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 (Stay•Safe: 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.
The benefits of peritoneal dialysis solution 291
Vol. 63(3): 283 - 303, 2022
158.93 mL/d to 115.00 mL/d. The pooled
urine volume in patients using LS was great-
er than using CS (MD 153.15 mL/d, 95% CI
96.62 to 209.68; p<0.00001; I2=0%; Table
2). Overall, our meta-analysis indicated that
the LS had a significant effect on RRF with
an increase in daily urine output compared
with the CS group.
Small solute clearance
At 6 months, Kim et al. 23 and Park et
al.17 published the data of total Kt/V and
peritoneal Kt/V showing that there was no
statistical difference between the two groups
(p=0.99; p=0.18). After one year follow up,
five studies involving 360 patients reported
the effect of LS on total Kt/V in PD patients
15,17,21-23. Compared to the CS group, the LS
group showed significantly increased Kt/V
(MD 0.13, 95% CI 0.06 to 0.20; p=0.0002).
Overall, we found that patients with LS had
higher total Kt/V than with CS (MD 0.11,
95% CI 0.05 to 0.17; p=0.0007; I2=0%) (Fig.
4) and the CS group had a higher peritoneal
Kt/V than the LS group (MD -0.10, 95% CI
-0.20 to -0.01; p=0.03; I2=0%) (Table 2).
Our subgroup analyses showed no sta-
tistical differences of total CrCl and perito-
neal CrCl between the LS and CS groups at
6 and 12 months (Table 2). We excluded the
total CrCl data of the follow-up period from
the study performed by Kim et al.22 who re-
ported the significant difference between
the two groups at baseline but no statisti-
cal difference observed at 12 months. The
study by Park et al.17 was excluded because
this study published that peritoneal CrCl
was higher in the LS group at baseline and
there was no significant difference after 6
months.
Fig 3. Effect of low-GDP PD solution on RRF (mL/min).
292 Chen et al.
Investigación Clínica 63(3): 2022
Peritoneal Ultrafiltration and Glucose
Load
Five studies 3,15,17,21,23 published the
daily peritoneal UF volume in the follow-
up period. Park et al.17 indicated that
the CS group had higher UF than the
LS group at baseline and 6 months. Af-
ter exclusion of this study, we pooled the
data at 6 months, showing the higher
UF in the CS group (MD -261.97 mL/d,
95% CI -427.73 to -96.21; p=0.002). In
the subgroup analyses of 12 months, Choi
et al.21 who included all prevalent PD pa-
tients with more than half number of an-
uric, revealed the outcome that UF was
significantly higher in the LS group than
in the CS group at all follow-up visits.
The exclusion of this study did materially
change the results of the meta-analysis
or the subgroup analyses. Table 3 showed
that patients with the LS had less daily
peritoneal UF volume than the CS (MD
-193.45 mL/d, 95% CI -315.36 to -71.54;
p=0.002; I2=36%). The subgroup analy-
ses of glucose load suggested that there
was no statistically significant difference
between patients using the LS and CS at
6 and 12 months.
Blood Pressure
The balANZ Trial 3 and the study by Park
et al. 17 followed up the blood pressure of the
two groups. There was no significant differ-
ence between the two -groups in controlling
blood pressure during 1 year of follow-up
(SBP, p=0.91; DBP, p=0.59) (Table 3).
Peritoneal Solute Transport Rate
Five studies 3,17,21-23 published the D/
Pcr. In the study by Kim et al. 23, the D/
Pcr was higher in the LS group than in the
CS group, and this difference persisted
throughout the treatment period. Similar
results were obtained from Park et al. 17, but
after 6 months, the D/Pcr showed no differ-
ence between the two groups. The patients
of two groups in these three included stud-
Fig. 4. Effect of low-GDP PD solution on total Kt/V.
The benefits of peritoneal dialysis solution 293
Vol. 63(3): 283 - 303, 2022
Table 3
Comparison of low glucose degradation products (GDP) versus standard glucose dialysate.
Outcome or subgroup
title
No. of
studies
No. of patients
(LS/CS) Statistical method Effect size p Heterogeneity
Residual renal function
6 months 2 120/106 Mean Difference (IV, Random, 95% CI) 1.28 [0.52, 2.03] 0.0009 I2=0%
12 months 7 267/253 Mean Difference (IV, Random, 95% CI) 0.60 [0.18, 1.02] 0.005 I2=11%
24 months 2 55/68 Mean Difference (IV, Random, 95% CI) 0.16 [-0.87, 1.19] 0.76 I2=0%
Total 442/427 Mean Difference (IV, Random, 95% CI) 0.66 [0.34, 0.99] <0.0001 I2=4%
Daily Urine Volume
6 months 3 196/181 Mean Difference (IV, Random, 95% CI) 155.42 [37.84, 273.00] 0.01 I2=0%
12 months 5 238/224 Mean Difference (IV, Random, 95% CI) 158.93 [83.22, 234.64] <0.0001 I2=7%
24 months 1 42/48 Mean Difference (IV, Random, 95% CI) 115.00 [-146.33, 376.33] 0.39
Total 476/453 Mean Difference (IV, Random, 95% CI) 153.15 [96.62, 209.68] <0.00001 I2=0%
Peritoneal Ultrafiltration
6 months 2 117/114 Mean Difference (IV, Random, 95% CI) -261.97 [-427.73, -96.21] 0.002 I2=0%
12 months 3 123/124 Mean Difference (IV, Random, 95% CI) -200.57 [-389.25, -11.88] 0.04 I2=48%
24 months 1 42/48 Mean Difference (IV, Random, 95% CI) 65.00 [-234.81, 364.81] 0.67
Total 282/286 Mean Difference (IV, Random, 95% CI) -193.45 [-315.36, -71.54] 0.002 I2=36%
glucose load
6 months 3 203/185 Mean Difference (IV, Random, 95% CI) 1.35 [-1.76, 4.47] 0.40 I2=0%
12 months 5 250/234 Mean Difference (IV, Random, 95% CI) 0.25 [-3.25, 3.74] 0.89 I2=0%
24 months 1 42/48 Mean Difference (IV, Random, 95% CI) 4.30 [-17.76, 26.36] 0.70
Total 495/467 Mean Difference (IV, Random, 95% CI) 0.90 [-1.41, 3.21] 0.45 I2=0%
Small solute clearance
total Kt/V
6 months 2 120/104 Mean Difference (IV, Random, 95% CI) -0.00 [-0.25, 0.25] 0.99 I2=45%
12 months 5 192/168 Mean Difference (IV, Random, 95% CI) 0.13 [0.06, 0.20] 0.0002 I2=0%
24 months 0
294 Chen et al.
Investigación Clínica 63(3): 2022
Outcome or subgroup
title
No. of
studies
No. of patients
(LS/CS) Statistical method Effect size p Heterogeneity
Total 312/274 Mean Difference (IV, Random, 95% CI) 0.11 [0.05, 0.17] 0.0007 I2=0%
Peritoneal Kt/V
6 months 2 120/106 Mean Difference (IV, Random, 95% CI) -0.08 [-0.19, 0.04] 0.18 I2=0%
12 months 2 100/80 Mean Difference (IV, Random, 95% CI) -0.16 [-0.33, 0.01] 0.06 I2=0%
24 months 0
Total 220/186 Mean Difference (IV, Random, 95% CI) -0.10 [-0.20, -0.01] 0.03 I2=0%
total CrCl
6 months 2 120/106 Mean Difference (IV, Random, 95% CI) 4.82 [-6.96, 16.61] 0.42 I2=45%
12 months 3 151/133 Mean Difference (IV, Random, 95% CI) 3.60 [-2.48, 9.67] 0.25 I2=34%
24 months 0
Total 271/239 Mean Difference (IV, Random, 95% CI) 3.39 [-0.75, 7.53] 0.11 I2=17%
Peritoneal CrCl
6 months 1 48/43 Mean Difference (IV, Random, 95% CI) 1.50 [-2.91, 5.91] 0.05
12 months 2 99/96 Mean Difference (IV, Random, 95% CI) -0.08 [-2.09, 1.93] 0.94 I2=0%
24 months 1 91/91 Mean Difference (IV, Random, 95% CI) 2.00 [-1.07, 5.07] 0.20
Total 238/230 Mean Difference (IV, Random, 95% CI) 0.67 [-0.90, 2.24] 0.40 I2=0%
Peritoneal Solute
Transport Rate
D/Pcr
6 months 0
12 months 2 54/40 Mean Difference (IV, Random, 95% CI) 0.00 [-0.02, 0.02] 1 I2=0%
24 months 1 37/47 Mean Difference (IV, Random, 95% CI) 0.00 [-0.04, 0.04] 1
Total 91/87 Mean Difference (IV, Random, 95% CI) 0.00 [-0.02, 0.02] 1 I2=0%
D/D0 glucose
6 months 1 41/39 Mean Difference (IV, Random, 95% CI) -0.05 [-0.11, 0.01] 0.09
12 months 2 52/43 Mean Difference (IV, Random, 95% CI) -0.03 [-0.06, 0.00] 0.08 I2=40%
Table 3. Continuación
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Vol. 63(3): 283 - 303, 2022
Outcome or subgroup
title
No. of
studies
No. of patients
(LS/CS) Statistical method Effect size p Heterogeneity
24 months 0
Total 93/82 Mean Difference (IV, Random, 95% CI) -0.03 [-0.05, -0.01] 0.01 I2=17%
Blood Pressure
systolic blood pressure
6 months 2 155/142 Mean Difference (IV, Random, 95% CI) 0.96 [-3.67, 5.60] 0.68 I2=0%
12 months 2 126/113 Mean Difference (IV, Random, 95% CI) 2.89 [-2.41, 8.18] 0.29 I2=0%
24 months 1 42/48 Mean Difference (IV, Random, 95% CI) -10.80 [-19.24, -2.36] 0.01
Total 323/303 Mean Difference (IV, Random, 95% CI) -0.29 [-5.04, 4.46] 0.91 I2=53%
diastolic blood pressure
6 months 2 155/142 Mean Difference (IV, Random, 95% CI) 1.01 [-1.84, 3.85] 0.49 I2=0%
12 months 2 126/113 Mean Difference (IV, Random, 95% CI) 1.10 [-1.88, 4.07] 0.47 I2=0%
24 months 1 42/48 Mean Difference (IV, Random, 95% CI) -3.10 [-8.51, 2.31] 0.26
Total 323/303 Mean Difference (IV, Random, 95% CI) 0.53 [-1.40, 2.45] 0.59 I2=0%
Nutritional Status
Serum albumin
6 months 3 203/185 Mean Difference (IV, Random, 95% CI) -0.09 [-0.28, 0.10] 0.35 I2=59%
12 months 5 225/209 Mean Difference (IV, Random, 95% CI) -0.16 [-0.28, -0.05] 0.005 I2=45%
24 months 1 42/48 Mean Difference (IV, Random, 95% CI) -0.20 [-0.41, 0.01] 0.06
Total 470/442 Mean Difference (IV, Random, 95% CI) -0.14 [-0.23, -0.05] 0.002 I2=45%
nPNA
6 months 3 203/185 Mean Difference (IV, Random, 95% CI) -0.02 [-0.07, 0.02] 0.29 I2=0%
12 months 5 250/234 Mean Difference (IV, Random, 95% CI) -0.03 [-0.07, 0.01] 0.18 I2=0%
24 months 1 42/48 Mean Difference (IV, Random, 95% CI) 0.00 [-0.12, 0.12] 1
Total 495/467 Mean Difference (IV, Random, 95% CI) -0.02 [-0.05, 0.00] 0.10 I2=0%
SGA score
6 months 1 79/67 Mean Difference (IV, Random, 95% CI) 0.20 [-0.19, 0.59] 0.31
Table 3. Continuación
296 Chen et al.
Investigación Clínica 63(3): 2022
ies 3,21,22 had high average transport status.
Overall, there was no statistically signifi-
cant difference in the D/Pcr between the
two groups (MD 0.00, 95% CI -0.02 to 0.02;
p=1.00; I2=0%) (Table 3).
However, two studies 22,23 with a differ-
ence on D/D0 glucose were small sample
trials. The pooled analysis suggested that
the CS had a higher D/D0 than the LS
(MD -0.03, 95% CI -0.05 to -0.01; p=0.01;
I2=17%) (Table 3).
Overall, the D/Pcr and D/D0 glucose of
all patients included in this subgroup analy-
sis indicated that both the LS group and the
CS group had high-average transport charac-
teristics of peritoneal membrane 6.
Nutritional Status
Our meta-analysis indicated that pa-
tients using the LS had lower serum albumin
than the CS (MD -0.14 g/dL, 95% CI -0.23 to
-0.05; p=0.002; I2=45%) (Table 3).
In the meta-analysis of five studies
3,15,17,21,23, we found there was no significant
difference in nPNA between the two groups
(MD -0.02 g/kg/d, 95% CI -0.05 to 0.00;
p=0.10;I2=0%) (Table 3).
Only two studies 17,21, publishing the
data of SGA were small sample trials. We
found that the LS group had a better SGA
score than the CS group (MD 0.33, 95% CI
0.08 to 0.57; p=0.009; I2=21%) (Table 3).
All-cause Mortality
All seven studies 3,15,17,21-24 published the
effect of LS on patients’ survival. No patient
died in the two groups at 6-month follow-up.
At 12 months five studies 15,17,21-23 involving
417 patients and at 24 months two studies
involving 215 patients were included in the
subgroup analysis, suggesting that there was
no significant difference between the two
groups, respectively (Table 3).
DISCUSSION
Our study suggests that low GDP solu-
tion preserves RRF in PD patients over time,
Outcome or subgroup
title
No. of
studies
No. of patients
(LS/CS) Statistical method Effect size p Heterogeneity
12 months 2 115/100 Mean Difference (IV, Random, 95% CI) 0.36 [-0.02, 0.73] 0.06 I2=45%
24 months 0 0 Mean Difference (IV, Random, 95% CI)
Total 194/167 Mean Difference (IV, Random, 95% CI) 0.33 [0.08, 0.57] 0.009 I2=21%
all-cause mortality Total events
(LS/CS)
6 months 0 I2=0%
12 months 5 9/10 Odds Ratio (M-H, Fixed, 95% CI) 0.80 [0.32, 2.03] 0.64 I2=0%
24 months 2 10/9 Odds Ratio (M-H, Fixed, 95% CI) 1.18 [0.46, 3.03] 0.73
Total 19/19 Odds Ratio (M-H, Fixed, 95% CI) 0.97 [0.50, 1.88] 0.93 I2=0%
Table 3. Continuación
The benefits of peritoneal dialysis solution 297
Vol. 63(3): 283 - 303, 2022
particularly in one year of treatment, and
improves the dialysis adequacy especially
the urea clearance without increasing the
peritoneal solute transport rate. In addition,
low-GDP solution was found to have no bene-
fits on blood pressure, nutritional status and
all-cause mortality.
The low GDP solution preserves more
RRF as they may cause less intraperitoneal
inflammation, thereby reducing peritoneal
ultrafiltration and fluid losses. It is sup-
ported by a crossover designed RCT by EU-
RO-BALANCE 14, which showed more urine
volume and better clearance of both urinary
urea and creatinine with the neutral pH low
GDP glucose containing dialysates alongside
lower serum concentrations of AGE mark-
ers. In addition, these findings were also con-
firmed by several clinical trials, suggesting
better preservation of RRF compared with
the conventional PD solutions 3,23. The im-
proved preservation of RRF with low GDP so-
lution was observed at all study time points
40. Kim et al. 23 firstly declared the benefi-
cial effect of low GDP solution on RRF with
more urine volume in a prospective RCT. The
balANZ trial 3, as the largest RCT, observed
that the rate of decline of renal function did
not reach statistical significance in the first
and the second year, but there was a signifi-
cant delay in time to anuria. However, these
beneficial effects on RRF were not substan-
tiated by other studies 15,17,21,22,24. Szeto et
al. 15 failed to show any difference in RRF
and urine output between the two groups
because the small sample size was not ad-
equately powered to elucidate the effect on
RRF. Similarly, Fan et al. 16 reported negative
results from a larger number of patients,
which was due to the lack of homogeneity
for the patients in each study group. There-
fore, meta-analysis, differing from included
single study, can exert statistical power and
result in a highly reliability outcome. The
benefits of low-GDP solution are biologically
plausible, as GDPs have been demonstrated
to exert nephrotoxic effects directly on renal
tubular cells 11. One potential and underpin-
ning mechanism is that low-GDP solution
better preserves RRF in PD patients via re-
duction of GDP and the AGE in the systemic
circulation 27. The other possible reason for
the beneficial effect of low GDP solution on
RRF could be that decreased peritoneal UF
results in more urine output and higher re-
sidual renal clearance 28,29.
Weekly Kt/V is an important param-
eter for evaluating PD treatment adequacy.
Our data indicate that although the use of
the low GDP dialysates was not associated
with increasing creatinine clearance (either
total CrCl or peritoneal CrCl) or decreas-
ing blood pressure (either SBP or DBP), it
exhibited significant benefit in weekly Kt/V
in 12 months of treatment. While patients
using conventional PD solutions had a small
advantage in the peritoneal Kt/V (p=0.03)
which was consistent with the analysis of
peritoneal UF (p=0.002) despite similar
glucose load (p=0.73) (Supplementary Fig-
ure S3 and S6). Our study analyzed the nu-
tritional status including serum albumin,
nPNA and SGA score, which is important to
evaluate the adequacy of peritoneal dialysis
and CAPD patients survival 36. However, se-
rum albumin suffered from a moderate level
of statistical heterogeneity, which could not
be satisfactorily explained 37. Improved nu-
tritional status with low GDP PD solution
was confirmed by the increase of SGA in the
LS group. Inconsistency of these parameters
for evaluating nutritional status may be due
to heterogeneity among studies 27.
Most of the clinical studies find that
low GDP solution reduces peritoneal UF ac-
companied by high average PSTR, whereas
our review revealed that low GDP solution
improved the dialysis adequacy with no ex-
pense of PSTR represented by D/Pcr and D/
D0 glucose at 4 hours. Two studies by Choi et
al.21 and Tranaeus et al.30 showed similar find-
ings but with a high level of clinical hetero-
geneity. McDonald et al.31 thought that the
reduction of peritoneal UF was an important
298 Chen et al.
Investigación Clínica 63(3): 2022
cause of technique failure. However, exces-
sive peritoneal UF may also play a causal
role in the decline of RRF by provoking in-
travascular volume depletion 32,33. Thus, it is
difficult to delimit UF volume as a clinical
outcome, which is affected by many other
variables such as fluid status, UV, PSTR and
glucose load 34.
PSTR has been recognized as an im-
portant factor for the assessment of clinical
outcomes, including technical failure and pa-
tient survival 35. Although the study by Kim
et al. 23 was excluded for analyzing the effect
of low GDP PD solution on PSTR because of
a difference at baseline, the significant dif-
ference still existed at 6 and 12 months. It
also supported our outcome that low GDP so-
lution contributed to the lower UF without
the difference of PSTR. Taken together, our
results highlighted that the assessment for
PSTR should be focused on process carefully
rather than just an absolute value at the end
of the study 34.
Concerning the survival advantage with
low GDP PD solution, retrospective studies
from Korea 38,39 suggested that the biocom-
patible solution improved the survival in pa-
tients with PD and reduced mortality risk
by 39%. However, our data showed that low
GDPs in PD solution have no statistical im-
pact on the survival of PD patients at 1 year
or even longer follow-up period.
Several limitations of this study should
be considered. First, most of the studies
included patients who were receiving RAS
(renin-angiotensin system) blockers that
might be effective in slowing the decrease in
RRF in PD patients. In addition, the prima-
ry endpoints of the studies and the dose of
peritoneal dialysis in patients were different.
Furthermore, RCTs investigating the effects
of neutral pH, low GDP PD solution on RRF
and adequacy were limited in number and
publication bias. The Balance® (Fresenius
Medical Care, Bad Homburg, Germany), the
only one particular solution analyzed in our
meta-analysis, may not enough to represent
the neutral pH, low GDP PD solutions. At
last, PD treatment adequacy should be inter-
preted clinically rather than be evaluated by
solute and fluid removal 28.
CONCLUSIONS
This meta-analysis suggests that low
GDP PD solution significantly preserved
residual renal function and improved dialy-
sis adequacy without increasing the perito-
neal solute transport rate (Table 4). Future
randomized trials with adequate statistical
power are needed to determine whether low
GDP PD solution affects long-term clinical
outcomes.
ACKNOWLEDGEMENTS
We would like to acknowledge everyone
for their helpful contributions on this paper.
Ethics approval and consent
to participate
The ethic approval was obtained from
the Ethic Committee of Ningbo Medical
Center Lihuili Hospital.
Consent to publish
All of the authors have consented to
publish this research.
Competing interests
All authors declare no conflict of interest.
Funding
National Natural Science Foundation of
China (No. 81700621).
Authors’ contributions
Each author has made an important
scientific contribution to the study and has
assisted with the drafting or revising of the
manuscript.
The benefits of peritoneal dialysis solution 299
Vol. 63(3): 283 - 303, 2022
Table 4
Summary of findings for the main comparison
Low-glucose degradation product versus standard glucose dialysate
Patient or population: PD patients
Setting: community
Intervention: low GDP dialysate
Comparison: standard glucose dialysate
Outcomes Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(Grade)
Comments
Residual renal function MD 0.66 (0.34, 0.99) 442
(11)
high Benefits reached significance as the
study duration continued from 6 to
12 months
Daily Urine Volume MD 153.15 (96.62,
209.68)
476
(9)
high Benefits reached significance as the
study duration continued from 6 to
12 months
Small solute clearance
total Kt/V MD 0.11
(0.05, 0.17)
312
(7)
high Benefit reached significance after one
year followed up
Peritoneal Kt/V MD -0.10
(-0.20, -0.01)
220
(4)
moderate Benefit reached significance after one
year followed up
total CrCl MD 3.39
(-0.75, 7.53)
271
(5)
Very low
Peritoneal CrCl MD 0.67
(-0.90, 2.24)
238
(4)
Very low Benefit reached significance at 6
months followed up
Peritoneal Ultrafiltration MD -193.45 (-315.36,
-71.54)
282
(6)
high Benefits reached significance as the
study duration continued from 6 to
12 months
glucose load MD 0.90
(-1.41, 3.21)
495
(9)
Very low
Blood Pressure
systolic blood pressure MD -0.29
(-5.04, 4.46)
323
(5)
Very low
300 Chen et al.
Investigación Clínica 63(3): 2022
Low-glucose degradation product versus standard glucose dialysate
Patient or population: PD patients
Setting: community
Intervention: low GDP dialysate
Comparison: standard glucose dialysate
Outcomes Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(Grade)
Comments
diastolic blood p
ressure
MD 0.53
(-1.40, 2.45)
323
(5)
Very low
Peritoneal Solute
Transport Rate
D/Pcr MD 0.00
(-0.02, 0.02)
91
(3)
Very low
D/D0 glucose MD -0.03
(-0.05, -0.01)
91
(3)
high
Nutritional Status
Serum albumin MD -0.14
(-0.23, -0.05)
470
(9)
high Benefit reached significance after one
year followed up
nPNA MD -0.02
(-0.05, 0.00)
495
(9)
Very low
SGA score MD 0.33
(0.08, 0.57)
194
(3)
high
All-cause mortality OR 0.97
(0.50, 1.88)
19
(7)
Very low
Table 4. CONTINUACIÓN
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