Saudi J Kidney Dis Transpl 2014;25(1):156-160

2014 Saudi Center for Organ Transplantation

Letter to the Editor
Polyflux 210H Hemodialysis Membrane Targets to Improve Filtration
To the Editor,
The ideal hemodialysis filter should have
pores large enough to clear all uremic toxins,
including large molecules. However, this poses
the threat of allowing back-diffusion of small
toxins and loss of albumin, which forfeits the
goal of toxin removal. Thus, the real challenge
is the design of pores that strike an optimal ba-
lance between clearing as many uremic toxins
while at the same time minimizing back-
diffusion and retaining useful molecules.
It is fairly understood how the pore size in
ultrafiltration membranes affects its perfor-
mance characteristics.
1,2
Solute clearance de-
pends on both molecule characteristics
3
and
membrane properties.
4
Understanding the con-
tribution of both factors is essential to improve
the design of better membranes. Thus far, the
membrane properties have been mainly studied
by their manufacturers, and there are only very
independent research on this subject. Effective
diffusivity (D
eff
) is a significant parameter in
hemodialysis, as it quantitatively describes
how effectively a molecule diffuses through a
medium as compared with its free diffusivity
(D
o
) in solution. It is dependent on the hin-
drance of the capillary wall that the molecules
are passing through. As the diffusion hin-
drance increases, the clearance of uremic to-
xins decreases.
Polyflux 210H, a popular capillary hemo-
dialysis filter produced by Gambro Dialysa-
toren GmbH, Hechingen, Germany, is made
up of 12,000 Polyamix
TM
fibers with an over-
all surface area of 2.1 m
2
. Recently, we have
determined the inner pore density as 5.45
1.41% and the capillarys wall thickness as
46.88 m 1.65 for this dialyser.
5
Each fiber
consists of three layers: Innermost skin layer,
outermost finger layer and a large middle
spongy layer for structural support.
6
Industrial
tools are available to modify these structures.
With this knowledge, we aimed this study to
examine how changes in inner pore number
and fiber diameter affect clearances of known
molecules such as urea, glucose, Endothelin,
2-microglobulin and complement factor D
through Gambros Polyflux

210H.
Initially, the characteristics of the fenestra-
tions on the surfaces of the Polyflux 210H
capillaries were ascertained using scanning
electron microscopy (SEM), as has been done
by our team earlier in a previous study using
the SEM
5
. Next, the tension in the capillary
fibers as a result of applied pressure was esti-
mated using LaPlaces law as follows: T = (P
R) / t, where, T is the tension in the fiber
wall, P is the pressure across the wall, R is the
outside radius of the fiber and t is the fiber
thickness.
Following this, the hindrance factors affec-
ting molecular flux were calculated. There are
two types of hindrance factors: The hindrance
due to diffusion (K
diff
) and the hindrance due to
convection (K
conv
). Both are attributed to
solutewall hydrodynamic interactions.
7
Basi-
cally, free diffusivity (D
o
) of toxins is a func-
tion of the toxins molecular weight (MW),
and can be calculated as follows: D
o
= 1.76
Saudi Journal
of Kidney Diseases
and Transplantation
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10
-4
(MW)
(-0.552)
.
8
The effective diffusivity (D
eff
) of toxins through
hemodialysis hollow fiber membranes can be
calculated as follows: D
eff
= D
o
[ / (2 - )]
2
=
D
o
K
diff
,
9
where is the fraction of open space
on the inner surface and [ / (2 - )]
2
is K
diff
,
the hindrance factor due to diffusion. K
conv
is
the hindrance factor due to convection, and is
a function of the pressure gradient across the
membrane wall.
SEM was performed to ascertain the charac-
teristics of the fenestrations on the surfaces of
the Polyflux 210H capillaries. Figure 1
shows an SEM photomicrograph of the cross-
section of a Polyflux 210H capillary.
Capillary wall pressure was measured assu-
ming that the inlet pressure at the proximal end
of the dialyzer is 300 mm Hg applied pressure;
the tension exerted on each capillarys wall
was estimated to be 0.066 mm Hg/fiber (1.3
10
-3
psi/fiber). The calculation was made using
LaPlaces law.
Table 1 summarizes the free diffusivity, D
o
,
and the effective diffusivity (D
eff
) of albumin,
glucose and selected uremic toxins. The D
eff
is
the product of D
o
and the hindrance due to dif-
fusion, K
diff
. The diffusion hindrance that
exists at the surface in contact with the blood
Figure 1. SEM photomicrograph of the cross-
section of a Polyflux 210H capillary at 250.
The layered structure of the capillaries are
illustrated in an earlier study.
5
is equivalent to (/2-)
2
, where = 0.054, and
is the mean of the fenestrated inner surface of
the capillarys surface.
The theoretical potential of modifying pore
density and capillary diameters to improve
clearances of known molecules was examined.
As the pore density increases, the diffusion
hindrance drops. For example, if, theoretically,
the pore density is doubled, the calculated
increases to 10.8% and the effective diffusi-
vities of the molecules will multiply by a
factor of 4.23.
Similarly, if the pressure at the inlet of the
dialyzer is maintained at 300 mm Hg and the
wall thickness of each capillary remains the
same, but the capillarys width was doubled,
the capillary wall pressure estimated from
Laplace law will then double to 0.132 mm
Hg/fiber. Note that the pressure inside the ca-
pillary is different from the trans-membrane
pressure. We measured the intra-capillary wall
pressure from LaPlaces Law, T = (P R) / t
defined earlier.
There are different mathematical models to
measure diffusion through asymmetrical struc-
tures such as tortuous dialysis membranes.
Numerous studies have addressed the pore size
dispersion in membranes.
10-12
While the pore
size dispersion was modeled in one study,
13
another study focused on the effect of the
dialyzer design on solid clearance.
14
In another
approach, researchers used the perception of
fractional rejection of solutes to determine the
pore size distribution of ceramic and poly-
meric membranes.
15
Also, mathematical mode-
ling of mass transfer in an artificial kidney
yielded results that coincided within 10% of
the clinical ones.
16
Utilizing mini-modules
proved very advantageous to determine the
solutes transit through hollow fiber mem-
branes.
17
Also, the pore dispersion in cellulose
membranes was found to affect the passage of
large molecules.
18
Image examination is a no-
vel technique that proved competent in esti-
mating the practical pore size in permeable
membranes.
10
The newly developed Al
2
O
3
membranes that have nanopores have also
been investigated with respect to their sieving
characteristic
19
and the improvement of hemo-
Letter to the Editor 157
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Table 1. Free and effective diffusivities of albumin and selected uremic toxins.
Molecule
Free diffusivity,
D
o
x 10
-8
(cm
2
/s)
(a) Effective diffusivity,
D
eff
x 10
-10
(cm
2
/s)
Polyflux

210H
(at = 0.054)
K
diff
= 0.00077
(b) Effective
diffusivity,
D
eff
x 10
-10
(cm
2
/s)
Polyflux

210H
(at = 0.108)
K
diff
= 0.00325
(c) Effective
diffusivity,
D
eff
x 10
-10
(cm
2
/s)
Polyflux

210H
(at = 0.1332)
K
diff
= 0.00509
(d) Effective
diffusivity,
D
eff
x 10
-10
(cm
2
/s)
Polyflux

210H
(at = 0.0666)
K
diff
= 0.00118
Urea 1836.42 141.41 598.38 934.94 217.91
Glucose 1001.39 77.11 326.29 509.82 118.82
Endothelin 174.10 13.41 56.73 88.64 20.65
2-microglobin 56.53 4.35 18.42 28.78 6.70
Complement Factor D 38.43 2.96 12.52 19.57 4.56
Albumin 21.33 1.64 6.95 10.86 2.53
a) Calculations based on actual membrane measurements (inner pore density as 5.45 1.41% and the capillary wall thickness as 46.88 m 1.65
[unpublished data])
b) Calculations based on the assumption of doubling the pore density
c) Calculations based on the assumption of doubling the pore density, doubling the capillaries diameters and reducing the capillaries number by
half
d) Calculations based on the assumption of doubling the capillaries diameters and reducing the capillaries number by half
1
5
8
L
e
t
t
e
r

t
o

t
h
e

E
d
i
t
o
r
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dialysis.
14
Different methods were also fol-
lowed to characterize the pore sizes and their
densities in those Al
2
O
3
membranes. For
example, the pore count was estimated using
area fraction in aluminum oxide tubular mem-
branes. In this study, NIH Image J software
was used to calculate the pore density.
20
We used the equation that correlates the
effective diffusivity (D
eff
) through a fenes-
trated surface to the free diffusivity (D
o
).
9
As
illustrated in Table 1, the effective diffusivity
increased by at least 4.1-times when the pore
density on the inner walls of the capillaries
was only doubled. This is significant for future
designs of capillaries.
From LaPlaces law, our theoretical calcula-
tion of the stress on the capillary walls prove
that doubling the diameter of the capillaries
while maintaining the wall thickness will
double the wall tension in the membrane. This
will lead to better clearance of middle mole-
cules that are mainly cleared by convection. In
addition, assuming that the inside diameter of
the capillaries is doubled, pore density is
doubled, but the fiber number is halved to
maintain the final dialyzer size, K
diff
decreased
by a factor of 6.61 from 7.7 10
-4
to 5.09
10
-3
. Thus, these modifications can have posi-
tive results on the total clearance, particularly
the middle molecules, as illustrated through
our calculations in Table 1.
To summarize, our results demonstrate that
(a) reducing K
diff
will increase the clearance of
toxins, (b) doubling the pore density will in-
crease D
eff
, (c) doubling the capillaries width
will increase D
eff
and (d) doubling the pore
density together with doubling the capillary
width will increase D
eff
further than each sce-
nario by itself.
However, there are several limitations to this
study. The calculations used in this study are
based on theoretical concepts and require
experimental support in vivo. The contribution
of molecular characteristics to hindrance factor
was not addressed. In addition, applied fields
such as the electrical fields on the surface of
the membrane can add to the complexity of
filtration. For example, some molecules can
change shape in the presence of electrical
fields.
21
Further, the calculation of convective
hindrance requires further experiments and
therefore was not addressed. Convection plays
a major role in the clearance of lager mole-
cules. Nevertheless, we feel that the data is
robust enough to put the pore structure into the
picture for future studies.
Acknowledgments
This research was supported by a grant from
the Western Economic Diversification and
Interprice Saskatchewan, Canada.
Conflict of Interest Statement
The authors had no involvements that might
raise the question of bias in the work reported
or in the conclusions, implications or opinions
stated. We declare that we have no conflict of
interest pursuing this study. We also certify
that neither this manuscript nor one with subs-
tantially similar content under our authorship
has been published or is being considered for
publication elsewhere. We certify that all the
data calculated during this study is presented
in this manuscript, and no data from the study
has been or will be published separately.
Dr. A. Hedayat
1
,
Dr. A. Shoker
2
1
College of Dentistry, University of
Saskatchewan,
2
Saskatchewan Transplant
Program, St. Pauls Hospital, Saskatoon,
Canada
E-mail: ass787@mail.usask.ca
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