the above
principles.
Several questions regarding the removal capacity of
these new-generation membranes can be raised: (i) how
do these new membranes behave as compared to their
equivalents of the previous generation; (ii) what is the relative gain in efficacy for the different physico-chemical
types of uraemic solute (small water-soluble, proteinbound, LMWPs) [4] and (iii) is there a difference in behaviour in function of the applied dialysis strategy?
The present study was undertaken to answer the above
questions, applying in the same patients two membranes
made from the same polyethersulfone backbone, either the
first-generation DIAPES-HF800 membrane or the secondgeneration Polynephron membrane in a haemodialysis
(HD), a pre-dilution haemodiafiltration (pre-HDF) and a
post-dilution haemodiafiltration (post-HDF) setting. The
reduction ratio (RR) of a broad range of uraemic retention
solutes was evaluated.
Materials and methods
Patients
Fourteen stable, adult Stage 5D kidney disease patients (10 males, 4 females, mean age 74.0 8.4 years), who had been on thrice weekly maintenance dialysis for at least 6 months were enrolled in the study. Mean
dialysis duration was 39 34 months. The primary renal diagnoses were
diabetic nephropathy (n ¼ 5), chronic glomerulonephritis (n ¼ 3), renal
vascular disease (n ¼ 2), renal cortical necrosis (n ¼ 1), post-partum shock
(n ¼ 1) and cause unknown (n ¼ 2).
Study design
The study was performed with a prospective, cross-over, randomized
open-label design, which is illustrated in Figure 1. Patients were randomized for two dialysers containing two different membrane types based on
the same polyethersulfone polymer: PES-170DS (containing the
DIAPES-HF800 membrane; Membrana GmbH, Wuppertal, Germany)
and ELISIO-170H1 (containing the Polynephron membrane), both
produced by Nipro Corp. Membrane characteristics are illustrated in
Table 1. Each patient received one week of three consecutive treatments
with HD, pre-HDF and post-HDF with each of the two dialysers. The order
Fig. 1. Flow chart of the study.
2625
of dialyser type but not that of the dialysis mode was randomized. Before
the start of the study and before changing the dialyser type a wash-out
period of two weeks consisting of low-flux dialysis (FX 10; Fresenius
Medical Care, Bad Homburg, Germany) was performed. Between the
reallocation of dialysis modes, one wash-out week was always included.
The study was approved by the local ethics committee and was registered in clinicaltrials.gov (NCT00735059). Written informed consent was
obtained from all participants.
Systems and treatment strategies
All treatments were performed with Fresenius 4008H and 5008H (Fresenius Medical Care) dialysis machines.
Treatment and patient characteristics are illustrated in Table 2.
Sample collection and laboratory analysis
Samples were collected during the third (mid-week) session of each respective period. Pre- and post-dialysis blood samples were drawn from the
inlet line before starting the blood pump (pre-dialysis) and exactly 30 s
after setting the blood pump at 50 mL/min (post-dialysis).
Continuous partial sampling of spent dialysate was carried out with a
collection pump inserted into the dialysate outlet line via a special connector. At the end of the dialysis session a sample was collected after
stirring.
Blood and dialysate samples were collected on ice. Blood samples were
centrifuged (3000 r.p.m. for 10 min) and all samples were stored at 80C
until analysis.
Urea (MW: 60.1 Da) was measured by a standard clinical analyser. b2microglobulin (b2m) (MW: 11.8 kDA), cystatin C (MW: 13.3 kDa), myoglobin (MW: 17.6 kDa), free retinol-binding protein (MW: 21.2 kDa) and
albumin were determined using an immune nephelometric assay (BN
ProSpec; Siemens Dade-Behring, Marburg, Germany). Uric acid (MW:
168.1 Da), hippuric acid (MW: 179.2 Da), indole-3-acetic acid
(MW: 175.2 Da), indoxylsulphate (MW: 212.1 Da) and p-cresylsulphate
(MW: 187.2 Da) were analysed with reversed phase high-performance liquid
chromatography, as previously reported [5]. Only the total concentration of
the protein-bound solutes (hippuric acid, indole acetic acid, indoxylsulphate
and p-cresylsulphate) was determined.
Calculations and statistics
For the protein-bound compounds and LMWPs, concentration postdialysis (Cpost(c)) was corrected for extracellular volume changes based
on differences in the patient’s pre- (BWpre) and post-dialysis body weight
(BWpost) Cpost/corr ¼ Cpost/(1 1 ((BWpre BWpost)/0.2 BWpost)) [6].
RR was calculated according to the formula RR (%) ¼ ((C0 Cpost(c))/
C0) 3 100, where C is concentration [either before or after treatment (C0
and Cpost)].
Albumin losses into dialysate were calculated according to the equation: albumin losses (g) ¼ CAlb (QD 1 QUF) 3 t, where CAlb is albumin
concentration in a representative sample of spent dialysate, where (QD 1
QUF) is the sum of dialysate flow, infusion flow and ultrafiltration flow
(correction of interdialytic weight gain).
Statistical comparisons were made among the two membrane types and
among the three dialysis strategies.
Statistical evaluation was performed with GraphPad Prism 4 (GraphPad software, Inc., USA, CA). Data were checked for normality with
Kolmogorov–Smirnov test. Data are represented as mean SD. Comparative statistical analysis of differences between treatment modes was
performed by one-way analysis of variance with correction for multiple
2626
N. Meert et al.
DIAPES-HF800 only in the HD mode and superiority
of convection to diffusion only for DIAPES-HF800.
comparisons. Comparison between dialysers was performed with paired
t-test. A P-value of <0.05 was considered statistically significant.
Protein-bound compounds
Results
RRs of the protein-bound compounds [hippuric acid
(50% bound), indole acetic acid (65% bound), indoxylsulphate (90% bound) and p-cresylsulphate (95%
bound)] were in the range of 35 to 69%.
Comparing the two dialysers, there were no differences
between the two membranes (Figure 2C–F).
When comparing the dialysis strategies, for hippuric acid
and indole acetic acid, there were also no differences noted
(Figure 2C and D). However, for indoxylsulphate as well as
for p-cresylsulphate, RR with both dialysers was higher in
HDF compared to HD without difference among convective strategies (Figure 2E and F).
In summary, for protein-bound compounds, the secondgeneration membrane offers no advantage. However, when
comparing strategies, convection is superior to diffusion
with both membranes, without difference between both
convective strategies.
For all compounds determined, RRs were evaluated comparing (i) dialyser type and (ii) dialysis strategy per solute
group.
Water-soluble compounds
RRs of small water-soluble compounds (urea and uric acid)
ranged from 71 to 80%. Comparing the two dialysers,
urea RR (Figure 2A) was only significantly higher
with the Polynephron in the HD mode. For uric acid
(Figure 2B), the RRs were similar for the two dialysers in
all three treatment modes.
Comparing the dialysis strategies, only for the
DIAPES-HF800 dialyser significant differences were
found which were for urea in the order post-HDF > preHDF > HD (Figure 2A). For uric acid, only the difference
between HD (71%) and post-HDF (75%) reached significance (Figure 2B).
In summary, there are only subtle differences for the
small water-soluble compounds, with slightly but significantly more removal of urea with Polynephron versus
Low-molecular weight proteins
RRs of the four LMWPs were as follows: b2m (MW: 11.8
kDA) 59 to 75%, cystatin C (MW: 13.3 kDa) 55 to 77%,
myoglobin (MW: 17.6 kDa) 38 to 76% and retinol-binding
protein (MW: 21.2 kDa) 12 to 31%.
Comparing the two dialysers, the RR of LMWPs was
higher with Polynephron for all treatment modes as compared to DIAPES-HF800 (Figure 2G–J).
Comparing the dialysis strategies, for b2m and cystatin C
(Figure 2G and H), the RR for Polynephron in both HDF
treatment modes was higher as compared to HD. Both HDF
modes were not different from each other. For DIAPESHF800, the differences between all treatment modes were
significant and in the order post-HDF > pre-HDF > HD.
For myoglobin (Figure 2I), the RR for both dialysers in
post-HDF was higher as compared to the respective RRs
in pre-HDF and HD. Pre-HDF and HD, however, were not
different from each other. For retinol-binding protein, there
were no differences between the three treatment modes for
both filters (Figure 2J).
Table 1. Membrane characteristicsa
Effective length (mm)
Surface area (m2)
UF coeff (mL/h/mmHg)
Membrane thickness (lm)
SC b2mb
SC myoglobinb
SC albuminb
Average pore diameter (nm)
DIAPES-HF800
Polynephron
257
1.7
46
30
0.59
0.24
0.0052
7.5
271
1.7
74
40
0.81
0.95
0.0058
7.8
a
UF coeff, ultrafiltration coefficient; SC, sieving coefficient.
EN1283 human blood (haematocrit 32%, total protein 60 g/L); blood
flow, 300 mL/min; filtration flow, 60 mL/min. Pore size determined from
sieving curves.
b
Table 2. Dialysis and patient characteristicsa
DIAPES-HF800
Qb,eff (mL/min)
QD (mL/min)
Qinf (mL/min)
t (min)
UFV (L)
BW pre (kg)
BW post (kg)
Hct pre (%)
Polynephron
HD
Pre-HDF
Post-HDF
HD
Pre-HDF
Post-HDF
300
500
300
800
141 6 4
251 6 19
1.9 6 1.2
73 6 16
72 6 16
37 6 3
300
800
72 6 2
252 6 19
2.0 6 0.9
73 6 15
71 6 16
37 6 4
300
500
300
800
146 6 5
251 6 19
2.1 6 1.2
73 6 15
71 6 15
37 6 5
300
800
71 6 4
251 6 19
2.2 6 1.0
73 6 15
71 6 15
36 6 3
250 6 18
2.1 6 1.0
73 6 16
72 6 16
37 6 3
254 6 22
2.4 6 1.2
73 6 15
72 6 15
37 6 4
a
Qb,eff, effective blood flow; QD, dialysate flow; Qinf, infusion flow; t, treatment duration; UFV,
ultrafiltration volume; BW pre, body weight pre-dialysis; BW post, body weight post-dialysis; Hct
pre, haematocrit pre-dialysis.
Removal study of new-generation high-flux dialyser
2627
Fig. 2. RR (%, mean 6 SD, n ¼ 14) of the water-soluble compounds (A: urea, B: uric acid), protein-bound solutes (C: hippuric acid, D: indole acetic
acid, E: indoxylsulphate, F: p-cresylsulphate) and LMWPs (G: b2-microglobulin, H: cystatin C, I: myoglobin, J: retinol-binding protein) in HD, pre-HDF
and post-HDF. DIAPES-HF800 data are illustrated by the white bars and Polynephron by the grey bars. Comparison of dialysers: *P < 0.05, **P <
0.01, ***P < 0.001 versus DIAPES-HF800. Comparison of dialysis strategies: with DIAPES-HF800: §P < 0.05, §§P < 0.01, §§§P < 0.001 versus
HD; P < 0.01, P < 0.001 versus pre-HDF; with Polynephron: #P < 0.05, ##P < 0.01, ###P < 0.001 versus HD; cxxcP < 0.01 versus pre-HDF.
In summary, there is a distinct superiority of the secondgeneration membrane in removal of LMWPs. Comparing
dialysis strategies, convection is superior to diffusion. For
the first-generation membrane, post-dilution is superior to
pre-dilution. For the second-generation membrane, this
superiority of post-HDF reached statistical significance
only for the solute myoglobin.
Albumin
The mean loss of albumin in dialysate per session varied
between 1.8 0.6 and 5.7 2.1 g (Figure 3). Between
both dialyser types, there were no differences, unless in
the post-dilution HDF mode where Polynephron caused
less albumin losses in comparison with DIAPESHF800. When comparing strategies, post-dilution HDF
2628
Fig. 3. Albumin losses into dialysate (mean 6 SD, n ¼ 14). DIAPESHF800 data are illustrated by the white bars and Polynephron by the grey
bars. Comparison of dialysers: *P < 0.05 versus DIAPES-HF800. Comparison of dialysis strategies: with DIAPES-HF800: §§§P < 0.001 versus
HD; P < 0.001 versus pre-HDF; with Polynephron: ##P < 0.01versus
HD; xccxP < 0.01 versus pre-HDF.
induced more albumin losses than the two other
modalities.
Discussion
This study evaluates the impact of up-to-date polymer
chemistry and membrane manufacturing on the removal
of uraemic solutes during diffusive and convective dialysis
strategies. On one hand, two high-flux membranes that are
composed of the same polymer but manufactured with different spinning techniques were compared. As compared to
the first-generation membrane (DIAPES-HF800), the second generation (Polynephron) has thicker capillary walls
(40 versus 30 lm), a larger pore size (78 versus 75 Å)
and narrower distribution of pore size, altogether aiming
at a better elimination of large molecules without higher
losses of albumin. On the other hand, both dialysers are
tested in three different dialysis strategies (HD, pre-HDF
and post-HDF).
Our main findings are (i) removal is superior with the
second-generation versus first-generation high-flux dialyser for the removal of LMWPs irrespective of the dialysis
strategy (Figure 2G–J), whereas no marked differences in
removal were found for small water-soluble or proteinbound compounds (Figure 2A–F); (ii) albumin losses are
smaller with the second-generation dialyser during postHDF and similar for the other strategies (Figure 3); (iii)
convective strategies are slightly superior to HD for the
protein-bound compounds with the highest binding (Figure
2E and F) and the LMWPs (Figure 2G–J).
The superiority of the second-generation dialysers in removing LMWPs highlights that not all large pore membranes should be considered the same, even if pore size
or the polymers from which they are made are identical;
this was suggested also by a previous study, which was,
however, based on filters from two different manufacturers
[7, 8]. Based on our results, we can in addition stress that
the new-generation dialyser results in a higher LMWPs
removal (steeper sieving curve), without substantially
affecting albumin losses.
N. Meert et al.
Comparisons with previous studies calculating RR of
LMWPs are rather difficult because of the often considerably differing treatment parameters and should be interpreted with care. In the literature, we found several
studies but we selected two representative studies to compare our data [9, 10]. In comparison to the study of Krieter
et al., we can conclude that the RR of b2-microglobulin and
cystatin C were similar with the RRs obtained with the
Polynephron in our study. However, for the larger
LMWPs (myoglobin and retinol-binding protein), the Polynephron resulted in 5–16% higher RRs. Compared to
the study of Maduell et al., we can conclude that the RR of
b2-microglobulin is only slightly higher (4–8%) with Polynephron. The RR of myoglobin was markedly higher
(13–37%) with Polynephron.
For the LMWPs, differences among convective strategies (post-dilution > pre-dilution) are more pronounced
for the first-generation dialyser (Figure 2G–I). For the
second-generation dialyser, post-HDF is superior compared to the other techniques only for myoglobin. For retinol-binding protein, the differences among dialysis
strategies did not reach significance, probably due to the
fact that this molecule is not well removed during the treatments since it forms a complex with transthyretin in
plasma, resulting in a MW of 76 kDa [11].
It should be noted that the effective length of the newgeneration dialyser is longer than that of the older one,
which conceivably could result in increased internal filtration and back filtration. This could partly explain the superior RR of LMWPs with Polynephron compared to
DIAPES-HF800, even in a HD setting.
For the protein-bound compounds no benefit of the newgeneration dialyser could be demonstrated. Based on these
findings, it might be assumed that only the free fraction of
these solutes is eliminated essentially by diffusion. If this is
indeed the mechanism at play, the distribution and structure
of pores would have little impact on removal of these solutes which all have a low MW. One could hypothesize that
loss of protein-bound solutes into dialysate is to a large
extent related to losses together with albumin. Hence, since
DIAPES-HF800 was linked to more substantial albumin
losses during post-HDF, one might conclude that this effect
might have been responsible at least in part for the lack of
difference between both membranes. However, in a previous study, no correlation was found between the amount
of albumin and that of several protein-bound solutes lost
into the dialysate [12]. In addition, the calculated amount of
solute lost bound to albumin was <2% of the total amount
of each molecule lost into dialysate (unpublished data, Rita
De Smet). Another mechanism that could play a role in
removal is solute adsorption to the membrane. The study
design, however, does not allow the differentiation in the
importance of different aspects of removal.
On the other hand, we found an increase in removal with
convection compared to diffusion. These findings are in
accordance with the results of a previous study from our
group where we demonstrated superiority of post-HDF
compared to high-flux dialysis in lowering the pre-dialysis
concentration of the protein-bound compounds with the
highest binding, such as p-cresylsulphate [13]. In contrast,
Krieter et al. [9] could not detect a difference in removal of
Removal study of new-generation high-flux dialyser
the protein-bound solutes, p-cresylsulphate and indoxylsulphate, between post-HDF and high-flux HD. We do not
have a direct explanation for this discrepancy, although it
may be that the study of Krieter et al. was under powered
(n ¼ 8) to detect a difference. Again, in agreement with the
results of a previous study [5], we could not demonstrate a
difference in removal of protein-bound solutes between
pre-dilution and post-dilution HDF.
Since the main elimination mechanism of the small
water-soluble compounds is diffusion, neither a reorganization of the pore structure nor the introduction of convection
could cause a substantial increase in their removal.
It should be noted that the QD applied in HD (500 mL/
min) is lower in comparison to the QD in HDF (800 mL/
min). However, this is likely to be essentially important for
the clearance of small solutes [14]. The results should also
be interpreted with care since the calculated RR may overestimate true removal for solutes with multicompartmental
kinetics.
The question could be raised here of to what extent
would the increased removal of the study solutes impact
on clinical outcomes. Outcome superiority of large pore
(high-flux) membranes in more effectively removing
LMWPs than membranes with smaller pores has been demonstrated in a number of secondary analyses of large controlled trials [15–17] and in the patient group with low
serum albumin (<4 g/dL) of the membrane permeability
outcomes study [18, 19]. In a subanalysis of the HEMOstudy, pre-dialysis b2-microglobulin averaged over the
entire observation period was inversely correlated to
outcomes [20, 21].
For this study, it is difficult to predict the clinical relevance since it was developed as an acute study focussing on
the reduction of serum concentrations during a dialysis
session. Whether the new-generation dialysers have a positive impact on clinical outcome can only be demonstrated
by long-term clinical studies using a similar set-up.
Transmembrane albumin losses were similar, or for
post-HDF, even inferior to those with the first-generation
membrane, corroborating the alleged steep decline of
the sieving curve once the size of albumin is reached.
The pathophysiologic impact of transmembrane albumin
losses during dialysis remains currently unclear. In any case,
it can be assumed that they contribute to protein depletion
and hence may be linked to malnutrition, a current problem
encountered in a large proportion of the dialysis population
[22]. Nevertheless, the question can be raised whether hypoalbuminaemia in CKD is really related to albumin losses,
rather than to defects in albumin synthesis [23].
Conclusions
Second-generation large pore dialysers have a superior removal capacity for the LMWPs without increased albumin
loss; independent of the dialyser used (first or second generation), post-dilution haemodiafiltration is the most adequate dialysis strategy with regard to the removal of a
broad range of uraemic retention solutes.
Acknowledgements. The authors thank the nursing staff for their continuing assistance in the management of the patients.
2629
Transparency declarations. This study was supported by the Nipro Corporation, Japan. This work was partially funded by a governmental research grant from the Bijzonder Onderzoeksfonds (BOF, grant no.
0733502) and by the European Uraemic Toxin (EUTox) Work Group.
EUTox is a Consortium of European researchers involved in studies and
reviews related to uraemic toxicity. It was created under the auspices of the
European Society for Artificial Organs and is a work group of the European Renal Association—European Dialysis and Transplantation Association (ERA-EDTA) and is composed by 24 research groups throughout
Europe. The research group of R.V. has been supported by research grants
from Fresenius Medical Care, Baxter, Gambro and Bellco. S.E. is working
as post-doctoral fellow for the Belgian Fund for Scientific Research Flanders (FWO). The results presented in this paper have not been published
previously in whole or part, except in abstract format.
References
1. Ward RA. Protein-leaking membranes for hemodialysis: a new class
of membranes in search of an application? J Am Soc Nephrol 2005;
16: 2421–2430
2. Ronco C, Nissenson AR. Does nanotechnology apply to dialysis?
Blood Purif 2001; 19: 347–352
3. Ronco C, Bowry SK, Brendolan A et al. Hemodialyzer: from macrodesign to membrane nanostructure; the case of the FX-class of hemodialyzers. Kidney Int Suppl 2002; 80: 126–142
4. Vanholder R, De Smet R, Glorieux G et al. Review on uremic toxins:
classification, concentration, and interindividual variability. Kidney
Int 2003; 63: 1934–1943
5. Meert N, Eloot S, Waterloos MA et al. Effective removal of proteinbound uraemic solutes by different convective strategies: a prospective trial. Nephrol Dial Transplant 2009; 24: 562–570
6. Bergstrom J, Wehle B. No change in corrected beta 2-microglobulin
concentration after cuprophane haemodialysis. Lancet 1987; 1: 628–629
7. Ouseph R, Hutchison CA, Ward RA. Differences in solute removal by
two high-flux membranes of nominally similar synthetic polymers.
Nephrol Dial Transplant 2008; 23: 1704–1712
8. Vanholder R, Pedrini LA. All high-flux membranes are equal but
some high-flux membranes are less equal than others. Nephrol Dial
Transplant 2008; 23: 1481–1483
9. Krieter DH, Hackl A, Rodriguez A et al. Protein-bound uraemic toxin
removal in haemodialysis and post-dilution haemodiafiltration.
Nephrol Dial Transplant 2010; 25: 212–218
10. Maduell F, Navarro V, Cruz MC et al. Osteocalcin and myoglobin
removal in on-line hemodiafiltration versus low- and high-flux hemodialysis. Am J Kidney Dis 2002; 40: 582–589
11. Raghu P, Sivakumar B. Interactions amongst plasma retinol-binding
protein, transthyretin and their ligands: implications in vitamin A
homeostasis and transthyretin amyloidosis. Biochim Biophys Acta
2004; 1703: 1–9
12. De Smet R, Dhondt A, Eloot S et al. Effect of the super-flux cellulose
triacetate dialyser membrane on the removal of non-protein-bound and
protein-bound uraemic solutes. Nephrol Dial Transplant 2007; 22:
2006–2012
13. Meert N, Waterloos MA, Van Landschoot M et al. Prospective evaluation of the change of pre-dialysis protein-bound uremic solute concentration with post-dilution on-line hemodiafiltration. Artif Organs
2010; 34: 580–585
14. Bhimani JP, Ouseph R, Ward RA. Effect of increasing dialysate
flow rate on diffusive mass transfer of urea, phosphate and {beta}2microglobulin during clinical haemodialysis. Nephrol Dial Transplant 2010; 25(12):3990–3995
15. Chauveau P, Nguyen H, Combe C et al. Dialyzer membrane permeability and survival in hemodialysis patients. Am J Kidney Dis 2005;
45: 565–571
16. Cheung AK, Levin NW, Greene T et al. Effects of high-flux hemodialysis on clinical outcomes: results of the HEMO study. J Am Soc
Nephrol 2003; 14: 3251–3263
17. Krane V, Krieter DH, Olschewski M et al. Dialyzer membrane characteristics and outcome of patients with type 2 diabetes on maintenance hemodialysis. Am J Kidney Dis 2007; 49: 267–275
2630
18. Locatelli F, Hannedouche T, Jacobson S et al. The effect of membrane
permeability on ESRD: design of a prospective randomised multicentre trial. J Nephrol 1999; 12: 85–88
19. Locatelli F, Martin-Malo A, Hannedouche T et al. Effect of membrane
permeability on survival of hemodialysis patients. J Am Soc Nephrol
2009; 20: 645–654
20. Cheung AK, Rocco MV, Yan G et al. Serum beta-2 microglobulin
levels predict mortality in dialysis patients: results of the HEMO
study. J Am Soc Nephrol 2006; 17: 546–555
N. Meert et al.
21. Cheung AK, Greene T, Leypoldt JK et al. Association between serum
2-microglobulin level and infectious mortality in hemodialysis patients. Clin J Am Soc Nephrol 2008; 3: 69–77
22. Stenvinkel P. Malnutrition and chronic inflammation as risk factors for
cardiovascular disease in chronic renal failure. Blood Purif 2001; 19:
143–151
23. Kaysen GA, Rathore V, Shearer GC et al. Mechanisms of hypoalbuminemia in hemodialysis patients. Kidney Int 1995; 48: 510–516
Received for publication: 20.2.10; Accepted in revised form: 13.12.10