JNEPHROL 2013; 26 ( Suppl 21): S120-S139
BEST PRACTICE
DOI: 10.5301/JN.2013.11637
Functional assessment of the peritoneal
membrane
Vincenzo La Milia1
Reviewers: Giovambattista Virga2, Giampaolo Amici3,
Silvio Bertoli4, Giovanni Cancarini5
Table of Contents
1. Introduction
1. Introduction
2. When should the PET be performed?
3. Which PET to use?
4. Which PET parameters to assess?
5.How should patients be classified according to the results
of the 3.86%-PET?
6. How to use the results of the PET to prescribe and optimize PD therapy
7. Other tests
8. Test standardization
9. Test protocols
Key words: Pet, Ultrafiltration failure, Peritoneal trans-
port, Classes of peritoneal transport, Sodium sieving,
mini-pet
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Nephrology and Dialysis Unit, A. Manzoni Hospital,
Lecco - Italy
2
Nephrology and Dialysis Unit, Camposampiero Hospital,
Camposampiero, Padua - Italy
3
Department of Nephrology and Dialysis, S. Maria dei
Battuti Regional Hospital, Treviso - Italy
4
Nephrology and Dialysis Unit, IRCCS Multimedica, Sesto
S. Giovanni, Milano - Italy
5
Nephrology and Dialysis Unit, A.O. Spedali Civili di
Brescia, Brescia - Italy
1
The functional assessment of the peritoneal membrane is
of paramount importance for the performance of peritoneal dialysis (PD) as: (i) it provides useful information on
the correct prescription of the peritoneal dialysis regimen;
and (ii) it makes it possible to monitor changes in peritoneal membrane function over time.
The functional assessment of the peritoneal membrane
involves the performance of a number of tests. The most
important and best-known of these tests is the peritoneal equilibration test (PET), developed and described
by Twardowski et al in 1987 (1). A number of other, more
complex tests (2, 3) have been derived from the PET originally developed by Twardowski (classic PET), while others
are based on the fundamental principles of the PET. The
PET is based on the principle that the concentration of the
solutes present in the blood, but not initially in the dialysis
fluid, will tend to equilibrate with that of the dialysate, after a varying period of time. This equilibration rate can be
used to classify patients into transporter categories, with
clear dialysis prescription indications.
2. When should the PET be performed?
A peritoneal membrane functional assessment test should
be performed at the start of dialysis treatment (after 4-8
© 2013 Società Italiana di Nefrologia - ISSN 1121-8428
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weeks and within 3 months from the start of PD and repeated at least once a year and whenever a clinical issue
(inadequate depuration or ultrafiltration [UF]) arises whose
interpretation may benefit from the performance of the
test. The test should not be performed during episodes
of peritonitis (it increases the small solute transport rate
and reduces UF), and it is recommended to wait at least
1 month after the complete resolution of the peritonitis
before performing it (4-7).
For the same reason, a similar interval should be considered after abdominal surgery (including laparoscopic
procedures) or inflammations or infections involving the
abdominal organs.
The functional characteristics of the peritoneal membrane
tend to stabilize shortly after the start of PD (8, 9). The first
functional assessment of the peritoneal membrane should
be conducted after about 4-8 weeks and no more than 3
months after the start of PD (10), to avoid treating the patient
with an inadequate regimen for a prolonged period.
The matter of repeating the PET at different time points in
the same patient remains controversial. Some guidelines
(10), given the substantial stability of peritoneal transport,
for the majority of patients, recommend not repeating the
PET at pre-set intervals, rather to repeat the test when
clinical problems arise (sodium-water retention, inadequate dialysis etc.). Other guidelines (11) suggest performing the PET at least once a year and whenever clinically indicated. In some cases, repeating the PET at least
once a year presented the advantage of anticipating the
diagnosis of clinical problems.
To conclude:
1. the first PET should be performed 4-8 weeks and no more
than 3 months after starting PD;
2. the PET should be performed at least once a year and
whenever clinically indicated;
3. the PET should not be performed during an episode of
peritonitis and should be performed at least 1 month after its resolution. The PET must not be performed for 1
month after surgery, including laparoscopic procedures,
or infections/inflammations of the abdominal organs.
3. Which PET to use?
The peritoneal function test of choice should be that performed using 3.86% glucose solution over 4 hours (3.86%PET). This test must include the evaluation of sodium sieving in the dialysate 60 minutes after the start of the test (ΔNa
at 60 minutes).
Although the clinical evidence available is inadequate to
allow us to claim that one test is superior to another, the
3.86%-PET provides more information than the classic PET
performed using a 2.27% glucose solution.
Significant emphasis is placed on the hydration status of
patients in PD and on peritoneal UF capacity. This is due
both to the demonstration that an increase in the already
adequate total purification (Kt/V = 1.9, creatinine clearance
[CrCl] = 60 L) of 20%-30% is not associated with a corresponding result in terms of better survival (12), and to the
increasingly consistent evidence that the removal of fluids
(and sodium) is very important for patient survival (13-16).
This has been shown both in patients who, on account of
their peritoneal membrane transport characteristics, have
low peritoneal UF, such as fast (high) transporters (13) or
reduced total water excretion (14) and, above all, in anuric
patients (15, 16). It is probable that this high mortality can
be attributed to greater water and sodium retention in fast
(high) transporters due to the rapid dissipation of the osmotic gradient that occurs in these patients, with a consequent
loss in UF capacity by the peritoneal membrane.
To better study the peritoneal membrane’s UF capacity, it
has been suggested that the classic PET using a 2.27% solution be replaced with the PET using a 3.86% solution (11).
Indeed, with the 3.86%-PET, the peritoneal membrane’s UF
capacity is easier to quantify, because of the higher quantity of UF that can be obtained: This also allows a better
estimate of the number of patients with ultrafiltration failure
(UFF).
A patient is defined as having UFF when on the 2.27%-PET,
he/she has a UF <100 mL or on the 3.86%-PET a UF <400
mL, with a test bag volume of 2 L (11). It therefore goes
without saying that the 2.27%-PET is more likely to yield
incorrect UF evaluations. Indeed, the coefficient of variation of UF has been quantified at approximately 50% for the
2.27%-PET (17) and <10% for the 3.86%-PET (18). In addition, 3.86%-PET also makes it possible to study sodium
sieving during the first part of the test, by means of the dialysate to plasma (D/P) sodium concentration at 60 minutes, or
better with the reduction in sodium concentration (∆Na) in the
dialysate at 60 minutes (11). According to the 3-pore model
(19), ∆Na at 60 minutes is an indirect expression of free water
transport by the peritoneal membrane. Adequate free water
transport indicates good peritoneal membrane function in
terms of UF.
For all these reasons, it is preferable to use the 3.86%-PET.
In any case, there is a hypothetical possibility that the use of
a 3.86% glucose solution for PET can make it impossible to
compare data with previous results obtained using the classic 2.27%-PET. However, all of those experiences comparing 3.86%-PET with 1.36%-PET (20, 21) and with 2.27%PET (22, 23) have shown that there are no differences in
© 2013 Società Italiana di Nefrologia - ISSN 1121-8428
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Best Practice on: Functional assessment of the peritoneal membrane
patient classification with the different types of PET solution,
using D/PCreat.
To conclude, it is preferable to perform 3.86%-PET, rather
than 2.27%-PET, due to the greater accuracy in determining peritoneal UF and the possibility of evaluating free water transport by the peritoneal membrane, albeit indirectly.
Lastly, due to its lower coefficient of variation, the 3.86%PET is a more reproducible test for the study of peritoneal
UF in prospective studies.
4. Which PET parameters to assess?
The most useful parameters for the functional assessment
of the peritoneal membrane that can be obtained with the
3.86%-PET are the dialysate (D) to plasma (P) creatinine
concentration ratio (D/PCreat) at the end of the test (240th
minute), the UF obtained at the end of the test and sodium
sieving expressed by the dip in the concentration of sodium
in the dialysate 60 minutes from the start of the test (∆Na).
Both the speed of small solute transport and the peritoneal
membrane’s ability to generate UF are fundamental for the
evaluation of peritoneal membrane function; however, individual variability is high, and it is therefore of paramount
importance to determine these characteristics in the individual patient by performing the test for evaluating peritoneal
membrane function.
The PET is a semiquantitative evaluation of the peritoneal
membrane’s transport capacity determined by means of the
rate at which the concentrations of a solute reach equilibrium in the plasma and dialysate. The D/P of a given solute,
after a given time, indicates the degree and rate of equilibration between concentrations; the higher the D/P for a solute,
the faster equilibrium between dialysate and plasma will be
reached and therefore the higher the peritoneal permeability
for that solute. The D/P can be determined for any solute
transported from the plasma to the PD solution. The D/P
has been evaluated for creatinine, urea, some electrolytes,
phosphorus and proteins. As glucose is present in high concentrations in the dialysate (up to 3,860 mg/dL) and is then
absorbed by plasma through the peritoneal membrane and
rapidly metabolized, it does not make sense to use the D/P
for glucose (plasma glucose concentrations vary little during
PET); instead it is possible to use the ratio between the glucose concentration in the dialysate after a given time (t) and
the concentration of glucose present in the solution at the
start of the test (D/D0). D/D0 is the glucose absorption rate.
The original PET devised by Twardowski (1) is a test lasting 4 hours, performed using a 2.27% glucose solution, that
evaluates the D/P of certain small solutes, particularly creatinine (D/PCreat), and the ratio between glucose concentraS122
tions (D/D0). By analyzing D/PCreat and D/D0 during the PET,
we can plot the peritoneal membrane’s permeability (Fig. 1)
and on the basis of the D/PCreat value (D/D0 is less commonly
used) at the end of the PET, patients can be classified into 4
categories: high (H) transporters, average-high (H-A) transporters, low-average (L-A) transporters and low (L) transporters. The 4 transporter classes are obtained by adding/
subtracting standard deviation (SD) to/from the mean value
of D/PCreat and D/D0. In practice, patients above mean D/
PCreat plus 1 SD are classified as H; patients with values
for these parameters between the mean and mean plus 1
SD are classified as H-A, patients with values between the
mean and mean minus 1 SD are classified as L-A and lastly,
patients with values lower than mean minus 1 SD are classified as L. For D/D0, the situation is specular (the higher the
value, the lower the transport class) (Fig. 1).
The same classification into transport classes can be obtained using the same method with the 3.86%-PET. However, the parameter that is almost always used to classify
patients is D/PCreat. The D/P of urea (D/PUrea) is used less frequently because, as urea has a higher diffusion rate than
creatinine, there is less interindividual variability in this parameter and less capacity for classifying patients according
to their small solute peritoneal transport rate characteristics.
The ratio between the concentration of glucose in the dialysate between the end and start of the test (D/D0) is less
commonly used than D/PCreat for several reasons: (i) when
the concentration of glucose is very high (>800 mg/dL), a
correct measurement is only possible with appropriate dilutions; (ii) D/PCreat and D/D0 do not always agree with regard
to patient classification; (iii) unlike D/PCreat, D/D0 cannot be
used to compare data when the PET is performed using solutions with a different glucose concentration.
As mentioned previously, sodium sieving is an expression
of free water transport during the first part of the exchange
with hypertonic solution. Sodium sieving is usually expressed with D/PNa at 60 minutes or as a difference in the
concentration of sodium in the dialysate at 60 minutes and
the concentration of sodium in the liquid in the fresh bag
(11). D/PNa at 60 minutes is used to correct this value for
sodium diffusion; in practice, if blood sodium is higher, there
should be a greater diffusion of Na from the plasma to the
dialysate.
In any case, it would be preferable to use the absolute variation of sodium concentration in the dialysate at 60 minutes
over the concentration of sodium in the liquid in the fresh
bag used for the PET (∆Na), for a number of reasons: (i) it is
not necessary to assay the concentration of sodium in both
the dialysate and the plasma (it also means not having to
correct for the concentration in the plasmatic water); (ii) peri-
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case of water-saline overload for the diagnosis of UFF. In
short, once we have ruled out mechanical issues related to
the catheter, which can be easily identified in a plain film
X-ray of the abdomen, the PET must be performed with a
3.86% glucose solution. Peritoneal UF at the end of the test
of lower than 400 mL is consistent with a diagnosis of UFF.
To summarize, according to UF at the end of the 3.86%PET, patients are classified as follows:
1. patients with normal peritoneal UF, if UF ≥400 mL;
2. patients with UFF, if UF <400 mL.
According to D/PCreat values in fast (high),
high-average and low-average (average) and
slow (low) transporters
Fig. 1 - Calculating peritoneal membrane’s permeability
based on glucose absorption rate as ratio of dialysis glucose
after a period of time, to dialysis glucose at start of test (D/D0)
and dialysate to plasma ratio (D/P) for creatinine.
toneal diffusion of sodium in the first 60 minutes of the PET
can be considered negligible (24); (iii) the ∆Na value is more
intuitive and more straightforward (for example, a ∆Na value
of 10 mmol/L indicates that the concentration of sodium in
the dialysate at 60 minutes has dropped by 10 mmol/L in
relation to the concentration of Na present in the liquid in the
bag at the start of the PET. This value, for concentrations of
Na in the plasmatic water of 145 mmol/L, corresponds to a
D/PNa value at 60 minutes of 0.84, which is far more difficult
to interpret than a ∆Na value of 10 mmol/L).
To conclude, the most useful parameters for patient classification obtained with the 3.86%-PET are
1. D/PCreat at the end of the PET;
2. total UF at the end of the PET;
3. ∆Na at 60 minutes.
5. How should patients be classified according to the results of the 3.86%-PET?
According to UF in patients with normal UF
(≥400 mL) or with UFF (<400 mL)
The use of the 3.86%-PET is required for the diagnosis of
UFF. The guidelines issued by the International Society for
Peritoneal Dialysis (11) accurately describe how to act in the
Patients can be classified with regard to transport status according to their D/PCreat values. The term fast transporters is
now preferred over high transporters, and slow transporters over low transporters. The PET is based on the different
speeds of small solute transport and the term high transporter may deceptively suggest that solute removal is always
high; whereas, in actual fact, when there are long pauses
due to the rapid dissipation of the osmotic gradient in these
patients, there is a low peritoneal drainage volume and a
potential lower removal of solutes than the low transporters,
as it coincides with the product of D/P x drain volume (25).
The classic breakdown of patients into 4 transporter classes
is not very useful from a clinical point of view, as averagefast (average-high) transporters have the same indications
and the same prognosis as average-slow (average-low)
transporters (26). It is therefore preferable, for simplicity, to
classify patients into 3 classes of transporter:
1. fast (high) transporters;
2. average transporters;
3. slow (low) transporters.
PET-based patient classification
The data obtained from the PET should be interpreted and
applied clinically. For many years, PET data referred to
that published originally by Twardowski (27). It is important to remember that in that study the number of tests
and patients studied was very small (103 PETs performed
in 86 patients) and the PD treatment time varied greatly
(0.1-84 months). For these reasons, it is preferable not
to use Twardowski’s original data to classify patients, although they remain very useful for making comparisons
between different populations.
It would therefore be preferable to classify patients according to the results of the PETs performed in the same center
© 2013 Società Italiana di Nefrologia - ISSN 1121-8428
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Best Practice on: Functional assessment of the peritoneal membrane
– i.e., to use the mean and SD of one’s own patients to perform the classification. This can, of course, be problematic
when the center treats very few patients with PD; in which
case, it would be preferable to compare the data with that
available in the literature. A number of studies have attempted to establish reference values for the parameters obtained
with the PET using a 3.86% glucose solution (28), whereas
others (29) use national registries with large samples.
Table I (32) compares the original results obtained by
Twardowski (1, 27), those obtained with a large North American population (30), a Central American population (31), a
European population (17) and the Australian-New Zealand
Registry (29), all obtained with a PET using a 2.27% glucose
solution, and the results obtained from a Dutch population
(28) and an Italian population (18) both obtained from a PET
using a 3.86% glucose solution.
As you can see, despite the different populations, the D/PCreat
values that should arouse our interest are those around 0.80
or higher and those around 0.60 or lower. Of course, it is
always better to consider the peritoneal permeability values
(expressed as D/PCreat) as a continuous entity rather than belonging to completely separate classes as when patients are
classified according to transport status; however, the above
limits are useful for identifying the categories of patient at
risk. Indeed, patients with D/PCreat values close to or higher
than 0.80 are exposed to all of the risks of fast (high) transporters (poor UF, prone to water-sodium retention). Whereas
patients whose values are close to or lower than 0.60 may
risk underdialysis if the prescription is inappropriate. Table
I may represent a useful tool for making comparisons and
classifying patients when numbers are limited.
To conclude, D/PCreat can be used to classify patients as:
1. fast (high) transporters if D/PCreat >0.80;
2. slow (low) transporters if D/PCreat <0.60;
3. average transporters for D/PCreat values between 0.60 and
0.80.
According to ∆Na values at 60 minutes in patients
with preserved sodium sieving (∆Na ≥5 mmol/L)
and in patients with reduced sodium sieving
(∆Na <5 mmol/L)
∆Na is an expression, albeit merely qualitative, of free water
transport across the peritoneal membrane. A reduction in,
or loss of, Na sieving and therefore reduced, zero or even
negative ∆Na, is symptomatic of a reduction in, or loss of,
free water transport capacity (32). Reduced or absent free
water transport may contribute to reduced UF capacity or
UF failure (UFF), as it represents approximately 50% of peritoneal UF in the first part of an exchange with a hypertonic
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solution. In addition, ∆Na alterations can be associated with
severe peritoneal membrane damage (18). A ∆Na value ≥5
mmol/L can indicate patients with good free water transport
in relation to those in whom it is reduced (18).
To conclude, ∆Na at 60 minutes for a 3.86%-PET can be
used to classify patients as:
1. patients with preserved free water transport if ∆Na ≥5
mmol/L;
2. patients with reduced free water transport if ∆Na <5
mmol/L (18).
Table II shows the main characteristics of the 3 transporter
classes.
6. How to use the results of the PET
to prescribe and optimize PD therapy
Due to the high interindividual variability of peritoneal membrane transport characteristics, test results must be used
for the correct prescription and optimization of the PD regimen best suited to the individual patient.
1. For rapid (high) transporters, automated peritoneal dialysis (APD) is indicated, using icodextrin for the long dwell, if
necessary.
Since its appearance as part of a clinical scenario, the PET
has been used to prescribe the PD regimen best suited to
the individual patient (33). Initially, the aim was to prescribe
the dialysis regimen able to obtain the greatest possible
purification (in terms of Kt/V and/or creatinine clearance).
Although it would seem logical for fast (high) transporters
to obtain a better purification capacity, this high peritoneal
transport of small solutes was increasingly associated with
higher mortality and morbidity (34). The water-sodium retention experienced by these patients, particularly if on continuous ambulatory peritoneal dialysis (CAPD), due to the
rapid dissipation of the intraperitoneal osmotic gradient, is
thought to be one of the causes of this higher mortality.
The PET, with its simplicity, has made it possible to treat fast
(high) transporters in the most appropriate manner. Indeed,
knowledge of the rapid absorption of the glucose present in
PD solutions has led to the prescription of very long dwells
in these patients and the prescription of short dwells which
are naturally most compatible with APD (33), even with daytime empty mode.
More recently, the commercial availability of icodextrin (3536) and its capacity to generate adequate UF even in fast
(high) transporters has proven useful for using the long daytime dwell, and also obtaining a considerable increase in
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TABLE I
D/PCreat AND TRANSPORTER CLASSES IN VARIOUS PERITONEAL DIALYSIS POPULATIONS
Fast
Average-fast
Mean ± SD
Average-slow
Slow
No. patients
Twardowski
(1, 27)
TARGET (USA)
(30)
Mexico
(31)
UK
(17)
ANZA-DATA
(29)
NL
(28)
Italy
(18)
>0.80
>0.79
>0.80
>0.78
>0.81
>0.82
>0.80
0.65-0.80
0.67-0.79
0.68-0-80
0.65-0.78
0.69-0.81
0.72-0.82
0.71-0.80
0.65 ± 0.15
0.67 ± 0.12
0.68 ± 0.12
0.65 ± 0.13
0.69 ± 0.12
0.50-0.61
0.55-0.66
0.56-0.67
0.52-0.64
0.57-0.68
0.62-0.71
0.62-0.70
<0.50
<0.55
<0.56
<0.52
<0.57
<0.62
<0.62
86
1,229
86
574
3,702
81
95
0.72 ± 0.10 0.71 ± 0.09
D/PCreat = dialysate to plasma (D/P) creatinine concentration ratio.
D/PCreat = ratio between the creatinine concentration in the dialysate and plasma; D/D0 = ratio between the concentration of glucose in the dialysate, at time t, and in the fresh solution; RV = residual peritoneal volume; UF = peritoneal ultrafiltration; UFF = ultrafiltration failure; FWT = free water transport; OCG = osmotic conductance to glucose of the peritoneal membrane; ∆Na = difference in the concentration of sodium in the fresh solution and in the dialysate after 60 minutes; PAR = peritoneal absorption rate.
purification. The characteristics of peritoneal transport, revealed on the PET, therefore suggest that patients with fast
(high) transport status (at the start of PD or developed later)
should be treated by APD associated (in the long daytime
dwell) with icodextrin, provided there are no contraindications (intolerance, allergy, hernia etc.).
One recent meta-analysis (13) of a number of prospective
observational studies confirmed a worse prognosis (particularly in terms of survival) for high transporters than for
patients with lower or slower transport characteristics. The
most interesting aspect of this study was the confirmation
that treatment with APD, in a subgroup of patients, made
the peritoneal transport characteristic noninfluential in terms
of patient survival. This observation was recently confirmed
(37), highlighting that survival for fast (high) transporters is
better when treated with APD than with CAPD.
In addition, some authors (38) have reported that with the
advent of APD (and icodextrin) the mortality of fast (high)
transporters, which in the past was much higher than for
other transporter types, has become similar to that of patients belonging to other transporter categories.
2. For slow (low) transporters, manual CAPD is indicated,
with high single exchange volumes (high-dose CAPD). If
such volumes are not tolerated or in the event of dialysis
and/or UF inadequacy, the switch to hemodialysis should
be considered.
As observed during early studies on PET (33), slow (low)
transporters have lower purification capacities than other
transporter categories and may be inadequately dialyzed
when short exchanges, such as those in APD, are used.
Furthermore, also in CAPD, particularly when weight and
body surface area are high, these patients may not be
adequately dialyzed using standard volumes of 2,000 mL
per single exchange; in this case, the indication is to use
higher volumes. Some recent studies have observed that
slow (low) transporters obtain better survival with CAPD
than with APD (37).
3. A considerable reduction in Na sieving at 60 minutes (∆Na
<5 mmol/L) suggests a reduction in peritoneal free water
transport, and often, an increase in osmolarity (concentration of glucose) of the solution does not correspond to an
increase in UF. This can be confirmed by quantifying free
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TABLE II
MAIN CHARACTERISTICS OF THE THREE PERITONEAL TRANSPORT CLASSES
Type of transport
Fast (high)
Average
Membrane characteristics
Recommendations
Fast small solute equilibration rate (D/PCreat
>0.80)
Good purification capacity with short dwells
Rapid dissipation of the osmotic gradient
due to glucose
In some cases, UFF (UF < 400 mL) after 4
hours of 3.86%-PET. In some cases ∆Na <5
mmol/L
APD with short dwells (1-2 hours)
Avoid long dwells with solutions
containing glucose. Use icodextrin
for longer dwells
Halfway between the fast and slow classes
of transporters
Slow small solute equilibration rate (D/PCreat
<0.60)
Slow (low)
Long-term maintenance of the osmotic gradient for glucose. Good UF∆Na ≥5 mmol/L is
common (often >10 mmol/L)
Method (CAPD and CCPD) and solutions chosen according to the patient’s requirements and overall purification data
CAPD (APD only in small built patients). High volumes (>2,000 mL) if
purification is inadequate. Use less
hypertonic glucose solutionsIcodextrin not essential
∆Na = difference in the concentration of sodium in the fresh solution and in the dialysate after 60 minutes; APD = automated
peritoneal dialysis; CAPD = continuous ambulatory peritoneal dialysis; CCPD = continuous cycling peritoneal dialysis; D/PCreat =
dialysate to plasma (D/P) creatinine concentration ratio; PET = peritoneal equilibration test; UF = ultrafiltration; UFF = ultrafiltration failure.
water transport. In this case, icodextrin should be used to
increase UF. The PET should be repeated at short intervals
(3 months) and in the event of a further reduction in UF and/
or ∆Na, a switch to hemodialysis should be considered.
A significant reduction in Na sieving (∆Na <5 mmol/L) at
60 minutes suggests a reduction in free water transport
and, therefore a reduction in aquaporin-1 channel function (18). Free water transport depends on the osmotic
gradient and therefore on the concentration of glucose.
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Consequently, when it is reduced or absent, the increase
in the concentration of glucose in the dialysis solutions
will not cause an increase in UF. The reduction in peritoneal free water transport can be quantified, using appropriate tests, confirming that in such situations, increasing the concentration of glucose is futile. In such cases,
icodextrin can be useful for increasing UF.
In some patients, it may be useful to repeat the PET at short
intervals and in the event of a further loss of peritoneal UF
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capacity and/or a further reduction in ∆Na, the possibility of
switching to hemodialysis should be considered.
4. The volume of dialysate drained at different time points
during the test can be particularly useful when prescribing
the dialysis mode, in order to obtain optimum UF. If the
test is performed with a long nighttime dwell with a 1.36%
glucose solution and the drainage volume obtained is
lower than that infused, it is likely that the patient is not
suited to long dwells with weak glucose solutions.
It goes without saying that the above indications are categorical when the residual renal function, which buffers
the effects of incorrect PD prescriptions, is reduced or
eliminated altogether.
Test results are useful for evaluating changes in peritoneal membrane function over time and for evaluating any
functional “exhaustion” of the peritoneal membrane. In
particular, special attention should be paid to those patients in whom the small solute transport rate increases,
and who thus become fast (high) transporters, and in
whom peritoneal UF capacity reduces to failure, during
follow-up.
The loss of free water transport and of the osmotic conductance to glucose should suggest severe alterations in
peritoneal membrane function and may indicate a need to
switch the patient to hemodialysis.
The peritoneal membrane’s functional characteristics
(small solute transport and UF) may vary with an increase
in dialytic age, and these changes may require adjustments to the dialysis regime or a switch to hemodialysis
(38-41).
Typically, some patients experience an increase in the
small solute transport rate and a reduction in UF capacity (17) which, on occasions, calls for the prescription of
icodextrin and/or a switch to automated PD. The failure of
these measures may constitute an indication for a switch
to hemodialysis treatment.
Paradoxically, the success of these measures could favor the onset of other clinical problems; indeed, in the
past, when APD and icodextrin were not available, patients with UF capacity deficits were usually switched
to hemodialysis; use of these new treatment options
allows a considerable increase in the period for which
these patients are treated with PD, concealing the clinical significance of UFF, which sometimes represents the
first sign of severe future complications. It is therefore
important to be aware that patients with a high dialytic
age on PD must be closely monitored in terms of both
clinical presentations and peritoneal function, for conditions such as peritoneal sclerosis and encapsulating
peritoneal sclerosis, the frequency of which is directly
related to dialytic age. This does not mean that these
patients need to be switched to hemodialysis, but that
they should be closely monitored with regular peritoneal
permeability tests and instrumental procedures (such
as abdominal CT scans), but also and above all, in frequent, regular clinical follow-ups, special attention must
be dedicated to semeiotic aspects and questions concerning kinesthesis.
7. Other tests
Other tests based on the same principles as the PET include
the mini-PET (for quantifying peritoneal free water transport), the double mini-PET (for quantifying the osmotic conductance to glucose), the 3.86%-PET combined with the
mini-PET (for quantifying the parameters of both tests) and
the Uni-PET (3.86%-PET combined with the double miniPET for quantifying the parameters of both tests).
The mini-PET
The PET has made an enormous contribution to our knowledge of peritoneal membrane pathophysiology, with the
advantage of being very simple to conduct and interpret.
However, the results of the PET are cannot be used to analyze all of the pathophysiological mechanisms involved in
peritoneal membrane function. Even the changes made to
the classic test, such as the use of a 3.86% solution, only allow a better assessment of peritoneal UF; they do not completely explain all of its characteristics.
Analysis of the D/PNa at 60 minutes was the first, simple
attempt to provide a rough estimate of the entity of free
water production. The need to measure UF in its various
components, and to understand its genesis, led to the
development of other tests that are easy to perform in
normal clinical settings and straightforward in terms of interpretation.
The advent of the mini-PET (24) made it possible to quantify
free water transport (UF across the ultrasmall transcellular
pores or aquaporin-1 channels), separately from the other
components of peritoneal UF. With the mini-PET, it is also
possible to evaluate its variation over time, by repeating the
test periodically, over just 1 hour, using a 3.86% solution.
The reduction or loss of free water transport would appear
to act as an indicator of severe peritoneal membrane damage or even a predictor of severe complications such as encapsulating peritoneal sclerosis (42). The little data present
in literature suggests that a patient has a free water transport deficit when it is lower than 100 mL (43).
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The double mini-PET
The double mini-PET (43) consists of performing 2 consecutive 1-hour mini-PETs, the first with a 1.36% solution and
the second with a 3.86% solution. Based on complex presuppositions, the double mini-PET is performed with very
simple methods and interpreted using simple mathematical
calculations. The double mini-PET, the evolution of the miniPET, also makes it possible to measure the osmotic conductance to glucose – i.e., the capacity to generate UF with
the osmotic stimulus of glucose that is more or less hypertonic. In actual fact, it indicates the amount of UF that can be
obtained by increasing the concentration of glucose in the
PD solution. A significant reduction in osmotic conductance
(<1.5 μl/min per mm Hg) is the expression of a reduction in
the capacity of the small and ultrasmall pores to respond
to the osmotic stimulus of glucose (43). Indeed, osmotic
conductance measures the capacity to generate UF by both
pores, and therefore a reduction indicates a decrease in the
peritoneum’s overall capacity to generate UF. Once again in
this case, icodextrin is required to increase UF.
In addition, for example, the 3.86%-PET does not provide
any indication as to whether UFF is due to the peritoneal
membrane’s incapacity to generate UF due to reduced or
absent osmotic conductance to glucose, or whether the
reduced UF is to be attributed to the rapid reabsorption of
a quantity of ultrafiltrated fluid in the first part of the peritoneal exchange by means of the rapid dissipation of the
osmotic gradient due to the reabsorption of glucose. As Figure 2 clearly shows, in relation to a normal curve (A) for the
increase in intraperitoneal volume during an exchange with
3.86% glucose solution, the behavior of both curves B and
C is compatible with a diagnosis of UFF (UF at 4 hours <400
mL). However, in the case of curve B, a good quantity of
UF forms during the first part of the peritoneal exchange,
and subsequently this UF is eliminated due to reabsorption
of the liquid by the peritoneal membrane: In this case, the
prescription of APD is correct and can be boosted by prescribing icodextrin for the long dwell. With curve C, the peritoneal membrane presents reduced or absent osmotic conductance to glucose, and the glucose is unable to generate
adequate UF in any part of the exchange: In this case, APD
would be destined to fail, as would increasing the osmolarity
of the glucose solution. The only option is to attempt using
icodextrin (both for patients on APD and those on CAPD),
with the precaution of switching the patient to hemodialysis
if icodextrin is unable to obtain adequate UF (it goes without
saying that all of this only applies if the patient has no residual renal function) . UF measured by mini-PET or double miniPET or Uni-PET (see below) with a 3.86% glucose solution,
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Fig. 2 - Changes in intraperitoneal volume during an exchange with 3.86% glucose solution.
after 1 hour represents the “early” quantity of peritoneal UF
and identifies those patients who could benefit from short
peritoneal dwells.
The dwell times of some of these tests are very similar to
those used in APD. These tests make it therefore possible to
evaluate how small solute transport and liquid transport take
place in the peritoneum, using both the solution with lowest
osmolarity (1.36% glucose solution) and that with the highest osmolarity (3.86% glucose solution), in the peritoneal
dwell times typical of APD.
In cases of UFF, the double mini-PET provides additional indications for the prescription of the most suitable PD mode
and a switch to hemodialysis. The analysis of the few patients with UFF (43) using the double mini-PET showed that
the reduction in the osmotic conductance of these patients
appears to involve both the small pores and the ultrasmall
pores or aquaporin-1 channels – i.e., the damage involves
both pore systems needed to produce peritoneal UF. This
test could, therefore, constitute an instrument for the early
prediction of peritoneal membrane damage a long before
UFF develops, or alternatively, it could be of help in the presence of a suspected evolution toward rare but severe complications such as encapsulating peritoneal sclerosis.
The 3.86%-PET combined with the mini-PET
The mini-PET and double mini-PET provide useful information on some peritoneal membrane functions but do not
provide values for the D/P of the small solutes (in particular,
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D/PCreat) comparable to those of a 4-hour PET, such as the
3.86%-PET (24, 44) used to classify patients into transporter
classes.
To obtain information on both the 3.86%-PET and the miniPET, it was suggested to combine both PETs using a temporary drain, after a 1-hour dwell, subsequent assessment
of the drain volume (by weighing), collection of an aliquot
of drained liquid, reinfusion of the effluent, a further 3-hour
peritoneal dwell and a final drain (45). However, it is preferable to collect the temporary drain aliquot after it has been
reinfused (leaving a small amount at the end of reinfusion) to
reduce the risks of contamination-induced peritonitis. This
combined PET provides D/PCreat values similar to those obtained with a 3.86%-PET without temporary drain, and free
water transport can be quantified as with the mini-PET.
The Uni-PET
Whereas the previous PET (combined 3.86%-PET) is performed after a 1-hour 1.36%-PET, here the 3.86%-PET is
combined with the double mini-PET. This Uni-PET (46) allows the quantification of all of the parameters of all the previous tests. The Unit-PET, which lasts 5 hours, is currently
the most complete test for evaluating peritoneal membrane
function.
Other tests based on the PET principle are the dialysis adequacy and transport test (DATT) (47) and the accelerated
peritoneal examination (APEX) test (48). The DATT calculates
the D/PCreat on 24-hour dialysate in CAPD.
The DATT was used in the Adequacy of Peritoneal Dialysis
in Mexico (ADEMEX) (12, 49) study, and various other studies have shown a good correlation between DATT and PET
data; however, this has only been validated in patients on
CAPD, and not in those on APD.
The APEX test (48) summarizes peritoneal permeability to
solutes in a single number, using the glucose D/D0 and urea
D/P curves: In actual fact, it calculates the time at which the
glucose and urea equilibration curves (using the percentages) cross; the shorter the APEX time the higher or faster
the peritoneal permeability, and conversely, the longer the
APEX time, the lower or slower the peritoneal permeability.
The APEX test has a limited use for dialysis purposes, and it
is most commonly used in children (50).
Of all the tests not based on the same principles as the
PET, the most common is the personal dialysis capacity test
(PDC) test (involving the calculation of the peritoneal area
available for exchange, liquid reabsorption and peritoneal
protein clearance). The PDC test lasts 24 hours and is performed in the patient’s home by performing 5 exchanges
with different dwell times (2 short, 2 medium, 1 long) and
different glucose concentrations, for CAPD, or by adding to
a nighttime APD session, 2 daytime exchanges for patients
on APD (51). The test uses the computerized mathematical
model based on the 3-pore model (19) to evaluate the following parameters: (i) surface area over diffusion distance
(A0/ΔX), which represents the actual surface area available
for diffusion and is proportionate to the D/PCreat value of the
PET; (ii) liquid reabsorption from the peritoneal cavity; (iii) the
estimated flow across the large pores (JvL) over peritoneal
albumin clearance.
It has been postulated that the PDC test has superior completeness to the classic PET, and this is probably true (52,
53). However, the PDC test presents a series of drawbacks
such as the risk of inaccuracy (the test is performed by patients in their homes) due to bag overfilling, the flush-beforefill maneuver, the collection by patients of dialysis aliquots
or because of transportation of the bags to the center. In
addition, the PDC test requires the use of a complex computerized mathematical model and does not take into account sodium kinetics, free water transport and the osmotic
conductance to glucose in the same way the new tests do.
Lastly, the PDC test has been validated on fewer patients
than the PET.
Most likely, the true advantage of the PDC test, over tests
based on the PET principle, is that it measures the peritoneal
clearance of protein or albumin, which could constitute an
important morbidity and mortality factor in PD (54).
One last test not based on PET principles is the peritoneal
function test (PFT) (55, 56); this test also requires a computerized mathematical model to process the results and is
based on PT50 – i.e., the time required for a solute to meet
exactly half the equilibration between dialysate and plasma
(D/P = 0.50 or 50%). To perform the test, 24-hour dialysate
(and also urine) must be collected at different dwell times.
The test after computerized processing provides information
on membrane solute transport, total clearance, the fluid balance and nutritional parameters. There are no studies available in the literature performed using this test, other than
those proposed by the author who devised it.
Table III shows the main advantages and disadvantages of
the most commonly used tests, and Figure 3 shows an algorithm to be used according to the results of certain peritoneal function tests.
8. Test standardization
Regardless of the test used, stringent standardization
of test methods is required. The standardization of tests
based on PET principles should involve the following points
as described in the sections that follow: (i) duration of the
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Fig. 3 - An algorithm for the monitoring of peritoneal transport. ∆Na = difference in the concentration of sodium in the
fresh solution and in the dialysate after 60 minutes; APD =
automated peritoneal dialysis; CAPD = continuous ambulatory peritoneal dialysis; FWT = free water transport; HD = hemodialysis; OCG = osmotic conductance to glucose of the
peritoneal membrane; PD = peritoneal dialysis; PET = peritoneal equilibration test; UF = ultrafiltration.
exchange (usually at nighttime) preceding the PET, (ii) icodextrin not being used for the exchange (usually nocturnal)
preceding the PET, (iii) infusion volume = 2,000 mL, (iv) patient position during infusion and drainage, (v) duration of
the infusion and drainage, (vi) time points for blood and dialysate specimen collection, and (vii) laboratory methods.
Duration of the exchange (usually at nighttime)
preceding the PET
If possible, perform an 8-hour exchange with a 1.36% glucose solution. If this is not possible, have the patient arrive
with a peritoneal cavity that has been full for at least 45 minutes. In the original version of the PET, patients were required
to have a nighttime exchange 8-12 hours before the PET (1,
57). This duration was justified by the fact that the classic PET
was devised for patients on CAPD in which the duration of the
nighttime dwell varies within this interval. Subsequently other
PD modes were suggested, such as incremental PD, in which
1-2 exchanges a day are initially performed; daytime ambulatory peritoneal dialysis (DAPD) (58), in which there is no nighttime exchange and the patient’s peritoneal cavity remains
empty during the night; and APD (58), in which the treatment
is performed during the night with the aid of a cycler and in
which the dwells are very short (1-2 hours or less).
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It has been observed that D/PCreat values are higher and D/D0
values are lower when the PET is performed after a period
of 9-13 hours in empty mode (59) than with a PET preceded
by an 8-12 hour nighttime dwell, with a full peritoneal cavity.
Other authors have shown that the D/PCreat and D/D0 values
obtained with a PET preceded by an 8-hour vs. 3-hour dwell
are very similar (60, 61).
To conclude, it is of fundamental importance that just
before the PET, the patient did not have an empty peritoneal cavity for any length of time. It is therefore advisable that when the patient arrives at the center to have
the PET, their peritoneal cavity is full and that the dwell
before the test (in the case of APD) lasts no less than 45
minutes. Other centers prefer for the PET to be preceded
by an 8-12-hour nighttime dwell, even for APD (62).
Having an 8-hour nighttime dwell, possibly with a 1.36%
glucose solution, provides important information in addition
to the PET itself and is required by certain PET data processing programs such as Adequest. Indeed, if the volume
drained is lower than that infused (usually 2,000 mL), after
the nocturnal dwell, this could suggest that it is inappropriate to prescribe very long dwells with solutions that are not
very hypertonic to that particular patient.
To conclude, where possible, have the patient perform one
8-hour exchange with 1.36% glucose solution. If this is
not possible, have the patient arrive with a full peritoneal
cavity and use an exchange duration of no less than 45
minutes.
Do not use icodextrin for the exchange (usually
nocturnal) preceding the PET
In the standardization of the original PET, the authors (1)
did not indicate the type of solution to be used for the
dwell, usually at nighttime, prior to the PET. This problem
emerged in particular with the marketing of icodextrin and
its clinical use in PD (35, 36). Indeed it has been shown
that D/PCreat values are higher and D/D0 values are lower
when the dwell prior to the PET (nighttime) is performed
using icodextrin than with a 1.36% or 2.27% glucose solution – i.e., there is an increase in the peritoneal membrane’s permeability to small solutes (63). In that study
by Lilaj et al, the peritoneal UF values during PET did not
appear to be influenced by the type of solution present in
the peritoneal cavity in the exchange prior to the PET. This
increase in peritoneal membrane permeability also persists even when 2 consecutive flushes are performed using 2.27% glucose solution before the PET, to remove the
influence of the residual volume of icodextrin when performing the test as such (64). Conversely, D/PCreat and D/
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TABLE III - ADVANTAGES AND DISADVANTAGES OF THE MOST COMMON PERITONEAL FUNCTION TESTS
Test
Advantages
Disadvantages
D/PCreat and D/D0: patient categorization.
Does not evaluate:1. Na sieving 2.
FWT3. OCG
D/PCreat and D/D0: patient categorization Diagnosis of UFF. Measures
Na sieving (∆Na).
FWT not quantifiable
OCG not evaluable
Mini-PET (3.86%)
Measures Na sieving (∆Na).
Measures FWT.
Short duration (1 hour).
D/PCreat and D/D0 at 60 minutes not
standardized. UF not evaluable.
OCG not evaluable.
Double mini-PET (1.36%-3.86%)
Measures Na sieving (∆Na).
Measures FWT. Measures OCG.
Short duration (2 hours).
D/PCreat and D/D0 at 60 minutes not
standardized. UF not evaluable.
Combined PET (3.86%) with
temporary drain
D/PCreat and D/D0: patient categorization. Measures Na sieving (∆Na).
Measures FWT.
OCG not evaluable
Uni-PET (3.86%-PET combined with
double mini-PET) with temporary
drain
D/PCreat and D/D0: patient categorization. Measures Na sieving (∆Na).
Measures FWT Measures OCG.
Lasts 5 hours
PDC® test
Measures effective peritoneal surface area with patient categorization. Measures PAR. Measures
peritoneal protein clearance.
Na sieving not evaluable FWT not
evaluable. OCG not evaluable.
Special software required for interpretation.
Classic PET (2.27%)
Modified PET (3.86%)
D/PCreat = ratio between the creatinine concentration in the dialysate and plasma; D/D0 = ratio between the concentration of
glucose in the dialysate, at time t, and in the fresh solution; UF = peritoneal ultrafiltration; UFF = ultrafiltration failure; FWT = free
water transport; OCG = osmotic conductance to glucose of the peritoneal membrane; ∆Na = difference in the concentration of
sodium in the fresh solution and in the dialysate after 60 minutes; PAR = peritoneal absorption rate.
D0 values were similar to baseline after a 12-week period
of treatment with icodextrin, in the nighttime exchange,
if the PET was preceded by an 8-hour exchange with a
solution containing glucose and not icodextrin. It would
therefore seem that icodextrin causes an acute increase in
the permeability of the peritoneal membrane, with mechanisms that are still unclear (65).
To conclude, even in patients using icodextrin on a chron-
ic basis, it is necessary that the nighttime exchange immediately prior to the PET is performed with a 1.36% (or
2.27%) glucose solution.
Infusion volume: 2,000 mL
The classic PET is performed using 2,000 mL of 2.27%
glucose solution. In one study, the PET performed with a
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volume of 1,500 mL appeared to give results no different
from the PET performed with 2,000 mL (66); however, in
this study, the PET with different volumes was performed
in different populations and not in the same group of patients. The test should, therefore, be performed with a volume of 2,000 mL in adult patients, and smaller volumes
should be reserved for use in those patients, often of slight
build, who do not tolerate such volumes (in this case, the
results of the PET will be used to perform serial tests in
the same patient, and caution is required when using this
data for any comparison with the other patients).
All PD solution bags (except those for APD) have a nominal volume of 2,000 mL; however, when this volume is
quantified, the result is almost always higher (67). One recent study (68) showed that the bags used in 316 PETs
contained a median volume of 2,096 mL, despite having
a declared nominal value of 2,000 mL. Were the nominal
volume of the solutions in the bags to be used to quantify peritoneal UF during the PET, peritoneal UF would be
overestimated.
In addition, even when conducting a PET, the flush-before-fill maneuver is usually performed, after the previous exchange has been drained, with an unknown quantity of fresh solution that ends up in the drain bag. The
failure to quantify this volume used for the flush-beforefill, which is usually 100-200 mL (69), can lead to errors
in the quantification of PET UF (67) and may also cause
alterations in the classic PET equilibration parameters.
Indeed, it is possible to obtain a dilution of the solutes
(e.g., urea, creatinine etc.) contained in the drainage bag
if the flush-before-fill volume is transferred into it, and
therefore the D/P values obtained for such solutes are
lower than the real values, whereas the D/D0 values will
be higher. In both cases, there will be an underestimation of transporters belonging to the faster (higher) categories, which may cause the incorrect prescription of
dialysis in patients on PD.
The overestimation of UF that may occur in PD, due to
the overfilling of the bags and the flush-before-fill maneuver, can assume considerable volumes when 24-hour
UF is evaluated in CAPD (70), whereas it would appear
to be less important in APD (71). Thanks to the formulae
for calculating Kt/V and dialysis creatinine clearance, using the total removal of such solutes and not their concentration in the drain liquid, there are no consequences
even when the volume used to flush the lines is mixed
with that drained from the peritoneal cavity at the end of
the exchange.
Overestimation of UF, particularly in CAPD, can have clinically significant consequences (e.g., with an average overfill
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of 100 mL per CAPD bag and with a mean volume of 200
mL for each flush-before-fill, a peritoneal UF of 1,200 mL/
day can be estimated for a CAPD patient, whereas, in actual
fact, it is null). It cannot be ruled out that this “error” may
have contributed to the water-sodium retention typical of
many PD patients (70).
To conclude, when performing the PET, it is necessary:
(a) to use a volume of 2,000 mL; (b) to measure the actual
volume of solution to be infused, which can be easily obtained by weighing the bag and subtracting the tare (empty bag at the end of the infusion); and (c) to quantify the
volume used for the flush-before-fill, subtract this amount
from the volume of the solution to be infused and remove
the same amount of fluid without mixing it with the liquid
drained at the end of the test. A simple way of doing this
is to cut the transfer set at the connection with the infusion bag, transfer all of the nighttime dwell into a container, connect the transfer set to a 50-mL syringe, close
the patient’s extension set, open the infusion set, draw off
a known amount of fluid (e.g., 30 mL) for line flushing, and
start solution infusion for the PET.
Patient position during infusion and drainage
The supine position is used during the infusion, and the
seated position during the drainage. In the standardization
of the classic PET, the patient drains the nighttime dwell
fluid in an orthostatic position, to allow the best possible
drainage. In an upright position, the peritoneal fluid tends
to collect at the bottom of the pelvic cavity where the end
of the peritoneal catheter should be positioned, thus obtaining the best conditions for drainage.
During the infusion of the solution used for PET, the patient
should be in a supine position and switch from one side
to the other every 400 mL of infusion (every 2 minutes), to
mix the residual volume with the infused solution. There is
no scientific evidence that the patient has to switch sides;
however, it is recommended to do so, at least before the first
collection of dialysate.
In the standardization of the classic PET, to collect the dialysate specimens, 200 mL of dialysate is drained into the drain
bag, 10 mL is drawn off under sterile conditions (for the lab)
and the remaining 190 mL is reinfused into the peritoneal
cavity. Once the dialysate has been collected, the patient is
able to get up and walk around freely; to do so, the patient
has to be repeatedly disconnected from and reconnected to
the peritoneal infusion-drain set. In addition, this method of
collecting dialysate involves a risk of peritonitis due to the
potential for contamination of the fluid that is then reinfused
into the peritoneal cavity.
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To avoid the above problems, it is preferable to cut the
line where it connects with the drainage bag and connect
it to a 50-mL syringe (with a conical tip) to be used to accurately measure the flush-before-fill volume and perform
dialysate collection (see below). In this way, the patient
remains connected to the peritoneal infusion-drain system and, therefore, remains lying down or sitting for the
duration of the test. The nighttime dwell dialysate and that
of the PET can be collected in 2 different containers and
quantified (by weighing or using a graduated flask). This
of course requires the presence of the patient for the duration of the PET at the chosen site, but avoids the possible interference of the increase in intraabdominal pressure, due to the orthostatic position and deambulation, on
the mechanisms of peritoneal transport and the genesis
of peritoneal UF (72).
To conclude, it is preferable to keep the patient supine or
seated for the duration of the PET. It is not recommended to perform multiple connections and disconnections
or the dialysate reinfusion maneuver after collecting an
aliquot from the infusion bag, due to the risk of peritonitis. Cutting the line and connecting it to a 50-mL syringe
appears to be the preferable way to collect dialysate.
Of course, when performing the 3.86%-PET combined
with a mini-PET or Uni-PET requiring a temporary drainage, the dialysate has to be reinfused after it has been
weighed. However, the dialysate specimen should not be
collected before reinfusion, even when collected under
sterile conditions, and it is safer to leave a small aliquot of
dialysate at the end of the reinfusion to be collected once
reinfusion is complete.
Duration of the infusion and drainage
No more than 10 minutes for the infusion should be used
and no less than 20 minutes for the drainage. The peritoneal
cavity must be completely emptied before performing the
PET. The drainage should be performed in an upright standing or sitting position and must last at least 20 minutes.
The solution used for the PET must be infused as rapidly
as possible, usually in no more than 10 minutes. Indeed,
the test’s zero time is made to coincide with the end of the
infusion of the solution. In any case, the exchanges between
the blood and the solution across the peritoneal membrane
commence during the infusion of the first few milliliters of
solution. A longer infusion time would increase the total effective duration of the PET, with the possibility that the D/P
of the solutes could be higher and the D/D0 lower than the
actual values. For the same reason, the drainage time at the
end of the test should be as short as possible but at the
same time allow a complete emptying of the peritoneal cavity, and, again to standardize the PET, it should not last less
than 20 minutes.
Time points for blood and dialysate specimen
collection
The time points for blood and dialysate specimen collection depend on the test used. In the standardization of the
classic PET, dialysate specimens are collected at time 0 (immediately after the end of the infusion of the solution chosen for the PET), 120 minutes from the start of the PET and
after the complete drainage of the peritoneal cavity at the
end of the test. In all cases, the aliquot collected is 10 mL,
and it should be taken into consideration when calculating
peritoneal UF.
We have seen that the classic PET involves draining approximately 200 mL of dialysate at times 0 and 120 minutes, specimen collection and the reinfusion of the remainder into the peritoneal cavity. As mentioned previously, this
maneuver involves a potential risk of peritonitis and should
be avoided.
One safer method, as indicated previously, is to cut the line
at the connection with the drainage bag and connect to it a
large syringe (50 mL) with a conical tip. This method makes
it possible to (a) collect the specimen (10 mL) of the solution chosen for the PET (having drawn off and discarded
30 mL for line flushing); (b) quantify the exact volume used
(e.g., 30 mL) for the flush-before-fill; (c) collect the dialysate
specimens (10 mL each) at times 0, 60 (where applicable)
and 120 minutes, preceded on each occasion by the aspiration of the 30 mL of dialysate needed to avoid taking the
dialysate from the lines’ dead space (author’s note: personal measurement). The quantity of “fresh” solution used to
wash the lines and for the lab tests (30 + 10 = 40 mL) should
be added to the final UF. The amount of dialysate used to
avoid the dead space effect (30 mL for each specimen) is
not mixed with the final drainage fluid, but discarded and
counted (added to the drainage amount) for the final calculation of the UF. The same applies for laboratory samples (10
mL) for each specimen, including that collected during the
final emptying. These amounts may seem negligible; however, in actual fact, if 3 aliquots are collected from the dialysate (30+10+30+10+30+10) and 1 from the final emptying
(10 mL), we will have 130 mL to add to the volume drained
at the end of the test. The final dialysate specimen (time
240 minutes) must be taken after completely draining the
peritoneal cavity.
To conclude, it is preferable to collect dialysate aliquots using a large syringe connected to the line.
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When calculating the D/D0, the classic PET (1) uses the
concentration of glucose in the dialysate collected at
time 0 and not the concentration of glucose in the “fresh”
solution. The aim is to avoid influencing any residual volume present in the peritoneal cavity even once the previous exchange has been completely drained. However,
even in the very first few minutes of the infusion, diffusion exchanges start to take place between blood and
dialysate across the peritoneal membrane, and, without
a doubt, part of the residual volume quantified using the
classic methodology (1) is nothing more than the result
of this solute transport. For this reason, it would be better to use the glucose concentration measured on the
“fresh” solution to be infused. The classic test involved
2 blood draws, the first at the end of the drainage of the
nighttime dwell, immediately before infusing the solution
chosen for the PET, and the second at the end of the
PET, immediately after the drainage, and the mean of the
2 was used to calculate the D/P values (1). The test was
subsequently simplified by performing a single blood
draw halfway through the PET (time 120 minutes) (27,
73, 74). As PD is a continuous treatment, it is unlikely
that during the PET there will be any significant alterations in the plasma concentrations of the solutes considered (creatinine, urea, sodium etc.), with the exception
of glucose, in some patients, when very hypertonic solutions are used. In addition, performing a single collection makes it possible to avoid potential errors between
determinations, due to the coefficient of variation for the
measurement method chosen. It is therefore possible to
perform the blood draw at any point of the PET, although
it is preferable to standardize it – e.g., by performing it
halfway through the test (time 120 minutes).
To conclude, in the classic PET, the performance of just 1
blood draw would appear to be the simplest and most suitable method.
In the 3.86%-PET, the collection of the fresh solution
used for the test and the dialysate must be performed
using the above methods: cutting the line and connecting a 50-mL syringe, to be performed on the fresh solution, on the dialysate after 60 minutes (for the Na sieving
calculation) and at the end of the PET (240 minutes). The
blood draw is performed 60 minutes from the start of the
test. In the 3.86%-PET, the procedure is identical to that
of the classic PET, with the exception of the dialysate
collection at 60 minutes, for the Na sieving calculation.
As far as the collections required for the other tests are concerned, see the instructions for the performance of the individual tests.
The specimens of the solution to be infused, the dialysate
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and blood should be analyzed immediately, or alternatively
frozen.
Laboratory methods
a) Use a correction factor when calculating the concentration of creatinine in the dialysis liquid and in the dialysate on account of the interference of glucose, if no
enzyme-based assay is used. It is a well-known fact that
high concentrations of glucose interfere with certain creatinine concentration assays (75), and it is therefore necessary to use a correction factor (CF), to be calculated for
each individual laboratory. This CF can be obtained from
the relationship existing between the concentrations of
creatinine, determined using a nonenzymatic method, and
increasing concentrations of glucose up to those present
in the bags of PD solution (1). This CF can be obtained
from the linear regression curve obtained from the concentrations of creatinine measured in solutions containing
different concentrations of glucose, similar to those used
in PD (76). A simpler method is to assay the concentration
of creatinine (even when it is certainly absent) in the fresh
PD bags at different concentrations of glucose (1.36%,
2.27% and 3.86%), preferably 2 or more determinations
per bag, divide the concentration of creatinine by the concentration of glucose, (i.e., CF = 1.15/1,360 = 0.000846)
and use the mean value as the correction – i.e., subtracting from the value of the creatinine assayed in the dialysate (i.e., 4.2 mg/dL), the value of glucose (i.e., 620 mg/
dL) multiplied by the CF: 4.2 (620 x 0.000846) = (4.2 mg/
dL − 0.525) = 3.675 mg/dL (concentration of creatinine
corrected for the influence of glucose) (see corresponding
calculator). It is precisely for the high glucose concentrations typical of PET specimens that it is relevant to correct
the measurement of creatinine in the dialysis fluids for the
nonspecific detection of chromogenic glucose with the
Jaffé reaction. In connection with this last consideration,
it is therefore important to measure the glucose in the liquids correctly, using suitable dilutions. The correction of
the overestimation of creatinine and the underestimation
of glucose are connected with one another for the calculation of D/P.
The plasma concentration of creatinine (and other solutes)
should also be corrected for plasmatic water (77) before calculating the D/P, to avoid obtaining D/P values for some solutes, such as urea in given situations, higher than the unit,
which is, of course, an error.
b) Perform adequate dilutions for the correct calculation
of the concentration of glucose in the dialysate when
higher than 800 mg/dL. Most laboratory instruments
© 2013 Società Italiana di Nefrologia - ISSN 1121-8428
JNEPHROL 2013; 26 ( Suppl 21): S120-S139
read the concentration of glucose correctly up to values
of approximately 800 mg/dL. It is therefore necessary to
perform dilutions on the dialysate specimens and, above
all, on the fresh solutions used for the PET. Laboratory
technicians should therefore be informed of the need to
perform these dilutions.
c. Use flame photometry or indirect potentiometry to assay the concentration of sodium in the dialysate. When
calculating Na sieving at 60 minutes for a 3.86%-PET (78),
while direct potentiometry should be avoided, it is possible to use indirect potentiometry (used in the majority of
laboratories), which gives results similar to those of flame
photometry, the best method for measuring sodium, particularly in the infusion fluid and dialysate.
9. Test protocols
the corrected concentration of creatinine to be used when
calculating D/PCreat, and CreatMeasured (measured in mg/
dL) is the creatinine concentration measured in the dialysate using the Jaffè method. The CF should be calculated
using the linear regression equation obtained by measuring, with the Jaffé method, the concentration of creatinine
in the fresh bags at different concentrations of glucose
(1.36%, 2.27% and 3.86%) (76). In any case, a more simple method consists of measuring (at least in duplicate)
the concentration of creatinine in fresh bags at different
glucose concentrations (1.36%, 2.27% and 3.86%), dividing the concentration of creatinine (in mg/dL), falsely
determined by the method in each fresh solution, by the
concentration of glucose (in mg/dL) and using the mean of
the 3 CFs as the CF to be included in the formulae.
Residual volume
Each test must have a dedicated protocol so that it can be
performed using the same method in different centers. Detailed instructions on how the various tests are performed
are available on the PD Study Group website (http://www.
dialisiperitoneale.org; in Italian only). Tests to be performed
on the blood, fresh solution and dialysate specimens collected during the various tests include
1. blood draw: glucose, creatinine, urea, sodium and total
proteins;
2. fresh solution specimen: glucose and sodium;
3. dialysate specimen at various time points: creatinine,
urea, glucose and sodium.
Note: When measuring the creatinine concentration in
the dialysate, use an enzymatic assay or perform suitable
corrections if using the Jaffé method (75). When measuring the sodium concentration in blood, fresh solution and
dialysate, use flame photometry or indirect potentiometry
(not direct potentiometry) (78). Perform the appropriate
dilutions when measuring the concentration of glucose
in fresh solution and dialysate. The calculations for the
various tests must be performed using standardized formulae, preferably using identical calculators in all centers.
Formulae
Correction factor
The residual volume (RV; in liters) (79) is calculated as
RV = [VInf × (S3-S2)]/(S1 − S3),
where
VInf = volume infused (in liters);
S1 = concentration of the solute (mg/L or mmol/L) in the
nighttime dwell dialysate;
S2 = concentration of the solute (mg/L or mmol/L) in the
fresh solution;
S3 = concentration of the solute (mg/L or mmol/L) in the dialysate at time 0.
The RV can be calculated with different solutes (urea, creatinine, glucose, potassium and protein). It is also possible to
use the mean value when RV is calculated with the various
solutes: Usually, the RV of urea and creatinine is calculated,
and the mean value used.
D/PCreat
For D/PCreat, use the concentration of creatinine in the dialysate (mg/dL) at the end of the test (use the CF, if necessary);
use the concentration of creatinine in plasmatic water (CreatininePW) (mg/dL) (77):
CreatininePW (in mg/dL) = u × CreatinineP (in mg/dL), where:
u = 1/(1 − Vlip − 0.00718 × TotProteinsP);
Vlip = the fractional volume of plasma lipids = 0.016;
TotProteinsP = total plasma protein concentration (g/dL).
D/D0
The CF for the concentration of creatinine in the dialysate if using a nonenzymatic method (Jaffé) is calculated as CreatCorrected = CreatMeasured – (Gluc ×
CF), where CreatCorrected is measured in mg/dL and is
For D/D0, use the concentration of glucose (mg/dL) in the
dialysate at the end of the test and the concentration of glucose (mg/dL) in the ‘fresh’ solution.
© 2013 Società Italiana di Nefrologia - ISSN 1121-8428
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Best Practice on: Functional assessment of the peritoneal membrane
Na sieving
For Na sieving, it is better to use the dip (∆DNa) in the concentration of Na in the dialysate, after 60 minutes of PET,
instead of D/PNa at 60 minutes (18); ∆DNa is the difference
between the concentration of sodium in the fresh solution
(mmol/L; measured) and the concentration of Na in the dialysate (mmol/L) at 60 minutes.
Free water transport
Free water transport (FWT) is quantified using the miniPET and with the 1-hour 3.86% double mini-PET and UniPET. FWT is measured in milliliters and is equal to total UF
(UFT; in mL), for the test, minus UF (mL) across the small
pores (UFSP) (24, 43): FWT = UFT – UFSP. UFSP (in milliliters) can be quantified as Na clearance during the 1-hour
3.86% mini-PET, double mini-PET and Uni-PET: UFSP =
(NaR×1,000)/Nap, where NaR (in mmol) is the Na clearance
and is calculated as: NaR = [volume of dialysate drained
(in liters) × concentration of Na (in mmol/L) in the drained
dialysate] − [the volume of fresh solution infused (in liters)
× the concentration of Na (in mmol/L) in the fresh solution
infused]; and where NaP = plasma sodium in mmol/L.
Osmotic conductance to glucose
Osmotic conductance to glucose (OCG) is quantified using
the data of the whole double mini-PET or some of the data
of the Uni-PET (43):
(V3.86 – V1.36) OCG = ----------------------------- × 1.7
19.3 × (G3.86 – G1.36) × t
where OCG is in ml/min per mm Hg; V3.86 and V1.36 are
the volumes (in milliliters) of dialysate drained at the end
of the test, using a 3.86% and 1.36% glucose solution,
respectively, during the double mini-PET, or the volumes
References
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2. Ho-dac-Pannekeet M, Atasever B, Struijk D, Krediet R. Analysis of ultrafiltration failure in peritoneal dialysis patients by
S136
(mL) of dialysate drained at 60 minutes, with the 3.86%
and 1.36% glucose solutions, respectively, during UniPET; 19.3 (mm Hg/mmol/L) is the product of the absolute
temperature for the gas constant at 37°C; G3.86 and G1.36
are the molar concentrations of glucose (mmol/L) in the
fresh solutions used for the double mini-PET or Uni-PET
and are calculated as follows: Glucose (mmol/L) = glucose (mg/dL) / 18; t is the mean peritoneal dwell time
during the 2 tests of the double Mini-PET or the first part
of the Uni-PET, which should be the same and equal to
the 60-minute dwell time plus 50% of the time required
for the infusion and drainage (in short, if the timing is
observed correctly, t will be equal to 60+5+10 = 75 minutes); 1.7 is a CF (43).
Calculators
An Excel spreadsheet is attached to these Best Practice
Guidelines to allow users to perform all of the calculations connected with the various tests analyzed (available for download from the PD Study Group website at
http://www.dialisiperitoneale.org; in Italian only). Calculations are not provided for the PDC test, as it requires
a copyright-protected software that is, however, readily
available on demand.
Financial support: No grants or funding have been received for
this study.
Conflict of interest: None of the authors has financial interest
related to this study to disclose.
Address for correspondence:
Vincenzo La Milia
Nephrology and Dialysis
A. Manzoni Hospital
Via Dell’Eremo 9/11
23900 Lecco, Italy
v.lamilia@ospedale.lecco.it
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