© I9 8 6 S . Karger A G .

Basel
Polycarbonalc-Workshop. Amsterdam 1985 0253-5068 86/0043 -D I0 2 S 2.75/0
Blood Purification 4: 102-111 (1986)

Biocompatibility and Hemodynamic Studies during

Polycarbonate versus Cuprophane Membrane Dialysis
D.C. Schohna, H.A. Jahna, M. Eberb, G. Hauptmann c
“Service de Néphrologie, Université Louis Pasteur, '’Centre Paul Strauss;
‘ Centre dc Transfusion Sanguine, Laboratoire du Complément, Strasbourg, France

Key Words. Polycarbonate membrane • Cuprophane membrane • Hemodialysis •

Biocompatibility • Complement fractions • Leukopenia • Pulmonary vascular resistances •
Pulmonary arterial pressure

Abstract. A new noncellulosic membrane (polycarbonate) has been tested in terms of bio­
compatibility and hemodynamic tolerance.The following results were obtained: The polycar­
bonate membrane manufactured by Gambro Hechingen induces activation of the comple­
ment system (slight decrease of CH50 and C3, no increase of C5a) to lower extent and causes a
less severe leukopenia than the cuprophane membrane. During dialysis with the polycarbon­
ate membrane hypoxemia does not occur and the pulmonary vascular resistances and pulmo­
nary arterial pressure remain stable. The good biocompatibility of the polycarbonate mem­
brane allows a better outcome of hemodialysis treatments.

Introduction cellulosic membranes appears important for

During hemodialysis the contact of the
blood with the dialyser membrane induces
modifications of several blood components
leading to e.g. complement activation [1,4,
5], leukocytopenia [1, 10] and thrombocyto­
penia [8], These modifications remain in
most instances asymptomatic but may in
some patients result in hemodynamic trou­
bles [2] or inflammatory reactions like the
acute-phase changes [6, 7, 11],
These phenomena have been reported to
be most pronounced with cellulosic mem­
better issues in hemodialysis treatment.
In this study we investigated the perfor­
mance and the tolerance of a polycarbonate
membrane (Gambrane-Gambro, Hechingen,
FRG) during hemodialysis in terms of bio­
compatibility and hemodynamics. Our aim
was to evaluate the importance of the effect
on (1) complement activation and leuko­
cytes, (2) blood gases, and (3) hemodynamic
parameters both in polycarbonate and cupro­
phane membrane hemodialysis.
The mechanisms and the sequence of the
humoral events and the relationship of the
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branes [9], Therefore the development of non observations with the organic or systemic
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Comparisons between Polycarbonate and Cuprophane Membranes
disturbances are not yet elucidated. The
cause of hypoxemia and hemodynamic trou­
bles are still matters of controversy, whereas
the pulmonary trapping of leukocytes seems
established.
Methods
We studied three groups o f chronic hemodialysis
patients (CHP) after having obtained their informed
consent. All these patients have been on hemodialysis
treatment for at least 6 months with cuprophane
membrane dialyscrs (2-3 times per week). They never
had any signs o f hemodynamic instability.
Group 1
The performances o f the M type polycarbonate
hollow-fiber hemodialyser were evaluated during 24
treatments in 12 CHP (mean age 39 ± 15 years: 6
women and 6 men). The mean venous hematocrit was
29.1 ± 3.3%, and total proteins 70.8 ± 2.9 g/l. The
following parameters were evaluated:
(I) Clearance o f urea, creatinine, uric acid and
phosphate during each treatment twice (at 30 min and
3 h of dialysis). The clearances were calculated with
following formula [13]:
K= •Q» + Qr • Cn„
C,„
The blood flow (QB) was measured on the inlet of
the dialyser using the air bubble technic. The clear­
ances were measured at various blood flows (Q») and
expressed in function o f Q». The dialysate flow
through the dialyser was kept constant at 500 ml/min
during the measurements.
(2) Ultrafiltration rale was measured by using an
electronic bed scale (Gambro). The ullrafillration rate
was measured several times during each treatment for
short periods o f time. The results were expressed in
function o f the real transmembrane pressures (TMP);
calculated with the usual formula [13]:
Phi + Pho Pdi r Pdo
Group 11
8 CHP (mean age 42 ± 17 yaers; 3 women and 5
men) were only submitted to the comparison tests for
biocompatibility. An intrapatient comparison was
103
performed between polycarbonate membrane (Gam-
branc. M type dialyser and cuprophane membrane
(Gambro Lundia plate 17 pm). The following parame­
ters were measured: leukocyte and thrombocyte
counts (Coulter counter); complement: CH*,Ü, C3. C4.
C5a (anaphylatoxin); blood gases: pO: and pCO;
(Corning pH meter); plasma acetate level (isotacho-
phoresis). The blood samples were drawn before and
during hemodialysis at 0. 15. 30, 60. 120 and 240 min.
The composition o f the dialysate was: acetate 38
mEq/1. Na 140 mEq/l. Ca .3.5 mEq/l.
Group 111
5 CHP (mean age 45 ± 11 years; 2 women and 3
man). Both biocompatibility tests and measurement of
hemodynamic parameters were performed on the M
type polycarbonate dialyser and on the 17-pm plate
cuprophane dialyser during I h with exclusion of the
dialysate fluid circulation and without any ultrafiltra­
tion in order to get the pure effects of the membranes.
The biocompatibility tests were the same as for
group II. The hemodynamic measurements comprised
arterial pressure (Dynamap), heart rate (ECG). pulmo­
nary arterial pressure and pulmonary wedge pressure
(Swan Ganz catheter), and cardiac output (thermodilu­
tion). Cardiac index, stroke index, pulmonary and sys­
temic resitances were calculated. Biocompatibilily tests
and hemodynamic measurements were performed si­
multaneously before the extracorporeal circulation and
at 0, 5, 10, 15, 30 and 60 min during the procedure.
Statistics
The results are expressed as mean ± SD (or SEM).
Statistical analysis was realized using Student'! t test
for paired samples.
Results
Performance
Clearances. The results are shown in fig­
ure 1. The urea clearance increases in a near-
linear way with the blood flow. Even with a
blood How above 250 ml/min, the urea clear­
ance curve does not reach a plateau and still
increases. For example the clearance at a
blood flow of 250 ml/min is 189 ml/min and
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at a blood flow of 350 ml/min is 244 ml/min.
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104
Fig. 1. Performance o f ihc M type polycarbonate
hollow-fiber hemodialyser. Clearance o f urea, creati­
nine and phosphate in relation to the blood flow.
When compared to surface-equivalent capil­
lary dialyser this clearance is higher. If we
compare the urea clearance obtained after
30 min of dialysis with that obtained after 3 h
we do not sec any difference.
The clearance curve for the endogenous
creatinine is comparable with that for urea.
The creatinine clearance at a blood flow of
300 ml/ntin is 203 ml/min. This new dialyser
displays also high phosphate and uric acid
clearances. At a blood flow of 300 ml/min,
the clearance of phosphate is 171 ml/min.
These results show good diffusive capaci­
ties in dependence of blood flow.
Ultrafiltration. The evolution of the ultra-
filtration rate in relation to the TMP is repre­
sented in figure 2. The mean value of the
ultrafiltration rate is about 3.4 ml/h/mm Hg.
This is a low ultrafiltration rate which allows
the use of this hemodialyser in most of the
patients.
Biocompatibility
Complement System. The results are
shown in figure 3. The plasma level of total
complement CH50 decreases in both situa­
Schohn/Jahn/Eber/Hauptmann
TMP, mm Hg
Fig. 2. Performance of the M type polycarbonate
hollow-fiber hemodialyser. Ultrafiltration rate (UF)
related to the TMP.
tions. but at least 50% more with cuprophane
membrane. With the polycarbonate mem­
brane, the CH50 was restored at the end of
hemodialysis but not during cuprophane he­
modialysis.
The C3 fraction behaves in a similar w'ay.
The C3 level during cuprophane dialysis lies
beneath that obtained during polycarbonate
membrane dialysis.
C5a (anaphylatoxin) was not modified by
the polycarbonate hemodialysis, whereas an
important increase was observed with cupro­
phane membrane dialysis. This behavior was
significantly different (p < 0.001) at 15 min
of hemodialysis.
The complement system is much more
activated by the cuprophane membrane. Poly­
carbonate membrane does not at all modify
C5a (anaphylatoxin).
Leukocytes and Thrombocytes. Leukope­
nia is less pronounced during hemodialysis
with polycarbonate membrane (decrease of
32%), whereas leukopenia reaches a 65% re­
duction with the cuprophane membrane.
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Thrombocytes are not modified during poly­
carbonate membrane hemodialysis. They de-
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Comparisons between Polycarbonate and Cuprophane Membranes
Fig. 3. Ev olution o f the total comple­
ment (CHso) and its fractions C5a and C3
during polycarbonate and cuprophane he­
modialysis. *p < 0.05; **p < 0.01.
creased when using cuprophane membrane
(fig- 4).
Blood Gases. Both type of membranes ex­
hibit a slight decrease of PaCoi with acetate
dialysate (fig. 4). Tremendous hypoxemia oc­
curred during cuprophane membrane dialysis
(fall ofPaOi by 35 mm Hgat 15 min). No hy­
poxemia was observed with polycarbonate mem­
brane. After 60 min we had a similarly de­
creased level of PaOs with both membranes.
Acetate Plasma Levels. Dialysis with
either membrane caused similar evolutions
of plasma acetate level.
105
Biocompatibility and Hemodynamics
In group III. the biocompatibility tests
were similar to those of group II, which is
interesting to notice because of the absence of
dialysate fluid during the first hour.
Low-Pressure System. The low-pressure
system is usually not affected by the acetate
dialysate [16]. Nevertheless, the absence of
dialysate during the first hour reinforces the
specific effect of membranes on hemody­
namic parameters. During extracorporeal cir­
culation with cuprophane membrane, pul­
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monary arterial pressure (PAP) increased,
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106
but not pulmonary wedge pressure (PWP).
The pulmonary vascular resistances (PVR)
increased. During extracorporeal circulation
with polycarbonate membrane no modifica­
tions were observed in the low-pressure sys­
tem (fig. 5, 6).
High-Pressure System. Usually dialysis
determines a decrease of systemic vascular
resistances (SVR) and an increase in stroke
index [15], In our procedure without dialysis
fluid no modification of arterial pressure
Schohn/Jahn/Ebcr/Hauptmann
Fig. 4. Evolution o f the leu­
kocytes (expressed as % o f pre­
dialysis value), thrombocyte
count. PaO; and PaCO; during
polycarbonate and cuprophane
hemodialysis. **p < 0.0 1 .
(AP) and (SVR) were observed. Cardiac in­
dex (Cl) and heart rate (HR) remained un­
changed. Neither of the membranes seems to
influence the high-pressure system (fig. 7).
The main result therefore of the mem­
brane effect on hemodynamics lies in the
low-pressure system and indicates a possible
relation either with the increased comple­
ment activation and pulmonary leukostasis
or with hypoxemia during dialysis with cu­
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prophane membrane.
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Comparisons between Polycarbonate and C'uprophanc Membranes
Fig. 5. Evolution o f leukocyte count, to­
tal complement (CHso), PaO; and PVR
during polycarbonate and cuprophane he­
modialysis. *p < 0.05; **p < 0.01.
Discussion
Our study explores the short-term bio­
compatibility of a recently manufactured
polycarbonate hemodialysis membrane by
Gambro. It is now well documented that
hemodialysis, mainly during the first hour, is
associated with a transient profound leuko­
penia [10], complement activation [4] by the
alternative pathway and impairment of the
pulmonary function. These phenomena have
107
been observed using different types of mem­
branes among which cuprophane causes the
most important modifications. If these phe­
nomena induce hypoxemia remains uncer­
tain. Craddock et al. [4] postulated the fol­
lowing hypothesis: the contact between
membrane and blood in the extracorporeal
circulation induces the alternative pathway
of complement; the fragment C5a of the C5
fraction is split off and induces leukocyte
137.73.144.138 - 11/8/2017 2:57:58 PM
aggregation [3]. The leukocyte aggregates [5]
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108
are trapped in the pulmonary vessels result­
ing in transient leukopenia, being a factor for
the hypoxemia observed during this period
[12, 14].
As shown in our results, the new mem­
brane appears to offer an improved biocom­
patibility compared to cuprophane. We ob­
served a smaller decrease of the total comple­
ment (CH50) and of its fraction C3 when
compared to cuprophane. The use of the poly­
carbonate membrane does not induce an
Schohn Jahn/Ebcr/Hauptmann
Fig. 6. Low-pressure system. Poly­
carbonate versus cuprophane hemodi­
alysis. *p < 0.05; **p < 0.01.
increase of C5a plasma levels as seen with the
cuprophane membrane. Other types of mem­
branes still have to be tested.
If we accept the hypothesis of Craddock et
al. [4], this lower activation of the comple­
ment system and the absence of C5a produc­
tion explains why we only observe slight
changes in leukocyte count with the polycar­
bonate membrane (-30% on average versus
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-70% with the cuprophane membrane; p <
0.001). The better biocompatibility of the
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Comparisons between Polycarbonate and Cuprophanc Membranes 109

polycarbonate membrane is a factor of stabil­ Moreover, the PVR modifications correlated

ity of the hemodynamic parameters. even closer with the arterio-venous oxygen
The increase of PVR observed with cu- difference (fig. 9). The degree of hypoxemia
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prophane membrane is inversely correlated observed during the first hour of blood-
(p < 0.001) with PaOo as shown in figure 8. cuprophane membrane contact may lead to
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I 10 Schohn Jahn Eber Hauptmann

PVR, dyn • s ' cm"5

♦10- 50 * 150 200 150 - \ 150 200
u - ------ 1 1 \o 1 1
-10-
-20- • \
-30- • \
s5 -¿.O- • \ 0
S -50- \
8 -60- Cuprophane b
V
a -70-
ALe Polycarbonate n = 7 n = 6 \
r = -0.33 r =-0.83 \
0O
C1
n.s. a <005

Fig. 9. Correlation between the

arterio-venous oxygen difference
(AV0;) and PVR during polycarbon­
ate and cuprophane hemodialysis.
Fig. 10. Correlation between the
mean decrease o f leukocytes ex­
pressed as % o f initial value and PVR
during polycarbonate and cuprophane
hemodialysis, n. s. = Not significant.
Fig. 11. Correlation between the
total complement (CH 50) and PVR
during polycarbonate and cuprophane
hemodialysis, n.s. = Not significant.

pulmonary vasoconstriction and to a signifi­ in comparison to the variations of PVR we

cant increase of PAP.
What is the cause of this hypoxemia? Sev­
eral mechanisms have been suggested to ex­
plain the hypoxemia observed with the cu­
prophane membrane: COs loss into an ace­
tate-containing dialysate [17, 18], pH modifi­
cation due to the buffer salt in dialysate [2]
and pulmonary leukostasis following com­
plement activation. Our study protocol
found a close inverse relationship: the greater
the decrease of CH50 in the plasma, the
higher the PVR. We found also a close rela­
tionship between the decrease of leukocyte
count and the increase in PVR (fig. 10). How­
ever, this relationship was not found in
healthy subjects [6] during sham hemodialy­
sis with cuprophane. In contrast, we found
only minor modifications of CH50 and PaO:
137.73.144.138 - 11/8/2017 2:57:58 PM

avoids the two first causes. But when we con­ and no modifications of PVR with the poly­
sidered the variations of CH5() plasma levels carbonate membrane (fig. 11).
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Comparisons between Polycarbonate and Cuprophane Membranes
Conclusion
The polycarbonate membrane manufac­
tured by Gambro Hechingen activates the
complement system (a slight decrease of
CH50 and C3, no increase of C5a) less than
the cuprophane membrane and also causes a
less pronounced leukopenia. During dialysis
with polycarbonate membrane hypoxemia
does not occur and PVR and PAP remain
stable. The good biocompatibility of the poly­
carbonate membrane allows a better out­
come of hemodialysis treatments.
References
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Université Louis Pasteur,
F -67091 Strasbourg (France)
Kings's College London
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