Invest Clin 63(3): 283 - 303, 2022 https://doi.org/10.54817/IC.v63n3a07
Corresponding author: Huimin Guo, Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to
Shandong First Medical University, No. 324, Jingwu Road, Huaiyin District, Jinan, Shandong, China. Tel.: 86-0531-
68776577. Email: guohuiminmail@126.com
The benefits of peritoneal dialysis (PD)
solution with low-glucose degradation
product in residual renal function
and dialysis adequacy in PD patients:
A meta-analysis.
Sheng Chen1, Jieshuang Jia2, Huimin Guo3 and Nan Zhu2
1Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang,
China.
2Department of Nephrology, Shanghai General Hospital, Shanghai, China.
3Department of Nuclear Medicine, Shandong Provincial Hospital Affiliated to Shandong
First Medical University, Jinan, Shandong, China.
Key words: glucose degradation products; peritoneal dialysis solution; residual renal
function; dialysis adequacy; meta-analysis.
Abstract. The peritoneal effects of low-glucose degradation product (GDP)-
containing peritoneal dialysis (PD) solutions have been extensively described. To
systematically evaluate the efficacy and safety of low GDP solution for PD patients,
specifically the effect on residual renal function (RRF) and dialysis adequacy, we
conducted a meta-analysis of the published randomized controlled trials (RCTs).
Different databases were searched for RCTs that compared low GDP-PD solutions
with conventional PD solutions in the treatment of PD patients with continuous
ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD).
The outcomes of RCTs should include RRF and may include small solute clear-
ance, peritoneal transport status, nutritional status, and all-cause mortality.
Seven studies (632 patients) were included. Compared with the conventional
solution, low-GDP solution preserved RRF in PD patients over time (MD 0.66
mL/min, 95% CI 0.34 to 0.99; p<0.0001), particularly in one year of treatment
(p<0.01), and improved weekly Kt/V (MD 0.11, 95% CI 0.05 to 0.17; p=0.0007)
without an increased 4-hour D/Pcr (MD 0.00, 95% CI -0.02 to 0.02; p=1.00).
Notably, the MD of RRF and urine volume between the two groups tended to
decrease as time on PD progressed up to 24 months. Patients using low GDP PD
solutions did not have an increased risk of all-cause mortality (MD 0.97, 95% CI
0.50 to 1.88; p=0.93). Our meta-analysis confirms that the low GDP PD solution
preserves RRF, improves the dialysis adequacy without increasing the peritoneal
solute transport rate and all-cause mortality. Further trials are needed to deter-
mine whether this beneficial effect can affect long-term clinical outcomes.
284 Chen et al.
Investigación Clínica 63(3): 2022
Beneficios de la solución de diálisis peritoneal (DP),
con producto de degradación bajo en glucosa, en la función
renal residual y la adecuación de la diálisis en pacientes en DP:
un metanálisis.
Invest Clin 2022; 63 (3): 283 – 303
Palabras clave: productos de degradación de glucosa; solución de diálisis peritoneal;
función renal residual; adecuación de diálisis; metanálisis.
Resumen. Los efectos peritoneales de las soluciones de diálisis peritoneal
(DP) que contienen productos de degradación bajos en glucosa (PIB) se han
descrito ampliamente. Para evaluar sistemáticamente la eficacia y la seguridad
de la solución de PIB bajo para pacientes en DP, específicamente el efecto sobre
la función renal residual (RRF) y la adecuación de la diálisis, realizamos un me-
tanálisis de los ensayos controlados aleatorios (ECA) publicados. Se realizaron
búsquedas en diferentes bases de datos de ECA que compararan la solución
de DP de bajo PIB con la solución de DP convencional en el tratamiento de
pacientes con EP con CAPD y APD. Los resultados de los ECA deben incluir
la RRF y pueden incluir la depuración de solutos pequeños, el estado nutricio-
nal, el estado del transporte peritoneal y la mortalidad por todas las causas.
Se incluyeron siete estudios (632 pacientes). En comparación con la solución
convencional, la solución de bajo PIB preservó la FRR en pacientes con EP a lo
largo del tiempo (DM 0,66 mL/min, IC del 95%: 0,34 a 0,99; p<0,0001), parti-
cularmente en un año de tratamiento (p<0,01), y mejoró el Kt/V semanal (DM
0,11, IC del 95%: 0,05 a 0,17; p = 0,0007), sin un aumento de D/Pcr a las 4
horas (DM 0,00, IC del 95%: -0,02 a 0,02; p = 1,00). Los pacientes que usaron
una solución para DP con bajo contenido de GDP no tuvieron un mayor ries-
go de mortalidad por todas las causas (DM 0,97; IC del 95%: 0,50 a 1,88; p =
0,93). Nuestro metanálisis confirma que la solución de DP de bajo PIB preserva
la FRR, mejora la adecuación de la diálisis sin aumentar la tasa de transporte
peritoneal de solutos y la mortalidad por todas las causas. Se necesitan más
ensayos para determinar si este efecto beneficioso puede afectar los resultados
clínicos a largo plazo.
Received: 06-01-2022 Accepted: 22-04-2022
INTRODUCTION
Peritoneal dialysis (PD) has become an
established form of renal replacement ther-
apy for patients with end-stage renal disease
(ESRD) in the past thirty years 1. In 2008,
there were approximately 196,000 PD pa-
tients worldwide, representing 11% of the
dialysis population 2 and the number is in-
creasing by at least 6% per annum 3.
Conventional peritoneal dialysis solu-
tions (CS) are acidic and contain high levels
of glucose degradation products (GDPs) as
a result of the heat sterilization process 9.
GDPs as a major factor in the bioincompat-
ibility of peritoneal solutions10, exert poten-
The benefits of peritoneal dialysis solution 285
Vol. 63(3): 283 - 303, 2022
tially negative effects on both the structural
and functional deterioration of peritoneum
and systemic metabolic disturbance, leading
to treatment failure and an increase in car-
diovascular morbidity and mortality 11. Re-
sidual renal function (RRF) plays a vital
role in the prognosis of patients on dialy-
sis4, which evaluates the excretion of small
solute and middle-molecular uremic tox-
ins 5, salt and water homeostasis, acid-base
balance, nutritional status and associated
survival6-8. Accumulating evidence from epi-
demiological and experimental researches
10,12-14 reveals that low-GDP peritoneal dialy-
sis solutions (LS) may play a role in retard-
ing RRF loss in PD patients 14. However, not
all clinical trials show encouraging results
of the perceived advantages that LSs have
on RRF 15,16. The impact of the low GDP in
RRF protection and other beneficial effects
remain insufficiently described, even though
there has been interest in evaluating the sys-
temic biocompatibility of these solutions 17.
Therefore, we conducted a meta-analysis to
examine the effect of LS on RRF and other
related factors known to affect PD in PD pa-
tients compared with CS.
SUBJECTS AND METHODS
Study Inclusion and Exclusion Criteria
Studies that met all the following basic
criteria were included in our meta-analysis:
(1) a randomized controlled trial (RCT) for
patients on continuous ambulatory perito-
neal dialysis (CAPD) or automated peritone-
al dialysis (APD) as the treatment of ESRD;
(2) LS was compared with CS. The crossover
randomized trials or RCTs that did not as-
sess RRF were excluded.
Search Strategy
We identified eligible RCTs by searching
the PubMed, Embase, Wiley, Scopus, Ovid
databases and abstracts presented at the
annual meetings of the American Society
of Nephrology (ASN), the National Kidney
Foundation (NKF), and the European Renal
Association (ERA), from inception to July
2014, using appropriate Medical Subject
Headings (MeSH) and text words: peritoneal
dialysis, glucose degradation products, bio-
compatible solution, low-GDP, APD, CAPD in
combination with “residual renal function”.
Further, the reference lists of retrieved ar-
ticles were then searched for additional rel-
evant studies. No language restrictions were
imposed.
Study Selection
We included RCTs examining the effect
of LSs on RRF in PD patients >18 years old
compared with CSs. PD modality was restrict-
ed as either CAPD or APD. The outcomes of
RCTs should include the RRF value, which is
measured as the arithmetic means of residual
renal clearances of urea and creatinine by
collecting 24-hour urine volume. Other end-
points for the evaluation may include small
solute clearance, peritoneal solute transport
rate (PSTR), nutritional status, and all-cause
mortality of PD patients. The study had at
least 12 months of duration of follow-up with-
out restriction on sample size. Two investiga-
tors (NZ and JW), independently, screened
titles and abstracts of all electronic citations
to select studies that met the inclusion crite-
ria for further analysis. All articles identified
by the investigators were retained.
Study Validity Assessment
We used the Cochrane Collaboration’s
bias tool and Jadad score for assessing the
risk of bias for the included studies. The
first approach incorporates assessment of
randomization (sequence generation and al-
location sequence concealment), blinding
(participants, personnel, and outcome asses-
sors), completeness of outcome data, selec-
tion of outcomes reported, and other sourc-
es of bias. The items were scored with “yes,”
“no,” and “unclear” 18. The Jadad scale score
ranged from 0 to 5 points about the random-
ization, double-blinding, and withdrawals
and dropouts 19.
286 Chen et al.
Investigación Clínica 63(3): 2022
Data Extraction
Two investigators extracted the useful
data independently and reached a consen-
sus on all eligible data. Relevant information
was obtained by contacting the correspond-
ing authors of the respective studies.
Study characteristics were extracted
from all included trials with respect to year
of publication, the study sample, baseline
characteristics of the trials, follow-up, and
the following reported outcomes of dif-
ferent follow-up months (baseline, 6, 12,
and 24 months): (1) RRF (mL/min) (2)
total weekly urea clearance (total Kt/V)
and peritoneal urea clearance (peritoneal
Kt/V), (3) total creatinine clearance (to-
tal CrCl) (L/week/1.73m2), and peritoneal
creatinine clearance (peritoneal CrCl) (L/
week/1.73m2), (4) daily urine volume (UV)
(mL), daily peritoneal ultrafiltration (UF)
(mL) and daily glucose exposure (g), (5)
dialysate-to-plasma ratio of creatinine at 4
hours of peritoneal equilibration test (PET)
(D/Pcr) and D/D0 glucose at 4 hours (D/
D0 glucose), (6) blood pressure (mmHg) in-
cluding systolic blood pressure (SBP) and di-
astolic blood pressure (DBP), (7) nutritional
data, including serum albumin (g/dL), sub-
jective global assessment (SGA) and normal-
ized protein nitrogen appearance (nPNA)
(g/kg/day), (8) all-cause mortality.
Data Synthesis and Analysis
Continuous outcomes results were pre-
sented as the mean difference (MD) and its
95% confidence intervals (CIs). Dichoto-
mous outcomes were reported as the risk ra-
tio (RR) and 95% CIs. Statistical pooling was
performed with a random-effect model, via
generic inverse variance weighting. All the
statistical analyses in this meta-analysis were
performed using Review Manager 5 software
(RevMan 2012) for the meta-analysis.
Hypothesis testing was set at the two-
tailed and results were considered statisti-
cally significant at 0.05 level. The I2 statistic
was calculated as a measure of statistical
heterogeneity, and I2 values of 25%, 50%, and
75% corresponded to low, medium, and high
levels of heterogeneity. When heterogeneity
was found (I2>25%), sensitivity analysis was
performed in an attempt to explain the find-
ings. When doing a pool for some outcome
assessment, we excluded the study which has
the significant difference at baseline to keep
two groups in all studies have the consistent
outcome at the baseline. For each parameter
estimate, an integrated analysis was given,
finally.
The meta-analysis was performed in
accordance with the recommendations by
Preferred Reporting Items for Systematic
reviews and Meta-Analyses (PRISMA) work-
group 20.
RESULTS
Study Characteristics
A total of 223 potentially relevant cita-
tions were identified and screened, of which
197 were selectively excluded from the study
because they were not clinical RCTs or did not
expose the outcome of interest. Twenty-six ar-
ticles were retrieved for detailed evaluation.
Overall, seven RCTs were included with a com-
bined total of 632 patients 3,15,17,21-24 (Fig. 1).
The details of the characteristics and
the demographic data of the RCTs includ-
ed in our analysis were summarized in Ta-
ble 1. These studies varied in sample size,
and follow-up duration differed from 12 to
24 months, spanning nearly 10 years. The
mean age of the populations ranged from
51~62 years and the mean of body mass
index (BMI) ranged from 23~28.4 kg/m2.
The prevalence of diabetes in the patients
was from 11%~56%. More than half of the
patients in both groups used angiotensin
converting-enzyme inhibitors (ACEI) or an-
giotensin II receptor blockers (ARB) and
half of the patients in both groups used di-
uretics in two studies 3,23. All trials evaluated
the LS (Balance: Fresenius Medical Care)
compared with a CS (StaySafe: Fresenius
Medical Care). Almost all studies included
incident CAPD patients except the Choi et
The benefits of peritoneal dialysis solution 287
Vol. 63(3): 283 - 303, 2022
al.21 study, and patients with CAPD modality
except the balANZ Trial 3.
Baseline of outcomes in these includ-
ed studies were shown in Table 2. Kim et al.22
demonstrated that there were no significant
differences of all outcomes between the two
groups except CrCl (LS group, 95.5±5.0 vs. CS
group, 78.6±11.8 L/week/1.73m2, p<0.05)
and nPNA (LS group, 0.85±0.07 vs. CS group,
1.06±0.11 g/kg/day, p<0.05). The D/Pcr at
the baseline was higher in the LS group than
in the CS group in the two trials studied by
Kim et al. 23 and Park et al.17. Moreover in the
study by Park et al. 17 peritoneal CrCl and was
higher in the LS group, peritoneal UF volume
was lower in the LS group at baseline in keep-
ing with higher peritoneal transport character-
istics in this group. Szeto et al.15 showed that at
baseline, the CS group had a better nutrition-
al status than the LS group (serum albumin,
p=0.004 and SGA, p=0.023), but the differ-
ence disappeared in 12 months.
Quality Assessment
Two investigators assessed the quality of
the included studies independently. All RCTs
were considered fair to good quality (Fig. 2).
Allocation methods and concealment were
generally, incompletely reported and there-
fore difficult to assess. Allocation conceal-
ment was adequate in four studies (43%).
Six studies (86%) were classified as low risk
of performance bias and only one study was
unclearly reported. However, no information
about the blinding of outcome assessment
(detection bias) of the studies was provided.
Completeness of outcome reporting and
intention-to-treat analysis methodology was
applied in 29% of included studies. Selective
reporting was observed in six studies (86%).
No other significant biases were identified
in these seven studies, except an unclear de-
scription of participant details in four stud-
ies. The Jadad score was 3 or higher (Table
1), even though the method of random se-
Fig 1. Flow chart showing the number of citations retrieved by individual searches and the number of trials
included in the review.
288 Chen et al.
Investigación Clínica 63(3): 2022
Table 1
Characteristics of the included RCTs in this analysis.
Study or
Author Year
Country Peritoneal
dialysis
(PD)
PD solution
(L/C)
Modality Sample
size, n
(L/C)
Mean age,
year
(L/C)
Male,
n(L/C)
Follow-up
duration,
mouth
DM, %
(L/C)
BMI(kg/
m2) (L/C)
Charlson’s
Index
score
(L/C)
Use of
ACEI/ARB,
(%) (L/C)
Use of
diuretics,
(%) (L/C)
Sum of
Jadad
Score
Bajo et al.
2011
Spain Incident
CAPD
Balance versus
Stay-safe
CAPD 13/20 62/59 10/9 24 11/38 NA NA NA NA 3
balANZ Trial New Zealand,
Australia,
Singapore
Incident
CAPD
Balance versus
Stay-safe
CAPD /
APD
91/91 59.3/57.9 52/48 24 33/34 27.7/28.4 NA 44.0/45.1 44/50.5 4
Choi et al.
2008
Korea Prevalent
CAPD
Balance versus
Stay-safe
CAPD 51/53 52.6/55.4 20/27 12 18/19 24.5/24.3 NA NA NA 3
Kim et al.
2003
South Korea Incident
CAPD
Balance versus
Stay-safe
CAPD 16//10 51.6/56.1 NA 12 38/30 NA NA NA NA 3
Kim et al.
2008
Korea Incident
CAPD
Balance versus
Stay-safe
CAPD 48/43 55.3/52.8 31/24 12 56/42 22.7/23.5 NA 64.6/58.1 52.1/55.8 3
Park et al.
2012
Korea Incident
CAPD
Balance versus
Stay-safe
CAPD 79/67 52.2/52.6 37/30 12 52/55 22.9/22.6 4.06/3.99 65.8/78.1 NA 4
Szeto et al.
2007
Hongkong Incident
CAPD
Balance versus
Stay-safe
CAPD 25/25 60.9/55.0 16/14 12 40/32 23.0/23.3 5.4/4.68 NA NA 4
Note: data are presented as mean or median (range). NA, not available. L/C, neutral pH and low-GDP PDSs/conventional PDSs; DM, diabetes mellitus; BMI,
body mass index; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.
The benefits of peritoneal dialysis solution 289
Vol. 63(3): 283 - 303, 2022
Table 2
The baseline of outcomes in the included RCTs.
Study or Author
Year
Bajo et al. 2011 balANZ Trial Choi et al. 2008 Kim et al. 2003 Kim et al. 2008 Park et al. 2012 Szeto et al. 2007
Groups LS CS LS CS LS CS LS CS LS CS LS CS LS CS
sample size (n) 13 20 91 91 51 53 16 10 48 43 79 67 25 25
RRF (mL/min) 7.0±4.3 5.8±3.9 7.0±6.0 7.0±6.0 7.9±17.7 8.9±22.9 4.3±0.4 3.2±1.2 6.84±6.69 5.71±3.76 3.9±3.1 3.7±2.6 3.91±2.09 3.67±2.27
Kt/V NA NA NA NA 1.9±0.4 1.9±0.4 2.83±0.17 2.52±0.29 2.41±1.01 2.08±0.59 2.4±0.6 2.3±0.6 2.28±0.35 2.23±0.62
peritoneal Kt/V NA NA NA NA 1.8±0.3 1.7±0.3 NA NA 1.63±0.4 1.46±0.4 1.7±0.4 1.7±0.5 NA NA
CrCl (L/week/
1.73m2) NA NA NA NA 55.2±15.2 55.9±22.8 95.5±5.0* 78.6±11.8 90±47.7 78±27.7 84.1±30.9 77.5±27.9 NA NA
peritoneal CrCl
(L/week/1.73m2) NA NA 38.3±9.0 36.3±11.9 49.2±7.0 48.3±6.3 NA NA 44.6±10.1 39.6±10.7 41.4±7.3* 37.9±6.9 NA NA
urine volume
(mL/d) NA NA 1556.0±691.0 1501.0±682.0 385.5±330.7 447.1±278.4 NA NA 783.0±630.0 698.0±430.0 880.0±732.0 717.0±536.0 870.0±620.0 900.0±710.0
peritoneal UF
(mL/d) NA NA 700 (2700
to 3500)
1090 (2400
to 2800) 1110.8±555.2 921.2±498.0 NA NA 865.0±338.0 923.0±430.0 621.0±520.0*962.0±527.0 560.0±600.0 560.0±690.0
glucose load
(g/d) NA NA 121.5±35.3 123.6±36.3 145.1±38.3 155. ±44.3 NA NA 121.0±21.1 121.0±48.7 100.8±11.1* 109.1±10.3 100.7±14.6 100.9±17.7
D/Pcr NA NA 0.67±0.1 0.62±0.1 NA NA 0.69±0.02 0.66±0.03 0.72±0.1* 0.67±0.1 0.74±0.12* 0.69±0.12 NA NA
D/P0 glucose NA NA NA NA NA NA 0.28 ±0.02 0.3± 0.03 0.32 ±0.14 0.35 ±0.14 NA NA NA NA
SBP (mmHg) NA NA 139.8±21.4 138.9±21.8 NA NA NA NA NA NA 131.6±19.3 131.4±20.8 NA NA
DBP (mmHg) NA NA 76.6±11.3 78.1±11.0 NA NA NA NA NA NA 82.2±11.9 81.3±12.1 NA NA
Serum alb (g/dL) NA NA 3.8±0.5 3.7±0.6 3.6±0.3 3.5±0.4 3.4±0.1 3.7±0.2 3.39±0.56 3.51±0.51 3.6±0.6 3.6±0.5 3.28±0.44* 3.65±0.41
SGA NA NA NA NA 6.0±0.7 6.1±0.9 NA NA NA NA 5.9±1.2 5.7±1.1 4.83±0.87* 5.24±0.78
nPNA (g/kg/d) NA NA 1.05±0.25 1.06±0.26 0.9±0.2 0.9±0.2 0.85±0.07* 1.06±0.11 0.92±0.23 0.89±0.19 0.91±0.18 0.9±0.25 1.07±0.19 1.18±0.19
Note: data are presented as mean±SD or median (range). NA, not available. Bold indicates the parameters have significant differences between the two groups
and asterisk (*) indicates p<0.05 versus CS group. RRF, mean of creatinine clearance (Ccr) and urea clearance (Curea); Kt/V, total weekly urea clearance;
peritoneal Kt/V, weekly peritoneal urea clearance; CrCl, total creatinine clearance; peritoneal CCr, peritoneal creatinine clearance; peritoneal UF, peritoneal
ultrafiltration; D/Pcr, dialyzate-to-plasma creatinine ratio at 4 hours of peritoneal equilibration test (PET); D/D0 glucose, D/D0 glucose at 4 hours of PET; SBP,
systolic blood pressure; DBP, diastolic blood pressure; SGA, subjective global assessment; nPNA, normalized protein nitrogen appearance.
290 Chen et al.
Investigación Clínica 63(3): 2022
quence generation, blinding of participants
and allocation concealment were not men-
tioned in most studies.
Outcome Measurement
PD patients in these different studies
were followed up for different periods, which
may have influenced the effectiveness of the
outcomes of this analysis. Therefore, sub-
group analysis was used to decrease clinical
heterogeneity according to the follow-up pe-
riods.
Residual Renal Function
Two studies 17,23 of seven RCTs were
undertaken to calculate the RRF of 226 pa-
tients after 6 months of follow-up, and in-
dicated that LS group was beneficial for
preserving RRF compared with the control
group (MD 1.28 mL/min, 95% CI 0.52 to
2.03, p=0.0009; I²=0%). Similar results
were obtained after 12 months of follow-up
in all studies including 520 patients (MD
0.60 mL/min, 95% CI 0.18 to 1.02, p=0.005;
I²=11%). The balANZ Trial 3 followed up 24
months and RRF was measured at baseline,
12 and 24 months, as well as the study by Bajo
et al.24, and the pooled data indicated no dif-
ference between the two groups (p=0.76).
As the studies duration continued from 6 to
24 months, the difference of RRF between
the two groups was reduced gradually. This
should be commented in the abstract and/or
conclusions. Considering the heterogeneity,
exclusion of the study 24 with a small sample
size did not materially change the results of
the meta-analysis or the subgroup analyses
Overall, the use of LS induced a reduction
in RRF decline compared with the control
group (MD 0.66 mL/min, 95% CI 0.34 to
0.99; p<0.0001; I2=4%; Fig. 3).
Daily Urine Volume
Three studies 3,17,23 with a total of 377
patients and five studies 3,15,17,21,23 with a to-
tal of 462 patients showed the 24h urine
volume separately at 6 and 12 months. The
24h urine volume in the LS group was high-
er than that in the CS group (MD 155.42
mL/d, 95% CI 37.84 to 273.00; p=0.01) at
6 months. A total of 238 patients were fol-
lowed up in the LS groups and 224 patients
were followed up in the CS groups after 1
year’s study. Patients with the LS had more
daily urine volume than the CS group (MD
158.93 mL/d, 95% CI 83.22 to 234.64;
p<0.0001). Only the balANZ Trial 3 reported
the urine volume at 24 months follow-up,
and there was no significant difference be-
tween the two groups. As the study duration
continued from 12 to 24 months, the MD of
the residual urine volume decreased from
Fig 2. Risk of bias graph: each risk of bias item is presented as percentages across all included studies.