Document 6519174

Peritoneal Dialysis International, Vol. 20, pp. 548–556
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Copyright © 2000 International Society for Peritoneal Dialysis
WHAT IS THE OPTIMAL FREQUENCY OF CYCLING IN
AUTOMATED PERITONEAL DIALYSIS?
Rafael A. Perez, Peter G. Blake, Susan McMurray, Lou Mupas,1 and Dimitrios G. Oreopoulos1
Optimal Dialysis Research Unit, London Health Sciences Centre and University of Western
Ontario; Toronto Hospital,1 University of Toronto, Ontario, Canada
Correspondence to: P. Blake, Division of Nephrology,
London Health Sciences Centre, Victoria Campus,
375 South Street, London, Ontario N6A 4G5 Canada.
[email protected]
Received 28 March 2000; accepted 20 June 2000.
548
ances, and 7 × 2 L is a consistently superior prescription
if 2-L dwells are being used. Although more costly, 9 ×
2 L should be considered if higher clearances are required.
KEY WORDS: Urea clearance; creatinine clearance; automated peritoneal dialysis; tidal peritoneal
dialysis.
n recent years, adequacy of peritoneal dialysis (PD)
has received a lot of attention (1–3). An increasing
proportion of the relatively high technique failure rate
on continuous ambulatory PD (CAPD) is attributed
to inadequate dialysis (4), and there is increasing
evidence that, just as in hemodialysis, low clearances
predispose to excess mortality (1,5).
The capacity to raise clearances on CAPD is somewhat limited by the ability and willingness of patients
to tolerate increased numbers of exchanges and
greater dwell volumes. Thus there is increasing use
of automated PD (APD) in patients perceived to be
inadequately dialyzed on CAPD. This, along with a
number of other factors, has contributed to marked
growth in the use of APD. A recent review reported
that, in 1997, 33%, 28%, and 26% of PD patients in
the United States, Canada, and worldwide, respectively, were maintained on this modality (6).
The growth of APD and the recognition of the significance of adequate dialysis make it important that
clinicians be aware of the prescription factors that
determine the clearances achieved on APD. However,
few systematic studies of the effects of varying particular prescription parameters have been published.
Knowledge in this area comes mainly from clinical
experience and from predictions based on the use of
computerized modeling programs, which have been
reasonably well validated in cross-sectional studies
comparing actual and predicted clearances (7–9).
Thus, the addition of day dwells to the APD prescription leads to marked increases in clearance (10,11).
Similarly, lengthening cycler time and raising cycler
dwell volumes also increase clearance (10,11), although the latter assumption has recently been ques-
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♦ Objective: The recent increase in the use of automated
peritoneal dialysis (APD) has led to concerns about the
adequacy of clearances delivered by this modality. Few
clinical studies looking at the effects of varying the individual components of the APD prescription on delivered
clearance have been done, and most published data are
derived from computer modeling. Most controversial is
the optimal frequency of exchanges per APD session.
Many centers prescribe 4 to 6 cycles per night but it is
unclear if this is optimal. The purpose of this study was to
address at what point the beneficial effect of more frequent cycles is outweighed by the concomitant increase
in the proportion of the total cycling time spent draining
and filling.
♦ Methods: A comparison was made between the urea
and creatinine clearances (CCrs) achieved by 4 different
APD prescriptions, used for 7 days each, in 18 patients.
The prescriptions were for 9 hours each and were all based
on 2-L dwell volumes, but differed in the frequency of exchanges. They were 5 × 2 L, 7 × 2 L, and 9 × 2 L, as well as
a 50% tidal peritoneal dialysis (TPD) prescription using
14 L. Ultrafiltration, dwell time, glucose absorption, sodium and potassium removal, protein excretion, and relative cost were also compared. Clearances due to day
dwells and residual renal function were not included in
the calculation.
♦ Results: Mean urea clearances were 7.5, 8.6, 9.1, and
8.3 L/night for the four prescriptions respectively. Urea
clearance with 9 × 2 L was significantly greater than with
the other three prescriptions (p < 0 0.05). Urea clearance
with 7 × 2 L and TPD were superior to 5 × 2 L (p < 0.05).
Mean CCr was 5.1, 6.1, 6.4, and 5.6 L/night, respectively.
Compared to 5 × 2-L, the 7 × 2-L, 9 × 2-L, and TPD prescriptions achieved greater CCr (p < 0.05). Taking both
urea and CCr into account, 9 × 2 L was the optimal prescription in 12 of the 18 patients. Ultrafiltration and sodium and potassium removals were all significantly
greater with the higher frequency prescriptions.
♦ Conclusion: The 5 × 2-L prescription significantly
underutilizes the potential of APD to deliver high clear-
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SEPTEMBER 2000 – VOL. 20, NO. 5
METHODS
Twenty stable adult APD patients (age > 16 years)
from the London Health Sciences Centre (LHSC) and
The Toronto Hospital PD programs were recruited for
the study. All were on APD with the HomeChoice cycler (Baxter, Deer Park, IL, U.S.A.). The only exclusion criterion was an episode of peritonitis in the
previous 6 weeks. Any patient developing peritonitis
during the study was excluded from subsequent
analysis or alternatively restudied 6 weeks later.
Patients were all treated with 2-L dwell volumes
and 9 hours’ cycling time per night for the duration
of the study. Over a 4-week period, each patient spent
7 days on each of four different prescriptions: (1) 5 ×
2-L exchanges over 9 hours; (2) 7 × 2-L exchanges over
9 hours; (3) 9 × 2-L exchanges over 9 hours; and
(4) TPD over 9 hours using 14 L of dialysate, with an
initial fill volume of 2 L, a reserve volume of 1 L, and
a tidal volume of 1 L. Tonicity of the bags was standardized on each prescription. One center used 2.5%
dextrose for all four prescriptions. At the other center, 2.5% bags were unavailable and a mix of 1.5%
and 4.25% bags was used to give a final dextrose concentration for the four prescriptions of 2.88%, 2.42%,
2.19%, and 2.42%, respectively.
The first 4 days on each prescription were to allow
the patient to stabilize in terms of volume status and
blood levels of urea and creatinine. On each of the
last 3 days of each 7-day period, the patients had cycler urea and creatinine clearances calculated. The
three consecutive measurements were averaged in
order to allow for day-to-day intrapatient variations
in the clearances achieved. Cycler clearances were
calculated as follows: The effluent volume for each
night was collected, quantified, and mixed, and a representative sample was sent for measurement of
dialysate urea, creatinine, protein, and glucose levels. The dialysate glucose was used to correct the dialysate creatinine value by a formula that had to be
calculated separately at each center’s laboratory. Because APD, unlike CAPD, is not a steady-state form
of dialysis, the blood urea and creatinine levels could
not be presumed to be always about the same. Thus,
blood samples for the calculation of clearances were
taken as near as possible to the midpoint of the time
the patient spent off the cycler (i.e., 1530 hr in a patient who cycled during the period between 2300 and
0800 hr). Blood samples were measured on 2 of the
3 days on which clearances were measured, with the
mean of the values on the first and third days being
used in the clearance calculation for the second day.
The majority of patients had both residual renal
function and/or day dwells, but clearances due to these
were ignored because they were not relevant to the
question being asked. Cycler clearances were expressed in liters per 9-hour cycler session and were
not normalized to body water (V) or surface area in
order that comparisons could be made between patients of different body sizes. However, because the
weekly normalized values are more familiar to clinicians, these were also calculated. In the case of Kt/V,
the Watson formula was used for calculation of V, and
for corrected CCr, the DuBois formula was used for
calculation of the body surface area (2,3).
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tioned (12). Most unclear, however, is the influence
of frequency of cycling (i.e., the dialysate flow rate)
on the clearances achieved. Theoretically, more cycles
in a given time will replenish the peritoneal cavity
with fresh dialysis solution more frequently and so
maximize the gradient for diffusion, thus increasing
clearance. However, more frequent cycling also leads
to a greater proportion of cycling time being spent
draining and filling, potentially making dialysis less
efficient. The question is, “At what point is the beneficial effect of more frequent cycles outweighed by
this concomitant increase in “down time”? In practice, many centers prescribe 4 – 6 cycles per night
and the question arises whether this is optimal
(13,14).
This issue was addressed by Pirpasopoulos et al.
in 10 patients in 1972; it was concluded that urea
and creatinine clearances (CCrs) were maximal with
2-L cycles every 45 minutes (15). In 1978, Robson
et al., in a group of 10 patients, found a linear rise in
clearances with increases in dialysate flow rates from
2 to 6 L/hour. They concluded that a dialysate flow
rate of 4 L/hour was best and gave maximum efficiency, but that cost would limit this approach for all
patients (16). Neither of these studies considered peritoneal transport status, which was not widely understood at the time. More recently, Kumano et al. used
their own urea kinetic modeling program to predict
clearances and showed that maximum urea clearances were achieved with 5 – 6, 2-L exchanges per
8 hours in low peritoneal transporters, and with
8 – 9 exchanges per 8 hours in high transporters (17).
Durand et al. looked only at CCrs and suggested that
these were maximum at a flow rate of 1.6 L/hour for
low transporters and 2.3 L/hour for high transporters, but the methodology underlying these observations was not described in detail (18). There is thus a
lack of contemporary studies examining these issues
using direct patient derived data and taking peritoneal transport status into account.
We investigated this important issue in a systematic manner by measuring urea and creatinine clearances in 18 patients, each treated for a week at a time
with each of four APD prescriptions. Three of these
prescriptions differed only in the frequency of cycling
and the fourth was based on tidal PD (TPD).
APD PRESCRIPTION
PEREZ et al.
550
PDI
time were considered. For the purposes of the calculation, use of the most cost-effective mix of 3-L and
5-L solution bags was presumed.
The study was approved by the institutional review board at each center, and consent was obtained
from each participating patient.
STATISTICS
Results are expressed as mean ± SD where relevant. Differences between results were assessed
using a paired t-test or an unpaired t-test, as indicated. Correlation between two variables was assessed
using Pearson’s correlation coefficient (r). The
Minitab 7.2 (Minitab, Inc., Reading, MA, U.S.A.) software package was used for data analysis.
RESULTS
PATIENTS
Eighteen of the 20 patients completed the study.
Of the 2 patients who dropped out, 1 died and the
other was unwilling to finish the study. The 18 patients comprised 11 males and 7 females; mean age
was 49.9 ± 18.2 years, with a range of 19 – 76 years.
Mean weight was 67.9 ± 13.2 kg, mean body surface
area was 1.77 ± 0.18 m2, and 22.2% (4/18) of the patients were diabetic. Based on the PET, 6 patients
were high transporters, 7 were high-average, 3 were
low-average, and 2 were low. This distribution reflects
the policy in the programs concerned, consistent with
recent recommendations, of directing higher transporters to APD (3).
CLEARANCES
There was a progressive rise in urea and creatinine clearances (L/night) as the number of cycles increased, with the TPD prescription achieving
clearances intermediate between the 5 × 2-L and the
7 × 2-L prescriptions (Table 1).
The urea clearance with 9 × 2 L was significantly
greater than with the other three prescriptions, and
that with 7 × 2 L was significantly greater than with
5 × 2 L (Table 1). The urea clearance with TPD was
significantly greater only than that using 5 × 2 L.
Creatinine clearance was significantly greater with
9 × 2 L than with 5 × 2 L and TPD. It was also greater
than with 7 × 2 L but this did not reach statistical
significance (Table 1). The 7 × 2-L prescription
achieved significantly greater CCr than 5 × 2 L. The
CCr achieved with TPD was significantly greater than
that with 5 × 2 L only.
When a weighted average of urea and creatinine
clearances was used to compare the four prescriptions,
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In addition to comparing urea and creatinine clearances separately on each of the four prescriptions, an
overall comparison of clearances on the four prescriptions was done using a weighted average of urea and
creatinine clearances. This was calculated for each
patient by defining the urea clearance on 5 × 2 L as
1.0, and that on the other prescriptions as a ratio relative to this and, similarly, by defining the CCr on 5 ×
2 L as 1.0, and that on the other prescriptions as a
ratio relative to this. The ratios for urea and creatinine clearances on each prescription were then added
to give an overall weighted value.
To allow an approximate comparison between the
study results and those predicted using a computer
software modeling program, the mean measured urea
and creatinine clearances for each transport type in
the study were compared with those predicted by the
PD Adequest (Baxter) software program for an average patient with the same transport type (7). Results
for low and low-average transporters were combined
because of the small numbers of such patients in the
study. For each transport type, and for both urea and
creatinine clearances, the actual measured and the
predicted clearance values were expressed as 1.0 for
the 5 × 2-L prescription and as a relative ratio for the
other three prescriptions. This allowed easy comparison of clearances with the different prescriptions. It
should be emphasized that the modeled clearances
are not based on the individual study patients but on
average patients of that transport type, and so some
dichotomy between results is to be expected.
In addition to clearances, protein excretion, glucose absorption, net ultrafiltration (UF), and dwell
time as determined by the cycler, were recorded for
each patient on days 4 to 7 on each prescription, and
mean values were calculated. Net UF was estimated
using the actual measured effluent volume rather
than the value recorded by the cycler. Glucose absorption was calculated by subtracting the quantity of
glucose in the effluent from that in the infused dialysate solution. At one center, all patients had sodium
and potassium removal assessed three times on each
prescription.
All patients had a short peritoneal equilibration
test (PET), as described by Twardowski et al. (19),
performed at the time or within 3 months of the study
and were categorized as high, high-average, lowaverage, or low transporters on the basis of the 4-hour
dialysate/plasma equilibration ratio for creatinine, in
the standard manner (19).
The cost of the four prescriptions was estimated
using contemporary data from one of the centers
(LHSC) and was done using a ratio such that the cost
of 5 × 2 L was taken as 1.0. Only the costs of solutions and tubing were taken into account. Neither the
costs of the cycler nor those of nursing and physician
SEPTEMBER 2000 – VOL. 20, NO. 5
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SEPTEMBER 2000 – VOL. 20, NO. 5
APD PRESCRIPTION
TABLE 1
Mean (±SD) Nightly Urea Clearance, Creatinine Clearance (CCr), and Ultrafiltration (UF) with Four Different
Automated Peritoneal Dialysis (APD) Prescriptions
APD prescription
5×2 L
7×2 L
9×2 L
Tidal PD
Urea clearance
CCr
(L/night)
(L/night)
UF
(mL/night)
7.48±0.65
5.08±0.63
877±480
6.05±0.73a 1220±542a
8.55±1.14a
9.06±0.90a,b,c 6.38±0.91a,c 1297±380a
8.34±1.23a
5.60±0.74a 1142±532a
a
p < 0.05 compared to the 5 × 2-L prescription.
p < 0.005 compared to the 7 × 2-L prescription.
c p < 0.005 compared to the tidal PD prescription.
b
WEEKLY Kt/V AND CCr
The weekly peritoneal Kt/V values achieved with
the four APD prescriptions, excluding the contribution of day dwells and residual renal function, were
1.48 ± 0.3, 1.69 ± 0.4, 1.76 ± 0.32, and 1.65 ± 0.42,
respectively. Kt/V with 9 × 2 L was significantly
greater than with the other three prescriptions (p <
0.005), and Kt/V with 7 × 2 L was significantly
greater than with 5 × 2 L (p < 0.0005). Kt/V using
TPD was only greater than that using 5 × 2 L (p <
0.05).
The weekly peritoneal CCr values with the four
APD prescriptions, again excluding the contribution
of day dwells and residual renal function, were 35.0 ±
5.3, 41.6 ± 4.8, 43.6 ± 4.8, and 38.6 ± 6.0 L/1.73 m2
body surface area, respectively. Creatinine clearance
with 9 × 2 L was significantly greater than that with
5 × 2 L and TPD (both p < 0.005). Creatinine clearance with 7 × 2 L was significantly greater than with
5 × 2 L (p < 0.0005) and TPD (p < 0.05). Creatinine
clearance using TPD was greater only than that using
5 × 2 L (p < 0.05).
COMPARISON
WITH
MODELED
VALUES
When a comparison between the study results and
those predicted by the PD Adequest program for patients of similar transport type was done, it showed a
general trend for CCr to increase with cycler frequency to a greater degree than predicted. Results
were much less discordant for urea clearance
(Table 3).
DWELL
TIMES
As expected, there was a decrease in dwell times
as the number of cycles increased (Table 4) (p < 0.005).
CLEARANCES BY PET
When the patients were classified by PET status,
the high and high-average transporters generally
tended to have greater urea and creatinine clearances
than their low and low-average counterparts. However, when the clearances in the high/high-average
group were compared with those in the low/lowaverage group using an unpaired t-test, the differ-
Figure 1 — Urea and creatinine clearances for high/highaverage (H/HAV) and low/low-average (L/LAV) transporters
(by PET) can be related to number of exchanges.
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it was noted that 9 × 2 L was superior in 12 patients,
and in 9 of these the advantage was more than 10%
compared to the second best prescription. The 7 × 2-L
prescription was best in only 3 patients, TPD was best
in only 2, and in no case was 5 × 2 L optimal (data
not shown).
ences were only significant for CCr with the 7 × 2-L
prescription, and for urea clearance with TPD (both
p < 0.05) (Figure 1).
Taken on their own, high and high-average transporters (n = 13) achieved significantly greater urea
clearances as the number of cycles increased (Table 2).
Again, in this subgroup, urea clearances with TPD
were greater only than those with 5 × 2 L. Creatinine
clearance with 9 × 2 L was greater than with all other
prescriptions but the difference was only significant
compared to 5 × 2 L and to TPD (Table 2).
In the smaller subgroup of low and low-average
transporters (n = 5), the urea clearance with 9 × 2 L
was significantly greater than with the other three
prescriptions, and urea clearance with TPD was no
better than that with 5 × 2 L. The CCr with 9 × 2 L
was also significantly greater in this subgroup
(Table 2).
Using the weighted average of urea and creatinine
clearances, it was noted that 9 × 2 L was superior in
7 of the 13 high/high-average transporters and in all
5 low/low-average transporters. The 7 × 2-L and TPD
prescriptions were best only in 3 and 2, respectively,
of the 13 high/high-average transporters (data not
shown).
PEREZ et al.
SEPTEMBER 2000 – VOL. 20, NO. 5
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TABLE 2
Mean (±SD) Nightly Urea Clearance, Creatinine Clearance (CCr), and Ultrafiltraion (UF) in the Different Peritoneal
Equilibration Test Subgroups, with Four Different Automated Peritoneal Dialysis (APD) Prescriptions:
High and High-Average (n=13 patients), Low and Low-Average (n=5 patients)
APD prescription
5×2 L
7×2 L
9×2 L
Tidal PD
High and High-Average
Urea clearance
CCr
UF
(L/night)
(L/night)
(mL/night)
7.50±0.69
8.88±1.0a
9.30±0.82a,b,c
8.81±0.10a
5.11±0.69
6.26±0.74a,c
6.43±1.0a,c
5.79±0.72a
Low and Low-Average
Urea clearance
CCr
UF
(L/night)
(L/night)
(mL/night)
824±554
1246±557a
1253±414a
1184±606a
7.40±0.63
7.70±0.11
8.47±0.89a,b,c
7.12±0.81
4.99±0.47
5.52±0.58
6.26±0.78a,b,c
5.13±0.6
1014±157
1152±556
1401±296a
1035±283
a
p < 0.05 compared to the 5 × 2-L prescription.
p < 0.05 compared to the 7 × 2-L prescription.
c p < 0.05 compared to tidal PD.
b
High
High-Average
Urea
APD prescription
5×2 L
7×2 L
9×2 L
Tidal PD
CCr
Urea
Low/Low-Average
CCr
Urea
CCr
A
P
A
P
A
P
A
P
A
P
A
P
1.0
1.18
1.29
1.19
1.0
1.22
1.35
1.15
1.0
1.29
1.36
1.21
1.0
1.05
1.14
1.09
1.0
1.19
1.20
1.16
1.0
1.12
1.17
1.07
1.0
1.17
1.17
1.07
1.0
1.06
1.09
1.06
1.0
1.04
1.14
0.96
1.0
1.07
1.10
1.03
1.0
1.11
1.25
1.03
1.0
1.02
1.02
1.02
A = actual measure; P= predicted measure by PD Adequest.
Values are expressed as a relative ratio to those achieved with the 5 × 2-L prescription.
For each prescription, there was a direct correlation
between the length of the dwell time and the urea
clearance achieved, with correlation coefficients between 0.29 and 0.52. Because the number of observations is relatively small, the correlation was significant
for the 9 × 2-L prescription only. Longer dwell times
on the same prescription suggest less time spent
draining and filling, due to more effective catheter
function.
ULTRAFILTRATION
The total UF with both 9 × 2 L and 7 × 2 L was
greater than with 5 × 2 L (Table 1). Ultrafiltration
with TPD was greater than with 5 × 2 L.
When the UF achieved was analyzed by PET status, the high and high-average transporters had similar UF with 9 × 2 L and 7 × 2 L, and both were
significantly greater than with 5 × 2 L (Table 2). Ultrafiltration with TPD was greater only than that with
5 × 2 L.
In the low and low-average transporters, there was
a stepwise rise in UF with increases in the number of
552
cycles but it was only significant when comparing
9 × 2 L and 5 × 2 L (Table 2).
OTHER
MEASURES
The quantity of glucose cycled and mean glucose
absorption rose as the number of cycles increased.
However, the percentage of glucose absorbed fell and
was significantly less with 9 × 2 L than with the other
three prescriptions (Table 4). There was no difference
in protein excretion between the four prescriptions
(Table 5).
Sodium removal with 9 × 2 L and with TPD significantly exceeded that with 5 × 2 L. Potassium removal was also significantly greater with 9 × 2 L and
7 × 2 L compared to 5 × 2 L (Table 5).
COST
Cost analysis showed the 7 × 2-L and TPD prescriptions to be 1.27, and the 9 × 2-L prescription to be
1.54, compared to a cost of 1.0 for the 5 × 2-L
prescription.
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TABLE 3
Comparison Between Actual and Predicted Urea Clearance and Creatinine Clearance (CCr) in High (n = 6),
High-Average (n = 7), and Low/Low-Average Transporters (n = 5) with Four Different
Automated Peritoneal Dialysis (APD) Prescriptions
SEPTEMBER 2000 – VOL. 20, NO. 5
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APD PRESCRIPTION
TABLE 4
Mean Dwell Time, Amount of Glucose Infused, Amount and Percentage of Glucose Absorbed
with Four Automated Peritoneal Dialysis (APD) Prescriptions (±SD)
Glucose
APD prescription
Dwell time
(min)
Infuseda
(mmol)
Absorbed
(mmol)
Absorbed
(%)
5×2 L
7×2 L
9×2 L
Tidal PD
78.4±3.64
49.4±3.18b
31.5±3.96b,c
27.6±2.23b,c,d
1358.3±100
1738.3±28b
2130±144.1b,c,d
1738.3±28b
642.1±211.9
672.7±196
702.3±266
682.4±256
46.8±14.2
38.7±11.4b
32.8±11.1b,c
39.3±15b
a
The amount of glucose infused is an average from the tonicity of the bags used at the two centers.
p< 0.05 compared to the 5 × 2-L prescription.
c p < 0.05 compared to the 7 × 2-L prescription.
d p < 0.05 compared to the 9 × 2-L prescription.
b
APD prescription
5×2 L
7×2 L
9×2 L
Tidal PD
a
b
Protein excretion
(g/night)
Sodium removal
(mmol/night)
Potassium removal
(mmol/night)
3.24±1.51
3.46±1.64
3.47±1.57
3.56±1.79
114.9±45.6
138.2±74.9
194.2±35.6a
181.6±79.8a
23.77±2.07
27.01±4.72a
29.86±6.13a,b
25.12±4.35
p < 0.05 compared to the 5 × 2-L prescription.
p < 0.05 compared to tidal PD.
DISCUSSION
The growth of APD worldwide in recent years has
been very marked (6). At the same time, there has
been an increase in awareness of the importance of
achieving adequate clearances in PD, and this has
been emphasized by the recent publication of guidelines suggesting appropriate clearance targets in both
the United States and Canada (2,3). Despite all this,
surprisingly little attention has been paid to how alterations in the various parameters of the APD prescription influence clearances achieved. Most information
in this area is based on modeled data from computer
programs. These have been reasonably well validated
in cross-sectional studies but not, until now, in systematic studies based on varying a single parameter
while keeping all others stable (7–9).
While there is no controversy about the ability of
adding day dwells or prolonging cycler time to augment APD clearances, the situation is less clear with
other aspects of the prescription. It is generally assumed that raising the cycler dwell volume increases
clearance, but this has been questioned in one recent
study (12). Similarly, the theoretical benefits of TPD
are recognized, but it has been found consistently in
clinical studies that, at least at standard volumes,
clearances achieved are not better and are often worse
than those with standard APD techniques (20–23).
Most controversial, however, is the influence of
cycle frequency on APD clearance. Computer programs suggest little benefit in increasing the number of cycles above 6 – 7 for a 9-hour session (10).
The conventional explanation is that the increase in
the total proportion of cycling time spent draining
and filling offsets the potential benefit of more frequently replenishing the peritoneal cavity with fresh
solution.
Two of the more recent studies have suggested that
the optimal cycling rate may be higher. Kumano et al.
found that 6 – 9 cycles gave the highest clearance in
an 8-hour APD session (17), while Durand et al. found
that, for CCr, the number was in the range of 7 – 10
per 9-hour session (18). Both of these studies, however, were based predominantly on modeled rather
than actual clinical data. Previous studies by
Pirpasopoulous et al. and by Robson et al. (from more
than 20 years ago and based on relatively small numbers of patients) suggest that 12 and 18 cycles per
9-hour treatment, respectively, would yield the best
urea and creatinine clearances (15,16).
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TABLE 5
Mean Nightly (±SD) Protein Excretion and Sodium and Potassium Removal with Four Different Automated
Peritoneal Dialysis (APD) Prescriptions [Sodium and Potassium Are from One Center Only (n=9)]
PEREZ et al.
554
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attempts are being made to augment peritoneal clearance. Addition of day dwells is likely to be more effective and less costly, but sometimes this is
contraindicated, or its potential is limited by patient
tolerance of daytime fluid due to mechanical symptoms or UF problems. Similarly, prolonging cycler time
is not always feasible for lifestyle reasons, and the
ability to increase cycle dwell volume may be limited
by mechanical concerns. Also, some investigators have
questioned the benefit of the latter strategy because
of theoretical concerns about compromising UF (12).
In all these situations, increasing the frequency of
cycles can be an effective strategy and should be
considered.
In general, the 14-L TPD prescription was superior to the 5 × 2-L standard prescription, but less effective than the 9 × 2-L, and not significantly different
from the 7 × 2-L prescription. The latter, of course,
represents the same amount of solution delivered in
a nontidal manner. The failure of TPD to perform well
is consistent with reports in recent literature (20–23).
At this stage, it seems reasonable to conclude that
TPD is ineffective for raising clearances and should
not be prescribed for this purpose. If there is any benefit for TPD in terms of clearances, it is probably not
seen unless much greater quantities of dialysis solution are used, and this is unlikely to be feasible in
routine practice (25). Of course, there may sometimes
be a case for some degree of TPD to be performed in
order to deal with pain occurring at the end of the
drain phase on APD.
It is difficult to explain why the influence of peritoneal transport status is relatively less in this study
than in those of Kumano (17) and Durand (18). It
should be pointed out, however, that the present study
was based on clinical measurements only and did not
use computer modeling, which may, for unclear reasons, exaggerate the effects of transport status on
clearance. The majority of patients in this study were
high or high-average transporters, as is often the case
in APD populations. However, the rise in clearances
with greater frequency of cycling was also seen in the
5 low and low-average transporters. The benefits of
increased cycling seen in this study also appear to be
somewhat greater than those predicted by commercial software programs, particularly in that increased
cycling leads to greater increments in clearance than
might be expected in low transporters. At least some
of this is accounted for by the better UF achieved with
increased cycling. In this context, it should be noted
that prediction of UF is less satisfactory than that of
clearance with existing computer programs (7–9).
However, it should also be noted that full modeling of
individual patients by the PD Adequest computer
program requires a more formalized PET than these
patients had, and so the comparison is based on aver-
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The present study addresses this question by systematically varying cycle frequency in a cohort of
18 APD patients, while maintaining all other prescription parameters constant. The results show that,
within the range of prescriptions studied, more cycles
consistently lead to more clearance. This is most
marked when the 5 × 2-L prescription is compared
with the 7 × 2-L and 9 × 2-L prescriptions. Five cycles
per night is a common prescription in clinical practice, but this study shows it to be inferior in terms of
urea and creatinine clearances, net UF, and sodium
and potassium removal.
The advantage of 9 × 2 L compared to 7 × 2 L is
less emphatic, although it was seen for both urea and
creatinine clearances, especially in high and highaverage transporters. The 9 × 2-L prescription also
tended to give greater sodium and potassium removal,
although the differences did not reach statistical
significance.
This benefit from more frequent cycling shows that
the loss of dwell time is effectively compensated by
the benefits of more frequent replenishment of the
peritoneal cavity with fresh dialysate, with consequent maximization of the gradient for diffusive clearance. Also, the shorter cycles are associated with better
maintenance of the glucose osmotic gradient, which
leads to better UF and further enhances clearance.
In terms of potential disadvantages of more frequent
cycling, there was no evidence in this study of any
increase in protein losses.
There has also been concern about exposure to more
glucose, with potentially adverse effects such as hyperglycemia, obesity, hyperlipidemia, and peritoneal
membrane damage. It is notable, however, that, while
the amount of instilled glucose increased with cycle
frequency, the percentage of infused glucose absorbed
fell significantly, and so the quantity absorbed rose
only modestly. Thus the potential toxicity from the
extra glucose load may be less than one might initially expect. There are no data, however, on the longterm effects of extra exposure to glucose.
Of course, more cycles require more dialysis solution and greater expense (24). The use of 14 and 18 L/
night is, respectively, 27% and 54% more costly than
that of 10 L. However, the percentage increase would
be relatively smaller if all costs of APD, including
nursing and physician time, were also taken into account. It might also be argued that any increased cost
may be offset by the potential improvement in outcomes resulting from increased clearance. Moreover,
there is a trend in many centers toward a standard
modality fee, such that the manufacturer of the tubing and solutions will charge the same amount of
money regardless of the APD prescription used.
This study does not conclude that increasing cycle
frequency is the strategy of choice in all patients when
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SEPTEMBER 2000 – VOL. 20, NO. 5
6.
7.
8.
9.
10.
11.
12.
13.
ACKNOWLEDGMENT
14.
The authors thank Baxter Canada for support of this
research and acknowledge in particular the help and advice
of Kimberly Thomas. This work was presented in part at
the 1997 meeting of the American Society of Nephrology.
15.
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