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Dialysis modality and survival: does the controversy live on?

Merchant, Asad Alia; Quinn, Robert R.b; Perl, Jeffreya

Current Opinion in Nephrology and Hypertension: May 2015 - Volume 24 - Issue 3 - p 276–283
doi: 10.1097/MNH.0000000000000114

Purpose of review Continued debate regarding the relative mortality risk for end-stage renal disease patients treated with either peritoneal dialysis or facility-based three times weekly conventional haemodialysis (CHD) stems from the absence of adequately powered randomized controlled trials, and the reliance on observational studies. These reports have yielded important trends, but also conflicting results. Here, we summarize the contemporary literature on survival comparisons between CHD and peritoneal dialysis, highlighting trends and important differences between studies.

Recent findings Large observational studies have not conclusively shown an overall survival advantage of either dialysis modality. Studies have consistently shown an early survival advantage for peritoneal dialysis relative to CHD. New insights including accounting for selection bias and the use of central venous catheters as incident haemodialysis access may explain much of this apparent early mortality difference. The relative mortality risk of peritoneal dialysis versus haemodialysis may be decreasing in more contemporary cohorts. Older patients, diabetic patients, and those with comorbidities may have a relatively worse prognosis on peritoneal dialysis compared to CHD.

Summary Overall, survival of incident end-stage renal disease patients is similar for CHD and peritoneal dialysis, but early survival differences may be driven by selection bias. Decisions regarding modality choice should be individualized, considering other important patient outcomes including quality of life. Whereas a future randomized controlled trial is ideally suited to address this question, practical limitations may continue to limit its development.

aDivision of Nephrology, and The Keenan Research Centre in the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Ontario

bDepartments of Medicine & Community Health Sciences, University of Calgary, Calgary, Alberta, Canada

Correspondence to Jeffrey Perl, St Michael's Hospital, 3-060 Shuter, 30 Bond St, Toronto, Ontario M5B 1W8, Canada. Tel: +1 416 864 6016; fax: +1 416 864 3042; e-mail:

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The worldwide incidence and prevalence of end-stage renal disease (ESRD) is increasing [1]. Currently, more than 80% of the world's ESRD patients are treated with conventional, facility-based three times weekly conventional haemodialysis (CHD), whereas peritoneal dialysis remains the most common form of home-based renal replacement therapy (RRT) [1]. Peritoneal dialysis is an attractive treatment option for patients wishing to pursue increased flexibility and autonomy, but more restrictive medical and psychosocial eligibility criteria have traditionally limited its use. Regional variability in the use of peritoneal dialysis is driven by differences in healthcare policy, physician and treatment reimbursement, relative costs, and physician knowledge and attitudes towards peritoneal dialysis [2,3]. Peritoneal dialysis growth is largest across developing countries [4], likely as a means to maximize RRT availability and use, while minimizing increasing dialysis-related healthcare expenditure. Across many countries, peritoneal dialysis remains less costly than facility-based haemodialysis with annualized treatment costs that are 60–70% of those for facility-based haemodialysis [5]. Moreover, peritoneal dialysis utilization has been increasing in the United States, from 6% in 2010 to nearly 10% in 2013 [6]. This resurgence has largely been attributed to a novel climate of favourable reimbursement that, in part, has incentivized the use of peritoneal dialysis over facility-based haemodialysis. In an era of renewed interest in peritoneal dialysis use, increasing attention will be focused on the examination of contemporary outcomes between peritoneal dialysis and CHD, including mortality, hospitalization, and health-related quality of life (HR-QOL). The relative mortality risks of the two modalities have long been debated, with over 30 years of literature published across several national registries worldwide. However, with ongoing evolution in the case-mix of patients, evolving technologies across both peritoneal dialysis and CHD, and the novel application of more sophisticated statistical and epidemiologic techniques aimed at addressing selection bias and other sources of confounding, ongoing re-examination of outcomes between the therapies is necessary. The purpose of the present narrative review is to highlight current and previous efforts aimed at establishing a randomized controlled trial (RCT) to explore outcomes comparing peritoneal dialysis and CHD, and to review contemporary survival differences between CHD and peritoneal dialysis across observational studies. We will review important insights that have emerged in our understanding of the relationship between dialysis modality and survival.

Box 1

Box 1

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A RCT would be ideally suited to compare the survival differences across the two dialysis modalities. Such an endeavour would not only serve to balance important differences in the characteristics of patients selected for peritoneal dialysis and CHD, but would also likely provide valid comparisons among the two groups of patients that are eligible for either peritoneal dialysis or CHD. Up until recently, this has only been attempted once; the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) was designed to compare the survival and QOL between peritoneal dialysis and haemodialysis patients in an intention-to-treat (ITT) analysis. Unfortunately, recruitment into the trial was prematurely terminated with only 38 patients randomized after 3 years. Therefore, the study was underpowered and failed to find any meaningful and significant survival differences between the two therapies [7].

Although the results of the trial were disappointing, it did serve to underscore the particular difficulty in recruiting and randomizing patients for dialysis trials. The majority of the screened patients in NECOSAD had no contraindications to either modality; however, they indicated a strong preference for a particular modality, and most refused to be randomized [7]. Nonmedical factors such as lifestyle considerations, the ability to perform self-care, and the availability of support and other resources are likely very important in modality decision-making [3]. Therefore, if future attempts at RCTs are to be successful across the developed world, a pragmatic approach that retains patient choice will be critical to its design, but such would seem a near impossibility.

Notwithstanding, there is a RCT underway comparing survival in Chinese peritoneal dialysis and CHD patients (China Q study – NCT01413074). The inclusion criteria for the trial are any ESRD patients aged 18 or older, and expected to start on RRT within 10 weeks after diagnosis. Patients must be eligible for either peritoneal dialysis or CHD, and those with previous kidney transplantation or already receiving dialysis are excluded. A total of 594 patients were to be randomized from 16 centres and followed for a minimum of 1 year after randomization. To date, 381 patients have been randomized, but mortality rates have been lower than expected, giving rise to concerns regarding the power of the study to compare survival differences between the two modalities. This has led investigators to change the primary outcome from survival to QOL as measured by the Kidney Disease Quality of Life Short Form Questionnaire (KDQoL-SF). The recruitment phase is expected to be complete by 2015 with results anticipated by 2016 after completion of follow-up (Xueqing Yu, Principle investigator of China Q study, personal communication).

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There have been numerous observational trials in many countries comparing peritoneal dialysis and haemodialysis mortality rates. The majority are large multicentre observational studies borne out of national and regional registry-based data [8–12,13▪,14–20,21▪,22,23▪,24,25] and have reported inconsistent findings (Table 1). For example, Mehrotra et al.[26] showed no difference in mortality risk among peritoneal dialysis and CHD cohorts in a large US Renal Disease System (USRDS) registry-based study (684 426 incident dialysis patients), while Heaf and Wehberg [21▪] found a persistent survival advantage for peritoneal dialysis patients in a study of 12 095 patients from the Danish Terminal Uremia Register. There are several potential reasons for these conflicting results. It may reflect differences in the case-mix of patients selected for peritoneal dialysis over CHD, and the breadth and scope of case-mix adjustment. For example, peritoneal dialysis patients in the USA are traditionally younger with fewer comorbidities compared to their CHD counterparts, whereas peritoneal dialysis patients in Australia and New Zealand are typically older with more comorbidities than their CHD counterparts. In addition, the majority of these studies have been conducted using large national registry-based datasets that may suffer from variable degrees of bias owing to the degree and extent of data validation. For example, a recent validation exercise of the medical evidence report of the United States Renal Data System revealed systematic under-reporting of comorbidities with a sensitivity of comorbidity reporting that was systematically higher for peritoneal dialysis patients than for haemodialysis patients [30].

Table 1

Table 1

Differences in the study designs and methodological techniques used may also explain the apparently discrepant findings in observational studies. For example, earlier studies included all prevalent dialysis patients [8,31,32], whereas subsequent studies restricted comparisons to incident dialysis populations. Moreover, some studies included follow-up within the first 90 days of RRT initiation, whereas follow-up across other studies only started after the first 90 days on dialysis and therefore excluded comparisons between patients who died in the first 90 days [10,12,13▪,16,17,19,33]. Weinhandl et al.[18], in 2010, demonstrated that the inclusion or exclusion of the first 90 days was critical to interpretations of modality-related survival, in that, excluding the first 90 days resulted in the loss of an apparent survival advantage of peritoneal dialysis over CHD.

Given that modality switches between peritoneal dialysis and CHD are frequent, some investigators have proposed that an as-treated analysis may be more appropriate than an ITT analysis [15]. In an as-treated analysis, patient mortality is attributed to the current modality, which the patient is receiving, while an ITT approach attributes the mortality to the patient's initial therapy, irrespective of whether or not a change has occurred to another modality. In this regard, ITT approaches better reflect clinical decision-making in that it bases outcomes on what modality is initially received without utilizing any future information on modality switches, which would obviously not have been known or easily predicted at the time of the modality decision. Furthermore, it is likely that an ITT analysis is also a more valid comparison, given that modality switches may be due to worsening health related to the initial therapy, and may even be considered a premorbid event. In some studies, a death that has occurred in a relatively short period after a switch in modality has been assigned as a death attributable to the initial modality serving as an additional sensitivity analysis [28]. Most studies have shown that an ITT analysis attenuates the survival advantage of peritoneal dialysis over haemodialysis [15,18,23▪]. Taken together, it is likely that both ITT and as-treated analyses are complimentary, and both provide important and useful information.

Another factor may be the differing statistical techniques used to adjust for the case-mix differences between the two populations. Across all statistical techniques there is the concern that unaccounted and unmeasured confounding variables that may significantly bias the results. Recent investigators have used increasingly sophisticated analytic models, such as propensity score matching. However, using the Dutch End-Stage-Renal Disease Registry, Liem et al.[34] demonstrated similar findings using propensity score models versus a traditional multivariable-adjusted model in assessing the impact of modality on survival. Moreover, in many cases, propensity score matching excludes either haemodialysis or peritoneal dialysis patients from the analyses which remain incomparable, thus creating a ‘fantasy’ population that increasingly veers away from ‘real world’ comparisons of populations of dialysis patients. Marginal structural models (MSMs), which, in many cases, use inverse proportional treatment and censoring weighting (IPTCW) to create regression models that account for time-dependent confounders, and balance treatment-specific known covariate distributions, also allow handling of informative censoring for events such as kidney transplantation rates. [13▪,26,28,29]. This is especially important as transplantation rates are traditionally disproportionately higher in some peritoneal dialysis cohorts relative to haemodialysis cohorts [26], and selective removal of transplanted patients potentially results in a study population with more comorbidities and a higher risk of mortality. Future studies will be required to see if these more sophisticated modelling techniques yield differing results when compared against traditional techniques with regards to the impact of dialysis modality on survival.

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Diabetes, age, and cardiovascular disease (CVD) are the most commonly analysed sub-groups in mortality comparisons of dialysis modalities. Observational studies have consistently demonstrated an interaction of diabetes with dialysis modality in the survival relationship [35▪▪]. Diabetes modifies the mortality associated with peritoneal dialysis compared to CHD, and diabetic patients traditionally have been shown to have inferior outcomes on peritoneal dialysis relative to CHD. It has been proposed that the glucose content in peritoneal dialysis solutions may be deleterious in terms of metabolic and glycaemic control, thus promoting a more atherogenic lipid profile among peritoneal dialysis patients. These studies are limited by the inability to control for modality-specific treatment-related practices (i.e. peritoneal dialysis glucose exposure minimization, aggressive glycaemic and lipid management) that may have the potential to modify outcomes among diabetic ESRD patients. The effect size of the interaction of diabetes in modality varies from study to study, and many studies have also demonstrated further effect modification by either age or sex, or both [35▪▪]. Outcomes on peritoneal dialysis are particularly inferior for female and older diabetic patients as compared to male and younger diabetic patients [9,25,32,36]. In one of these studies, the higher risk of death among female diabetic patients was mediated via infection-related mortality [9]. Furthermore, a study by Nessim et al.[37] demonstrated a higher peritoneal dialysis peritonitis risk among female diabetic patients as compared to female non-diabetic patients – a trend which was not seen in male diabetic patients. Therefore, taken together, it is possible that the adverse outcomes seen among female diabetic patients on peritoneal dialysis may be mediated by infection, and, in particular, possibly due to a higher risk of peritonitis.

The interaction of age with dialysis modality is similar to that with diabetes. Younger patients (age <65 years) have decreased mortality risk on peritoneal dialysis compared to CHD than older patients; the effect of age is even more pronounced in diabetic patients [21▪,25,26]. Younger non-diabetic patients aged below 65 years have better survival rates on peritoneal dialysis than CHD patients [21▪,26].

The presence of any comorbidities is associated with a worsening prognosis for peritoneal dialysis patients relative to haemodialysis patients. CVD and congestive heart failure (CHF) have specifically been demonstrated to increase the relative mortality risk of peritoneal dialysis compared to CHD [10,16,20]. The prevailing view prior to the study was that peritoneal dialysis would have a benefit in CHF patients as it offered a more stable haemodynamic profile, and decreased myocardial shear forces and stunning [38]. A propensity towards intravascular volume overload with peritoneal dialysis over CHD may explain the increased mortality. An alternative hypothesis is that end-stage CHF patients who have a very poor prognosis by virtue of significantly impaired cardiac function leading to hypotension may not tolerate CHD, and may preferentially receive peritoneal dialysis, thus leading to treatment-by-indication bias among this sub-group of patients.

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Historically, time-dependent survival comparisons have clearly shown that the relative mortality risk between peritoneal dialysis and CHD is modified by time on dialysis, with a consistent significant survival advantage in peritoneal dialysis patients compared to all CHD patients in the first year [12], and in some studies, this has extended up to 2–3 years [13▪,21▪,23▪,25,39]. Survival curves in most studies have tended to overlap or cross over at that point. The main hypothesis for the early survival advantage of peritoneal dialysis has been the preservation of residual renal function (RRF). RRF decreases the relative risk of death in both CHD [40] and peritoneal dialysis [41]. In addition, long-term peritoneal membrane exposure to dialysis solutions may lead to changes in the peritoneal membrane with more fibrosis [42], decreased ultra-filtration capacity, and poorer volume control [43]. It may also lead to loss of nutrients due to rapid transport, thus increasing the mortality risk over time, particularly in the face of the loss of RRF which typically occurs after the first 1–2 years of therapy [44,45].

The phenomenon of early peritoneal dialysis advantage has led to the proposal of an integrative care approach, in which case patients are started on peritoneal dialysis with the expectation that they will be switched to CHD when the mortality risk associated with peritoneal dialysis is higher than that of haemodialysis [46]. Van Biesen et al.[46] found that patients who were switched to CHD did equally well, compared to patients who had always been on CHD. However, this was a small retrospective study and it was not clear what criteria were employed in switching from peritoneal dialysis to CHD [46].

Quinn et al.[27] proposed that the early advantage of peritoneal dialysis over CHD was due to the disproportionate representation of acutely ill patients who started haemodialysis rather than peritoneal dialysis in the urgent and acute setting. Weinhandl et al.[18] proposed a similar mechanism to explain their finding of increased relative mortality of CHD over peritoneal dialysis, with the inclusion of the first 90 days of dialysis. Quinn et al. removed this potential early selection bias by restricting outcome comparisons to a cohort of 6573 Canadian patients who had received at least 4 months of pre-dialysis care and had been started on dialysis electively, as outpatients. In the adjusted analysis, there was no difference in risk of death in patients treated with peritoneal dialysis and CHD. Their findings provided strong evidence for the effect of selection bias in explaining the early peritoneal dialysis survival advantage [18].

An additional factor that may modify survival comparisons between peritoneal dialysis and CHD may be the increased early mortality risk imposed by central venous catheter (CVC) use among CHD patients. Perl et al.[28] studied the relative impact of haemodialysis-CVC in 2011 in a study of 40 526 incident dialysis patients from the Canadian Organ Replacement Registry (CORR) database. They demonstrated that initiation of CHD with a CVC was associated with higher 1-year mortality risk than initiation with peritoneal dialysis [hazard ratio 1.8, 95% confidence interval (CI) 1.6–1.9]. This relationship persisted over the 5-year follow-up period. There was a small, persistent advantage among the haemodialysis with an arterio-venous fistula or graft (HD-AVF/AVG) cohort compared to the peritoneal dialysis cohort [28]. This study demonstrated that the type of CHD vascular access at the time of dialysis initiation may be an important modifier of the relationship between modality and survival, either directly via the deleterious effects of CVC use or as a proxy for acuity of dialysis initiation in a sicker cohort of patients. Coentrao et al.[47] corroborated these results. They studied 152 Portuguese incident dialysis patients chosen from chronic kidney disease clinics. Those who started haemodialysis with a CVC faced a significantly increased early mortality risk within the first year as compared to their peritoneal dialysis counterparts [47].

In contrast to the above findings, Kumar et al.[23▪] recently showed that the survival advantage favouring peritoneal dialysis over CHD during the first year of dialysis initiation persisted in a cohort of patients who all received some degree of pre-dialysis care, and was restricted to CHD patients who started dialysis with an AVF/AVG. Using data from the Kaiser–Permanente healthcare system, Kumar et al.[23▪] studied 1073 propensity-matched peritoneal dialysis and CHD patients (all of whom started dialysis with an AVF or AVG), and found a higher adjusted cumulative risk of death in the CHD group compared to the peritoneal dialysis group in the first year in an ITT analysis. Unique patient characteristics, regional variability, and statistical techniques used for case-mix adjustments may be responsible for the discrepancies in their results and other previously published findings.

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Dialysis Outcomes and Practice Patterns Study (DOPPS) and USRDS data have shown an improvement in prognosis for both peritoneal dialysis and CHD over time [48,49]. With more than 20 years of available data, several investigators have elected to divide the cohorts by era of dialysis initiation [21▪,25,26,28]. All such analyses have consistently shown that there have been substantial improvements in prognosis for both CHD and peritoneal dialysis patients. It has also been clearly demonstrated that the relative survival rates of peritoneal dialysis versus CHD patients have improved with time. Median life expectancy was approximately 4.3 months lower among peritoneal dialysis patients relative to haemodialysis patients among those starting dialysis in 1999–2001 in the USA, as compared to a 1.8 month (non-significant) lower median life expectancy between CHD and peritoneal dialysis patients among those starting between 2002 and 2004 [26]. Similarly in Canada, patients who started dialysis between 1996 and 2000 faced an average of 8 months less survival on peritoneal dialysis relative to haemodialysis, as compared to a 1-month survival difference in Canada in the cohorts that started dialysis between 2000 and 2004 [25]. Whether or not the increasingly favourable peritoneal dialysis outcomes relative to haemodialysis truly reflect global improvements in peritoneal dialysis-specific practices that have led to better outcomes for peritoneal dialysis patients, or reflect inherent and unadjustable differences between the patient populations that have been selected for peritoneal dialysis versus haemodialysis in more contemporary cohorts, remains to be verified.

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Large observational studies have not conclusively shown an overall survival advantage of either dialysis modality. Recent studies have served to point out the important role selection bias has played in previous interpretations. A well-designed and appropriately powered RCT is likely the ideal way to truly determine the impact of dialysis modality on survival. However, to date, this has not been successful. It would therefore seem counter-intuitive to promote further studies that would remove the important role patient choice plays in dialysis modality selection. To date, no study has been conducted that has compared survival between peritoneal dialysis and haemodialysis restricted to a group of patients deemed eligible for both therapies, and analyses that have employed propensity score matching can only serve to attempt to restrict comparisons to a population that may be eligible for both therapies. At present, the debate on modality survival lives on, but given the shortened life expectancy faced by dialysis patients, emphasis should be placed on targeting interventions aimed at improving patient survival and QOL for both therapies, and refining the complementary roles that both modalities play in overall ESRD care.

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We would like to thank Dr Xueqing Yu, the principle investigator of the ChinaQ study, for his helpful input in preparing the manuscript.

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Financial support and sponsorship


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Conflicts of interest

R.Q. is the co-inventor of the Dialysis Measurement Analysis and Reporting System. He has also received an honorarium from Baxter Healthcare for speaking at Canadian PD University that was donated to charity. J.P. has received speaking honoraria from Baxter Healthcare, Amgen Canada, Davita Healthcare Partners, and has consulting fees from Baxter Healthcare, Shire, and Takeda, as well as research support from Baxter Healthcare. The remaining author has no conflict of interest.

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Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest
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haemodialysis; mortality; peritoneal dialysis; randomized controlled trials; survival

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