Nephrol Dial Transplant (2002) 17: 106–111
Original Article
Ionic dialysance vs urea clearance in the absence of
cardiopulmonary recirculation
Lucile Mercadal1, Sophie Tézenas Du Montcel2, Marie-Chantal Jaudon3, Abdelaziz Hamani1,
Hassane Izzedine1, Gilbert Deray1, Bernard Béné5 and Thierry Petitclerc1,4
Departments of 1Nephrology, 2Biostatistics, 3Biochemistry and 4Biophysics, Hôpital de la Pitié, Paris and
5
Hospal R&D Int., Lyon, France
Abstract
Background. Several studies have shown a slight
discrepancy between ionic dialysance (D) and dialyser
urea clearance (UK), even in the absence of access
recirculation. As it has been suggested that this
discrepancy could be due to the cardiopulmonary
recirculation, we studied the relationship between these
two parameters in a particular dialysis setting without
cardiopulmonary recirculation.
Methods. Paired measurement of urea clearance and
ionic dialysance were performed in five patients
without arterio-venous access who were dialysed via
an internal jugular vein twin catheter. Fifty paired
measurements were used for statistical analysis.
Vascular access recirculation was assessed by an ultra-
sound dilution technique. The measured value of ionic
dialysance was corrected (D0) for the effect of vascular
access recirculation and was compared with instant
urea clearance calculated from the dialysate side.
Results. The difference between the paired measure-
ments of D0 and UK (n s50) was equal to
0.6"16.9 mlumin (NS). With a statistical power of
90% and taking into account this standard deviation,
this study might have shown a difference of at least
10.9 mlumin. The correlation was highly significant
(P-0.0001). The discrepancy of the two parameters
varied with dialysis efficiency, with a decreasing
D0 : UK ratio for the higher dialysis efficiency.
Conclusions. Compared with our previous results
obtained in patients dialysed on arterio-venous access
and performed with similar methods, the relationship
between D0 and UK is modified. This difference
between D0 and UK gets lower in patients dialysed
on central catheters and this variance is in accord-
ance with that expected when the influence of the
cardiopulmonary recirculation on the measurement
Correspondence and offprint requests to: L. Mercadal, Department
of Nephrology, Hôpital de la Pitié, 83 bd de l’hôpital, F-75013 Paris,
France. Email: lucile.mercadal@psl.ap-hop-paris.fr
# 2002 European Renal Association–European Dialysis and Transplant Association
of ionic dialysance is taken into account. The limits
of agreement ("2 SD) between D0 and UK
("34 mlumin, Bland–Altman analysis) were higher
than expected and raised questions about the accuracy
of the measurement of each parameter via a central
venous catheter.
Keywords: access recirculation; cardiopulmonary
recirculation; haemodialysis; ionic dialysance; urea
clearance
Introduction
Ionic dialysance is a parameter calculated from the
dialysate conductivity at the dialyser inlet and outlet
for two steps of inlet dialysate conductivity, and tends
to become an on-line monitoring parameter of the
effective dialysis dose actually delivered to the patient
w1–3x. Because the characteristics of transfer through
the dialyser and the osmotic distribution volumes in
the blood, urea and electrolytes are very close, ionic
dialysance is expected to equal dialyser urea clearance
(UK). Ionic dialysance, however, has been reported as
being slightly lower than UK w4–6x. As it has been
suggested that this discrepancy could be due to the
influence of cardiopulmonary recirculation on ionic
dialysance, this study investigated the relationship
between ionic dialysance and UK in a dialysis setting
without cardiopulmonary recirculation. The measure-
ments were performed in patients dialysed via a central
venous catheter and without arterio-venous access.
Subjects and methods
All the patients dialysed in our centre via internal jugular
vein twin catheters (Canaud TwinCaths, Medcomp,
Harleysville, PA, USA) and without arterio-venous access
(neither fistula nor graft) were tested at least twice during
Ionic dialysance and urea clearance
1 year. Five patients were included. They were tested at most
once per month.
After insertion of the catheter in the internal jugular vein,
an anteroposterior chest X-ray was obtained for each patient
to verify that the distal extremity of the catheter was located
in the superior vena cava or the right atrium. All catheters
were inserted for long-term haemodialysis and were con-
sidered to be functioning well as they delivered a blood flow
up to 400 mlumin without problems regarding venous and
arterial pressures. During the 1-year period, three patients
were tested twice and two patients six times according to
the length of time they were dialysed in our centre.
Haemodialysis was performed with an Integra1 dialysis
monitor (Hospal, Italy). The dialysate flow rate was set at
500 mlumin. This monitor is equipped with the Diascan1
module for automatic measurement of ionic dialysance. The
hollow-fibre dialyser was the usual one used for each patient
(one: HG500 Hemophan, Cobe, Denver, CO, USA; two:
Alwall GFS Plus 16 Hemophan, Gambro, Lund, Sweden;
two: CT 190 biacetate, Baxter, Minneapolis, MI, USA). The
calculation of ionic dialysance (D) was performed auto-
matically every 30 min from measurements of dialysate
conductivity according to the method previously described
w2,3x and summarized in Appendix 1 and Figure 1.
UK was calculated from the dialysate side by sampling
the dialysate and arterial blood just after a measurement of
ionic dialysance (calculation is detailed in Appendix 2).
Various dialyser blood flow rates (QB) were tested (range
200–400 mlumin) for each catheter. A maximum of four
blood and dialysate samples were taken during a dialysis
session.
The reproducibility of UK was verified and the mass
balance error for urea (MBE) was estimated using formulas
detailed in Appendix 3. A MBE lower than 5% validated the
measurement of UK. In order to decrease blood sampling,
MBE was only calculated on 12 measurements of UK during
three dialysis sessions. Subsequently, the values of D and UK
higher than 85% or lower than 50% of QB were discarded
because they were out of the expected range of dialysis
efficiency considering all dialysis conditions.
The vascular access recirculation ratio (R) was measured
using an HD01 monitor (Transonic System Inc, Ithaca, NY,
USA) based on an ultrasound dilution technique w7x. For
each pair of dialyser UK and ionic dialysance measurements,
Fig. 1. Scheme of the record of the inlet and outlet dialysate
conductivity during a measurement of ionic dialysance where X1 and
X2 are the two given values of inlet dialysate conductivity, Y1 and Y2
the two measured values of outlet dialysate conductivity and Cp the
representation of the patient’s plasma conductivity.
107
the vascular access recirculation ratio was assessed twice and
the mean of these two values was used for statistical analysis.
The HD01 monitor also provides a measure of the effective
blood flow (QB) at the dialyser inlet.
The measured value of ionic dialysance (D) is related to the
value of ionic dialysance of the dialyser (D0) by the following
formula taking into account access recirculation (effective
ionic dialysance) (equation 7 in Appendix 1):
QB
1
R
QB
Qf
D0 ¼ D   (1)
D
1
R 1þ
QB
Qf
Mean UK and ionic dialysance were compared with
random effect for patient using SAS Mixed Procedure
(ANOVA with random effect, SAS Institute Inc.), t-test for
paired data, and Bland–Altman analysis w8x. Results are
expressed as mean"SD. All the tests were performed for
a 0.05 significance level.
Results
Seventeen measurements of UK and two measure-
ments of ionic dialysance were discarded because they
were higher than 85% or lower than 50% of QB, leaving
50 paired measurements of ionic dialysance and UK
for statistical analysis.
The relative error of the dosage of urea was equal to
3%. Of the 12 estimations of MBE of urea, only seven
gave an error lower than 5%.
The recirculation ratio was 4.1"5.4% for an
effective dialyser blood flow (QB) of 272"54 mlumin.
Ionic dialysance and D0 were equal, respectively, to
174"17 and 180"19 mlumin. Taking into account
patient effect, UK and D0 were highly correlated
(P-0.0001). The linear regression coefficient was
rs 0.75. The difference between the paired measure-
ments of D0 and UK was equal to 0.6"16.9 mlumin
(180"19 vs 180"26 mlumin, NS). Bland–Altman
analysis is presented in Figure 2. The limits of agree-
ment ("2 SD) was equal to "34 mlumin. Taking into
account this standard deviation, the study includ-
ing 50 measurements of D0 and UK might have
indicated a statistically significant difference if it had
been equal or superior to 10.9 mlumin, with a statistical
power of 90%.
The discrepancy between ionic dialysance and UK
was dependent on the dialysis efficiency (Figure 3),
even when UK was normalized by the urea distribu-
tion volume (estimated using the nomogram of
Daugirdas w9x). This result was corroborated by the
difference of the D0uUK ratio in two subgroups of
different dialysis efficiency (D0uUK s 1.06"0.11 for
UK -180 mlumin vs D0uUK s 0.96"0.06 for UK
P180 mlumin, P-0.001, Table 1).
Discussion
Ionic dialysance has been nominated as a surrogate
of UK by Polaschegg w1x and by our group w2x. Under
108 L. Mercadal et al.

in vitro conditions, ionic dialysance is identical to UK is influenced by the recirculation phenomenon

w2x. Recent clinical studies by our group and by others,
however, have reported a discrepancy between ionic
dialysance and UK in vivo w4–6x.
Ionic dialysance is based on measurements of inlet
and outlet dialysate conductivity. The relationship
between the inlet and outlet dialysate conductivity
Fig. 2. Bland–Altman analysis between ionic dialysance corrected
from the part due to access recirculation (D0) and dialyser urea
clearance (UK).
Fig. 3. Linear regression analysis between D0uUK and UK shows
the influence of the dialysis efficiency on the discrepancy between the
parameters. Linear regression is represented by the black line
(r s 0.64, P-0.05).
(Appendix 1). Because the measured value of ionic
dialysance, but not that of instant dialyser UK, is
influenced by recirculation, we investigated if the
recirculation phenomenon can explain the discrepancy
between these two parameters.
Concerning vascular access, the measured value (D)
of ionic dialysance was corrected to cancel out the
influence of access recirculation. This corrected value
(D0) was lower than the measured value (D) by about
3%. This decrease is in agreement with previous results
suggesting a decrease in ionic dialysance by about 10%
for an increase in recirculation ratio of 12.5% w4x.
Access recirculation was not measured in other studies
performed on patients with arterio-venous fistulas, but
was demonstrated to be absent in recent non-urea-
based methods in patients with properly cannulated
and a well-functioning 2-needle vascular access w10x.
We have previously verified the absence of access
recirculation in 30 of our patients with the ultrasound
velocity dilution technique w11x.
Cardiopulmonary recirculation also could influence
ionic dialysance. During a dialysis session in a patient
with an arterio-venous access, part of the blood going
back to the access was not reloaded in the capillary
system. In contrast, all the blood going back to the
access was reloaded through the capillary system in
patients dialysed on an internal jugular vein twin
catheter and without an arterio-venous access. Cardio-
pulmonary recirculation can be detected for about
2 min, approximately 20 s after the injection of a saline
bolus in the venous line w12x—a shorter duration
than that needed for the measurement of ionic
dialysance—approximately 6 min. This phenomenon
could decrease the value of ionic dialysance compared
with the direct measurement of the instant dialyser
UK, as it has been demonstrated with access recircula-
tion w1,2x. Lindsay et al. have already suggested this
fact, which was, however, not demonstrated experi-
mentally w13x. The correction for the resulting reduc-
tion in dialysis efficiency due to cardiopulmonary
recirculation is made by the following equation w12x:
D0
DAV ¼ ð2Þ
D0
1þ
CO
QA
where QA is blood flow in the arterio-venous
access, CO cardiac output flow, DAV and D0 ionic

Table 1. Relationship in subgroups of similar urea clearance (UK) mean values between ionic dialysance corrected from the part due to access
recirculation (D0) and dialyser UK in patients dialysed on arterio-venous access w6x with the assumption of no access recirculation and in
patients dialysed on central catheter

Central catheter (n s 50) Arterio-venous access (n s 88)

UK -180 mlumin (n s 22) UK P180 mlumin (n s 28) UK -180 mlumin (n s 65) UK P180 mlumin (n s 23)

UK (mlumin) 157"15 199"15 157"18 193"8

D0uUK 1.06"0.11 0.96"0.06* 0.95"0.06 0.90"0.03*

*P-0.001.
Ionic dialysance and urea clearance
dialysance, respectively, with and without cardio-
pulmonary recirculation effect. With current values
(COs4800 mlumin, QAs 800 mlumin), DAV is approx-
imately equal to 190 mlumin for D0 s 200 mlumin.
Thus, for this range of dialysance, cardiopulmonary
recirculation could decrease the dialysis efficiency
by about 5% during dialysis via an arterio-venous
access.
When we compare the results of the present study
to data we previously collected in patients dialysed
via arteriovenous fistula w6x, the relationship between
ionic dialysance and UK is modified. The protocol of
measurement of UK was the same in the two studies,
as was the method of determining the dosage of urea.
Considering the evolution of D0uUK with dialysis
efficiency, the discrepancy of these two parameters was
expected to be higher in the present study because of a
higher mean UK (174"17 mlumin in the present study
vs 168"25 mlumin; w6x). On the other hand, D0uUK
gets colser to 1. The observed modification is near the
one suggested by equation 2. This study might have
indicated a difference if it had been equal or superior
to 10 mlumin, as found in patients dialysed on arterio-
venous fistula, with a statistical power or 90%. The
difference between D0 and UK is clearly smaller on
patients dialysed on central venous catheters compared
with patients dialysed on arterio-venous fistula.
The influence of dialysis efficiency on D0uUK,
already detected by ourselves and others, remains
significant (Table 1). This study clearly shows that this
effect is not related to cardiopulmonary recirculation.
One hypothesis is that the assumption of a constant
plasma conductivity (Cp) during the measurement of
ionic dialysance in a patient is more likely to be
violated with a high UK. However, the over evaluation
of D due to this effect is negligible (Appendix 4). The
effect of dialysis efficiency on D0uUK also could
be related to the difference between the distribution
volume of urea and electrolytes in blood: this dif-
ference could become more significant with higher
dialysis efficiency.
The technique of sampling from central catheters
seems responsible for large errors in UK values. In
fact, many values of UK appeared to be out of the
expected range (17u69) and the dispersion of D0uUK
was double compared with our previous study w6x
(Table 1) with a weaker linear correlation coefficient
(0.75 vs 0.91). MBE confirmed many unacceptable
values (5u12) of urea transfer, whereas the reproduc-
ibility of the urea dosage (3%) was acceptable. Blood
sampling could be influenced by local conditions and
especially by incomplete mixing in the heart cavities
of blood coming from different territories w14x. In a
patient dialysed via an arterio-venous access, the
sampled blood is already mixed in the heart cavities.
In addition, flow in the superior vena cava varies over
the cardiac cycle, transiently stopping just before
ventricular systole. A high level of access recirculation
may occur during ventricular contraction due to the
retrograde movement of blood from the right atrium.
There may be no access recirculation except for this
109
period; if so, the observed recirculation value is the
average over cardiac cycles w15x. The reliability of
blood sampling could be decreased by this non-
homogenous and intermittent blood flow. Finally,
haemolysis of blood samples occurs more frequently
with catheter access than with stainless steel needles
w16x, and is a source of error in the electrolyte and
enzyme determinations. The measurement of ionic
dialysance seems less affected by these variations
of dialysis conditions (only two measurements were
discarded) perhaps because the evaluation of the
electrolyte transfer by serial measurements of the out-
let dialysate conductivity is less influenced by the local
conditions.
In conclusion, the calculation of ionic dialysance
from dialysate conductivity measurements takes into
account recirculation, and especially cardiopulmonary
recirculation, possibly explaining the discrepancy
between dialyser UK and ionic dialysance found in
patients dialysed on arterio-venous access. Thus,
measured ionic dialysance (D) clearly seems to be a
valid parameter for monitoring the effective dialysis
efficiency of a patient.
References
1. Polaschegg HD. Automatic non-invasive intradialytic clearance
measurements. Int J Artif Organs 1993; 16: 185–191
2. Petitclerc T, Goux N, Reynier AL, Béné B. A model for non-
invasive estimation of in-vivo dialyzer performances and
patient’s conductivity during hemodialysis. Int J Artif Organs
1993; 16: 585–591
3. Petitclerc T. Recent developments in conductivity monitoring
of haemodialysis session. Nephrol Dial Transplant 1999;
14: 2607–2613
4. Petitclerc T, Béné B, Jacobs C, Jaudon MC, Goux N.
Non-invasive monitoring of effective dialysis dose delivered
to the dialysis patient. Nephrol Dial Transplant 1995; 10:
212–216
5. Manzoni C, Di Filippo S, Corti M, Locatelli F. Ionic dia-
lysance as a method for the on-line monitoring of delivered
dialysis without blood sampling. Nephrol Dial Transplant 1996;
11: 2023–2030
6. Mercadal L, Petitclerc T, Jaudon MC, Béné B, Goux N,
Jacobs C. Is Ionic dialysance a valid parameter for quantification
of dialysis efficiency? Artif Organs 1998; 22: 1005–1009
7. Krivitski NM. Theory and validation of access flow measure-
ment by dilution technique during hemodialysis. Kidney Int 1995;
48: 244–250
8. Bland JM, Altman DG. Statistical methods for assessing
agreement between two methods of clinical measurement.
Lancet 1986; i: 307–310
9. Daugirdas JT, Depner TA. A nomogram approach to hemo-
dialysis urea modeling. Am J Kidney Dis 1994; 23: 33–40
10. Besarab A, Lubkowski T, Frinak S, Ramanathan S, Escobar F.
Detecting vascular access dysfunction. ASAIO J 1997;
43: M539–543
11. Mercadal L, Hamani A, Béné B, Petitclerc T. Determination of
access blood flow from ionic dialysance: theory and validation.
Kidney Int 1999; 56: 1560–1565
12. Schneditz D, Kaufman AM, Polaschegg HD, Levin NW,
Daugirdas JT. Cardiopulmonary recirculation during
hemodialysis. Kidney Int 1992; 42: 1450–1456
13. Lindsay RM, Blake PG, Rothera C, Kianfar C. The relationship
between effective ionic dialysance and urea clearance during
hemodialysis. ASAIO J 1998; 44: 74A (abstract)
110 L. Mercadal et al.
14. Edwards JD, Mayall RM. Importance of the sampling site Re-arranging equation (6) yields:
for measurement of mixed venous oxygen saturation in shock.
Crit Car Med 1998; 26: 1356–1360 QB
15. Sherman RA, Kapoian T. Recirculation, urea disequilibrium 1
R
QB
Qf
and dialysis efficiency: peripheral arteriovenous versus central D0 ¼ D   (7)
venovenous vascular access. Am J Kidney Dis 1997; 29: 479–489
1
R 1þ D
16. Raisky F, Marchal A, Blum D. Haemolyzed samples: QB
Qf
responsability of short catheters. Ann Biol Clin 1994; 52: 523–527

Received for publication: 16.1.01

Accepted in revised form: 19.7.01 Appendix 2
Urea clearance (UK ) was calculated for the dialysate
side according to the following formula:
Appendices (Qd þ Qf ÞCdUout
UK ¼
CwU
Appendix 1
where Qd is the dialysate flow at the dialyser inlet,
For a given inlet dialysate conductivity (Cdin), the set at 500 mlumin, Qf is the ultrafiltration rate, CdUout
outlet dialysate conductivity (Cdout) depends on the is the urea concentration in the spent dialysate, CwU
patient’s plasma conductivity (Cp) and on ionic is the plasma water urea concentration at the dialyser
dialysance (D) and is calculated by the following inlet. The concentration CwU is calculated as:
equation w2x:
  CwU ¼ CU uð1
0:01  ProtÞ
D D
Cdout ¼ 1
Cdin þ Cp ð3Þ where Prot and CU are respectively the plasma total
Qd þ Qf Qd þ Qf
protein concentration (gudl) and the plasma urea
Consequently, the measurement of two values of concentration (mmolul) measured at the dialyser inlet.
Cdout (Y1, Y2) for two levels of Cdin (X1, X2) allows the
calculation of Cp and D, assuming that the changes in Appendix 3
D and Cp are negligible during the short period
required for the measurement of X1, Y1, X2, and Y2 The MBE is calculated as follows:
(about 6 min). During each measurement of D, the MBE ¼
value X1 of Cdin prescribed for the patient is changed
automatically by the dialysis monitor by about ðQd þ Qf ÞCdUout
ðQBw CwU
QBwout CwUout Þ
2 100
1 msucm over 2 min, defining an X2 value of Cdin ðQd þ Qf ÞCdUout þ ðQBw CwU
QBwout CwUout Þ
(Figure 1). ð8Þ
Cp and D can be calculated by the following
equations: where QBw and QBwout are the water blood flow rates
at the dialyser inlet and outlet, respectively, and where
X1 Y2
X2 Y1
Cp ¼ ð4Þ CwU and CwUout are the plasma urea concentration at
ðX1
X2 Þ
ðY1
Y2 Þ the dialyzer inlet and outlet respectively.
QBwout is calculated as: QBw
Qf and QBw is
  calculated as:
Y1
Y2
D ¼ (Qd þ Qf Þ 1
(5)
X1
X2 QBw ¼ QB ½0:72  Ht þð1
0:01  ProtÞð1
HtÞ ð9Þ

The relationship between the inlet and outlet where QB, Ht and Prot are blood flow rate (calculated
dialysate conductivity is influenced by the recirculation by ultrasound), haematocrit and plasma total protein
phenomenon. The greater the access recirculation, concentration measured at the dialyser inlet.
the closer the outlet dialysate conductivity from the CwUout is calculated as CUoutu(1
0.01 3 Protout)
inlet dialysate conductivity, at each of the two levels where Protout and CUout are the plasma total protein
of inlet dialysate conductivity during the measure- concentration (gudl) and the plasma urea concentration
ment of ionic dialysance. Thus Y1
Y2uX1
X2 tends (mmolul) measured at the dialyser outlet, respectively.
towards 1 when increasing access recirculation and CwU is calculated in the same way.
ionic dialysance tends toward zero.
The measured value of ionic dialysance (D) is
related to the value of ionic dialysance of the dialyser Appendix 4
(D0) by the following formula taking into account the If Cp is not constant, equation (3) should be written
access recirculation (effective ionic dialysance) w2x: with Cp1 and Cp2. Using Cp2 s Cp1qe, equation (5)
1
R becomes:
D ¼ D0   (6)  
D0
Qf (Qd þ Qf Þ Y1
Y2
1
R 1
D¼ 1
(10)
QB
Qf 1
e uðX2
X1 Þ X1
X2
Ionic dialysance and urea clearance 111

The ratio of the real value of D to the calculated of e could be written as:
value is:
Dreal 1 DðLuminÞ  ðCp1ðmSucmÞ
X2ðmSucmÞ Þ  2ðminÞ
s es
D 1
e uðX2
X1 Þ VðLÞ
If X2)X1, Cp2 is higher than Cp1 and e is positive, or For D s 200 mlumin, Cp1
X2 s 1 mSucm (the max-
X2-X1, Cp2 is lower than Cp1 and e is negative. Thus imum of what is commonly observed with X1
X2
eu(X2
X1) is always positive and Dreal is lower than the equal to "1 mSucm according to Diascan operat-
calculated value of D. The ionic dialysance determined ing conditions), V s 40 l, e is equal to 0.01 mSucm and
by Diascan1 is over-estimated. the over-estimation is thus under 1%.
Because the osmotic distribution volume of sodium
is the total body water volume (V ), an approximation