JOURNAL OF DIALYSIS, 1(7),
727-736 (1977)
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ASYMETRIC POLYAMIDE HOLLOW-FIBER FILTERS IN THE HEMFILTRATION SYSTEM E. Streicher and H. Schneider Katharinenhospi tal , Kriegsbergstrasse 60 D-7000 Stuttgart 1, West Germany
ABSTRACT We tested the asymnetric polyamide hollow fiber as the f i l t e r Effective membrane thickness was l v , the diameter of the hollow fiber was 6001.1,and the total surface was 1 d . Membrane cutoff was determined a t 13,000 daltons molecular weight. A fully automated system was used t o replace the volume of ul t r a f i l t r a t e w i t h a balanced electrolyte solution. Clearance rates for BUN, creatinine, uric acid, and i n organic phosphate were calculated a t 70 75 ml/min when prediluting ( i .e., when balanced electrolyte solution is admitted t o the .arterial 1ine of the extracorporeal circuit). C1 earance rate for i n u l i n was determined a t 23 ml/min. Sieving coefficients f o r small molecular weight solutes were determined a t 1.0 and for inulin 0.4. This decrease i s explained by the development of a secondary protein layer and by unfavorable streaming conditions inside the hollow fiber. The ultrafiltrate remained free of protein. i n the hemfiltration u n i t .
-
The hemofiltration u n i t clinically tested i n our center con-
sists of a hemfiltration f i l t e r made o f asymnetric polyamide hollow fibers w i t h an effective membrane thickness of 151 and a fully automated proportioning system that replaces volume-identical u l t r a f i l t r a t e by a balanced electrolyte solution. (Fl’gure 1 ) .
The hollow-fiber hemofflters used i n our clinic are made under 727 Copyright 0 1977 by Marcel Dekker, Inc. All Rights Reserved. Neither this work nor any part m a y be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, rnicrofdming, m d recording, or by any information storage and retrieval system, without permission in writing from the publisher.
STREICHER AND SCBNEIDER
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728
FIGURE 1 Electronic micrography of a Berghof hollow fiber membrane made of aromatic polyamide.
l a b o r a t o r y conditions.
The inside diameter o f each hollow f i b e r
is about 600u and the t o t a l diameter i s 1 , 0 0 0 ~ . A bundle o f hollow f i b e r s w i t h a membrane surface of about 1 m2 i s i n s e r t e d i n t o a p l e x i g l a s s tube and p o t t e d w i t h a biocompatible resin.
After
t e s t i n g the t i g h t n e s s by 500 mn Hg a i r p r e s s u r e , the hollow-fiber
hemfilter i s f o r m a l i n - s t e r i l i z e d (Figures 2 and 3 ) .
ASYMMETRIC POLYAMIDE HOUOW-FIBER FILTER
729
Giesharz k p i l hrmembranen
J 1
r
L
J-
I1
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
Kappa
--
c-
Blut
I
!
Kapillaren im
mt
FIGURE 2 Scheme of a hemofiltration filter consisting of a bundle of asy metric polyamide hollow fibers, potted in a plexiglaas
-
- tube by
polyurethan rubber. Having a membrane surface 1 m2 l m @ h of plexiglass
- tube measure 50 cm, diameter 6 cm,
lume 170 ml
.
filling
VO
-
The membrane cutoff of our polyamide hollow fiber was deter-
mined a t 13,000 daltons (cytochrom C) i n laboratory tests. using aqueous solutions. protein
The ultrafiltrate was free of even traces of
.
Besides the hollow-fiber hemfilter. the most important part of our hemofiltration u n i t is a proportioning system that replaces automatically identical volumes of ul t r a f i l trate w i t h a balanced electrolyte solution.
The essential detail of the system is a
sterilized compartment that is separated into two equal compartY
ments by a t h i n membrane. One conpartment is first filled quickly w i t h the balanced electrolyte solution; and, after reaching a
certain volume, the system is switched by pressure monitoring and the other compartment is then slowly f i l l e d w i t h ultrafiltrate t o the same volume.
STREICHER AND SCHNEIDER
730
!
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
1
FIGURE 3 Hemofi I tration filter photography.
The ultrafiltration process i s .variably controlled by a roller pump to maintain a pre-set transmembrane pressure that i s not
significantly affected by the addition of the balanced electrolyte solution. While f i l l i n g the unit with ul trafil trate, the balanced electrolyte solution i s continuously admitted into the arterial
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
A S m T ' R I C POLYAMIDE HOLLOW-FIBER FILTER
P2 @-
P3
0-
-Infusion
wrv2
-
731
7 32
STREICHER AND SCHNEIDER Oidiltrat i d / m i n i
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
94
10.
FIGURE 5 Diafiltration volumes versus of the trans
- membrane pressure.
Blood flow conditions have been kept stabile 300 ml/rnin.
vacuum rather than by clamping the venous l i n e t o prevent traumatizing erythrocytes.
Similar curves can be obtained comparing u l t r a f i l tration rates and blood f l o w .
The r e s u l t s of our laboratory experiments
w i t h sheep show a maximal u l t r a f i l t r a t i o n r a t e a t about 300 m l /
min blood flow in the extracorporeal c i r c u i t .
Under c l i n i c a l
conditions, one should t r y (depending upon individual A-V f i s t u l a conditions) to obtain blood flow r a t e s of about 300 ml/min i n order t o achieve optimal efficiency (Figure 6 ) . Considering plasma clearance r a t e s of solutes w i t h d i f f e r e n t molecular weights, small molecular substance clearance r a t e s were calculated a t 70- 75 ml/min when prediluting ( i . e . , when the electrolyte solution was admitted i n t o the a r t e r i a l line) and
733
ASYMMETRIC POLYAMIDE HOLLOW-FIBER FILTER
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
Diirfiltrat ml/min
Blutfluss mllmin FIGURE 6
Di af i Itrat ion volumes versus blood f Iow. Diaf i Itration f iIters 2 0.4 m have been used in animal experiments. Trans membrane
-
pressure has been kept stabile 300 mm Hg.
Hst. N
Kreatinin Harns;lure O Po, 0 lnutest Substitution vor
---
nach
I 100
200
300
Ruttluss Im~I min 1
FIGURE 7 Plasma clearance rates of BUN, creatinine, uric acid, anorganic phosphate and inulin versus blood flow, when pre 2 was tested in a hemofilter 1.0 m
.
- or postdilution
STREICHER AND SCXNEIDER
734
5 0 - 6 0 ml/min when the s o l u t i o n was added t o t h e venous l i n e of the extracorporeal c i r c u i t .
I n u l i n clearance rates, taken as a
reference f o r middle molecules, were determined a t 23 ml/min and The s i e v i n g c o e f f i c i e n t f o r
15 ml/min r e s p e c t i v e l y (Figure 7).
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
small molecular weight solutes i s about 1.0.
The s i e v i n g co-
e f f i c i e n t f o r i n u l i n showed, under c l i n i c a l practice, a decrease t o 0.4,
a phenomenon which should be discussed more f u l l y :
The
laboratory t e s t s of our polyamide hol l o w - f i b e r hemofil t e r showed s i e v i n g c o e f f i c i e n t s o f 1.0 f o r solutes up t o a molecular weight o f 5,000 daltons using aqueous solutions.
When using human plasma,
the s i e v i n g c o e f f i c i e n t f o r i n u l i n was determined a t 0.7, and i n c l i n i c a l p r a c t i c e w i t h the solvent "blood,"
sieving coefficient
decreased even f u r t h e r t o 0.4 (Figure 8). This decrease o f t h e s i e v i n g c o e f f i c i e n t f o r middle molecules
._.____.
.--
Wasser
-* Plasma
Siebkoeff tzi ent
100
loo0
loo00
MG
FIGURE 8 Sieving coefficients obtained for substances with different mole cul ar weights using aqueous solutions, human plasma and blood
2
under identical conditions with a hernofiltration filter 1.0 m
.
-
ASYMMETRIC POLYAMIDE EOLLOW-FIBER FILTER
735
may be due t o the development o f a secondary protein layer, leadi n g t o a negative variation o f the o r i g i n a l membrane characteri s t i c and/or t o unfavorable laminar flow conditions inside the hollow fiber, which has a rapid central stream and wide (6001.1)
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
nearly stationary r i m stream.
Our observations l e d us t o con-
clude t h a t the decrease o f the sieving c o e f f i c i e n t f o r middle molecules, which does not e x i s t i n the RP-6 p o l y a c r y l o n i t r i l e membrane,
i s a stream-dependent phenomenon. When comparing clearance rates, there i s a d i s t i n c t dependence upon the s i t e o f the introduction o f the substitution f l u i d .
Con-
sidering j u s t u l t r a f i l t r a t i o n , volune, and clearance rates, hemof i l t r a t i o n seemed t o have a higher efficiency when the balanced e l e c t r o l y t e solution was substituted i n the a r t e r i a l l i n e . ever, when calculating the solute extraction (i.e.,
How-
the quantity
o f a solute removed per u n i t time), there i s no s i g n i f i c a n t d i f ference i n low molecular weight solute removal with e i t h e r a r t e r i a l o r venous s i t e introduction. removal ( i .e.,
Comparing middle molecule solute
i n u l i n ) , a r t e r i a l substitution o f the balanced
e l e c t r o l y t e solutfon has been shown t o be more favorable, an i n t e r e s t i n g phenomenon t h a t could be explained by b e t t e r cont a c t w i t h the f i l t e r membrane when p r e d i l u t i n g and evident i n the RP-6 p o l y a c r y l o n i t r i l e membrane t o almost the same extent (Figure 9). There are two considerations when d e t e n i n i n g the optimal place o f substitution:
On the one hand, more favorable extrac-
t i o n of middle molecules i s obtained by introducing the balanced e l e c t r o l y t e solution i n the a r t e r i a l l i n e o f the extracorporeal
7 36
STREICHER AND SCHNEIDER
Extrakhan I m g / h I
&+omid- Hohllaser
B
venos
Pa/yacry/onitri/ - R P 6
4000
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
Subst orteriell
a Subst
arterrell
Q
venos
3000
zooa
loo0
Krro
Hsl-
Horns.
PO4
Inrtest
FIGURE 9 Solute extraction ( BUN, creatinine, uric acid, anorganic phos
-
phate and inulin ) by the aromatic polyamide hollow fiber hemofilter
- Polyacrylonitrile membrane under identical condi ti ons in the same patient .
compared to the
RP 6
c i r c u i t ; on the o t h e r hand, a 30% gain of e l e c t r o l y t e s o l u t i o n i s needed when s u b s t i t u t i n g i n t o the venous l i n e .
A f t e r our
t r i a l s , however, proposing a s i e v i n g c o e f f i c i e n t o f 1 .O f o r middle molecules, as proved f o r the RP-6 p o l y a c r y l o n i t r i l e membrane, we t h i n k venous s u b s t i t u t i o n o f the balanced e l e c t r o l y t e s o l u t i o n i s t o be p r e f e r r e d i n c l i n i c a l use.
727-736 (1977)
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
ASYMETRIC POLYAMIDE HOLLOW-FIBER FILTERS IN THE HEMFILTRATION SYSTEM E. Streicher and H. Schneider Katharinenhospi tal , Kriegsbergstrasse 60 D-7000 Stuttgart 1, West Germany
ABSTRACT We tested the asymnetric polyamide hollow fiber as the f i l t e r Effective membrane thickness was l v , the diameter of the hollow fiber was 6001.1,and the total surface was 1 d . Membrane cutoff was determined a t 13,000 daltons molecular weight. A fully automated system was used t o replace the volume of ul t r a f i l t r a t e w i t h a balanced electrolyte solution. Clearance rates for BUN, creatinine, uric acid, and i n organic phosphate were calculated a t 70 75 ml/min when prediluting ( i .e., when balanced electrolyte solution is admitted t o the .arterial 1ine of the extracorporeal circuit). C1 earance rate for i n u l i n was determined a t 23 ml/min. Sieving coefficients f o r small molecular weight solutes were determined a t 1.0 and for inulin 0.4. This decrease i s explained by the development of a secondary protein layer and by unfavorable streaming conditions inside the hollow fiber. The ultrafiltrate remained free of protein. i n the hemfiltration u n i t .
-
The hemofiltration u n i t clinically tested i n our center con-
sists of a hemfiltration f i l t e r made o f asymnetric polyamide hollow fibers w i t h an effective membrane thickness of 151 and a fully automated proportioning system that replaces volume-identical u l t r a f i l t r a t e by a balanced electrolyte solution. (Fl’gure 1 ) .
The hollow-fiber hemofflters used i n our clinic are made under 727 Copyright 0 1977 by Marcel Dekker, Inc. All Rights Reserved. Neither this work nor any part m a y be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, rnicrofdming, m d recording, or by any information storage and retrieval system, without permission in writing from the publisher.
STREICHER AND SCBNEIDER
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
728
FIGURE 1 Electronic micrography of a Berghof hollow fiber membrane made of aromatic polyamide.
l a b o r a t o r y conditions.
The inside diameter o f each hollow f i b e r
is about 600u and the t o t a l diameter i s 1 , 0 0 0 ~ . A bundle o f hollow f i b e r s w i t h a membrane surface of about 1 m2 i s i n s e r t e d i n t o a p l e x i g l a s s tube and p o t t e d w i t h a biocompatible resin.
After
t e s t i n g the t i g h t n e s s by 500 mn Hg a i r p r e s s u r e , the hollow-fiber
hemfilter i s f o r m a l i n - s t e r i l i z e d (Figures 2 and 3 ) .
ASYMMETRIC POLYAMIDE HOUOW-FIBER FILTER
729
Giesharz k p i l hrmembranen
J 1
r
L
J-
I1
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
Kappa
--
c-
Blut
I
!
Kapillaren im
mt
FIGURE 2 Scheme of a hemofiltration filter consisting of a bundle of asy metric polyamide hollow fibers, potted in a plexiglaas
-
- tube by
polyurethan rubber. Having a membrane surface 1 m2 l m @ h of plexiglass
- tube measure 50 cm, diameter 6 cm,
lume 170 ml
.
filling
VO
-
The membrane cutoff of our polyamide hollow fiber was deter-
mined a t 13,000 daltons (cytochrom C) i n laboratory tests. using aqueous solutions. protein
The ultrafiltrate was free of even traces of
.
Besides the hollow-fiber hemfilter. the most important part of our hemofiltration u n i t is a proportioning system that replaces automatically identical volumes of ul t r a f i l trate w i t h a balanced electrolyte solution.
The essential detail of the system is a
sterilized compartment that is separated into two equal compartY
ments by a t h i n membrane. One conpartment is first filled quickly w i t h the balanced electrolyte solution; and, after reaching a
certain volume, the system is switched by pressure monitoring and the other compartment is then slowly f i l l e d w i t h ultrafiltrate t o the same volume.
STREICHER AND SCHNEIDER
730
!
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
1
FIGURE 3 Hemofi I tration filter photography.
The ultrafiltration process i s .variably controlled by a roller pump to maintain a pre-set transmembrane pressure that i s not
significantly affected by the addition of the balanced electrolyte solution. While f i l l i n g the unit with ul trafil trate, the balanced electrolyte solution i s continuously admitted into the arterial
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
A S m T ' R I C POLYAMIDE HOLLOW-FIBER FILTER
P2 @-
P3
0-
-Infusion
wrv2
-
731
7 32
STREICHER AND SCHNEIDER Oidiltrat i d / m i n i
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
94
10.
FIGURE 5 Diafiltration volumes versus of the trans
- membrane pressure.
Blood flow conditions have been kept stabile 300 ml/rnin.
vacuum rather than by clamping the venous l i n e t o prevent traumatizing erythrocytes.
Similar curves can be obtained comparing u l t r a f i l tration rates and blood f l o w .
The r e s u l t s of our laboratory experiments
w i t h sheep show a maximal u l t r a f i l t r a t i o n r a t e a t about 300 m l /
min blood flow in the extracorporeal c i r c u i t .
Under c l i n i c a l
conditions, one should t r y (depending upon individual A-V f i s t u l a conditions) to obtain blood flow r a t e s of about 300 ml/min i n order t o achieve optimal efficiency (Figure 6 ) . Considering plasma clearance r a t e s of solutes w i t h d i f f e r e n t molecular weights, small molecular substance clearance r a t e s were calculated a t 70- 75 ml/min when prediluting ( i . e . , when the electrolyte solution was admitted i n t o the a r t e r i a l line) and
733
ASYMMETRIC POLYAMIDE HOLLOW-FIBER FILTER
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
Diirfiltrat ml/min
Blutfluss mllmin FIGURE 6
Di af i Itrat ion volumes versus blood f Iow. Diaf i Itration f iIters 2 0.4 m have been used in animal experiments. Trans membrane
-
pressure has been kept stabile 300 mm Hg.
Hst. N
Kreatinin Harns;lure O Po, 0 lnutest Substitution vor
---
nach
I 100
200
300
Ruttluss Im~I min 1
FIGURE 7 Plasma clearance rates of BUN, creatinine, uric acid, anorganic phosphate and inulin versus blood flow, when pre 2 was tested in a hemofilter 1.0 m
.
- or postdilution
STREICHER AND SCXNEIDER
734
5 0 - 6 0 ml/min when the s o l u t i o n was added t o t h e venous l i n e of the extracorporeal c i r c u i t .
I n u l i n clearance rates, taken as a
reference f o r middle molecules, were determined a t 23 ml/min and The s i e v i n g c o e f f i c i e n t f o r
15 ml/min r e s p e c t i v e l y (Figure 7).
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
small molecular weight solutes i s about 1.0.
The s i e v i n g co-
e f f i c i e n t f o r i n u l i n showed, under c l i n i c a l practice, a decrease t o 0.4,
a phenomenon which should be discussed more f u l l y :
The
laboratory t e s t s of our polyamide hol l o w - f i b e r hemofil t e r showed s i e v i n g c o e f f i c i e n t s o f 1.0 f o r solutes up t o a molecular weight o f 5,000 daltons using aqueous solutions.
When using human plasma,
the s i e v i n g c o e f f i c i e n t f o r i n u l i n was determined a t 0.7, and i n c l i n i c a l p r a c t i c e w i t h the solvent "blood,"
sieving coefficient
decreased even f u r t h e r t o 0.4 (Figure 8). This decrease o f t h e s i e v i n g c o e f f i c i e n t f o r middle molecules
._.____.
.--
Wasser
-* Plasma
Siebkoeff tzi ent
100
loo0
loo00
MG
FIGURE 8 Sieving coefficients obtained for substances with different mole cul ar weights using aqueous solutions, human plasma and blood
2
under identical conditions with a hernofiltration filter 1.0 m
.
-
ASYMMETRIC POLYAMIDE EOLLOW-FIBER FILTER
735
may be due t o the development o f a secondary protein layer, leadi n g t o a negative variation o f the o r i g i n a l membrane characteri s t i c and/or t o unfavorable laminar flow conditions inside the hollow fiber, which has a rapid central stream and wide (6001.1)
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
nearly stationary r i m stream.
Our observations l e d us t o con-
clude t h a t the decrease o f the sieving c o e f f i c i e n t f o r middle molecules, which does not e x i s t i n the RP-6 p o l y a c r y l o n i t r i l e membrane,
i s a stream-dependent phenomenon. When comparing clearance rates, there i s a d i s t i n c t dependence upon the s i t e o f the introduction o f the substitution f l u i d .
Con-
sidering j u s t u l t r a f i l t r a t i o n , volune, and clearance rates, hemof i l t r a t i o n seemed t o have a higher efficiency when the balanced e l e c t r o l y t e solution was substituted i n the a r t e r i a l l i n e . ever, when calculating the solute extraction (i.e.,
How-
the quantity
o f a solute removed per u n i t time), there i s no s i g n i f i c a n t d i f ference i n low molecular weight solute removal with e i t h e r a r t e r i a l o r venous s i t e introduction. removal ( i .e.,
Comparing middle molecule solute
i n u l i n ) , a r t e r i a l substitution o f the balanced
e l e c t r o l y t e solutfon has been shown t o be more favorable, an i n t e r e s t i n g phenomenon t h a t could be explained by b e t t e r cont a c t w i t h the f i l t e r membrane when p r e d i l u t i n g and evident i n the RP-6 p o l y a c r y l o n i t r i l e membrane t o almost the same extent (Figure 9). There are two considerations when d e t e n i n i n g the optimal place o f substitution:
On the one hand, more favorable extrac-
t i o n of middle molecules i s obtained by introducing the balanced e l e c t r o l y t e solution i n the a r t e r i a l l i n e o f the extracorporeal
7 36
STREICHER AND SCHNEIDER
Extrakhan I m g / h I
&+omid- Hohllaser
B
venos
Pa/yacry/onitri/ - R P 6
4000
Ren Fail Downloaded from informahealthcare.com by TIB/UB Hannover on 01/10/15 For personal use only.
Subst orteriell
a Subst
arterrell
Q
venos
3000
zooa
loo0
Krro
Hsl-
Horns.
PO4
Inrtest
FIGURE 9 Solute extraction ( BUN, creatinine, uric acid, anorganic phos
-
phate and inulin ) by the aromatic polyamide hollow fiber hemofilter
- Polyacrylonitrile membrane under identical condi ti ons in the same patient .
compared to the
RP 6
c i r c u i t ; on the o t h e r hand, a 30% gain of e l e c t r o l y t e s o l u t i o n i s needed when s u b s t i t u t i n g i n t o the venous l i n e .
A f t e r our
t r i a l s , however, proposing a s i e v i n g c o e f f i c i e n t o f 1 .O f o r middle molecules, as proved f o r the RP-6 p o l y a c r y l o n i t r i l e membrane, we t h i n k venous s u b s t i t u t i o n o f the balanced e l e c t r o l y t e s o l u t i o n i s t o be p r e f e r r e d i n c l i n i c a l use.
