Long-term cardiovascular outcomes in peritoneal dialysis patients: a systematic review

INTRODUCTION

A peritoneal dialysis (PD) is a renal replacement therapy that utilizes the peritoneum as a natural semipermeable membrane to remove waste products, electrolytes, and excess fluids from the body through the infusion of dialysis fluid into the peritoneal cavity.¹ This approach is particularly beneficial for patients with end-stage kidney disease (ESKD), offering the convenience of home-based treatment and improved quality of life compared to conventional hemodialysis.^2–5 Globally, PD accounts for 11% of dialysis cases and 9% of kidney replacement treatment procedures.⁶ The global distribution of dialysis patients using peritoneal dialysis systems stands markedly different across developed and developing regions as developing nations maintain higher numbers.⁷

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among dialysis patients, contributing to approximately 45% of deaths in this population.⁸ People receiving dialysis treatment experience cardiovascular death risks which exceed those of the general population by 20 times.^9,10 Patients undergoing PD treatment experience specific cardiovascular risk elements connected to volume load from renal function loss and elevated glucose concentrations that rule PD solution chemistry as well as glucose degradation products that produce advanced glycation end-products.^11,12 Inflammation together with atherosclerosis and these additional factors substantially increase the risk of cardiovascular mortality. Medical experts have identified heart failure and sudden cardiac death as significant causes of cardiovascular death in dialysis patients beyond traditional atherosclerotic disease processes.¹³

Although PD represents a significant clinical issue for healthcare providers, we still need to understand specific long-term heart problems that occur in PD patients. Studies comparing cardiovascular risks between PD and additional dialysis treatments produce different results. some research suggests that home hemodialysis confers better protection against stroke and heart attacks and mortality from all causes than PD, while other reviews highlight PD as a cost-effective alternative for ESKD patients with cardiovascular risks.^14,15 Presence of peritonitis infection, a common PD-related complication that typically intensifies cardiovascular risks in this treatment.¹⁶ The basis of conducting this systematic review includes several key factors such as the global increase of PD treatment alongside its escalating prevalence rates in developing nations, along with varying research methods and outcome reports, and the necessity for consolidated insights to enable better clinical choices.^17,18

This review aims to comprehensively evaluate long-term cardiovascular outcomes in PD patients, identify modality-specific cardiovascular risk factors, compare outcomes between PD and other dialysis modalities where data permits, and assess the quality of existing evidence to inform future research directions. By addressing these objectives, this review seeks to provide an evidence-based foundation for optimizing cardiovascular care in the growing population of PD patients worldwide.

METHODS

This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review aimed to synthesize the available evidence on long-term cardiovascular outcomes in patients undergoing peritoneal dialysis (PD), identify PD-specific cardiovascular risk factors, and compare outcomes between PD and other dialysis modalities.

Search strategy

A comprehensive search of electronic databases was performed to identify relevant studies. Databases included PubMed, Embase, Scopus and Cochrane Library. The search covered all publications from January 2015 to December 2024. The search strategy utilized a combination of Medical Subject Headings (MeSH) terms and keywords related to peritoneal dialysis (e.g., "peritoneal dialysis," "PD," "continuous ambulatory peritoneal dialysis") and cardiovascular outcomes (e.g., "cardiovascular mortality," "myocardial infarction," "stroke," "heart failure"). Boolean operators ("AND," "OR") were applied to refine the search results.

In addition to database searches, manual screening of reference lists from relevant systematic reviews and primary studies was conducted to identify additional eligible articles. Grey literature sources, including conference proceedings and reports, were also reviewed to capture unpublished data that met inclusion criteria.

Study selection

Studies were selected based on predefined inclusion and exclusion criteria. The inclusion criteria were as follows.

Population

Adults aged 18 years or older undergoing peritoneal dialysis for end-stage kidney disease (ESKD).

Outcomes

Studies reporting long-term cardiovascular outcomes, including cardiovascular mortality, myocardial infarction, stroke, or hospitalization due to heart failure.

Study design

Randomized controlled trials (RCTs), cohort studies, case-control studies, and cross-sectional studies with a minimum follow-up duration of five years.

Exclusion criteria included non-English language studies, pediatric populations, animal studies, case series or reports with fewer than 50 participants, and studies with insufficient follow-up data.

Two independent reviewers screened titles and abstracts for relevance using Rayyan software for systematic reviews. Full-text articles were assessed for eligibility based on inclusion criteria. Disagreements between reviewers were resolved through discussion or consultation with a third reviewer.

Data extraction

Data extraction was performed using a standardized template designed to capture key study characteristics. Extracted information included.

Study characteristics

Author(s), year of publication, study design, sample size, geographic location.

Patient demographics

Age, sex, dialysis vintage, comorbidities.

Cardiovascular outcomes

Definitions of outcomes (e.g., myocardial infarction), event rates, hazard ratios (HRs), and confidence intervals (CIs).

Peritoneal dialysis-specific risk factors

Residual renal function status, glucose exposure from PD solutions, presence of peritonitis infection.

Data extraction was conducted independently by two reviewers to ensure accuracy and completeness. Any discrepancies in extracted data were resolved through consensus.

Quality assessment

The methodological quality of all included studies was evaluated using the ROBINS-I (risk of bias in non-randomized studies - of interventions) tool, which is specifically designed for cohort and other non-randomized studies.²⁰ This tool assesses risk of bias across seven domains: confounding, selection of participants, classification of interventions (exposures), deviations from intended interventions, missing data, measurement of outcomes, and selection of the reported result. For each study, two reviewers independently assessed risk of bias, with disagreements resolved by consensus. Studies were rated as having low, moderate, or serious risk of bias in each domain and overall.

Data synthesis

A narrative synthesis was conducted for all included studies to summarize findings related to long-term cardiovascular outcomes in PD patients. Subgroup analyses explored potential sources of heterogeneity based on geographic region (developed vs developing countries), PD modality (continuous ambulatory vs automated PD), and residual renal function status.

RESULTS

A comprehensive literature search was performed across four major electronic databases: PubMed/MEDLINE, Embase, Scopus and Cochrane Library, resulting in the identification of 716 studies.

After removing duplicates, 658 studies remained for title and abstract screening. Following a detailed full-text review, 20 studies were included in the final synthesis. Of these, 8 were prospective cohorts and 12 were retrospective cohorts, with no randomized controlled trials identified. The PRISMA flow diagram (Figure 1) illustrates the study selection process. Geographically, Chinese (n=10) and Taiwanese (n=6) cohorts dominated (16/20 studies), alongside studies from Türkiye (n=1), Portugal (n=1), Brazil (n=1), and South Korea (n=1). Sample sizes varied widely, ranging from 123 to 5,707 participants, with follow-up durations spanning 2.5 to 14 years. Adult populations were exclusively studied, with mean ages between 42.3 and 59.4 years. Comorbidities were prevalent, particularly diabetes (19–56%) and hypertension (53–94%), while cardiovascular disease (CVD) affected 7–44% of participants. Table 1 presents the study and participant characteristics of the included studies.

Intervention and comparator characteristics

Continuous Ambulatory Peritoneal Dialysis (CAPD) was the predominant modality, utilized in 12 studies, while two studies included Automated Peritoneal Dialysis (APD).^25,34 Dialysis prescription details, such as Kt/V targets or exchange frequency, were inconsistently reported, with only eight studies providing granular data. For instance, Tsai et al documented a weekly Kt/V of 1.9±0.3, while Hsieh et al reported a total weekly Kt/V of 2.08±0.56.^24,36

Peritonitis episodes, a critical complication in PD, were quantified in five studies, with rates ranging from 0.2 to 0.35 episodes per patient-year.^34,36 Comparators were heterogeneous: two studies contrasted PD with hemodialysis (HD) while others stratified outcomes by biomarkers or clinical parameters such as hypervolemia or residual renal function. Table 2 presents intervention/exposure and comparator details of the included studies.^27,28

Cardiovascular outcomes and risk factors

All-cause mortality, universally reported, ranged from 19.4% to 42.4%, with higher rates observed in studies with prolonged follow-up.^22,38 Cardiovascular mortality, analyzed in 15 studies, was significantly associated with modifiable risk factors bdominal aorta calcification (AAC) ratio was an independent predictor of cardiovascular mortality (HR 8.01 for AAC >39%).²¹ Hypervolemia, indicated by icodextrin use, increased cardiovascular event risk (HR 3.8), and hypoalbuminemia (<3.35 g/dl) was an independent predictor of cardiovascular events (HR 2.84).²⁵

Hypomagnesemia (<0.7 mmol/l) was a potent predictor of all-cause mortality (HR 1.58).²⁶ Elevated lipid ratios, such as TG/HDL-C ≥1.94 (HR 3.57) and non-HDL-C/HDL-C≥2.86 (HR 2.58), also independently predicted mortality.²³ Left ventricular diastolic dysfunction (LVDD) doubled the risk of mortality (HR 2.25), and low triiodothyronine (T3) levels were associated with a 14% reduction in mortality risk per 10 ng/dl increase (HR 0.86).^29,30

Secondary cardiovascular outcomes

Secondary outcomes highlighted the importance of cardiac pathology progression. Incidence of atrial fibrillation was 1.32-fold higher in PD patients compared to non-ESRD controls.²⁸ Cardiorenal syndrome (CRS), especially type IV, was independently associated with higher cardiovascular mortality (HR 2.10).22 Left ventricular fraction shortening (LVFS) was a robust predictor of cardiovascular events, with lower values linked to higher risk (HR 0.51 for highest vs. lowest tertile).³⁹

Inflammatory and hematologic biomarkers

Inflammatory markers were consistently associated with adverse outcomes. Neutrophil-to-lymphocyte ratio (NLR ≥2.87) predicted all-cause (HR 2.60) and cardiovascular mortality (HR 2.89).³³ Platelet-to-albumin ratio (PAR >7.27) was also a strong predictor of all-cause (HR 1.50) and cardiovascular mortality (HR 1.79).³⁵ Mean platelet volume (MPV ≥10.2 fl) was independently associated with mortality (HR 0.73 for all-cause; HR 0.69 for CV mortality).³¹

Technique failure and peritonitis

Technique failure, including transfer to HD or transplantation, was reported in 16–24% of patients. Peritonitis frequency was a strong, dose-dependent predictor of cardiovascular mortality (HR 1.22 for one episode, up to HR 3.84 for four or more episodes).³⁴ Hyperuricemia and higher peritonitis rates independently predicted technique failure.³⁶

Methodological quality and risk of bias

Figure 2 presents the risk of bias evaluation for the 20 included non-randomized studies using the ROBINS-I tool. Across domains, the majority of studies (13/20, 65%) exhibited a serious overall risk of bias, primarily due to unresolved confounding (e.g., unadjusted comorbidities), substantial missing data (15/20 studies lacked handling methods), or selection bias by Hu et al with registry-based sampling.

The remaining seven studies (35%) were rated moderate risk, reflecting partial confounding control but robust adjustment for key variables.^22,25,27,35 Notably, intervention classification, deviations from intended interventions, and outcome measurement were consistently rated low risk across all studies, suggesting reliable exposure and outcome definitions. However, the frequent serious ratings for confounding, missing data, and selection bias underscore inherent limitations in observational PD research, particularly from retrospective designs and registry data.

DISCUSSION

This systematic review combined evidence across 20 cohorts totaling more than 140,000 adults for PD and provides a complete synthesis of long-term outcomes and cardiovascular risk in this emergent population of patients. While the global uptake of PD has been increasing, especially in less developed regions, our findings reaffirm that cardiovascular disease (CVD) continues to remain the primary cause of death in PD patients, contributing to 40–55% of all-cause deaths across varied populations. This is consistent with previous large-scald meta-analyses and registry studies, where CVD was consistently presented as the leading COD in ESKD patients, with several fold higher of the risk compared to the general population.^33,41

Our analysis demonstrates that CV risk in PD patients is determined by a complex interplay of traditional and non-traditional risk factors. Age, diabetes, and preexisting cardiovascular disease are consistently identified as the main determinants of all-cause as well as cardiovascular death.²⁶ But, PD-specific factors, including chronic inflammation, metabolic derangements, and exposure to glucose-containing dialysate increase the risk in PD population. Vascular calcification, in particular abdominal aorta calcification (AAC) was also found being most powerful independent predictors of cardiovascular mortality in PD an AAC-ratio > 39% being associated with 8.2-fold relative risk.²¹ This goes along with previous work in dialysis (and non-dialysis) CKD patients that have shown that the presence of vascular calcification in a marker of advanced atherosclerosis and a harbinger of bad outcomes.⁴²

Malnutrition and inflammation, with hypoalbuminemia and increased inflammatory markers, also constituted important predictors of adverse results. Hypoalbuminemia (<3.35 g/dl) independently predicted cardiovascular events and all‐cause mortality consistently in our study, which was in accordance with the previously documented malnutrition‐inflammation complex syndrome among patients on dialysis.^25,30,43 Inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-albumin ratio (PAR), were robustly associated with mortality risk.^33,35 These findings are supported by broader evidence implicating chronic inflammation as a driver of atherosclerosis and cardiac dysfunction in CKD.⁴⁴

Electrolytes, especially hypomagnesemia, were independently associated with the all-cause and cardiovascular mortalities.²⁶ This would be biologically plausible as magnesium participates in the regulation of vascular tone, prevention of arrhythmias and endothelial function.⁴⁵ Metabolic risk factors, such as higher TG/HDL cholesterol ratios and higher non-HDL/HDL ratios, were equally closely associated with heightened mortality and reflected the atherogenic lipid profiles typically seen in PD patients.^31,41

Apart from these biochemical and clinical markers the statement points new prognostic markers e.g., heart rhythm complexity expressed by nonlinear HRV parameters such as DFA α1 and multiscale entropy (MSE). Tsai et al found that decreased heart rhythm complexity was independently associated with cardiovascular death and major adverse cardiovascular events and was superior to conventional linear HRV parameters.²⁴ This discovery implies that autonomic disturbances and impaired cardiac adaptability are neglected cardiac risk factors in PD and provides novel opportunities for risk stratification and intervention.⁴⁶

Our synthesis also highlights the importance of PD-related complications, particularly peritonitis, in determining both technique failure and CV outcomes. Peritonitis rate had a clear dose–response trend for cardiovascular mortality, with the risk increasing for each extra episode.³⁴ The systematic review by Sahlawi et al draws attention to the substantial heterogeneity of peritonitis definitions and presentation in different studies that precludes direct comparisons but emphasizes the importance of common outcome measures. Peritonitis is still in fact, a leading cause of technique failure and switch to hemodialysis, especially in the elderly/fail patients which are also exposed to a greater risk of both death and infection.^47,48 Review showed the comparison between PD and hemodialysis (HD), and meta-analyses by Loziers et al report that all-cause and cardiovascular mortality are generally comparable among modalities, with pooled risk ratios near unity and no significant differences in adverse cardiovascular events when comparing across modalities.⁴¹ However, a few subgroups, like the elderly and diabetes patients have marginally elevated risk on PD, which would represent greater comorbidity burden and more rapid loss of residual renal function.^27,48 Conversely, atrial fibrillation was less common among PD patients than among HD patients, probably because of more stability in hemodynamics and avoidance of rapid fluid shifts.^28,49

The strengths of this review include its strict inclusion of long-term follow-up studies, comprehensive adjustment for confounders in key analyses, and the inclusion of diverse international cohorts. However, several limitations must be acknowledged. The majority of studies were observational, single-center, or registry-based, which introduces some risk of residual confounding and of selection bias. A lot of studies did not mention their handling of missing data and definition of outcomes-most notably cardiovascular events and peritonitis-differed for which comparability was limited. Most of the included studies were in Asian populations, so this might limit the extrapolation of findings to Western countries with other patients’ characteristics and health systems. Besides, few studies provided detailed data on residual renal function or dialysis prescription, both of which are known to influence cardiovascular outcomes in PD.

In clinical practice, these findings underscore the importance of comprehensive risk assessment in PD patients, including regular evaluation of vascular calcification, nutritional and inflammatory status, and cardiac function. Interventions targeting modifiable risk factors-such as optimizing nutrition, using biocompatible PD solutions, and preventing peritonitis-should be prioritized. The emerging evidence for heart rhythm complexity and inflammatory biomarkers as prognostic tools may refine risk stratification and guide individualized care. Future research should focus on multicentre, prospective studies with standardized outcome definitions, greater representation of non-Asian cohorts, and interventional trials targeting inflammation, vascular calcification, and metabolic disturbances.

CONCLUSION

Despite providing crucial benefits in patient autonomy and hemodynamic stability, peritoneal dialysis is counterbalanced by continuous metabolic and infectious burdens. Several comparative analyses have shown that overall cardiovascular outcomes are comparable for PD compared with haemodialysis, but that specific high-risk subgroups on PD (in particular the elderly and those with diabetes or pre-existing CVD) may need monitoring and individualization of treatment. The review points to large heterogeneity in outcome definitions and reporting, indicating that standardized research methods and multicentre studies are urgently needed. However, addressing these modifiable risks through the implementation of comprehensive cardiovascular risk assessment and management, prevention of infective complications, and targeted interventions will be vital for improving survival and quality of life in patients with PD. Further studies should focus on the need for global representation, harmonized reporting of clinical end points and trials of interventions that will optimize cardiovascular management of this growing population.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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