Document 177344

Proceedings of the ISPD '98 -The VIIIth Congress of the ISPD
August 23 -26. 1998, Seoul. Korea
Peritoneal Dialysis International, Vol. 19 (1999), Supplement 2
0896-8608/99 $300 + 00
Copyright © 1999 International Society for Peritoneal Dialysis
Printe d in Canada AIl rights reserved
Gianpaolo Amici,1 Giovambattista Virga,2 and Claudio Ronco3
Nephrology Division, 1 S. Maria dei Bat tu ti Hospital, Treviso; Nephrology Service,2 P. Cosma Hospital,
Camposampiero; Nephrology Department,3 S. Bortolo Hospital, Vicenza, Italy
peritoneal dialysis (APD) is
A utomated
growing dialysis treatment in the world at
the fastest
KEYWORDS: Automated peritoneal dialysis; treatment
prescription; treatment monitoring; solute removal index;
patient selection.
Correspondence to: C. Ronco, Department of Nephrology, S. Bortolo Hospital, Viale Rodolfi, 36100 Vicenza,
The nomenclature of various APD schedules has been
widened in recent years owing to slight modifications of the
different techniques. It is therefore important to define the
various schedules using a common terminology that permits
standard definitions in the international literature.
The following terms are today in use:
.Automated peritoneal dialysis (APD): This broad term
encompasses every type of peritoneal dialysis performed
with the aid of a machine, also called a cycler, regardless
ofmodality: nightly only or continuous, tidal or not tidal
.Nightly intermittent peritoneal dialysis (NIPD): NIPD is
APD performed nightly only, with complete fill and
drain of the peritoneal cavity (intermittent flow technique
or non tidal modality) (1,7).
.Nightly tidal peritoneal dialysis (NTPD): NTPD is APD
performed nightly only, with partial fill and drain of the
peritoneal cavity (tidal modality, also called
"reciprocating" in the past) (1,7).
.Continuous cyclic peritoneal dialysis (CCPD): CCPD is
APD performed nightly (intermittent flow technique or
non tidal modality), with the addition
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the present time. The evolution of this peritoneal dialysis
(PD) modality is closely linked to the development ofnew
automatic machines and to recent advances in prescription
and monitoring of PD treatment.
Since 1960, machines have been introduced to perform
semiautomatic or fully automatic PD treatment. In the early
days, peritoneal dialysis was mostly intermittent (IPD),
featuring a total of 24 hours per week divided into three or
more sessions. The applied technology was similar to the
hemodialysis machines of those years. The slow peritoneal
transport of solutes limited the efficiency of the treatments
In recent years, knowledge derived from the equilibration dialysis concept of continuous ambulatory peritoneal
dialysis (CAPD) and the availability of plastic bags (2) have
contributed to a rediscovery of intermittent peritoneal
dialysis techniques. APD has today become a daily home
treatment with automated nightly exchanges and one or two
daily dwells, following the concept of reversed CAPD
(continuous cyclic PD: CCPD) (3,4). The development of
ad hoc machines, easy to use and with a simpler operator
interface (the cyclers) (1), represented a further key factor in
this process of evolution.
Another important step in APD is represented by
microchips and computers. These components, incorporated
into PD cyclers, gave the machines greater programming
flexibility. Thanks to these innovations, it is now possible to
prescribe individualized fill volumes, variable tidal volumes
and additional daytime automated exchanges, teledialysis,
and memorized delivery control. At the same time,
miniaturization of
all components now allows full portability, owing both to
reduced dimensions and to light weight (5). Today in the
U.S.A.,APD is used by 31.9% ofall PD patients, including
daytime dwell mode, daytime empty mode, and schedules
with one or more additional manual exchanges (6).
Because CAPD has recently displayed its limitations and
new trends are aiming at increasing the dialysis dose in
peritoneal dialysis, newer PD techniques alternative to
CAPD seem to represent the answer to the new
requirements. Higher adequacy targets, together with the
search for a better quality of life, seem to be more easily
matched by APD. The possibility of using newer dialysis
solutions represents a further step in the increased
application of automated peritoneal dialysis techniques.
of one (CCPD1) or two (CCPD2) daytime dwells (1,7).
.Continuous tidal peritoneal dialysis (CTPD): CTPD isAPD
performed nightly (tidal modality), with the addition of
one (CTPD1) or two (CTPD2) daytime dwells (1,7).
.Intermittent peritoneal dialysis (IPD): IPD is APD
treatment prescribed mainly for a total duration of 24
hours per week divided into three or more sessions. The
dialysate flow is continuous: that is, without dwells (1,7).
.Borderline techniques: These techniques involve CAPD
with one or more automated exchanges using simple
machines without all the characteristics of a modern
cycler. These techniques reduce the number of
connections and can aid patients performing additional
exchanges (8,9).
Optimal fill volume (individualized for body size and
intraperitoneal pressure) (10,11), individual peritoneal
transport characteristics (12,13), and total prescribed
dialysate volume per session are the most important
parameters influencing efficiency and limiting APD
Using NTPD only, patients with a 4-hour creatinine (Cr)
D/P > 0.65 and total volumes between 25 L and 30 L per
session can reach a peritoneal creatinine clearance (CrCl)
higher than 50 L per week (14). This result is also confirmed
by Twardowski et al who found an average CrCl of 47 L per
week in NTPD patients with a mean Cr D/P = 0.66 (15).
Using CTPD2 (two diurnal dwells) in anuric patients, only
those with a Cr D/P > 0.65 can reach both Dialysis
Outcomes Quality Initiative (DOQI) targets (Kt/V = 2.1 and
CrCl/ 1.73 = 63 L/week), but total dialysis volumes of more
than 20 L/1.73 per session are needed (16).
Using NIPD with a mean 14 L total volume per session,
a mean CrCl/1.73 of27 L/week was obtained in 7 patients
(74 kg, 1.8 m2) with a mean Cr D/P = 0.68 (17). Another
study demonstrated a CrCl of 42.5 L per week and a Kt/V of
1.55 in 9 patients (75 kg mean body weight) on NIPD with a
total volume per session of about 10 L (18). Both studies
demonstrated that, despite a good compromise between
efficiency and number of liters prescribed having been
sought, when volumes lower than 20 L per session in NIPD
are used, inadequate results are likely to be expected.
Thus, for all APD techniques, only patients with a
peritoneal permeability higher than the mean (high and highaverage) can reach adequacy targets with a total volume per
session not less than 20 L/1.73.
Tidal modality, usually prescribed at 50% exchange
volume, has demonstrated equal or superior clearances to
non tidal modalities using the same dialysis
The prescribed dose does not always correspond to the
delivered dose. Catheter malfunction, changes in peritoneal
transport, and poor patient compliance are the main causes.
Catheter malfunction can be detected by periodically
measuring inflow and outflow times. Changes in peritoneal
transport can be suspected when blood chemistry changes in
the presence of a constant PD regimen. A peritoneal
equilibration test (PET) should therefore be prescribed and
compared to previous results.
To effectively monitor cycler function and patient
compliance, two possibilities exist: the "electronic" method,
based on machine control, or the "human"
method, with frequent home visits.
Removable memory storage is now available to register
all data from home sessions, and telecommu nication
systems can connect the center and the cycler
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time and volume (19,20). The major advantage of this
method is the increase in dialysate flow with shorter
exchange times and, consequently, the possibility of raising
total prescribed volumes (14,19,21,22).
A rational approach to increase peritoneal clearance in
APD must consider using tailored fill volumes. Because
intra-abdominal pressures are higher in the sitting position
than in the upright and supine positions (23), larger volumes
of dialysate are better tolerated while the patient is supine, as
during nocturnal APD. Increased and individualized dwell
volumes, and prescriptions for suitable total volumes per
session in APD, permit longer dwell times and allow for
better results in patients with a peritoneal permeability lower
than the mean. Common dwell volumes in APD are 40
mL/kg (21) or 2.5 L/1.73 (9,10).
It has been suggested that intra-abdominal pressure
values be kept below 18 cm H2O (11). Increased intraabdominal volume and pressure can lead to reduced
ultrafiltration and, consequently, can reduce the expected
clearance increase in APD (24).
Another approach to reach an optimal APD pre scription
in every single patient is to consider computer-assisted
kinetic modeling (25). Programs for this purpose are easily
available -PD Adequest (Baxter Healthcare, Deerfield
Illinois, U.S.A.), Pack PD (Fresenius Medical Care, Bad
Homburg, Germany), PDC (Gambro AB, Lund, Sweden) and all have in common a reliable mathematical model
describing the peritoneal dialysis system and an individual
peritoneal function test as data entry (26-33). With all of
these programs, it is possible to simulate APD regimen
results to iteratively achieve the desired optimi zation in each
solutes is markedly different in intermittent and continuous
treatments (34,37-39).
Mter the "peak concentration hypothesis," the proposal of
solute removal index (SRI) as an adequacy index that
overcomes all the compartmental problems seems
interesting. The rationale for SRI is that the removed solute
mass is normalized for the pre-dialy sis compartment (body)
content. Pre-dialysis urea and creatinine compartments are
effectively best equilibrated because they are as distant as
possible from the end of the previous treatment (37-40). In
that moment (pre-dialysis), blood is fully representative of
total body water concentration. Because SRI considers
solute body content, it is actually easy to calculate only for
urea and creatinine that are distributed in total body water.
SRI has for urea the same value and significance as Kt/V,
while for creatinine it represents the Kt/V of that solute. This
last index is very seldom used but has the same rationale as
urea Kt/V because creatinine has the same distribution
compartment (total body water) (41).
It now appears clear that SRI is different from the
classical Kt/V and CrCl only in using pre-dialysis blood
concentration. Thus, by using the pre-dialysis blood
concentration for standard (direct measurement) ofKt/V and
CrCl, all the compartmental problems are easily avoided,
eliminating the need for increased or different adequacy
targets in hemo dialysis, CAPD, NIPD/NTPD, or
CCPD/CTPD (40,42).
Using a double index (Kt/V, CrCl), target discrepancies
can present a problem: that is, one clearance above the target
value and the other clearance below the target value. Target
discrepancies have been reported in several papers, in both
APD (16,42) and CAPD ( 43,44). The most common finding
is that Kt/V easily reaches adequacy targets while CrCl does
not. Factors affecting this discordance are the intermit tent
nature of APD treatment (42), the degree of residual renal
function (43), and the peritoneal transport characteristics
(15,44). It is recommended in cases of discordance between
the two indices that Kt/V should be given primacy (36,45).
Previous studies have already reported that a considerable day-to-day variability exists in adequacy indices
derived from 24-hour collections in PD. This variability
affects the evaluation of dialysis adequacy in any PD
modality. Consequently, when single measurements are
close to adequacy targets, it is advisable to repeat them to
reduce the variability (46,47).
The CANUSA study represents a big effort towards
determining optimal indices and targets in CAPD (48).
However, that study was conducted without randomization
into different dose groups, and, consequently, it has not
answered all questions about PD adequacy. Moreover, no
APD patients were studied; the question if APD can give
better outcomes than CAPD is
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at the patient's home. The first system seems more practical;
but, with the expansion of teletransfer of data via cable or
satellite, the future spread of teledialysis is to be expected.
However, the direct measurement of clearances is crucial
in the assessment of treatment adequacy. Creatinine and
urea clearance are the most widely used adequacy indexes
in peritoneal dialysis and thus in APD. Commonly,
creatinine clearance is normalized to body surface area and
urea clearance to body water (Kt/V) and expressed on a
weekly basis.
In a steady-state condition, the calculation of clearance
(that is, the ratio between dialysis removal and body
concentration) entails the direct measurement of removal by
total fluid collection and assay, and a plasma sample that
represents the body compartment concentration of the
considered solute (34). In APD, with a high-efficiency
nightly treatment and dry days or 1 -2 diurnal dwells, the
intermittence or the variable intensity of the therapy causes
a compartmental disequilibrium effect that is expressed by
fluctuations in plasma concentrations between the predialytic (evening) and post-dialytic (morning) plasma values
(16,18). This difference is more marked for urea than for
creatinine (18).
The use of the post-dialytic plasma value in clearance
measurement, which is lower than the pre-dialytic value,
significantly overestimates Kt/V by 6.3% (18) to 14% (16).
The variability ofoverestimation is due to the different
efficiency of APD and consequently to the different
compartmental effect.
It is actually considered standard practice that the blood
sample be taken during the day at a time equally distant
from the previous and the subsequent nocturnal APD
sessions (35). This practice is equivalent to calculating an
averaged mean of blood concentrations; but, is the
composition of all body compartments well estimated using
this method?
Following the concept of intermittence or variable
intensity, it is common opinion that optimal adequacy
targets are higher in NIPD (Kt/V = 2.2 and CrCl/ 1.73 = 66
L) than in CCPD (Kt/V = 2.1 and CrCl/1.73 = 63 L), and
that both are higher than those in CAPD (Kt/V = 2.0 and
CrCl/1.73 = 60 L) (36).
The problem of different adequacy targets with different
treatments is again dependent on the effect of blood
concentrations on the calculation of clearances. The
difference in targets between hemo dialy sis and PD has the
same origin (34).
Treatments that differ for intermittence and intensity
present extremely different blood profiles. These blood
profiles are not representative of total body composition,
and in various moments they present a non linear dynamic
compartmental disequi
librium. Moreover, pre -dialysis blood concentration of
open. For trial design purposes, the use of indices not
influenced by compartmental effects can allow an easy and
direct adequacy comparison between different APD and
CAPD techniques.
In APD, the use of new solutions with alternative
osmotic agents, nutritional integration, reduced sodium
content, and alternative buffers seems very promising
As soon as bags and connections for APD are available,
it will be possible to use mixtures of various solutions
tailored to patient needs. In APD, amino acids together with
glucose are very promising because of the simultaneous
absorption of calories and nitrogen for protein anabolism.
The optimal proportion of glucose to amino acids in the
mixture can be 7:1, giv ing an approximate intake of 1 g of
nitrogen for every 112 kcal. This mixture has been used in a
long-term study on children with favorable results (53).
A mixture of amino acids and bicarbonate-buffered
solutions can also give good results because of better acid
buffering and enhanced protein anabolism.
Glucose-free APD will possibly be used in the future,
using a mixture of glycerol and amino acids during the night
and icodextrin during the day for ultrafiltration failure type
I. The rationale is that small osmotic agents such as glycerol
and amino acids are ideal for good ultrafiltration in short
dwells like those of APD, while better ultrafiltration during
longer daytime dwells could be obtained with icodextrins.
Moreover, a period of glucose-free PD could allow
recovery of a membrane with type I ultrafiltration failure
(reduction, exhaustion, or glycosylation of aquaporins).
Bicarbonate will soon be available inAPD with online
mixing of dialysate to avoid carbonate precipitation, as in
hemodialysis. However, the bicarbonate solution now
available in two-chambered bags may present a satisfactory
stability once the two solutions are mixed together. In fact,
available studies performed in continuous renal replacement
therapies, where peritoneal dialysis solutions are often used,
show that a bicarbonate solution with electrolytes and
glucose is stable without precipitation for up to 72 hours
Future trends can also see catheters overcoming flow
limitations with double-lumen catheters specific for
continuous-flow APD or recirculated APD performed with a
cycler using double pump and on-line mo nitoring of
intraperitoneal pressure (55).
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The assessment of individual peritoneal transport,
commonly using the PET, is a very important step in
selecting patients for a successful APD program. Not all
categories of peritoneal transport can reach satisfactory
results in terms of treatment adequacy with all APD
regimens. From previous studies, treatment adequacy for
low-transport patients was 6%, for low-average 31 %, for
high-average 53%, and for high 10% (9).
Nightly APD (with dry day) -that is, NIPD/ NTPD -can
give adequate results only in hightransport patients (9).
Moreover, in high transporters, NIPD/NTPD is strictly
indicated because it can reduce protein loss, glucose
absorption, and fluid retention.
CCPD/CTPD is indicated in high-average transport
patients. These patients, because of their peritoneal
transport, cannot reach adequate clearances with
NIPD/NTPD even at high volumes (14,16). With the
addition of a long daytime dwell, the efficiency of APD is
greatly increased in these subjects and a further increase is
achievable with two daytime dwells (9,16,49).
The use of tidal modality can increase dialysate flow and
reduce drain and fill times. Coupled with larger volumes, it
can raise clearances, but always in high or high-average
transporters (14,19-22). Moreover, tidal APD can be
indicated in cases of catheter malfunction.
There are no rational indications for any APD prescription in low-average and low transport patients. These
patients , even with high volumes, are unable to reach
adequate clearances inAPD because of their slow peritoneal
transport (14,16). The only practical indication occurs for
patients who must be treated by peritoneal dialysis and who
cannot perform CAPD.
With no data about peritoneal transport characteristics,
APD can be indicated as a first treatment in anuric patients
with a big body size (> 80 kg) who cannot reach adequacy
targets in CAPD. A continuous APD technique
(CCPD2/CTPD2) with large tailored fill volumes would be
used. APD as first-choice treatment is also indicated in non
self patients, in children, in patients with hernias and leaks,
and for lifestyle needs.
APD as second treatment can be useful in CAPD patients
with burnout or with changes in peritoneal transport
characteristics towards a higher degree of
peritoneal permeability. In these situations, the APD option
can effectively reduce the dropout rate. APD can further
reduce the dropout rate because the rate of infectious
episodes seems lower with this technique (50) and
becauseAPD is generally very well accepted by the patients
Moreover, in the future, biosensors can be placed on
cyclers for many purposes. The intraperitoneal pressure can
be measured continuously for on-line optimization offill
volume. Closely linked to the pressure, flow speed can also
be measured for on-line optimization of exchange times. In
the peritoneal fluid, pO2' pCO2, and pH can be measured
for both on-line bicarbonate mixing and acid-base and
oximetry monitoring, and is possibly also useful for cases of
sleep apnea syndrome. Urea can also be easily monitored
on-line, together with the conductivity of the dialysate (in
the case of on-line fluid production). Lastly, white blood
cells in the dialysate can be monitored on-line for early
diagnosis of peritonitis (56).
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