Incremental start and clinical outcomes in peritoneal dialysis: International results from PDOPPS

Abstract

Background

The impact of incremental peritoneal dialysis (PD) on outcomes is poorly understood, and there is a paucity of evidence informing best practices regarding the dialysis dose at the commencement of PD. This international prospective cohort study aimed to compare PD prescription practices at dialysis commencement and their subsequent association with clinical outcomes.

Methods

Adult patients who started PD for less than three months at the time of enrolment in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) between 1 January 2014 and 31 December 2017 were included. Patients were defined as initiating incremental PD if prescribed a total of <4 exchanges/day for continuous ambulatory peritoneal dialysis (CAPD) or, with dry days or having PD less than seven days per week for automated peritoneal dialysis (APD). All other prescriptions were considered standard PD. The primary outcome was the transfer to haemodialysis (HD). Secondary outcomes included peritonitis rate, time to first peritonitis and mortality. Logistic regression analysed PD uptake and the Cox proportional hazards regression model analysed HD transfer, peritonitis and patient survival.

Results

Overall, 1365 PD patients from 128 facilities across seven countries were included. Fewer individuals started on incremental PD than standard PD (37% vs 63%, p < 0.001). Higher incremental PD uptake was associated with receiving treatment in Japan (odds ratio [OR] 2.35, 95% CI 1.05–5.26, p = 0.04; ref: Canada), age >75 years (OR 1.51, 95% CI 1.02–2.24, p = 0.04), icodextrin use (OR 8.54, 95% CI 6.26–11.64, p < 0.001), lower serum creatinine concentration at PD start (OR 1.01, 95% CI 1.01–1.01, p = 0.007) and higher number of PD patients at a facility (OR 1.01, 95% CI 1.00–1.01, p = 0.02). Crude HD transfer rates for the incremental and standard PD groups were 0.14 (95% CI, 0.12–0.16) and 0.15 (95% CI, 0.13–0.17) per patient-year of follow-up, respectively (incidence rate ratio [IRR], 0.93; 95% CI, 0.75–1.15; p = 0.49). There was no significant difference in the hazard of HD transfer between the incremental and standard PD groups (hazard ratio [HR] 0.87, 95% CI 0.68–1.12, p = 0.29). There were also no differences between the two groups concerning peritonitis and mortality.

Conclusions

Incremental PD start was prescribed in approximately one-third of patients and, in low certainty evidence, was associated with comparable risks of HD transfer, peritonitis and death.

Keywords

haemodialysis transfer incremental dialysis patient survival PDOPPS peritoneal dialysis outcomes

Introduction

Incremental peritoneal dialysis (PD) prescription is a strategy that utilises a lower-than-standard dose of PD to supplement residual kidney function (RKF) at the initiation of PD. The intention is to increase the PD dose at a later stage as clinically required in accordance with the recommendations of the 2020 International Society for Peritoneal Dialysis (ISPD) Guidelines for Prescribing Goal-Directed, High-Quality PD.¹ The potential advantages of incremental PD are less stress, anxiety, and burden at dialysis initiation, allowance of time to build trust and facilitate adherence^2,3 and promoting greater life participation.⁴ In addition, incremental PD is associated with reduced glucose exposure,⁵ thereby potentially leading to less peritoneal membrane dysfunction and systemic adverse effects (such as metabolic syndrome), fewer mechanical side effects (such as abdominal fullness, back pain, hernias, and heartburn), lower risk of peritonitis (as fewer daily PD procedures are involved), lower PD consumable costs and reduced environmental waste.^6–8 There is also evidence that incremental PD may be associated with better preservation of RKF.^5–7,9,10

Incremental PD is a more individual-centred approach that aims to personalise PD prescriptions to fit patients’ lifestyles and to avoid therapy-related burnout at dialysis initiation by capitalising on RKF. The 2020 ISPD guidelines describe several incremental PD strategies: (a) continuous ambulatory PD (CAPD) – less than four dwells daily, < 2 L dwell volumes or performed less than seven days a week; and (b) automated PD (APD) – performed <7 days a week, total daily volume <10 L or without a long day dwell.^1,11 However, there is no universally accepted definition of standard (full dose) PD, which makes a standardised definition of incremental PD challenging. In Australia and the United Kingdom, four 2 L exchanges daily are considered standard PD,^12,13 while in Hong Kong and China, three 2 L exchanges daily are considered standard PD.¹⁴ These inconsistent definitions of treatment¹⁵ potentially confound the evaluation of uptake and outcomes associated with incremental PD.

The global uptake of incremental PD is not well reported. Neri et al.¹⁶ reported that the number of incident patients initiating incremental PD in all public Italian PD centres gradually increased from 11.5% in 2005 to 27.5% in 2014. Similarly, Cheetham et al.¹⁷ reported increased uptake of incremental PD in Australia and New Zealand from 2.7% of incident patients in 2007 to 11.1% in 2017 (mean increase of 0.84%/year).

Currently, there is also a lack of high-certainty evidence to inform best practices at the commencement of PD. In this study, we used data from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) to determine the epidemiology of incremental PD and the association between this practice and clinical outcomes in 7 countries.

Methods

This study included Phase 1 data (2014–2017) from Australia, New Zealand (NZ), Canada, Japan, Thailand, the United States of America (USA), and the United Kingdom (UK).¹⁸ PDOPPS was approved by a central institutional review board (IRB) in the USA and local Human Research Ethics Committees at each study site. Written informed consent was obtained from each participant prior to their participation in the study. PDOPPS methods have been previously described.¹⁸ The extensive PDOPPS data collection took place at both patient and centre levels, using standardised and uniform data collection tools and procedures. Patient-level data collection involved demographic information, medical history, medication use, comorbidities, and PD treatment. This information was updated every four months, capturing hospitalisation episodes, PD-related infections, PD treatment changes and events, and PD access-related events and procedures. A questionnaire was also completed annually by participants, which included a standardised assessment of key patient-reported outcomes, quality of life (QOL), patient satisfaction, and centre-level questionnaires to assess specific centre practices, targets, and centre environmental elements (e.g., staffing, quality improvement programs, and local reimbursement policies). Data quality was maintained through training, data collection forms, standardised protocols, and close interaction among data-reporting staff at each study site.¹⁸

Study population

This study included incident adult patients receiving PD from the PDOPPS cohort who commenced PD between January 1, 2014, and December 31, 2017 (Phase 1 PDOPPS), with a dialysis vintage of less than three months at the time of PDOPPS enrollment. Data were obtained from the PDOPPS Registry, using real-time event-based reporting and an annual survey. The manuscript was prepared according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.¹⁹

Data collection

Information was collected on the date of kidney replacement therapy (KRT) commencement, sex, ethnicity, primary cause of kidney failure, body mass index (BMI), comorbid conditions (e.g., diabetes mellitus, cardiovascular disease), late referral to a nephrologist (defined as within three months of KRT commencement), smoking history, transplant waitlist status, PD modality, completion of peritoneal equilibration test (PET) within six months of PD initiation, serum creatinine at baseline, RKF (creatinine clearance), residual urine volume, type of PD fluid used (glucose, icodextrin, low glucose degradation product [GDP]), weekly Kt/V, residual and peritoneal Kt/V, dwell volume, number of exchanges used per day, number of days per week PD used, long dwell used (overnight for CAPD, daytime for APD), and centre characteristics (number of facilities, facility age, number of incident PD patients at each facility). Peritonitis episode summaries (including causative organisms, where known) and hospitalisations (including diagnoses and procedures) were obtained at a patient level by manual abstraction of data from medical charts and entry into a web-based data collection tool during study follow-up, except for patients receiving care at United States (US) large dialysis organisation (LDO) affiliated sites from which data were imported from electronic health records.

Exclusion criteria

The exclusion criteria included age less than 18 years, prior kidney replacement therapy (KRT), receiving hybrid dialysis (PD and HD concurrently), receiving treatment at a US LDO (data extracted from electronic health records did not collect the required individual patient data), missing interval summaries, and missing required data to classify patients into incremental and standard PD groups.

Definitions

Incremental PD was defined as <4 exchanges/day for patients receiving CAPD or anyone with dry days or less than seven dialysis days per week for individuals receiving APD.

All other prescriptions were considered standard PD. Haemodialysis (HD) transfer was defined as transfer to HD for ≥30 days, and death was defined as death on PD or within 30 days of transfer to HD.²⁰ Peritonitis-associated HD transfer was defined as a transfer from PD to HD for any period of time as part of the treatment for a peritonitis episode.²¹ Peritonitis-associated death was defined as death occurring within 30 days of the onset of peritonitis or death during hospitalisation due to peritonitis.²¹

Primary outcome

The primary outcome was HD transfer.

Secondary outcomes

The secondary outcomes were peritonitis and patient survival.

Statistical analysis

Results were expressed as frequency and percentages for categorical variables, mean ± standard deviation (SD) for normally distributed continuous variables, and median (interquartile range [IQR]) for non-normally distributed continuous variables. Differences between categorical variables were assessed with the chi-square test, non-parametric continuous variables with the Kruskal-Wallis test and Mann-Whitney U and parametric continuous variables with the Student's t-test. An intention-to-treat (ITT) analysis was conducted comparing incremental and standard PD.

Multivariable logistic regression analysis was used to assess variables associated with incremental PD uptake. Crude HD transfer, first peritonitis, and patient survival rates were calculated among incremental and standard PD groups and expressed per patient-years of follow-up. The incidence rate ratios (IRR) compared the outcomes between the incremental and the standard PD groups. A non-parametric hazards curve estimator was used to compare differences in hazards (Nelson-Aalen cumulative hazard estimates) for HD transfer,-peritonitis and mortality between incremental and standard PD groups. A log-rank test was used to estimate the statistical significance of the Nelson-Aalen cumulative hazard estimator curves. Multivariable Cox proportional hazards regression model assessed the predictors associated with the risk of first peritonitis, HD transfer, and death. Variables with p-values > 0.2 on univariable modelling were excluded from the multivariable modelling. The effect of missingness in these complete analyses resulted in considerable sample size depletion, such that multiple imputations by chained equations were considered, creating 20 complete imputed datasets for final analysis using Rubin's formula.²² All models accounted for patient clustering within facilities. Residual creatinine clearance (measured glomerular filtration rate [mGFR]), peritoneal and residual kidney Kt/V and PET test variables were excluded from the imputed model due to significant numbers of missing observations (≥40%). The Post-estimation commands, including the Schoenfield residual (res*) option, assessed the proportional hazards assumption. All statistical analyses were performed at the Australian PDOPPS data analysis centre using the STATA software package (version 15.0; STATA Corp LD, College Station, Texas 7845). A p-value of <0.05 was considered statistically significant, and all confidence intervals (CI) were reported at the 95% level.

Results

During the study period, 7569 patients were registered on the PDOPPS data set across 128 facilities, of whom 1365 were eligible to participate (Figure 1). The mean follow-up was 22 ± 12 months. A lower proportion of individuals started on incremental PD compared to standard PD (37% vs 63%, p < 0.001, Table 1). The use of incremental PD was more common in males, smokers, receiving PD in Japan and pre-dialysis nephrology care exceeding six months, a history of cardiovascular disease, active kidney transplant listing and lower serum creatinine concentrations (Table 1). Incremental PD was less commonly prescribed in Thailand (Supplemental Figure 1).

Table 1.

Baseline demographic and facility characteristics of study participants.

Patients in the incremental PD group received less than three CAPD exchanges daily (20%, 22%, and 58% received 1, 2 and 3 CAPD exchanges daily, respectively). In contrast, patients in the standard group received four or more exchanges daily, with more than 90% receiving four exchanges (95%, 4%, and 1% received 4, 5, and 6 CAPD exchanges daily, respectively; p < 0.001). Regarding exchange volumes, 47% of participants in the incremental PD group used ≤1.5L exchanges on CAPD, compared to 20% of those in the standard PD group (p < 0.001). Ambulatory peritoneal dialysis was more commonly used by individuals receiving incremental PD (60% vs 50%, p = 0.001), as were icodextrin (62% vs 17%, p < 0.001) and neutral pH, low-glucose degradation product (GDP) fluids (33% vs 23%, p < 0.001) On APD day dwell were used much less frequently by the incremental versus standard PD group (3% vs 100%, p < 0.001) (Table 1).

Peritoneal dialysis uptake

On multivariable logistic regression modelling, higher incremental PD uptake was associated with Japan (odds ratio [OR] 2.35, 95% CI 1.05–5.26, p = 0.04; ref: Canada), age >75 years (OR 1.51, 95% CI 1.02– 2.24, p = 0.04; ref: 60–74 years), icodextrin use (OR 8.54, 95% CI 6.26–11.64, p < 0.001), lower serum creatinine concentration at PD commencement (OR 1.01, 95% CI 1.01–1.01, p = 0.007) and higher number of PD patients at a facility (OR 1.01, 95% CI 1.00–1.01, p = 0.02). A lower incremental PD uptake was associated with pre-dialysis nephrologist care of less than one month (OR 0.46, 95% CI 0.22–0.97, p = 0.04; ref: pre-dialysis nephrologist care >1 month to <4 months), and transplant waitlist status, being evaluated or on hold (OR 0.52, 95% CI 0.34–0.81, p = 0.004, not referred OR 0.49, 95% CI 0.31–0.77, p = 0.002; ref: on active transplant list; Table 2).

Table 2.

Multivariable logistic regression analysis of covariates associated with incremental PD uptake.

Covariates	Odds ratio (95% CI)	p-value
Patient characteristics
Country
Australia and New Zealand	0.98 (0.63–1.52)	0.92
Canada	Reference	-
Japan	2.35 (1.05–5.26)	0.04
Thailand	0.91 (0.41–2.01)	0.81
United Kingdom	1.09 (0.64–1.85)	0.75
United States of America	1.16 (0.74–1.81)	0.53
Age (years)
< 45	1.25 (0.81–1.92)	0.32
45–59	1.24 (0.89– 1.73)	0.19
60–74	Reference	-
≥ 75	1.51 (1.02–2.24)	0.04
Male sex	1.30 (0.96–1.77)	0.09
Race
White	Reference	-
Black	1.15 (0.65–2.06)	0.62
Asian	0.82 (0.48–1.38)	0.45
Other/Not reported	0.92 (0.53–1.59)	0.76
BMI, kg/m²
Underweight (< 18.5)	0.68 (0.34–1.34)	0.29
Normal weight (18.5–24.9)	Reference	-
Pre-obesity (25–29.9)	0.72 (0.51–1.02)	0.07
Obese (≥ 30)	0.98 (0.67–1.44)	0.92
Pre-dialysis nephrologist care
None at all	0.97 (0.33–2.85)	0.94
≤ 1 month	0.46 (0.22–0.97)	0.04
> 1 month to < 4 months	Reference	-
≥ 4 months to < 6 months	0.93 (0.42–2.10)	0.87
≥ 6 months	1.04 (0.59–1.82)	0.90
Smoking (current/former)	1.11 (0.82–1.51)	0.48
Comorbid conditions
Diabetes	0.85 (0.64–1.13)	0.26
Cardiovascular disease	0.98 (0.73–1.32)	0.92
Transplant waitlist status, %
Active	Reference	-
Being evaluated/On hold	0.52 (0.34–0.81)	0.004
Not referred	0.49 (0.31–0.77)	0.002
Serum creatinine μmol/L	0.99 (0.99–0.99)	0.007
Icodextrin use	8.53 (6.28–11.59)	<0.001
Neutral pH, low-GDP fluid use	1.28 (0.74–2.21)	0.38
Facility age	1.00 (0.99–1.02)	0.76
Total number of prevalent patients at facility	1.01 (1.00–1.01)	0.02

Haemodialysis transfer

HD transfer occurred in 137 (27%) participants in the incremental PD group and 218 (25%) in the standard PD group, equating to incident rates [IR] of 0.14 [95% CI 0.12–0.16] and 0.15 [95% CI 0.13–0.17] per patient-years of follow-up, respectively (IRR 0.93, 95% CI 0.75–1.15, p = 0.49). The median times to HD transfer were 3.7 years (interquartile range [IQR] 2.5–6.0] in the incremental PD group and 3.6 years (IQR 2.0–4.6) in the standard PD group (p = 0.14). In the multivariable Cox proportional hazards risk regression model, there was no significant difference in the hazards of HD transfer between the two groups (HR 0.87, 95% CI 0.68–1.12, p = 0.29; Table 3). In the incremental PD group, 44 (31%) patients who transferred to HD had experienced peritonitis compared to 86 (41%) in the standard PD group (p = 0.06), 11 (8.2%) versus 25 (11.8%), (p = 0.37), respectively, transferred to HD within one month of a peritonitis episode.

Table 3.

Multivariable Cox proportional hazard regression analysis of covariates associated with risk of haemodialysis transfer.

Covariates	Hazard ratio (95%CI)	p-value
Incremental peritoneal dialysis	0.87 (0.68–1.12)	0.29
Country
Australia and New Zealand	0.72 (0.44–1.17)	0.18
Canada	Reference	-
Japan	1.13 (0.58–2.21)	0.72
Thailand	1.58 (0.80– 3.10)	0.19
UK	1.08 (0.63–1.85)	0.77
USA	0.62 (0.42–0.94)	0.03
Male sex	1.08 (0.83–1.39)	0.59
Age (years)
< 45	1.22 (0.86–1.39)	0.27
45–59	0.94 (0.71–1.23)	0.65
60–74	Reference	-
≥ 75	0.89 (0.63–1.39)	0.54
Race
White	Reference	-
Black	1.78 (1.16–2.74)	0.008
Asian	0.73 (0.43–1.25)	0.26
Other/Not reported	1.02 (0.69–1.50)	0.91
BMI, kg/m²
Underweight (< 18.5)	1.39 (0.82–2.36)	0.22
Normal weight (18.5–24.9)	Reference	-
Pre-obesity (25–29.9)	1.25 (0.92–1.67)	0.15
Obese (≥ 30)	1.54 (1.12–2.12)	0.008
Pre-dialysis nephrologist care
None at all	1.04 (0.48–2.26)	0.92
≤ 1 month	1.20 (0.70–2.07)	0.51
> 1month - < 4 months	Reference	-
≥ 4months - < 6 months	0.62 (0.29–1.57)	0.21
≥ 6 months	0.99 (0.62–1.57)	0.97
Smoking (current/former)	1.14 (0.90–1.44)	0.28
Comorbid conditions
Diabetes	1.24 (0.97–1.59)	0.09
Cardiovascular disease	1.21 (0.92–1.59)	0.17
Transplant waitlist status, %
Active	Reference	-
Being evaluated/On hold	0.94 (0.66–1.33)	0.73
Not referred	0.86 (0.61–1.21)	0.38
Creatinine (μmol/L), mean (SD)	0.99 (0.99–1.00)	0.81
Icodextrin use	0.97 (0.73–1.29)	0.84
Neutral pH, low-GDP fluid use	1.33 (0.85–2.08)	0.20
Facility age (years)	0.99 (0.98–1.00)	0.46
Total number of PD patients at facility	1.00 (0.99–1.00)	0.42

Peritonitis

During follow-up, 304 patients experienced peritonitis: 110 (22%) in the incremental group (IR 0.13 per patient-years, 95% CI 0.11–0.16), and 194 (23%) in the standard PD group (IR 0.15 per patient-years, 95% CI 0.13–0.17; IRR 0.87, 95% CI 0.69–1.10, p = 0.23). In the incremental PD group, 25% of patients experienced their first peritonitis episode at 1.99 years (95% CI, 1.47–2.26) compared to 1.86 years (95% CI, 1.40 −2.18) in the standard PD group (p = 0.38). In the multivariable Cox proportional hazards regression model, the risk of peritonitis in the incremental group was not significantly different from that in the standard group (hazard ratio [HR] = 0.91, 95% CI = 0.66–1.50, p = 0.32; Table 4). There was no significant interaction between incremental PD and type of PD modality on the risk of peritonitis (p = 0.12).

Table 4.

Multivariable Cox proportional hazard regression analysis of covariates associated with the first peritonitis episode.

Covariates	Hazard ratio (95%CI)	p-value
Patient characteristics
Incremental peritoneal dialysis	0.91 (0.66–1.15)	0.50
Country
Australia and New Zealand	0.53 (0.30–0.93)	0.03
Canada	Reference	-
Japan	0.59 (0.24–1.44)	0.25
Thailand	0.77 (0.17–3.4)	0.73
UK	0.79 (0.40–1.59)	0.51
USA	0.64 (0.30–1.32)	0.23
Male sex	0.81 (0.62–1.06)	0.12
Age (years)
< 45	1.00 (0.68–1.49)	0.98
45–59	0.98 (0.73–1.33)	0.92
60–74	Reference	-
≥ 75	1.08 (0.76–1.53)	0.67
Race
White	Reference	-
Black	1.22 (0.72–2.05)	0.46
Asian	0.73 (0.41–1.28)	0.27
Other/Not reported	1.07 (0.67–1.71)	0.77
BMI, kg/m²
Underweight (< 18.5)	1.39 (0.79–2.46)	0.26
Normal weight (18.5–24.9)	Reference	-
Pre-obesity (25–29.9)	0.92 (0.67–1.28)	0.64
Obese (≥ 30)	1.18 (0.84–1.67)	0.34
Pre-dialysis nephrologist care
None at all	0.48 (0.17–1.34)	0.16
≤ 1 month	0.85 (0.48–1.51)	0.58
> 1month - < 4 months	Reference	-
≥ 4months - < 6 months	0.74 (0.38–1.42)	0.36
≥ 6 months	0.66 (0.42–1.05)	0.08
Smoking (current/former)	1.37 (1.06–1.77)	0.02
Comorbid conditions
Diabetes	0.94 (0.73–1.22)	0.66
Cardiovascular disease	1.07 (0.78–1.48)	0.67
Transplant waitlist status, %
Active	Reference	Reference
Being evaluated/On hold	1.49 (0.92–2.41)	0.11
Not referred	1.69 (1.04–2.74)	0.03
Creatinine (μmol/L), mean (SD)	1.00 (0.99–1.00)	0.05
PD modality
CAPD	Reference	-
APD	0.79 (0.61–1.03)	0.08
Icodextrin use	1.11 (0.82–1.50)	0.51
Neutral pH, low-GDP fluid use	1.73 (1.04–2.88)	0.03
Facility age	1.00 (0.99–1.01)	0.91
Prevalent patients at a PD facility	1.00 (0.99–1.00)	0.85

Patient survival

There were 79 (15.5%) deaths in the incremental PD group IR 0.08 (95% CI 0.06–0.10) and 136 (15.9%) in the standard PD group IR 0.09 (95% CI 0.08–0.11) per patient-years of follow-up; (IRR 0.87, 95% CI 0.66–1.15, p = 0.32). Median survival times were 4.4 years [IQR 3.4–5.5] in the incremental PD group and 3.9 years [IQR 2.8–5.7] in the standard PD group (p = 0.04). In the Cox proportional hazards risk regression model, there was no significant difference in patient survival between the two groups (HR 1.13, 95% CI 0.78–1.64, p = 0.52) (Supplemental Table 1). Peritonitis-associated death occurred in 3 (3.8%) patients in the incremental group versus 6 (4.4%) in the standard PD group (p = 0.48).

Discussion

The present study demonstrated marked variation in incremental PD uptake and outcomes across seven countries (Australia, New Zealand, Canada, Japan, Thailand, the United Kingdom, and the United States) in 128 participating facilities. Overall, approximately one-third of patients in the study were prescribed incremental PD, which is associated with similar rates of HD transfer, peritonitis, and patient survival compared with standard PD.

Our findings align with earlier studies, which showed no difference in HD transfer rates between incremental and standard PD groups. In an extensive retrospective analysis using electronic medical records of a dialysis organisation in the United States between 2015 and 2019, Naljayan et al.²³ found no significant difference in HD transfer between incremental and standard groups receiving either CAPD (6.20 vs 5.70 events per patient-year; IRR 1.08 [95% CI 0.32–3.67]) or APD (5.7 vs 5.2 events per patient-year, IRR 1.08 [95% CI 0.64–1.84]).²³ Similarly, Liu et al.²⁴ found no significant difference in HD transfer rates between incremental PD and propensity-matched full dose PD cohorts (p = 0.32). In a registry-based study from Australia and New Zealand, Cheetham et al.¹⁷ did not report any significant difference in HD transfer rates at 30 or 180 days between the incremental and standard PD groups. These findings suggest that an incremental start PD strategy does not appreciably alter the time spent on PD or the risk of HD transfer. This may be related to the counterbalancing effects of favourable factors (such as reduced peritoneal membrane glucose exposure, fewer connections and reduced dialysis burden) and unfavourable factors (such as lower initial PD dose). Alternatively, it may be related to the different indications for selecting incremental versus full dose PD reflecting personalised choice according to goals of care.

Our study also did not find any difference in the risk of peritonitis between incremental and standard PD groups, which is consistent with the findings of other studies. Yan et al.⁶ reported non-significantly different rates of peritonitis in CAPD patients receiving three exchanges daily compared with four exchanges (0.13 vs 0.20 episodes per year, p = 0.20). Sandrini et al.⁷ also reported peritonitis rates that were not significantly different between incremental PD (0.09 episodes per year) and standard PD (0.23 episodes per year). These findings suggest that incremental start PD does not appreciably modify the risk of peritonitis compared with full dose PD, even though it is associated with fewer connections and potentially reduced opportunities for contamination. Alternatively, the findings may reflect selection bias with residual confounding.

Although the current study reported a proportionately lower death rate and a longer median survival time for incremental PD than standard PD, these results were not replicated in the adjusted analysis. Previous studies comparing survival between incremental PD and standard PD reported conflicting results. Some studies found comparable outcomes,^2,6,7,9,17 a few reported better survival,^24,25 and one reported potential harm.²⁶ Jeloka et al. reported better survival in the incremental PD group than in the standard PD group using a single nocturnal icodextrin exchange over five years of follow up.²⁵ Another study reported time-related reduced all-cause mortality and cardiovascular mortality in the incremental group in the second year of PD compared to standard PD.²⁴ In a retrospective cohort study of CAPD patients from China between 2005 and 2015, 43% received < 4 exchanges/day and 65% ≥ 4 exchanges/day. A significantly lower risk of death, by 30% and 35%, was observed in patients receiving ≥ 4 exchanges/day compared with <4 exchanges/day. Excess mortality in the < 4 exchanges/day group was attributed to the inability to meet the minimum solute clearance and ultrafiltration targets.²⁶ These differences in survival among various studies are likely related to variations in study design, small sample size,⁹ heterogeneity in the definition of incremental PD,^7,9 differences in patient characteristics, and analytic methodology.^2,26

Although the ISPD^1,11 guidelines attempted to define what constitutes an incremental strategy, there continues to be wide regional and international variability in how these studies report incremental PD. Some studies have defined incremental PD by the number of exchanges per day, the number of days per week exchanges are performed, or the total weekly exchange volume between the studies defining incremental PD. The current study used a definition of incremental PD aligned with the ISPD guidelines, using less than four 2L exchanges on CAPD to define incremental PD.^6,16,26 We could not conduct a sensitivity analysis using the alternative definition of less than 42L per week, as reported by Cheetham et al. 2023,¹⁷ due to the significant missingness of the values for dwell volumes that would be needed to classify incremental and standard groups in this way.

The current study also found significant geographic variation in standard PD uptake, with a higher uptake observed in Japan compared to other countries participating in the PDOPPS. This may, in part, be related to the smaller body size in the Japanese PDOPPS cohort (mean BMI, 22.9 kg/m²) compared with the average BMI of the PDOPPS cohort (26.3 kg/m²). On the other hand, the baseline measured GFR and Kt/V urea values were lower in the Japanese cohort (6.2 mL/minute and 0.82, respectively) compared to the overall PDOPPS cohort (8.1 mL/minute and 1.2).

The major strength of the PDOPPS study is that it is the largest observational cohort study of PD patients globally, involving 1365 randomly selected PD patient populations from 128 facilities across seven countries. Patient characteristics, PD prescription details, and clinical outcomes were systematically and prospectively collected for individual patients. In addition, PDOPPS undertook regular surveys from the medical directors of participating centres to elucidate the facility policies. However, there are several limitations worth noting, including the study's observational design, variability in how incremental PD was defined and implemented across regions, a significant degree of missing data for several variables (particularly RKF, peritoneal membrane characteristics and urea clearance targets) and risk of selection bias as patients in the incremental PD group had more pre-dialysis care and were more likely to be listed for transplantation. The absence of longitudinal data on PD fluid volume and number of exchanges used precluded evaluation of PD prescription patterns over time. These limitations might risk decreasing study power, generating biased estimates and introducing bias, thus undermining the registry's ability to draw valid inferences if the data were not missing at random. A robust statistical methodology with multivariable imputation was employed to mitigate the effects of missingness data. However, variables with significant missingness (i.e. > 40%) were excluded from the imputation model to avoid inaccuracy in the estimates. In addition, the present study did not evaluate important patient-reported outcomes, such as quality of life, patient satisfaction and treatment burden. As many PD patients did not meet the inclusion criteria, the possibilities of ascertainment bias, coding bias, and residual confounding could not be excluded. Finally, although there were reasonably high numbers of events for each of the outcomes examined (HD transfer n = 355, peritonitis n = 305, death n = 215), the possibility of a type II statistical error cannot be excluded.

In conclusion, we found that incremental PD was utilised in approximately one-third of patients receiving PD across seven countries and, in low certainty evidence, was associated with similar clinical outcomes to standard (full dose) PD with respect to HD transfer, peritonitis and mortality. This suggests that incremental PD, which is less expensive than standard PD, may be a safe and viable option as a strategy for PD commencement.

Supplemental Material

sj-docx-1-ptd-10.1177_08968608251385614 - Supplemental material for Incremental start and clinical outcomes in peritoneal dialysis: International results from PDOPPS

Supplemental material, sj-docx-1-ptd-10.1177_08968608251385614 for Incremental start and clinical outcomes in peritoneal dialysis: International results from PDOPPS by Ashik Hayat, Melissa S Cheetham, Yeoungjee Cho, Junhui Zhao, Keith McCullough, Douglas S Fuller, Rathika Krishnasamy, Neil Boudville, Ana E Figueiredo, Yasuhiko Ito, Talerngsak Kanjanabuch, Jeffrey Perl, Beth M Piraino, Ronald L Pisoni, Cheuk C Szeto, Isaac Teitelbaum, Graham Woodrow, Ken Tsuchiya, David W Johnson, and Louis L Huang in Peritoneal Dialysis International

Footnotes

Declaration of conflicting interests

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: DWJ reports grants and personal fees from Baxter Healthcare, grants and personal fees from Fresenius Medical Care, others from Amgen, personal fees from Astra Zeneca, personal fees from AWAK, grants from National Health and Medical Research Council of Australia, personal fees from Ono, personal fees from Lilly, and personal fees from Bayer, outside the submitted work. YC reports grants and personal fees from Baxter Healthcare, Fresenius Medical Care, and the National Health and Medical Research Council of Australia outside the submitted work. RK reports grants from Bayer Australia, Baxter International, and Astra Zeneca outside the submitted work. MC has received travel support from Amgen and is supported by a Queensland Advancing Clinical Research Fellowship. TK has received consultancy fees from VISTERRA, Alexion/AstraZeneca, and VISIONARY as a country investigator and is currently a recipient of the National Research Council of Thailand. Additionally, TK has received speaking honoraria from Astra Zeneca, Fresenius Medical Care, and Baxter Healthcare. All the other authors declared no competing interests.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

PDOPPS was approved by a central institutional review board (IRB) in the USA and local Human Research Ethics Committees at each study site.

Informed consent

Written informed consent was obtained from each participant before participation in the study.

Author contributions

Not applicable.

Acknowledgements

Not applicable.

ORCID iDs

Ashik Hayat

Yeoungjee Cho

Keith McCullough

Neil Boudville

Ana E Figueiredo

Talerngsak Kanjanabuch

Cheuk C Szeto

Isaac Teitelbaum

David W Johnson

Supplemental material

Supplemental material for this article is available online.

References

Brown

Blake

Boudville

, et al. International Society for Peritoneal Dialysis practice recommendations: prescribing high-quality goal-directed peritoneal dialysis. Perit Dial Int 2020; 40: 244–253.

Ankawi

Woodcock

Jain

, et al. The use of incremental peritoneal dialysis in a large contemporary peritoneal dialysis program. Can J Kidney Health Dis 2016; 3: 2054358116679131.

Auguste

Bargman

. Incremental peritoneal dialysis: new ideas about an old approach. Semin Dial 2018; 31: 445–448.

Manera

Johnson

Craig

, et al. Patient and caregiver priorities for outcomes in peritoneal dialysis: multinational nominal group technique study. Clin J Am Soc Nephrol 2019; 14: 74–83.

Hayat

Cho

Hawley

, et al. Association of Incremental peritoneal dialysis with residual kidney function decline in patients on peritoneal dialysis: the balANZ trial. Perit Dial Int 2023; 43: 374–382.

Yan

Fang

Lin

, et al. Three versus 4 daily exchanges and residual kidney function decline in incident CAPD patients: a randomized controlled trial. Am J Kidney Dis 2017; 69: 506–513.

Sandrini

Vizzardi

Valerio

, et al. Incremental peritoneal dialysis: a 10 year single-centre experience. J Nephrol 2016; 29: 871–879.

Nardelli

Scalamogna

Cicero

, et al. Incremental peritoneal dialysis allows to reduce the time spent for dialysis, glucose exposure, economic cost, plastic waste and water consumption. J Nephrol 2023; 36: 263–273.

Lee

Chung

Park

, et al. Incremental peritoneal dialysis may be beneficial for preserving residual renal function compared to full-dose peritoneal dialysis. Sci Rep 2019; 9: 10105.

10.

Garofalo

Borrelli

De Stefano

, et al. Incremental dialysis in ESRD: systematic review and meta-analysis. J Nephrol 2019; 32: 823–836.

11.

Blake

Dong

Davies

. Incremental peritoneal dialysis. Perit Dial Int 2020; 40: 320–326.

12.

Gillis

Wilkie

. Peritoneal dialysis. Medicine 2019; 47: 603–608.

13.

Australia

. An introduction to peritoneal dialysis. Melbourne, VIC, Australia: Kidney Health Australia, 2016.

14.

Lai

. Optimal peritoneal dialysis for patients from Hong Kong. Perit Dial Int 1999; 19: S26–31; discussion S2-4.

15.

Cheetham

Cho

Krishnasamy

, et al. Incremental versus standard (full-dose) peritoneal dialysis. Kidney Int Rep 2022; 7: 165–176.

16.

Neri

Viglino

Marinangeli

, et al. Incremental start to PD as experienced in Italy: results of censuses carried out from 2005 to 2014. J Nephrol 2017; 30: 593–599.

17.

Cheetham

Cho

Krishnasamy

, et al. Multicentre registry analysis of incremental peritoneal dialysis incidence and associations with patient outcomes. Perit Dial Int 2023; 43: 383–394.

18.

Perl

Davies

Lambie

, et al. The peritoneal dialysis outcomes and practice patterns study (PDOPPS): unifying efforts to inform practice and improve global outcomes in peritoneal dialysis. Perit Dial Int 2016; 36: 297–307.

19.

von Elm

Altman

Egger

, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453–1457.

20.

Htay

Cho

Pascoe

, et al. Multicenter registry analysis of center characteristics associated with technique failure in patients on incident peritoneal dialysis. Clin J Am Soc Nephrol 2017; 12: 1090–1099.

21.

Chow

Cho

, et al. ISPD Peritonitis guideline recommendations: 2022 update on prevention and treatment. Perit Dial Int 2022; 42: 110–153.

22.

Rubin

. Multiple imputation for nonresponse in surveys. New York, NY: JohnWiley & Sons. Inc, 1987.

23.

Naljayan

Hunt

McKeon

, et al. Use of incremental peritoneal dialysis: impact on clinical outcomes and quality of life measure. J Nephrol 2023; 36: 1897–1905.

24.

Liu

Peng

, et al. Incremental peritoneal dialysis and survival outcomes: a propensity-matched cohort study. J Nephrol 2023; 36: 1907–1919.

25.

Jeloka

Sanwaria

Chaudhari

, et al. “Ico-Alone” single nocturnal exchange to initiate peritoneal dialysis in patients with residual renal function-five year, single centre experience. Indian J Nephrol 2013; 23: 276–279.

26.

Chen

, et al. Number of daily peritoneal dialysis exchanges and mortality risk in a Chinese population. Perit Dial Int 2018; 38: S53–S63.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.05 MB