Association of Incident Dialysis Modality With Patient Survival: A Systematic Review and Meta-analysis

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In a context where randomization to either peritoneal dialysis (PD) or hemodialysis (HD) proved to be extremely challenging, previous meta-analyses were greatly limited due to the inclusion of historical studies. Methods We performed a systematic review by searching multiple databases up to April 22nd, 2022. The primary outcome was the association between dialysis modality (PD vs HD) and mortality assessed via hazard ratios (HR). Subgroup analyses were conducted to explore potential sources of heterogeneity, including sex, age, diabetes, dialysis vintage, geographical location, HD access, and study cohort inclusion period. Results Database search yielded 5317 citations, from which, 27 observational studies met the eligibility criteria, including 1 033 362 incident dialysis patients. The pooled mortality HR for PD versus HD was 1.01 (95% CI 0.93–1.10). Heterogeneity was substantial ( I 2 = 94%) and was largely explained by different baseline features of the included populations. A statistically significant subgroup effect was demonstrated for age (> 65 vs.<65 years; p = 0.01), geographical location of the studies (Oceania vs. Europe vs. Asia vs. North America; p < 0.01), and HD vascular access (central venous catheter vs. arteriovenous fistula; p < 0.01, only one study included). Conclusions This meta-analysis suggests that overall PD and incentre HD likely carry equivalent survival benefits. However, differences were detected among subgroups based on age, geographic location, HD access type, but not on sex, diabetes status, dialysis vintage and study cohort inclusion period. peritoneal dialysis hemodialysis mortality survival diabetes systematic review metanalysis Figures Figure 1 Figure 2 Figure 3 Figure 4 1. INTRODUCTION An aging population and modifiable lifestyle risk factors accompanied by a decline in early-life infectious diseases have resulted in the rise of chronic diseases as a predominant global health threat with profound socioeconomic and public health consequences 1 , 2 . The global burden of chronic kidney disease (CKD) is substantial and growing, with approximately 10% of adults worldwide affected by some form of CKD, resulting in 1.2 million deaths and 28 million years of life lost each year 3 , 4 . Chronic kidney disease is characterized by progressive, irreversible kidney function deterioration culminating in end-stage renal disease (ESRD). Renal replacement therapy (RRT), either in the form of chronic dialysis or kidney transplantation, is a life-sustaining treatment for people with ESRD. Because of the shortage of kidney donors and of the concomitant comorbidities that might preclude kidney transplantation dialysis remains the prevailing treatment option for most people with ESRD 1 , 5 . In the 1980s, the introduction of peritoneal dialysis (PD) into clinical practice, initially raised the question of which dialysis modality, between PD and hemodialysis (HD), should be preferred 6 , 7 . Although the choice of the dialytic technique should consider several factors, patient survival is undoubtedly one of the most relevant. Several observational studies have previously compared PD and HD in the ESRD population, but the survival benefit of one modality over the other has not yet been determined since results conflict across studies 8 – 13 . Moreover, despite those results were analyzed after stratification based on several factors (e.g. age, diabetes mellitus status, and dialysis duration), patient subgroups that might benefit more from either PD or HD in terms of mortality rates have not yet been clearly identified. To date, only two randomized controlled trials attempted to compare mortality risk between the two dialysis modalities. However, the first investigation was halted prematurely due to insufficient enrollment 14 , while in the second study the primary outcome was changed to health-related quality of life due to insufficient statistical power 15 . Those results showed the enormous challenge, if not the impossibility, to perform an adequately powered random allocation in this setting. To overcome this hurdle, few meta-analyses aimed at summarizing the evidence deriving from observational studies have been carried out 16 – 21 . Nevertheless, all these papers included historical cohorts and were mainly restricted either to elderly populations or individuals with diabetes. However, in the new millennium the rapid diffusion of automated peritoneal dialysis (APD) in clinical practice, along with the advent of icodextrin 22 , promoted a better patient fluid control contributing to solve the problem of fast transport in PD 23 – 26 . During the same period HD-specific improvements have also occurred with the introduction of biocompatible membranes and the diffusion of on-line high-flux hemodiafiltration 27 , 28 . However, over the last two decades, a consistent and substantial reduction in mortality rates for patients starting PD has been reported, although such improvements were not observed for HD patients 29 . This differential change in outcomes mandates a new analysis focused on populations treated with modern dialytic techniques to reflect the current therapeutical standards. Hence, whether HD or PD provides a survival advantage to patients with ESRD still remains an unresolved issue. 2. METHODS 2.1 Data source and search strategy A comprehensive search of several databases was performed on April 22nd, 2022. Date limits were applied from 2000 forward. Animal studies were excluded. Databases searched were Ovid MEDLINE(R) 1946 to Present and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase 1988+, Ovid Cochrane Central Register of Controlled Trials 1991+, Ovid Cochrane Database of Systematic Reviews 2005+, Web of Science Core Collection via Clarivate Analytics (1975+), and Scopus via Elsevier (1788+). The search strategy was designed and conducted by an experienced librarian with input from the study’s investigators. Controlled vocabulary supplemented with keywords was used to search for studies describing the association of incident dialysis modality with patient survival. The actual strategy listing all search terms used and how they are combined is available in the Supplementary. Citations were managed with the reference management program, Covidence®, while data were first collected in Microsoft® Excel v.16.86 and then analysed through R statistical software 30 . This systematic review's protocol was prospectively registered in PROSPERO (No. CRD42022328308). We adhered to the adapted PRISMA guidelines for systematic reviews (checklist in the Supplementary). 2.2 Study selection and data extraction We included studies which satisfied the following inclusion criteria: (i) comprising adult patients (> 18 years old) with end-stage kidney on dialysis treatment; (ii) comparing any chronic PD treatment (continuous ambulatory PD [CAPD]; automated PD [APD] and its variants: continuous cyclic PD [CCPD], nocturnal intermittent PD [NIPD], intermittent PD [IPD] and tidal PD [TPD]) versus any type of HD and its variants (hemofiltration, hemodiafiltration, acid-free biofiltration); (iii) providing data on mortality for the patients included with an intention-to-treat analysis; (iv) including patients who started dialysis after 2000 (in case of studies including patients before and after 2000, we include them if there were enough data to extract only the patients from 2000 onwards); (v) classifying the patients according to dialysis modality received 90 days post-initiation of therapy; and (vi) with at least 50 patients per group. We excluded studies (i) which evaluate combined HD and PD strategies; (ii) where hemodialysis comprises intensive dialysis (i.e. greater than 3.5 times per week, or greater than 6 hours per treatment); (iii) where the comparison was between home-HD and PD; (iv) which included the comparison in patients coming back to dialysis after kidney transplant failure; (v) where the results were only presented as as-treated analysis; and (vi) where patients who shifted dialysis method were censored or not included. Two reviewers (L.N. and D.Z.) screened all titles and abstracts independently. Studies included at this level by either reviewer were included for full-text screening by the same reviewer pair. Discrepancies were solved through discussion or by consultation of a third reviewer (M.P.). Extracted data included study design, year of publication, start and end date of patients’ inclusion, number of patients for each group (HD and PD), and main characteristics of the included patients (sex, age, presence of diabetes, coronary artery disease [CAD], congestive heart failure [CHF], and peripheral vascular disease [PAD]). 2.3 Quality assessment and certainty of evidence Risk of bias assessment was performed using the Newcastle-Ottawa tool for observational studies 31 . Potential disagreements were resolved through discussion. Certainty of evidence (CoE) of the primary outcome was assessed using the GRADE approach 32 . 2.4 Statistical analysis The primary outcome was mortality as assessed by time-to-event analysis and reported using hazard ratios (HR). Therefore, we collected from each study a pre-computed HRand the corresponding confidence interval (CI) comparing PD and HD. HR’s and their standard errors were pooled using a generic inverse variance approach and a random-effects model with a restricted maximum likelihood ratio estimator of between study heterogeneity. We planned several a priori determined subgroup analyses to explore heterogeneity. These analyses were based on risk of bias, sex, age, diabetes status, dialysis vintage (duration), geographic location (continent of study origin), dialysis access type, and year of the patients’ inclusion in the study. We tested the interaction between subgroups and generated a P value for the difference based on heterogeneity statistic Q 33 . All analyses are performed using R statistical software 30 . Meta-analyses were performed using the R package “meta” and its subgroup analysis function using the “subgroup” argument 34 . 3. RESULTS 3.1 Search results and characteristics of included studies The results of the literature search are presented in the PRISMA flow diagram in Figure 1. The initial search identified 5317 citations. After duplicate removal and exclusion on title and abstract screening, 249 studies qualified for a full text review. Two hundreds and twenty-two studies were excluded for specific reasons (Fig. 1). Consequently, a total of 27 studies met our eligibility criteria contributing to the final meta-analysis 11–13,35–58 . The characteristics of the included studies are summarized in Table 1. All analyzed papers were retrospective cohort studies published between 2007 and 2021: twenty-two studies were registry-based, three were from multi-center cohorts 39,47,57 and one single-center study 36 . Cohort periods ranged from 2000 to 2015. There was wide geographical variability, with nine studies conducted on North American populations 11,12,45,46,49,51,56–58 , an eight on European cohorts 13,37,39,40,50,52–54 , an additional eight studies reporting on Asian patients 36,41,43,44,47,48,55,59 , and two on dialysis patients from Australia/New Zealand 35,38 , as shown in Table 1. Few studies compared mortality risks in populations with specific characteristics, such as those with either diabetes 47 , a previous history of stroke 55 or age > 75 years 37,38 . All studies considered incident patients who initiated dialysis over a period from 2000 to 2017. The overall number of included patients was 1 033 362, from which a total of 847 660 were on HD vs 185 702 on PD. Among them, 81 736 patients underwent a process of matching (Tab. 1). Table 2 depicts the main characteristics of the included populations. 3.2 Risk of bias and study quality Three studies were considered at high risk of bias primarily due to lack of adjustment for potential confounding variables 35,47,51 , while four studies were judged to have unclear risk of bias since the modality of the intention to treat analysis was not explained in detail 36,37,43,55 (Supplementary Table S1). On the other hand, the remaining 20 studies were deemed at low risk of bias 11–13,38–42,44–46,48–50,53,54,56–58,60 . 3.3 Overall mortality Analysis of all the studies showed no statistically significant difference in mortality between PD and incenter HD (HR=1.06 [95% CI 0.97 – 1.15, I 2 = 94%]), (Fig. 2). There was a significant interaction based on risk of bias, hence, we considered the estimate derived from the 17 studies at low risk of bias to be the best available estimate (HR=1.01 [95% CI, 0.93 – 1.10, I 2 = 94%]. Subsequent subgroup analyses were performed only on studies at low risk of bias. 3.4 Subgroup analyses When considering an age cut-off of 65 years, we observed a statistically significant subgroup effect (p=0.01). Age was a significant effect modifier and could partially explain heterogeneity. The age group younger than 65 years had a more prominent reduction in mortality with PD compared to HD (HR 0.75, CI 0.56-0.99). There was substantial heterogeneity between the studies within each of these subgroups (age>65: I 2 =96%; age<65: I 2 =46%]. We also observed a statistically significant subgroup effect when considering the continent of origin of the included studies (Oceania vs. Europe vs. Asia vs. North America; p<0.01). Thus, geographic location was a significant effect modifier. The lowest HRs were in Europe (HR 0.89, CI 0.77-1.03) and North America (HR 0.95, CI 0.87-1.05), whereas higher HRs were observed in Oceania (HR 1.25, CI 1.07-1.47) and Asia (HR 1.21, CI 1-10-1.32). We detected substantial heterogeneity in each subgroup, except Oceania whose result was based on a single study. There was a statistically significant subgroup effect for the vascular access types in HD (p<0.01), but this estimate was derived from only one study. No statistically significant subgroup effect was found for sex, diabetes, dialysis vintage, and study cohort inclusion period (Figure 3 and Figure 4). 3.5 Certainty of Evidence The GRADE evidence profile is shown in table 3. Although the presence of heterogeneity among the studies was adequately explained by different baseline features of the included populations, the final certainty of evidence concerning the primary outcome was graded as low, due to the nonrandomized nature of the available studies. 4. DISCUSSION To the best of our knowledge, this is the first systematic review and meta-analysis to comprehensively investigate the survival benefits of PD compared with in-centre HD based exclusively on contemporary cohorts. In a context where patients randomization to the two different dialysis modalities proved to be extremely challenging (if not unrealistic) 14 , 15 , previous comparative analysis and systematic reviews of PD/HD mortality were unequivocally limited due to the inclusion of both historical and heterogeneous studies 16 – 21 . To minimize the effect of selection bias and, at the same time, obtain results which could be reasonably applied to the modern dialytic cohorts, we employed strict inclusion criteria during the process of study selection. Firstly, we decided to exclude all the data concerning patients who started dialysis before 2000. This year was used as “watershed” since it may correspond to the widespread diffusion of APD 61 and the use of icodextrin in PD practice 62 , 63 along with the advent of biocompatible membranes and the dissemination of on-line high flux hemodiafiltration 27 , 28 . In addition, to exclude patients at risk for early mortality we considered only studies that classified patients according to the dialysis modality received 90 days post-initiation of therapy 64 , 65 . Furthermore, we selected exclusively “intention-to treat” analysis excluding “as-treated” evaluation. “Intention-to treat” analysis allocates patient death based on the starting treatment modality, while “as-treated” analysis allocates patient death according to the treatment modality at the moment of the event. Considering that the rate of transfer of PD patients to HD is significantly higher than the opposite (HD to PD) and that most modality changes are associated with increased mortality after transfers 66 , 67 , we believed that only analysis adjusting for these changes allows to evaluate the effect of initial treatment modality. Despite all these precautions, the level of certainty of the meta-analysis results according to the GRADE profile 32 was unavoidably categorized as “low”, due to the impossibility to include randomized clinical trials. In our systematic review and meta-analysis we did not find a significant difference in overall mortality risk between PD and in-center HD patients. However, the HR of death for PD versus in-center HD was heterogenous among cohort studies [ I 2 = 94%, P < 0.01]. Hence, subgroup analyses were conducted to explore potential sources of heterogeneity, including sex, age, diabetes, dialysis vintage, geographical distribution, HD access, and study cohort inclusion period. The analyses revealed a statistically significant subgroup effect for age, geographical distribution of the individual studies, and HD vascular access. We observed a significant survival benefit for PD in subjects with an age lower than 65 years. These data strengthened the previous evidence that in young patients PD has a survival advantage over HD 20 . Since PD is a self-management treatment and intraluminal peritonitis is the most frequent and impactful event 68 , 69 , a younger age might help maximize therapy compliance, while minimizing incidence and severity of complications through either a scrupulous execution of the exchanges or/and an early referral of potential hurdles. Conversely, our results diverge from the common belief that individuals with diabetes present a less favorable survival in PD 19 , 20 . This condition has been traditionally referred to the constant exposure to glucose in the dialysate that may worsen glycemic homeostasis 70 . Furthermore, individuals with diabetes possess more often a higher peritoneal transport rate that could make more challenging the achievement of volume and adequacy targets 71 . However, the advent of new glucose-sparing dialysates 72 , such as icodextrins 73 or amino acids 74 , along with the routinary use of APD in clinical practice, may justify these different results. Currently, the renovated interest for free- or low-glucose peritoneal solutions is demonstrated by ongoing clinical trials which aim at evaluating the efficacy and safety of novel xylitol-carnitine and polydextrine-composed peritoneal solutions 75 , 76 . These novelties along with the technological advancements of systems for PD will require soon a re-evaluation of the outcomes regarding individuals with diabetes on PD. In addition, our analyses challenge the theory that PD offers a survival advantage during the first year of therapy compared to HD, with this benefit diminishing as dialysis vintage increases 11 , 46 , 50 , 55 . Based on this hypothesis, a “PD-first policy” followed by a planned transition to HD has been proposed 77 . Conversely, the notion of PD as the most suitable bridge to kidney transplantation for potential candidates has been reinforced 78 . Our new data challenge the applicability of these concepts to modern cohorts and discourage transitioning from PD to HD in patients after the first few years of dialytic treatment. Furthermore, in line with evidence from the last two decades that survival among PD has been superior compared to HD 11 , 13 , 29 , 52 , 58 , 79 , 80 , we did not detect a statistically significant subgroup effect for study cohort inclusion period. As mentioned above, with the emergence of new dialysates and dialyzers, improvement of the ultrafiltration capacity, increased attention to preserving residual renal function and peritoneal membrane integrity, improved dialysis adequacy as well as management of anemia, mineral and nutrition parameters, great advances in PD have been accomplished. These advancements, along with the early evidence, call for future analyses in the coming years focused exclusively on data from the last decade. It is noteworthy to remark that all the PD advancements previously described are not yet equally accessible worldwide. This observation in combination with additional dissimilarities either in quality of the dialysis modality provided or in patient population characteristics (e.g. prevalence of diabetes in dialysis incident patients) across continents may explain the geographical differences that were observed in our analysis. In fact, we detected a statistically significant subgroup effect when considering the continent of origin of the included studies (Oceania vs. Europe vs. Asia vs. North America). Lowest HRs resulted in Europe (0.89, 0.77–1.03) and North America (0.95, 0.87–1.05), while higher HRs were obtained in Oceania (1.25, 1.07–1.47) and Asia (1.21, 1-10-1.32). Unfortunately, it was not possible to extensively investigate by meta-analysis the effect of HD vascular access types on the relationship of dialysis modality and mortality. The only available study confirms that PD has a clear survival benefit over HD patients starting dialysis with a CVC 39 , reinforcing the potentially advantage that PD could confer to subjects who are judged ineligible for arteriosus venous fistula creation 65 . Conversely, new data are required to explore the mortality outcome among incident PD patients and subjects initiating HD with an AVF. Although this systematic review and meta-analysis was conducted according to a rigorous methodology, our study has several limitations. First, it is important to emphasize that the evidence derived from observational studies is inevitably inferior to that from randomized trials. Second, even though most studies attempted to minimize the adverse effects through adjustment, unknown or unmeasured confounders may still undermine the robustness of the outcomes. Third, as part of the included articles were registry-based, a degree of inherent inaccuracies in coding and record completeness may be expected. These points should be weighed against the meticulous systematic approach of this study, the exclusion of historical cohorts, and the use of numerous and clearly defined inclusion criteria. In conclusion, evidence derived from the results of this systematic review and meta-analysis evaluating the effect of incident dialysis modality on mortality indicates that, overall, PD and in-center HD carry similar survival rates. However, differences were detected among subgroups. These discrepancies seem to depend mainly on age and continent of origin, but not on sex, diabetic status, and dialysis vintage. Thus, given that randomized controlled trials have proven to be challenging, if not impracticable, this study provides reassurance that PD and in-center HD offer equivalent survival benefits, potentially aiding in the selection of dialysis modality in the modern era. Declarations Declaration of Conflicting Interest: We have read and understood BMC Nephrology’s policy on disclosing conflicts of interest and declare that we have none. Ethics Approval and consent to partecipate: not applicable (systematic review and meta-analysis). Consent for publication: not applicable (systematic review and meta-analysis).. Availability of data and materials: the datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing Interests: none. Funding: none. Authors’ contributions: Research idea and study design: LN, MP; data acquisition: LN, MO, DZ, AS, EC; data analysis/interpretation: LN, MP, MM, MaP; statistical analysis: MP, MM; supervision or mentorship: MM, GC, CA, MaP. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Acknowledgements: none. References USRDS. 2024 Annual Data Report [Internet]. Chronic Kidney Disease. 2024 [cited 2024 Dec 2];Available from: https://usrds-adr.niddk.nih.gov/2024 Nugent RA, Fathima F, Feigl AB. The Burden of chronic kidney disease on developing Nations: A 21st Century. Nephron Clin Pract. 2011;118:c269–277. Collaboration GCKD. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. 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Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period. Nephrol Dial Transpl. 2016;31:120–8. Wagner M, Ansell D, Kent DM, et al. Predicting mortality in incident dialysis patients: an analysis of the United Kingdom renal registry. Am J Kid Dis. 2011;57:894–902. Waldum-Grevbo B, Leivestad T, Reisæter AV, Os I. Impact of initial dialysis modality on mortality: a propensity-matched study. BMC Nephrol 2015;16. Wang IK, Liang WM, Lin CL, et al. Impact of dialysis modality on the survival of patients with end-stage renal disease and prior stroke. Int Urol Nephrol. 2016;48:139–47. Wang V, Coffman CJ, Sanders LL, et al. Comparing mortality of peritoneal and hemodialysis patients in an era of Medicare payment reform. Med Care. 2021;59:155–62. Wong B, Ravani P, Oliver MJ, et al. Comparison of patient survival between hemodialysis and peritoneal dialysis among patients eligible for both modalities. Am J Kid Dis. 2018;71:344–51. Yeates K, Zhu N, Vonesh E, Trpeski L, Blake P, Fenton S. Hemodialysis and peritoneal dialysis are associated with similar outcomes for end-stage renal disease treatment in Canada. Nephrol Dial Transpl. 2012;27:3568–75. Young OK, Yeong JC, Ji IK, et al. The impact of intima-media thickness of radial artery on early failure of radiocephalic arteriovenous fistula in hemodialysis patients. J Korean Med Sci. 2006;21(2):284–9. Van De Luijtgaarden MWM, Jager KJ, Segelmark M, et al. Trends in dialysis modality choice and related patient survival in the ERA-EDTA Registry over a 20-year period. Nephrol Dial Transpl. 2016;31:120–8. Ronco C, Kliger AS, Amici G, Virga G. Automated peritoneal dialysis: clinical prescription and technology. Perit Dial Int. 2000;20:S70–6. Mistry CD, Gokal R. Optimal use of glucose polymer (icodextrin) in peritoneal dialysis. Perit Dial Int. 1996;16(Suppl 1):S104–8. Mistry C, Mallick N, Gokal R. Ultrafiltration with an isosmotic solution during long peritoneal dialysis exchanges. Lancet. 1987;2:178–82. Robinson BM, Zhang J, Morgenstern H, et al. Worldwide, mortality risk is high soon after initiation of hemodialysis. Kidney Int. 2014;85:158–65. Foley RN, Chen SC, Solid CA, Gilbertson DT, Collins AJ. Early mortality in patients starting dialysis appears to go unregistered. Kidney Int. 2014;86:392–8. Nadeau-Fredette AC, Sukul N, Lambie M, et al. Mortality trends after transfer from peritoneal dialysis to hemodialysis. Kidney Int Rep. 2022;7:1062–73. Nessim SJ, Bargman JM, Vanita Jassal S, Oliver MJ, Na Y, Perl J. The impact of transfer from hemodialysis on peritoneal dialysis technique survival. Perit Dial Int. 2015;35:297–305. Chen JHC, Johnson DW, Hawley C, Boudville N, Lim WH. Association between causes of peritoneal dialysis technique failure and all-cause mortality. Sci Rep. 2018;8:3980. Lambie M, Zhao J, McCullough K, et al. Variation in peritoneal dialysis time on therapy by country results from the peritoneal dialysis outcomes and practice patterns study. Clin J Am Soc Nephrol. 2022;17:861–71. Nardelli L, Scalamogna A, Cicero E, Castellano G. Incremental peritoneal dialysis allows to reduce the time spent for dialysis, glucose exposure, economic cost, plastic waste and water consumption. J Nephrol 2022;Sep 20. Churchill DN, Thorpe KE, Nolph KD, et al. Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. J Am Soc Nephrol. 1998;9:1285–92. Low S, Liew A. Peritoneal dialysis fluids. Sem Dial. 2024;37:10–23. Wolfson M, Ogrinc F, Mujais S. Review of clinical trial experience with icodextrin. Kidney Int. 2002;62:S46–52. Faller B. Amino acid-based peritoneal dialysis solutions. Kidney Int Suppl. 1996;56:S81–5. Bonomini M, Davies S, Kleophas W et al. Rationale and design of ELIXIR, a randomized, controlled trial to evaluate efficacy and safety of XyloCore, a glucose-sparing solution for peritoneal dialysis. Perit Dial Int 2024;Online ahead of print. Gronda E, Gallieni M, Pacileo G, et al. Rationale and design of PURE, a randomized controlled trial to evaluate peritoneal ultrafiltration with PolyCore™ in refractory congestive heart failure. Kidney Blood Press Res; 2024. Blake PG. Integrated end-stage renal disease care: the role of peritoneal dialysis. Nephrol Dial Transpl. 2001;16:61–6. Nardelli L, Scalamogna A, Messa P, et al. Peritoneal dialysis for potential kidney transplant recipients: pride or prejudice? Med (Kaunas). 2022;58:214. Quinn RR, Hux JE, Oliver MJ, Austin PC, Tonelli M, Laupacis A. Selection bias explains apparent differential mortality between dialysis modalities. J Am Soc Nephrol. 2011;22:1534–42. Marshall MR, Polkinghorne KR, Kerr PG, Agar JWM, Hawley CM, McDonald SP. Temporal changes in mortality risk by dialysis modality in the Australian and New zealand dialysis population. Am J Kid Dis. 2015;66:489–98. Tables Tables 1 to 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files SUPPLEMENTARYPDHD..docx TABLES.docx Cite Share Download PDF Status: Published Journal Publication published 24 Oct, 2025 Read the published version in BMC Nephrology → Version 1 posted Editorial decision: Revision requested 14 Jul, 2025 Reviews received at journal 14 Jul, 2025 Reviews received at journal 08 Jul, 2025 Reviewers agreed at journal 08 Jul, 2025 Reviewers agreed at journal 03 Jul, 2025 Reviewers invited by journal 03 Jul, 2025 Editor invited by journal 24 Jun, 2025 Editor assigned by journal 24 Jun, 2025 Submission checks completed at journal 18 Jun, 2025 First submitted to journal 18 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6873929","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":480467218,"identity":"0e29052a-dad1-45fd-a27f-174043999530","order_by":0,"name":"Luca Nardelli","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYBACPijN2MDO3HDgA5DFxk5ACxtcCzNjw8EZIBFmUrQw84CYBLWwnz3AXFBzT7afmbHxsM2vbfJ8zAyMHz7m4NHCk5fAPONYsfHMZsaGw7l9tw3bmBmYJWduw6NFgseAmYctIXHDYZCWntuMQC1szLwEtfxLSNwP0mLZc9ueOC28bUBbgN4/zPDjdiJhLTw5Bod5+xKMZwBtOdjbcDu5jZmxGa9f+NnPGD7m+ZYg29/efPjDjz+3bee3Nx/88BGPFhA4AGcxtoHJBvzqUcEfUhSPglEwCkbBSAEADXdLWsjlQL4AAAAASUVORK5CYII=","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":true,"prefix":"","firstName":"Luca","middleName":"","lastName":"Nardelli","suffix":""},{"id":480467219,"identity":"a2701842-4b19-4b33-9b09-d9ac4d067986","order_by":1,"name":"Matteo Passerini","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Matteo","middleName":"","lastName":"Passerini","suffix":""},{"id":480467220,"identity":"06c6a860-1c3b-484c-95bc-fd065a422573","order_by":2,"name":"Dalia Zubidat","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Dalia","middleName":"","lastName":"Zubidat","suffix":""},{"id":480467221,"identity":"d9293d0c-3a7e-4472-b4a3-c9bdafde7e67","order_by":3,"name":"Anna Sikharulidze","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Sikharulidze","suffix":""},{"id":480467226,"identity":"d153d9fa-fbc0-49e8-b55d-5dce6dfa7626","order_by":4,"name":"Elisa Cicero","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Elisa","middleName":"","lastName":"Cicero","suffix":""},{"id":480467227,"identity":"e58014a1-f59e-4270-93d2-f14b77781918","order_by":5,"name":"Carlo Alfieri","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Carlo","middleName":"","lastName":"Alfieri","suffix":""},{"id":480467228,"identity":"fe1dce8b-ca4a-437b-a91d-9df199e5644e","order_by":6,"name":"Manuel Podestà","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Manuel","middleName":"","lastName":"Podestà","suffix":""},{"id":480467229,"identity":"9e2c196a-8e2a-4628-af05-c20961661d84","order_by":7,"name":"Giuseppe Castellano","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Giuseppe","middleName":"","lastName":"Castellano","suffix":""},{"id":480467230,"identity":"2bddea8b-6b66-4447-89f5-4213b2105c14","order_by":8,"name":"Mohammad Hassan Murad","email":"","orcid":"","institution":"Mayo Clinic 6","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Hassan","lastName":"Murad","suffix":""}],"badges":[],"createdAt":"2025-06-11 17:08:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6873929/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6873929/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12882-025-04530-4","type":"published","date":"2025-10-24T16:17:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86227012,"identity":"e4719bbc-e5c1-4f0c-8ce8-bec04f99e8f0","added_by":"auto","created_at":"2025-07-08 08:11:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57171,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA flow diagram\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6873929/v1/706dffe206b881e898177f47.jpg"},{"id":86227014,"identity":"a5c32f60-5649-4895-a5ab-f2eb00ebd6ca","added_by":"auto","created_at":"2025-07-08 08:11:48","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":85938,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plot for meta-analysis of studies comparing all-cause mortality risk of PD versus in-centre HD.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCI = confidence interval; HR = hazard ratio; SE = standard error.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6873929/v1/b53a85351d5f9594170ca478.jpg"},{"id":86227381,"identity":"9a6b96dc-e536-4ee4-9840-aaf84ed2a87c","added_by":"auto","created_at":"2025-07-08 08:19:48","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":295704,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plots for meta-analyses of PD versus HD mortality risk by (A) sex; (B) age; (C) diabetes; (D) time period.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCI = confidence interval; HR = hazard ratio; SE = standard error.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6873929/v1/7968d4fa501ddb6d7b313f22.jpg"},{"id":86227379,"identity":"496adb6f-ee05-4e5d-962b-e822da2e8965","added_by":"auto","created_at":"2025-07-08 08:19:48","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":266008,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eForest plots for meta-analyses of PD versus HD mortality risk by (A) dialysis vintage; (B) geographical continent; (C) vascular access.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCI = confidence interval; HR = hazard ratio; SE = standard error.\u003c/p\u003e","description":"","filename":"Picture4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6873929/v1/c9f062e5b97271f5a22492f0.jpg"},{"id":94490597,"identity":"5ee89088-46a7-434e-bd8d-f0727dd1f72f","added_by":"auto","created_at":"2025-10-27 17:12:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1462162,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6873929/v1/46b5e1f2-c057-427e-a258-bfce438b480c.pdf"},{"id":86227016,"identity":"f39ded49-2c01-4d7a-bd19-c4c6b3c8924d","added_by":"auto","created_at":"2025-07-08 08:11:48","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":526889,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYPDHD..docx","url":"https://assets-eu.researchsquare.com/files/rs-6873929/v1/443369efc10f1dd21455bca9.docx"},{"id":86227020,"identity":"97b05155-2586-480c-86b6-9dc667f5daac","added_by":"auto","created_at":"2025-07-08 08:11:48","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":247669,"visible":true,"origin":"","legend":"","description":"","filename":"TABLES.docx","url":"https://assets-eu.researchsquare.com/files/rs-6873929/v1/0888a1a0192775b406ddb7b9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAssociation of Incident Dialysis Modality With Patient Survival: A Systematic Review and Meta-analysis\u003c/p\u003e","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eAn aging population and modifiable lifestyle risk factors accompanied by a decline in early-life infectious diseases have resulted in the rise of chronic diseases as a predominant global health threat with profound socioeconomic and public health consequences\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The global burden of chronic kidney disease (CKD) is substantial and growing, with approximately 10% of adults worldwide affected by some form of CKD, resulting in 1.2\u0026nbsp;million deaths and 28\u0026nbsp;million years of life lost each year\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eChronic kidney disease is characterized by progressive, irreversible kidney function deterioration culminating in end-stage renal disease (ESRD). Renal replacement therapy (RRT), either in the form of chronic dialysis or kidney transplantation, is a life-sustaining treatment for people with ESRD. Because of the shortage of kidney donors and of the concomitant comorbidities that might preclude kidney transplantation dialysis remains the prevailing treatment option for most people with ESRD\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. In the 1980s, the introduction of peritoneal dialysis (PD) into clinical practice, initially raised the question of which dialysis modality, between PD and hemodialysis (HD), should be preferred\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough the choice of the dialytic technique should consider several factors, patient survival is undoubtedly one of the most relevant. Several observational studies have previously compared PD and HD in the ESRD population, but the survival benefit of one modality over the other has not yet been determined since results conflict across studies\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10 CR11 CR12\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMoreover, despite those results were analyzed after stratification based on several factors (e.g. age, diabetes mellitus status, and dialysis duration), patient subgroups that might benefit more from either PD or HD in terms of mortality rates have not yet been clearly identified.\u003c/p\u003e \u003cp\u003eTo date, only two randomized controlled trials attempted to compare mortality risk between the two dialysis modalities. However, the first investigation was halted prematurely due to insufficient enrollment\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e, while in the second study the primary outcome was changed to health-related quality of life due to insufficient statistical power\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Those results showed the enormous challenge, if not the impossibility, to perform an adequately powered random allocation in this setting.\u003c/p\u003e \u003cp\u003eTo overcome this hurdle, few meta-analyses aimed at summarizing the evidence deriving from observational studies have been carried out\u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Nevertheless, all these papers included historical cohorts and were mainly restricted either to elderly populations or individuals with diabetes.\u003c/p\u003e \u003cp\u003eHowever, in the new millennium the rapid diffusion of automated peritoneal dialysis (APD) in clinical practice, along with the advent of icodextrin\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e, promoted a better patient fluid control contributing to solve the problem of fast transport in PD\u003csup\u003e\u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. During the same period HD-specific improvements have also occurred with the introduction of biocompatible membranes and the diffusion of on-line high-flux hemodiafiltration\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eHowever, over the last two decades, a consistent and substantial reduction in mortality rates for patients starting PD has been reported, although such improvements were not observed for HD patients\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. This differential change in outcomes mandates a new analysis focused on populations treated with modern dialytic techniques to reflect the current therapeutical standards. Hence, whether HD or PD provides a survival advantage to patients with ESRD still remains an unresolved issue.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Data source and search strategy\u003c/h2\u003e \u003cp\u003eA comprehensive search of several databases was performed on April 22nd, 2022. Date limits were applied from 2000 forward. Animal studies were excluded. Databases searched were Ovid MEDLINE(R) 1946 to Present and Epub Ahead of Print, In-Process \u0026amp; Other Non-Indexed Citations and Daily, Ovid Embase 1988+, Ovid Cochrane Central Register of Controlled Trials 1991+, Ovid Cochrane Database of Systematic Reviews 2005+, Web of Science Core Collection via Clarivate Analytics (1975+), and Scopus via Elsevier (1788+). The search strategy was designed and conducted by an experienced librarian with input from the study\u0026rsquo;s investigators. Controlled vocabulary supplemented with keywords was used to search for studies describing the association of incident dialysis modality with patient survival. The actual strategy listing all search terms used and how they are combined is available in the Supplementary. Citations were managed with the reference management program, Covidence\u0026reg;, while data were first collected in Microsoft\u0026reg; Excel v.16.86 and then analysed through R statistical software\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis systematic review's protocol was prospectively registered in PROSPERO (No. CRD42022328308). We adhered to the adapted PRISMA guidelines for systematic reviews (checklist in the Supplementary).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study selection and data extraction\u003c/h2\u003e \u003cp\u003eWe included studies which satisfied the following inclusion criteria: (i) comprising adult patients (\u0026gt;\u0026thinsp;18 years old) with end-stage kidney on dialysis treatment; (ii) comparing any chronic PD treatment (continuous ambulatory PD [CAPD]; automated PD [APD] and its variants: continuous cyclic PD [CCPD], nocturnal intermittent PD [NIPD], intermittent PD [IPD] and tidal PD [TPD]) \u003cem\u003eversus\u003c/em\u003e any type of HD and its variants (hemofiltration, hemodiafiltration, acid-free biofiltration); (iii) providing data on mortality for the patients included with an intention-to-treat analysis; (iv) including patients who started dialysis after 2000 (in case of studies including patients before and after 2000, we include them if there were enough data to extract only the patients from 2000 onwards); (v) classifying the patients according to dialysis modality received 90 days post-initiation of therapy; and (vi) with at least 50 patients per group. We excluded studies (i) which evaluate combined HD and PD strategies; (ii) where hemodialysis comprises intensive dialysis (i.e. greater than 3.5 times per week, or greater than 6 hours per treatment); (iii) where the comparison was between home-HD and PD; (iv) which included the comparison in patients coming back to dialysis after kidney transplant failure; (v) where the results were only presented as as-treated analysis; and (vi) where patients who shifted dialysis method were censored or not included.\u003c/p\u003e \u003cp\u003eTwo reviewers (L.N. and D.Z.) screened all titles and abstracts independently. Studies included at this level by either reviewer were included for full-text screening by the same reviewer pair. Discrepancies were solved through discussion or by consultation of a third reviewer (M.P.). Extracted data included study design, year of publication, start and end date of patients\u0026rsquo; inclusion, number of patients for each group (HD and PD), and main characteristics of the included patients (sex, age, presence of diabetes, coronary artery disease [CAD], congestive heart failure [CHF], and peripheral vascular disease [PAD]).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Quality assessment and certainty of evidence\u003c/h2\u003e \u003cp\u003eRisk of bias assessment was performed using the Newcastle-Ottawa tool for observational studies\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Potential disagreements were resolved through discussion. Certainty of evidence (CoE) of the primary outcome was assessed using the GRADE approach\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eThe primary outcome was mortality as assessed by time-to-event analysis and reported using hazard ratios (HR). Therefore, we collected from each study a pre-computed HRand the corresponding confidence interval (CI) comparing PD and HD. HR\u0026rsquo;s and their standard errors were pooled using a generic inverse variance approach and a random-effects model with a restricted maximum likelihood ratio estimator of between study heterogeneity. We planned several a priori determined subgroup analyses to explore heterogeneity. These analyses were based on risk of bias, sex, age, diabetes status, dialysis vintage (duration), geographic location (continent of study origin), dialysis access type, and year of the patients\u0026rsquo; inclusion in the study. We tested the interaction between subgroups and generated a P value for the difference based on heterogeneity statistic Q\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. All analyses are performed using R statistical software\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Meta-analyses were performed using the R package \u0026ldquo;meta\u0026rdquo; and its subgroup analysis function using the \u0026ldquo;subgroup\u0026rdquo; argument\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003e3.1 \u003cem\u003eSearch results and characteristics of included studies\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe results of the literature search are presented in the PRISMA flow diagram in Figure 1. The initial search identified 5317 citations. After duplicate removal and exclusion on title and abstract screening, 249 studies qualified for a full text review. Two hundreds and twenty-two studies were excluded for specific reasons (Fig. 1). Consequently, a total of 27 studies met our eligibility criteria contributing to the final meta-analysis\u003csup\u003e\u0026nbsp;11–13,35–58\u003c/sup\u003e. The characteristics of the included studies are summarized in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll analyzed papers were retrospective cohort studies published between 2007 and 2021: twenty-two studies were registry-based, three were from multi-center cohorts\u003csup\u003e39,47,57\u003c/sup\u003e and one single-center study\u003csup\u003e36\u003c/sup\u003e. Cohort periods ranged from 2000 to 2015. There was wide geographical variability, with nine studies conducted on North American populations\u003csup\u003e11,12,45,46,49,51,56–58\u003c/sup\u003e, an eight on European cohorts\u003csup\u003e13,37,39,40,50,52–54\u003c/sup\u003e, an additional eight studies reporting on Asian patients\u003csup\u003e36,41,43,44,47,48,55,59\u003c/sup\u003e, and two on dialysis patients from Australia/New Zealand\u003csup\u003e35,38\u003c/sup\u003e, as shown in Table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFew studies compared mortality risks in populations with specific characteristics, such as those with either diabetes\u003csup\u003e47\u003c/sup\u003e, a previous history of stroke\u003csup\u003e55\u003c/sup\u003e or age \u0026gt; 75 years\u003csup\u003e37,38\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAll studies considered incident patients who initiated dialysis over a period from 2000 to 2017. The overall number of included patients was 1 033 362, from which a total of 847 660 were on HD vs 185 702 on PD. Among them, 81 736 patients underwent a process of matching (Tab. 1). Table 2 depicts the main characteristics of the included populations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.2 Risk of bias and study quality\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThree studies were considered at high risk of bias primarily due to lack of adjustment for potential confounding variables\u003csup\u003e35,47,51\u003c/sup\u003e, while four studies were judged to have unclear risk of bias since the modality of the intention to treat analysis was not explained in detail\u003csup\u003e36,37,43,55\u0026nbsp;\u003c/sup\u003e(Supplementary Table S1). On the other hand, the remaining 20 studies were deemed at low risk of bias\u003csup\u003e11–13,38–42,44–46,48–50,53,54,56–58,60\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.3 Overall mortality\u003c/p\u003e\n\u003cp\u003eAnalysis of all the studies showed no statistically significant difference in mortality between PD and incenter HD (HR=1.06 [95% CI 0.97 – 1.15,\u003cem\u003e\u0026nbsp;I\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e = 94%]), (Fig. 2). There was a significant interaction based on risk of bias, hence, we considered the estimate derived from the 17 studies at low risk of bias to be the best available estimate (HR=1.01 [95% CI, 0.93 – 1.10, \u003cem\u003eI\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e = 94%]. Subsequent subgroup analyses were performed only on studies at low risk of bias.\u003c/p\u003e\n\u003cp\u003e3.4 Subgroup analyses\u003c/p\u003e\n\u003cp\u003eWhen considering an age cut-off of 65 years, we observed a statistically significant subgroup effect (p=0.01). Age was a significant effect modifier and could partially explain heterogeneity. The age group younger than 65 years had a more prominent reduction in mortality with PD compared to HD (HR 0.75, CI 0.56-0.99). There was substantial heterogeneity between the studies within each of these subgroups (age\u0026gt;65: \u003cem\u003eI\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=96%; age\u0026lt;65: \u003cem\u003eI\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e=46%]. We also observed a statistically significant subgroup effect when considering the continent of origin of the included studies (Oceania vs. Europe vs. Asia vs. North America; p\u0026lt;0.01). Thus, geographic location was a significant effect modifier. The lowest HRs were in Europe (HR 0.89, CI 0.77-1.03) and North America (HR 0.95, CI 0.87-1.05), whereas higher HRs were observed in Oceania (HR 1.25, CI 1.07-1.47) and Asia (HR 1.21, CI 1-10-1.32). We detected substantial heterogeneity in each subgroup, except Oceania whose result was based on a single study. There was a statistically significant subgroup effect for the vascular access types in HD (p\u0026lt;0.01), but this estimate was derived from only one study. No statistically significant subgroup effect was found for sex, diabetes, dialysis vintage, and study cohort inclusion period (Figure 3 and Figure 4). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3.5 Certainty of Evidence\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe GRADE evidence profile is shown in table 3. Although the presence of heterogeneity among the studies was adequately explained by different baseline features of the included populations, the final certainty of evidence concerning the primary outcome was graded as low, due to the nonrandomized nature of the available studies.\u0026nbsp;\u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003e To the best of our knowledge, this is the first systematic review and meta-analysis to comprehensively investigate the survival benefits of PD compared with in-centre HD based exclusively on contemporary cohorts.\u003c/p\u003e \u003cp\u003eIn a context where patients randomization to the two different dialysis modalities proved to be extremely challenging (if not unrealistic)\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e, previous comparative analysis and systematic reviews of PD/HD mortality were unequivocally limited due to the inclusion of both historical and heterogeneous studies \u003csup\u003e\u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTo minimize the effect of selection bias and, at the same time, obtain results which could be reasonably applied to the modern dialytic cohorts, we employed strict inclusion criteria during the process of study selection.\u003c/p\u003e \u003cp\u003eFirstly, we decided to exclude all the data concerning patients who started dialysis before 2000. This year was used as \u0026ldquo;watershed\u0026rdquo; since it may correspond to the widespread diffusion of APD\u003csup\u003e\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e\u003c/sup\u003e and the use of icodextrin in PD practice\u003csup\u003e\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e,\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e\u003c/sup\u003e along with the advent of biocompatible membranes and the dissemination of on-line high flux hemodiafiltration \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. In addition, to exclude patients at risk for early mortality we considered only studies that classified patients according to the dialysis modality received 90 days post-initiation of therapy\u003csup\u003e\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e,\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e. Furthermore, we selected exclusively \u0026ldquo;intention-to treat\u0026rdquo; analysis excluding \u0026ldquo;as-treated\u0026rdquo; evaluation. \u0026ldquo;Intention-to treat\u0026rdquo; analysis allocates patient death based on the starting treatment modality, while \u0026ldquo;as-treated\u0026rdquo; analysis allocates patient death according to the treatment modality at the moment of the event. Considering that the rate of transfer of PD patients to HD is significantly higher than the opposite (HD to PD) and that most modality changes are associated with increased mortality after transfers\u003csup\u003e\u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e,\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e\u003c/sup\u003e, we believed that only analysis adjusting for these changes allows to evaluate the effect of initial treatment modality.\u003c/p\u003e \u003cp\u003eDespite all these precautions, the level of certainty of the meta-analysis results according to the GRADE profile\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e was unavoidably categorized as \u0026ldquo;low\u0026rdquo;, due to the impossibility to include randomized clinical trials.\u003c/p\u003e \u003cp\u003eIn our systematic review and meta-analysis we did not find a significant difference in overall mortality risk between PD and in-center HD patients.\u003c/p\u003e \u003cp\u003eHowever, the HR of death for PD versus in-center HD was heterogenous among cohort studies [\u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;94%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01]. Hence, subgroup analyses were conducted to explore potential sources of heterogeneity, including sex, age, diabetes, dialysis vintage, geographical distribution, HD access, and study cohort inclusion period. The analyses revealed a statistically significant subgroup effect for age, geographical distribution of the individual studies, and HD vascular access.\u003c/p\u003e \u003cp\u003eWe observed a significant survival benefit for PD in subjects with an age lower than 65 years. These data strengthened the previous evidence that in young patients PD has a survival advantage over HD\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Since PD is a self-management treatment and intraluminal peritonitis is the most frequent and impactful event\u003csup\u003e\u003cspan citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e,\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e, a younger age might help maximize therapy compliance, while minimizing incidence and severity of complications through either a scrupulous execution of the exchanges or/and an early referral of potential hurdles.\u003c/p\u003e \u003cp\u003eConversely, our results diverge from the common belief that individuals with diabetes present a less favorable survival in PD\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. This condition has been traditionally referred to the constant exposure to glucose in the dialysate that may worsen glycemic homeostasis\u003csup\u003e\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u003c/sup\u003e. Furthermore, individuals with diabetes possess more often a higher peritoneal transport rate that could make more challenging the achievement of volume and adequacy targets\u003csup\u003e\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e\u003c/sup\u003e. However, the advent of new glucose-sparing dialysates\u003csup\u003e\u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e\u003c/sup\u003e, such as icodextrins\u003csup\u003e\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u003c/sup\u003e or amino acids\u003csup\u003e\u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e74\u003c/span\u003e\u003c/sup\u003e, along with the routinary use of APD in clinical practice, may justify these different results. Currently, the renovated interest for free- or low-glucose peritoneal solutions is demonstrated by ongoing clinical trials which aim at evaluating the efficacy and safety of novel xylitol-carnitine and polydextrine-composed peritoneal solutions\u003csup\u003e\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e,\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e\u003c/sup\u003e. These novelties along with the technological advancements of systems for PD will require soon a re-evaluation of the outcomes regarding individuals with diabetes on PD.\u003c/p\u003e \u003cp\u003eIn addition, our analyses challenge the theory that PD offers a survival advantage during the first year of therapy compared to HD, with this benefit diminishing as dialysis vintage increases \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e,\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e. Based on this hypothesis, a \u0026ldquo;PD-first policy\u0026rdquo; followed by a planned transition to HD has been proposed\u003csup\u003e\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e\u003c/sup\u003e. Conversely, the notion of PD as the most suitable bridge to kidney transplantation for potential candidates has been reinforced\u003csup\u003e\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur new data challenge the applicability of these concepts to modern cohorts and discourage transitioning from PD to HD in patients after the first few years of dialytic treatment.\u003c/p\u003e \u003cp\u003eFurthermore, in line with evidence from the last two decades that survival among PD has been superior compared to HD\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e,\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e,\u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e\u003c/sup\u003e, we did not detect a statistically significant subgroup effect for study cohort inclusion period.\u003c/p\u003e \u003cp\u003eAs mentioned above, with the emergence of new dialysates and dialyzers, improvement of the ultrafiltration capacity, increased attention to preserving residual renal function and peritoneal membrane integrity, improved dialysis adequacy as well as management of anemia, mineral and nutrition parameters, great advances in PD have been accomplished. These advancements, along with the early evidence, call for future analyses in the coming years focused exclusively on data from the last decade.\u003c/p\u003e \u003cp\u003eIt is noteworthy to remark that all the PD advancements previously described are not yet equally accessible worldwide. This observation in combination with additional dissimilarities either in quality of the dialysis modality provided or in patient population characteristics (e.g. prevalence of diabetes in dialysis incident patients) across continents may explain the geographical differences that were observed in our analysis. In fact, we detected a statistically significant subgroup effect when considering the continent of origin of the included studies (Oceania vs. Europe vs. Asia vs. North America). Lowest HRs resulted in Europe (0.89, 0.77\u0026ndash;1.03) and North America (0.95, 0.87\u0026ndash;1.05), while higher HRs were obtained in Oceania (1.25, 1.07\u0026ndash;1.47) and Asia (1.21, 1-10-1.32).\u003c/p\u003e \u003cp\u003eUnfortunately, it was not possible to extensively investigate by meta-analysis the effect of HD vascular access types on the relationship of dialysis modality and mortality. The only available study confirms that PD has a clear survival benefit over HD patients starting dialysis with a CVC\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e\u003c/sup\u003e, reinforcing the potentially advantage that PD could confer to subjects who are judged ineligible for arteriosus venous fistula creation\u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e. Conversely, new data are required to explore the mortality outcome among incident PD patients and subjects initiating HD with an AVF.\u003c/p\u003e \u003cp\u003eAlthough this systematic review and meta-analysis was conducted according to a rigorous methodology, our study has several limitations. First, it is important to emphasize that the evidence derived from observational studies is inevitably inferior to that from randomized trials. Second, even though most studies attempted to minimize the adverse effects through adjustment, unknown or unmeasured confounders may still undermine the robustness of the outcomes. Third, as part of the included articles were registry-based, a degree of inherent inaccuracies in coding and record completeness may be expected. These points should be weighed against the meticulous systematic approach of this study, the exclusion of historical cohorts, and the use of numerous and clearly defined inclusion criteria.\u003c/p\u003e \u003cp\u003eIn conclusion, evidence derived from the results of this systematic review and meta-analysis evaluating the effect of incident dialysis modality on mortality indicates that, overall, PD and in-center HD carry similar survival rates. However, differences were detected among subgroups. These discrepancies seem to depend mainly on age and continent of origin, but not on sex, diabetic status, and dialysis vintage.\u003c/p\u003e \u003cp\u003eThus, given that randomized controlled trials have proven to be challenging, if not impracticable, this study provides reassurance that PD and in-center HD offer equivalent survival benefits, potentially aiding in the selection of dialysis modality in the modern era.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDeclaration of Conflicting Interest:\u0026nbsp;\u003c/strong\u003eWe have read and understood BMC Nephrology’s policy on disclosing conflicts of interest and declare that we have none.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and consent to partecipate:\u0026nbsp;\u003c/strong\u003enot applicable (systematic review and meta-analysis).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003enot applicable (systematic review and meta-analysis)..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003ethe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u0026nbsp;\u003c/strong\u003enone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003enone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions:\u003c/strong\u003e Research idea and study design: LN, MP; data acquisition: LN, MO, DZ, AS, EC; data analysis/interpretation: LN, MP, MM, MaP; statistical analysis: MP, MM; supervision or mentorship: MM, GC, CA, MaP. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003enone.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eUSRDS. 2024 Annual Data Report [Internet]. Chronic Kidney Disease. 2024 [cited 2024 Dec 2];Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://usrds-adr.niddk.nih.gov/2024\u003c/span\u003e\u003cspan address=\"https://usrds-adr.niddk.nih.gov/2024\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNugent RA, Fathima F, Feigl AB. The Burden of chronic kidney disease on developing Nations: A 21st Century. Nephron Clin Pract. 2011;118:c269\u0026ndash;277.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollaboration GCKD. Global, regional, and national burden of chronic kidney disease, 1990\u0026ndash;2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395:709\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie Y, Bowe B, Mokdad AH, et al. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kid Int. 2018;94:567\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSong M. Quality of life of patients with advanced chronic kidney disease receiving conservative care without Dialysis. Semin Dial. 2016;29:165\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTenckhoff H, Schechter H. 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Nephrol Dial Transpl. 2001;16:61\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNardelli L, Scalamogna A, Messa P, et al. Peritoneal dialysis for potential kidney transplant recipients: pride or prejudice? Med (Kaunas). 2022;58:214.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQuinn RR, Hux JE, Oliver MJ, Austin PC, Tonelli M, Laupacis A. Selection bias explains apparent differential mortality between dialysis modalities. J Am Soc Nephrol. 2011;22:1534\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarshall MR, Polkinghorne KR, Kerr PG, Agar JWM, Hawley CM, McDonald SP. Temporal changes in mortality risk by dialysis modality in the Australian and New zealand dialysis population. Am J Kid Dis. 2015;66:489\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"peritoneal dialysis, hemodialysis, mortality, survival, diabetes, systematic review, metanalysis","lastPublishedDoi":"10.21203/rs.3.rs-6873929/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6873929/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAlthough the choice of dialysis technique is based on several factors, patient survival is undoubtedly one of the most relevant. In a context where randomization to either peritoneal dialysis (PD) or hemodialysis (HD) proved to be extremely challenging, previous meta-analyses were greatly limited due to the inclusion of historical studies.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003e We performed a systematic review by searching multiple databases up to April 22nd, 2022. The primary outcome was the association between dialysis modality (PD vs HD) and mortality assessed via hazard ratios (HR). Subgroup analyses were conducted to explore potential sources of heterogeneity, including sex, age, diabetes, dialysis vintage, geographical location, HD access, and study cohort inclusion period.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDatabase search yielded 5317 citations, from which, 27 observational studies met the eligibility criteria, including 1 033 362 incident dialysis patients. The pooled mortality HR for PD versus HD was 1.01 (95% CI 0.93\u0026ndash;1.10). Heterogeneity was substantial (\u003cem\u003eI\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;94%) and was largely explained by different baseline features of the included populations. A statistically significant subgroup effect was demonstrated for age (\u0026gt;\u0026thinsp;65 vs.\u0026lt;65 years; p\u0026thinsp;=\u0026thinsp;0.01), geographical location of the studies (Oceania vs. Europe vs. Asia vs. North America; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and HD vascular access (central venous catheter vs. arteriovenous fistula; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, only one study included).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis meta-analysis suggests that overall PD and incentre HD likely carry equivalent survival benefits. However, differences were detected among subgroups based on age, geographic location, HD access type, but not on sex, diabetes status, dialysis vintage and study cohort inclusion period.\u003c/p\u003e","manuscriptTitle":"Association of Incident Dialysis Modality With Patient Survival: A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-08 08:11:43","doi":"10.21203/rs.3.rs-6873929/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-14T04:40:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-14T04:25:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-09T00:15:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"110142279233913245858145856987789957423","date":"2025-07-08T10:57:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197542378252840125904797572632671258808","date":"2025-07-04T03:09:14+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-03T08:40:04+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-24T15:14:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-24T14:59:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-18T17:20:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2025-06-18T17:17:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e418f4ec-1179-4306-a90e-952b090eea80","owner":[],"postedDate":"July 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:35:49+00:00","versionOfRecord":{"articleIdentity":"rs-6873929","link":"https://doi.org/10.1186/s12882-025-04530-4","journal":{"identity":"bmc-nephrology","isVorOnly":false,"title":"BMC Nephrology"},"publishedOn":"2025-10-24 16:17:08","publishedOnDateReadable":"October 24th, 2025"},"versionCreatedAt":"2025-07-08 08:11:43","video":"","vorDoi":"10.1186/s12882-025-04530-4","vorDoiUrl":"https://doi.org/10.1186/s12882-025-04530-4","workflowStages":[]},"version":"v1","identity":"rs-6873929","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6873929","identity":"rs-6873929","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}