Comparison of iCodextrin and GluCose solutions for lonG dwell

Peritoneal Dialysis International, Vol. 31, pp. 179-188 doi:10.3747/pdi.2009.00264

0896-8608/11 $3.00 + .00Copyright © 2011 International Society for Peritoneal Dialysis

179

Comparison of iCodextrin and GluCose solutions for lonG dwell exChanGe in peritoneal dialysis: a meta-analysis of randomized Controlled trials

Hualin Qi,1 Chen Xu,2 Haidong Yan,1 and Jun Ma2

Department of Nephrology,1 East Hospital, and Department of Nephrology,2 Tongji Hospital; Tongji University School of Medicine, Shanghai, China

Correspondence to: J. Ma, Department of Nephrology, Tongji Hospital, Tongji University School of Medicine, 389 Xin Cun Road, Shanghai 200065, China.

[email protected] 27 December 2009; accepted 14 September 2010.

♦ Background: Icodextrin is widely used in peritoneal dialysis (PD); however, the safety and efficacy of icodextrin are unclear. In the present study, we performed a system-atic review of randomized controlled trials (RCTs) that compared icodextrin and glucose for the once-daily long dwell in PD.♦ Methods: Electronic searches were performed in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to select all eligible studies. Eligible studies, as determined by consensus using predefined criteria, were reviewed, and data were extracted onto a standard form.♦ Results: In the 9 RCTs that were identified, patients using icodextrin were found to have much greater net ultrafiltra-tion (UF) and a lower incidence of negative net UF compared to patients using 1.5%, 2.5%, and 4.25% glucose solutions. Additionally, icodextrin has a markedly increased UF ef-ficiency ratio and peritoneal clearance of creatinine and urea nitrogen, but residual renal function was not different from patients using glucose solutions for PD. No significant differences were observed between icodextrin and glucose groups with respect to risk of mortality, peritonitis, and total adverse events. Although rashes occurred significantly more often in icodextrin groups, few differences were noted between icodextrin and glucose groups when withdrawal rates secondary to adverse events were compared.♦ Conclusions: This meta-analysis suggests that icodextrin provides patients with greater fluid removal and small sol-ute clearance and does not cause any damage to residual renal function. Icodextrin is particularly appropriate for use in patients with high peritoneal transport status.

Perit Dial Int 2011; 31:179-188 www.PDIConnect.comepub ahead of print: 30 Nov 2010 doi:10.3747/pdi.2009.00264

KEY WORDS: Icodextrin; systematic review; meta-analysis; clinical outcomes.

Peritoneal dialysis (PD) has been a successful modality for chronic renal replacement therapy for more

than 30 years. Currently, glucose is the main osmotic agent in PD, but it is associated with several long-term complications. Glucose solutions may positively affect ultrafiltration (UF) via the osmotic gradient between the peritoneal capillaries and the dialysis solution (1–3). However, as a result of its rapid absorption across the peritoneal membrane, the osmotic gradient of glucose is lost over longer dwell periods, particularly in patients with high peritoneal transport characteristics, leading to reduced UF and even loss of UF capacity (4). The frequen-cy of loss of UF in PD patients necessitating a transfer to hemodialysis has been reported to vary between 17.7% and 24% (5,6). The cumulative risk of developing per-manent UF loss has been reported to be 3% after 1 year, 10% after 3 years, and 31% after 6 years of continuous ambulatory PD (CAPD) treatment (7). A further limita-tion of glucose-based solutions is that absorption of glucose can contribute to metabolic complications such as hyperglycemia, hyperinsulinemia, hyperlipidemia, and obesity (8). In addition, there has been growing concern that the hyperosmolality and low pH of this solution may damage the peritoneum and thereby threaten its viability as a dialyzing membrane (9,10). Thus, the need for a more physiological solution containing an osmotic agent that would provide sustained UF and minimize metabolic complications has led to an extensive search for alternatives (11).

Icodextrin, a glucose polymer with an average molecu-lar weight of 17000 Da, acts as a colloid osmotic agent. Compared with glucose-based PD solutions, icodextrin has many advantages, including its ability to provide a sustained, positive net UF for at least 16 hours, mak-ing it particularly useful for the long dwell exchange in patients on CAPD and automated PD (APD). It has been shown that, in patients with UF failure, icodextrin can extend the time on PD (12). Emerging evidence suggests this iso-osmotic solution may be less damaging to the

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QI et al. MarCH 2011 – Vol. 31, No. 2 PDI

were published in English-language medical journals. Because of carryover effects, all crossover trials were excluded from our meta-analysis (16). Disagreements, if any, regarding the eligibility of a study were resolved by a third party through consensus.

DATA EXTRACTION AND QUAlITY ASSESSMENT

A standard method was used to record the following properties of each study: study characteristics (design, sample size, duration of follow-up); participants (age, sex, estimated glomerular filtration rate, cause of end-stage renal disease); PD regimens (concentration of glucose, modality, and method of measuring peritoneal equilibration test); and outcomes. We considered the following outcomes: effectiveness [net UF, peritoneal clearances of creatinine and urea nitrogen, incidence of negative net UF, UF efficiency ratio (UFE), and preser-vation of residual renal function] and safety (mortality, rash, PD-related peritonitis, and total adverse events). One reviewer extracted the data and a second checked for accuracy. Attempts to contact authors were made when further information was required to extract data for the outcome of interest.

The quality of included studies was assessed indepen-dently by 2 reviewers using the checklist developed by the Cochrane Renal Group and Jadad score. The quality items assessed were allocation concealment, intention-to-treat analysis, completeness to follow-up, and blinding of investigators, participants, and outcome assessors. When data were missing or incomplete, investigators of the trials were contacted by written correspondence for clarification.

STATISTICAl ANAlYSIS

Treatment effects were summarized with the relative risk (RR) measure and its 95% confidence interval (CI) for dichotomous outcomes and the weighted mean differ-ence and its 95% CI for continuous outcomes. Standard deviations (SDs) were imputed using interquartile ranges and full ranges. The methods used for calculating SDs are referenced in the Cochrane handbook (17). The weighted mean difference was used to pool the values for net UF, UFE, residual renal function, and peritoneal clearances of creatinine and urea nitrogen, which were reported using the same scale of measurement in all studies. The RR was used to pool the values for incidence of long-dwell nega-tive UF, mortality, peritonitis incidence, adverse events, and withdrawal rate. The estimates from individual RCTs were pooled using the random-effects model when appropriate. The fixed-effect model was also computed

peritoneal membrane than glucose-based dialysates (13–15). Currently, a 7.5% icodextrin-based solution (Extraneal; Baxter Healthcare, Castlebar, Ireland) is ap-proved for marketing in 31 countries and is used by over 8000 PD patients worldwide.

Although the efficacy and safety of icodextrin have been described in a majority of publications, some stud-ies show conflicting results. The primary objective of the present meta-analysis is to address the efficacy and safety of 7.5% icodextrin PD solution for the long dwell exchange in PD patients and to establish indications for icodextrin.

METhoDs

We systematically reviewed randomized controlled trials (RCTs) that evaluated the efficacy and safety of 7.5% icodextrin PD solutions for the long dwell exchange in PD.

SEARCH STRATEGY

Identification of RCTs was done by electronic searches in MEDlINE (1966 to June 2010), EMBASE (1980 to June 2010), and the Cochrane Central Register of Controlled Trials (CENTRAl) (up to June 2010) using optimally sen-sitive search strategies developed by the Cochrane Col-laboration. The key terms “renal replacement therapy,” “renal dialysis,” “peritoneal dialysis,” “icodextrin,” and “glucose” were used with the Dickersin filter. Studies considered relevant by 1 or 2 reviewers were retrieved for further review. The reference lists of included trials and relevant reviews were also reviewed for pertinent trials. We also contacted the authors of included studies for information about further studies.

STUDY SElECTION

Each potentially relevant study was independently assessed by 2 reviewers for inclusion in the review using predetermined eligibility criteria and a preprinted form. Studies meeting the following criteria were considered to be eligible: (1) study design: parallel randomized controlled studies with 10 or more allocated participants in at least 2 intervention groups; (2) population: adults on PD (CAPD for at least 3 months or APD for at least 30 days); (3) comparison: 7.5% icodextrin and glucose PD solutions for the long dwell exchange in PD; and (4) outcomes: efficacy (net UF during the long dwell, peritoneal clearances of creatinine and urea nitrogen, incidence of negative net UF, and preservation of residual renal function) and safety (mortality, rash, PD-related peritonitis, and total adverse events). All included trials




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PDI MarCH 2011 – Vol. 31, No. 2 COMPARISON OF ICODEXTRIN AND GlUCOSE SOlUTIONS IN PD

to evaluate robustness and susceptibility to outliers. Heterogeneity of treatment effects between studies was formally tested using Q (heterogeneity χ2) and I2 statistics. Subgroup analysis was planned to explore how possible sources of heterogeneity (diabetic status, glu-cose concentration, peritoneal solute transporter status) might have influenced the treatment effect. Sensitivity analysis was performed to assess the influence of indi-vidual studies on the pooled estimate by excluding one study at a time, as described previously. When the point estimate of the revised pooled estimate was outside the 95% CI of the original estimate, the study in question was deemed to have excess influence.

These analyses were undertaken using RevMan 5.0 (The Cochrane Collaboration, UK). Funnel plots, Egger’s regression asymmetry test, and Begg’s test were used to probe for publication bias using STATA software (version 11.0; Stata Corp., College Station, TX, USA). Statistical significance was set at p < 0.05 for all analyses.

REsULTs

TRIAl FlOW AND STUDY CHARACTERISTICS

The decision process that was used to differentiate among studies considered for inclusion is shown in Figure 1 as a flow chart. A combined electronic search identified 936 potentially relevant studies, from which 810 stud-ies were initially excluded. The full-text versions of 34 studies were retrieved, 22 of which were subsequently excluded. Among other studies, 3 articles (18–20) came from the same study at different stages and another 2 ar-ticles (21,22) from 1 study were published in different journals. Finally, 9 trials published in 12 articles (18–29) with a total of 1190 participants were included in this present review, yielding 633 subjects in the icodextrin group and 557 subjects in the glucose group. The popula-tion and study characteristics administered in the RCTs are listed in Table 1. Not all outcomes were in the criteria reported by each trial. Quality assessment of the studies is summarized in Table 2.

Authors of all included trials were contacted for clarification regarding trial methodology and additional unpublished data; only 2 (26,28) replied to our queries. All studies had a parallel design.

ASSESSMENT OF PUBlICATION BIAS

To assess the presence of publication bias, a funnel plot was performed, which showed little asymmetry (Figure 2). Moreover, Egger’s test indicated no statistical evidence of publication bias (bias = 1.82, p = 0.11; Figure 2).

EFFICACY

Five categories of efficacy were considered and the data available for each varied.

Of the 9 trials, only 6 provided net UF and SD or stan-dard error (SE) during the long dwell. Other trials report-ed net UF change, total UF, or only UF but without SD or SE. There was evidence of heterogeneity between studies (χ2 = 13.82, p = 0.03, I2 = 57%). Therefore, we compared icodextrin with different glucose concentrations (1.5%, 2.5%, 4.25%) respectively. Compared to 1.5%, 2.5%, and 4.25% glucose, net UF was increased significantly in pa-tients who used icodextrin for PD (icodextrin group; Table 3). Next, we compared icodextrin with glucose according to peritoneal membrane transport characteristics. Of all the trials, 3 reported high/high-average transporters and 2 reported low/low-average transporters. Because 1 trial (27) reported high and high-average transport-ers separately, we analyzed it as 2 trials. Results show that icodextrin is superior to glucose for net UF in high-average/high and low-average but not low/low-average transporters (Table 3).

Four trials mentioned the incidence of negative net UF during the long dwell. Across 4 trials, heterogeneity was not significant (χ2 = 3.67, p = 0.3, I2 = 18.2%). The icodextrin group was found to have significantly lower incidence of negative net UF (4 trials, 677 patients; RR 0.13, 95% CI 0.07 – 0.25) in comparison to glucose. In

Figure 1 — Flow chart indicates the number of citations re-trieved by individual searches and the final number of included trials; reasons for exclusions are provided. CCTR = Cochrane Controlled Trials Register; PD = peritoneal dialysis.




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TABl

E 1

Char

acte

rist

ics

of th

e Po

pula

tion

s in

the

Rand

omiz

ed C

ontr

olle

d Tr

ials

Incl

uded

in T

his

Revi

ew

Re

fere

nce

Mis

try

(22)

Po

sthu

ma

(18)

W

olfs

on (

26)a

Plum

(27

) Ko

ning

s (2

5)

Davi

es (

24)

Fink

elst

ein

(23)

Pa

niag

ua (

29)

lin

(28)

(I/G

) (I

/G)

(I/G

) (I

/G)

(I/G

) (I

/G)

(I/G

) (I

/G)

(I/G

) (I

/G)

Year

19

94

2000

20

024w

20

0252

w

2002

20

03

2003

20

05

2009

20

09Sa

mpl

e (n

) 10

6/10

3 19

/19

90/8

5 17

5/11

2 20

/19

22/1

8 28

/22

47/4

5 30

/29

98/1

03Ag

e (y

ears

; mea

n)

55/5

5 49

/56

54/5

5 54

/55

46/4

5 53

/56

56/5

4 50

/53

59/6

1 57

/55

Mal

e (n

) 71

/67

10/1

7 34

/26

93/5

0 17

/13

14/1

5 15

/10

28/2

8 12

/16

51/4

5rG

FR (

ml/

min

; mea

n)

NA

2.4/

2.8

NA

2.

4/2.

4 5.

4/4.

1 N

A N

A N

A 2.

4/2.

5Fo

llow

-up

dura

tion

(m

onth

s)

6 24

1

13

3 4

6 1

12

1Ca

use

of E

SRD

(%)

Di

abet

es

10/8

0/

5 27

/25

30/3

5 10

/10

NA

0/10

30

/36

100/

100

25/2

0

Hyp

erte

nsio

n 23

/23

NA

27/2

2 23

/21

5/0

NA

7/10

28

/22

—

14/1

3

Glom

erul

onep

hrit

is

16/1

6 26

/32

16/1

9 15

/18

45/3

7 N

A 29

/27

13/2

2 —

42

/36

Ot

her

51/5

3 74

/63

30/3

4 32

/26

40/5

3 N

A 64

/53

29/2

0 —

19

/31

PET

met

hod

Stan

dard

N

A St

anda

rd

Stan

dard

St

anda

rd

Stan

dard

St

anda

rd

Stan

dard

St

anda

rdD/

P cr

eati

nine

N

A N

A N

A 0.

36/0

.37b

0.64

/0.6

5 0.

76/0

.78

0.85

/0.8

3 0.

81/0

.79

NA

Peri

tone

al tr

ansp

ort

H

igh

(%)

NA

NA

18/1

2 12

/7

NA

NA

100/

100

100/

100

100/

100

9/15

H

igh

aver

age

(%)

NA

NA

42/4

3 48

/54

NA

NA

40

/32

lo

w a

vera

ge (

%)

NA

NA

34/4

2 38

/35

NA

NA

—

—

—

35/4

6

low

(%

) N

A N

A 6/

3 2/

4 N

A N

A —

—

—

14

/7Co

ncen

trat

ion

of g

luco

se

1.5%

/4.2

5%

2.5%

2.

5%

2.5%

1.

5%

2.5%

4.

25%

2.

5%

2.5%

Mod

e of

PD

CAPD

CC

PD

CAPD

/APD

AP

D CA

PD /

CCPD

CA

PD/A

PD

APD

CAPD

CA

PD

rGFR

= re

sidu

al g

lom

erul

ar fi

ltra

tion

rate

; ESR

D =

end-

stag

e re

nal d

isea

se; P

ET =

per

iton

eal e

quili

brat

ion

test

; D/P

= d

ialy

sate

-to-

plas

ma

rati

o; P

D =

peri

tone

al d

ialy

sis;

I/G

= ic

odex

trin

/glu

cose

; NA

= no

t ava

ilabl

e; C

APD

= co

ntin

uous

am

bula

tory

PD;

CCP

D =

cont

inui

ng c

yclin

g PD

; APD

= a

utom

ated

PD.

a Inc

lude

s 2

tria

ls: a

4-w

eek

effi

cacy

stu

dy a

nd a

52-

wee

k sa

fety

stu

dy.

b D/D

0 glu

cose

.




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addition, we compared icodextrin with different glucose concentrations respectively. Incidence of negative net UF in the icodextrin group was lower than in those with different glucose concentrations.

The third measure of efficacy was the UF efficiency ratio (UFE), defined as net UF volume (in milliliters) per gram of carbohydrate absorbed from the long dwell dialysate. The UFE associated with icodextrin was significantly higher compared with that in the glucose group (Figure 3).

There was no evidence of heterogeneity between stud-ies for the other two efficacy parameters. Compared to the glucose group, peritoneal clearances of creatinine and urea nitrogen were increased significantly in the icodextrin group (Figure 4). However, residual renal function was not preserved in patients from the 7.5% icodextrin group (Figure 5).

TABlE 2Quality Assessment of Randomized Controlled Trials Included in This Systematic Review

Centers Allocation Intention-to- lost to JadadReference (n) concealment Blinding treat analysis follow-up score

Mistry (22) 11 Adequate No Yes 71/209 3Posthuma (18) 2 Unclear No No 25/38 2Wolfsona (26) Multiple Adequate Yes Yes 12/175a 5 118/287a

Plum (27) 8 Unclear No No 6/39 2Konings (25) 1 Adequate No No 8/40 3Davies (24) 3 Adequate Yes Yes 8/50 5Finkelstein (23) Multiple Adequate Yes Yes 7/92 5Paniagua (29) 1 Adequate No No 23/59 3li (28) 7 Adequate Yes Yes 18/201 5

a Includes 2 trials: a 4-week efficacy study and a 52-week safety study.

Figure 2 — Funnel plot of publication bias. se = standard error; rr = relative risk.

TABlE 3Comparison of the Effects of Icodextrin and Glucose on Net Ultrafiltration During the long Dwell

Studies Patients Results Heterogeneity Overall effectOutcome analyzed (n) (n) WMD 95% CI (p valuea) (p valueb)

Different concentration glucose solutions 6 698 287.08 241.28–332.88 0.03 0.00 1.5% glucose 1 105 460.00 332.38–587.62 NA 0.00 2.5% glucose 4 428 268.26 215.74–320.78 0.35 0.00 4.25% glucose 2 165 215.16 77.49–352.83 0.16 0.00Different PET categories High/high average 4 212 339.60 224.14–455.07 0.39 0.00 low average 2 151 146.79 70.18–223.40 0.42 0.00 low 2 91 50.96 –50.54, 152.45 0.14 0.33

PET = peritoneal equilibration test; WMD = weighted mean difference; CI = confidence interval; NA = not available.a p < 0.05 indicates the presence of significant heterogeneity across trials. The analysis of heterogeneity is applicable only where

more than 1 trial provided data on the relevant outcome.b p < 0.05 indicates the presence of significant overall effect.




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SAFETY

Five categories of safety were considered and the data available for each varied. However, there was no evidence of heterogeneity between the different studies in any of the five safety parameters assessed.

No differences were detected between icodextrin and glucose groups with respect to risk of mortality (4 trials, 735 patients; RR 0.94, 95% CI 0.50 – 1.76), rates of per itonitis (5 tr ials, 2371 patients; RR 0.94, 95% CI 0.73 – 1.21), and total adverse events (3 trials, 449 patients; RR 1.08, 95% CI 0.75 – 1.58). However, rash occurred signif icantly more of ten in the icodextr in group (4 tr ials, 795 patients;

RR 2.57, 95% CI 1.52 – 4.35; Figure 6) compared with the glucose group.

All trials reported rate of withdrawal because of adverse events and the data available for each varied. However, there was no evidence of heterogeneity be-tween studies. No differences were detected between icodextrin and glucose groups with respect to rate of withdrawal due to adverse events (9 trials, 1190 patients; RR 1.02, 95% CI 0.78 – 1.34).

SENSITIVITY ANAlYSIS

We performed a sensitivity analysis to evaluate the robustness of this meta-analysis. The quality of one

Figure 3 — Comparison of the effects of icodextrin and glucose on the ultrafiltration efficiency ratio (UFE). IV = inverse variance statistical method.

Figure 4 — Comparison of the effects of icodextrin and glucose on the peritoneal clearances of creatinine and urea nitrogen. IV = inverse variance statistical method.




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trial (18–20) was poor and many patients were lost to follow-up. The results were not altered significantly when this trial was removed from the analysis.

DIsCUssIoN

In this meta-analysis we identified the current RCTs that compare the efficacy and safety of icodextrin and glucose for the once-daily long dwell in PD. Our meta-analysis showed an increase in net UF, small solute clearance, and UFE and a significant decrease in the percentage of patients with negative net UF during the long dwell with 7.5% icodextrin PD solution compared with glucose solutions. Significant differences with respect to other important clinical benefits, such as risk of mortality, rate of withdrawal secondary to severe adverse events, and preservation of residual renal function, were not found in the studies of both icodextrin and glucose PD solutions. Total adverse events and peritonitis rates were also not different between both PD solutions, but rash events hap-pened more frequently in patients receiving icodextrin than in those receiving glucose. Compared to glucose patients, PD patients treated with icodextrin experienced substantial improvement in quality of life (30).

Previously, one meta-analysis demonstrated that a higher peritoneal membrane solute transport rate was

associated with fluid retention, a higher mortality risk, and a trend to higher technique failure (31). Icodextrin addresses one of the critical areas of vulnerability in fluid management in patients on PD: maintaining adequate UF during the long dwell. Studies that examined the relationship between patient transport status and net UF (22,23,25,27) showed that the improvements in net UF with icodextrin were greatest in patients with high and high-average membrane transport characteristics. Con-sistent with that observation, evidence derived from our review showed better UF in patients receiving icodextrin with high, high-average, and low-average but not low transport characteristics. However, since the follow-up time lasted less than 1 year, these studies did not report mortality or technique failure. Therefore, future studies should extend the follow-up period.

Preservation of residual renal function is of great im-portance as it has been shown to be a predictor of patient survival on PD (32–34). Compared to glucose, icodextrin produced increased sustained UF during the long dwell period. Did potential volume depletion result in a drop in residual urine volume, thus counterbalancing the beneficial effects of increased UF? Some studies showed that icodextrin is associated with a more rapid loss of residual renal function compared to glucose (25,26); however, other studies showed no difference (20) or

Figure 6 — Comparison of rash caused by icodextrin and glucose. M-H = Mantel–Haenszel statistical method.

Figure 5 — Comparison of the effects of icodextrin and glucose on residual renal function. IV = inverse variance statistical method.




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contradictory results (27). Results from our review did not show any difference in end-of-study period endog-enous creatinine clearance (i.e., residual renal function) between either osmolarity solution. The heterogeneity of the published results can, in part, be related to dif-ferences in inclusion criteria: patients who already have a low glomerular filtration rate at entry are unlikely to suffer significantly more damage. On the other hand, this would suggest that icodextrin has a relative protective effect in preserving urine volume when UF is increased. An alternative explanation might be that the extracellular fluid compartment contracted due to a reduction in the interstitial rather than the intravascular space (25). But this dramatic change in fluid removal caused fluid deple-tion and subsequent hypotension (26) in the patients with reduction in urine volume and residual renal function. It is becoming increasingly clear that one of the primary responsibilities of clinicians in the management of PD patients is the balance between adequate control of fluid status and preservation of residual renal function.

Numerous clinical studies (18–30,35–37) and more than 9 years of post-marketing surveillance have confirmed that icodextrin is a safe and well-tolerated osmotic alternative PD solution to glucose. The most significant adverse effect reported to date is a cutane-ous hypersensitivity reaction (38,39). Our meta-analysis results also showed that the incidence of skin rashes was increased significantly in patients using icodextrin. The rash usually develops early in therapy, is self-limited, and resolves without sequelae after discontinuation of icodextrin.

Although increased levels of maltose and oligosaccha-rides were reported in all the trials, no adverse clinical effects were ascribed to icodextrin or its metabolites. Use of icodextrin was associated with a significantly greater UFE, indicating that more ultrafiltrate was pro-duced for each gram of carbohydrate absorbed from the dialysate. Reduction of daily carbohydrate absorption through the use of icodextrin may help to reduce the risk of metabolic complications, appetite suppression, obesity, and peritoneal glucose exposure. Our evidence shows too that peritonitis rates are not different between icodextrin- and glucose-treated PD patients. In short, no differences between groups were found for the incidence of total adverse events in our meta-analysis.

This meta-analysis has several limitations: (1) Trial quality varied greatly among RCTs (Table 2). Specifi-cally, some trials had a higher percentage of patients lost to follow-up (18,22,26) compared to the other trials used in this study. (2) Since icodextrin is a solu-tion containing a spectrum of high molecular weight polysaccharides that are absorbed slowly across the

peritoneal membrane, it has been suggested that certain patient groups, such as diabetics, may benefit from the use of such a non-glucose solution. But only one trial reported and analyzed the outcome of diabetic patients independently. (3) The follow-up period between the different RCTs was heterogeneous (variance between 1 year and < 1 year) (23–26,30) and inadequately powered to detect events (i.e., increased the likelihood of type 2 statistical errors). This variability is difficult to account for in meta-analysis and may not be explored further given the overall small number of available RCTs. There-fore, these trials are not appropriate for assessment of long-term clinical outcomes. In short, the results of this review should be interpreted with caution owing to the inherent limitations of the included trials. It does therefore appear that the data from currently available RCTs are not sufficient for us to reach definitive conclu-sions about the relative clinical effectiveness and safety of icodextrin and glucose with respect to important clinical outcomes.

Given the limitations of the trials identified in this re-view and the advances that have occurred in PD solutions over the past 10 years, there is a great need for a large well-designed good-quality RCT comparing icodextrin with glucose solution, with a look at clinically important outcomes accompanied by an economic evaluation to reliably inform both patients and nephrologists about the relative clinical effectiveness of these PD solutions and the cost implications to healthcare providers. Such a trial could also be used to explore patient satisfaction and treatment preferences for these PD solutions. Future studies should take into account the high dropout rate noted in the previous trials and recruit a sufficiently large study population to offset patients likely to be lost during the trial period.

DIsCLosUREs

The authors have no financial conflicts of interest.

ACkNowLEDgMENTs

We are grateful to the following authors who provided supple-mental information regarding their work: M. Wolfson (26) and A.W. lin (28).

REFERENCEs

1. Nolph KD, Ryan l, Moore RH, legrain M, Mion C, Oreo-poulos DG. Factors affecting ultrafiltration in continu-ous ambulatory peritoneal dialysis. Perit Dial Bull 1984; 4:14–19.




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Comparison of iCodextrin and GluCose solutions for lonG dwell