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Cochrane Database of Systematic Reviews Protocol - Intervention

Urgent‐start peritoneal dialysis versus haemodialysis for people with chronic kidney disease

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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

This review aims to look at the benefits and harms of urgent‐start PD (defined as initiation of PD within 2 weeks of catheter insertion) compared to HD (defined as initiation of HD using a CVC) in adults and children with CKD requiring long‐term RRT.

Background

Description of the condition

People with chronic kidney disease (CKD) requiring long‐term renal replacement therapy (RRT) is a common and growing problem affecting over two million people worldwide (AIHW 2016; Couser 2011; Gilg 2016). Even though one of the main predictors of better patient survival is having an established dialysis access at the time of dialysis commencement (Pisoni 2009; Ravani 2013), a large proportion of patients commence treatment via a central venous catheter (CVC) (40% to 80%) (ANZDATA 2015; Moist 2014; Rao 2016; USRDS 2015). In part, this is due to many patients (20% to 30%) who present ‘late’ to a nephrology service that necessitates commencement of dialysis urgently or in unplanned manner (Foote 2014). In other cases, it could be the consequence of health system failure such as a lack of established responsive dialysis access programme with limited access to a surgical or interventional nephrology service. In this setting, most patients start haemodialysis (HD) via a CVC, which then places them at a heightened risk of infection, prolonged hospitalisation, mortality (Perl 2011) as well as future complications from central vascular stenosis (Shingarev 2012). A recent systematic review, that included a total of 586,337 patients, identified that the use of CVC led to the highest risk of death, fatal infections, and cardiovascular events, compared with other types of vascular access (Ravani 2013). Moreover, these patients are more likely to remain on facility‐based HD (Morton 2010) rather than to transition to home‐based dialysis program such as peritoneal dialysis (PD), which confers an initial survival advantage (Kumar 2014; Masterson 2008).

PD is a type of home‐based dialysis that uses the peritoneum in a person’s abdomen as the membrane through which fluid and dissolved substances are exchanged with the blood. PD solution is introduced through a PD catheter, which is placed in the lower abdomen permanently (Mehrotra 2016). PD has many benefits at the patient‐level, including initial survival advantage compared to HD, easier to master technique, better preservation of residual kidney function, better patient‐level satisfaction, and preservation of vascular access for future use (Tokgoz 2009). PD can also offer annual cost savings of up to 40% compared to facility HD (KHA 2012; KHA 2016). However, uptake of PD remains relatively low and only accounts for approximately 11% of the global dialysis population (Jain 2012). The decision‐making process which leads to undertake a home therapy is complex and can be influenced by social circumstances, education, and the capacity to undertake training (Machowska 2016). However, one of the contributors to limited growth in PD may relate to the reluctance to utilize PD as the dialysis modality of choice without permanent dialysis access, which is driven by the practice to delay treatment by at least two weeks from the time of PD catheter insertion to lower the risk of catheter‐related complications such as leaks (Dombros 2005; Figueiredo 2010). However, these practices are guided by recommendations based on weak level of evidence (Dombros 2005; Figueiredo 2010).

More recently, urgent‐start PD has been promoted as an alternative form of urgent, unplanned dialysis treatment, which is has been reported to be effective and potentially has fewer adverse consequences based on findings from observational studies (Casaretto 2012; Ghaffari 2012; Jo 2007; Koch 2012; Lobbedez 2008; See 2017).

Description of the intervention

Traditionally, new CKD patients who require dialysis urgently but without having a permanent functional dialysis access are subjected to undergo HD via central venous dialysis catheter. In order to avoid the CVC and its related complications, urgent‐start PD, has been introduced as an alternative form RRT for unplanned chronic kidney disease (CKD) patients who require dialysis urgently. Currently, there is no universally agreed definition regarding the duration between PD catheter insertion and commencement that qualifies as urgent‐start PD. The International Society for Peritoneal Dialysis (ISPD) recommends the use of PD catheters at least two weeks after its insertion (Figueiredo 2010). The duration between PD catheter insertion and commencement (Ranganathan 2017), fill volume and insertion technique may have an impact on outcomes observed following urgent‐start PD and therefore will be considered as part of subgroup analyses in the present review.

How the intervention might work

Urgent‐start PD is initiated with low fill volumes in the supine position using a cycler to minimize the risk of peri‐catheter leak. Treatment can be delivered in both inpatient and outpatient settings.

Why it is important to do this review

The vast majority of evidence relating to outcomes from urgent‐start PD has been generated from single‐centre observational studies with relatively small patient numbers (Casaretto 2012; Ghaffari 2012; Jo 2007; Koch 2012; Lobbedez 2008), which has resulted in ad hoc implementation rather than a ‘standard’ care across the world.

Objectives

This review aims to look at the benefits and harms of urgent‐start PD (defined as initiation of PD within 2 weeks of catheter insertion) compared to HD (defined as initiation of HD using a CVC) in adults and children with CKD requiring long‐term RRT.

Methods

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (RCTs), quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods), and non‐RCTs comparing urgent‐start PD to HD treatments via CVC.

Types of participants

Participants to be considered in this review are both adults and children with CKD, who require dialysis treatment without established dialysis access in place.

Inclusion criteria

Participants to be included in this review are both adults and children with CKD, who require dialysis treatment. Participants will have had a PD catheter inserted to undergo PD or a CVC for HD.

Exclusion criteria

The review will not include data obtained from patients with acute kidney injury.

Types of interventions

Studies comparing urgent‐start PD and HD via CVC will be included in this review.

  • Intervention: patients commenced on urgent‐start PD, defined as initiation of PD therapy within two weeks of catheter placement.

  • Comparator: patients commenced on urgent‐start HD, defined as initiation of HD therapy using a CVC (cuffed and uncuffed at commencement).

Types of outcome measures

Primary outcomes

  • Catheter‐related infectious complications occurring within 30 days (early complication) and 90 days (late complication)

    • Bacteraemia (defined as blood culture positive for bacteria) after commencement of dialysis (proportion of patients developing bacteraemia)

    • Peritonitis as defined by the ISPD guidelines (Li 2010) after commencement of dialysis (proportion of patients developing peritonitis)

    • Exit site or tunnel tract infection as defined by the ISPD guidelines (Li 2010) after commencement of dialysis (proportion of patients developing exit site or tunnel tract infections)

  • Catheter‐related non‐infectious complications occurring within 30 days (early complication) and 90 days (late complication)

    • Exit site bleeding requiring intervention (e.g. additional application of suture) after commencement of dialysis (proportion of patients developing exit site bleeding)

    • Catheter malfunction, defined as catheter flow problems requiring intervention (medical (e.g. urokinase) or surgical (e.g. catheter replacement)) or malposition after commencement of dialysis (proportion of patients developing catheter malfunction)

    • Catheter re‐adjustment, defined as catheter malfunction requiring intervention to re‐adjust or replace the catheter (proportion of patients requiring catheter re‐adjustment procedure)

  • Home dialysis (proportion of patients on home dialysis (e.g. PD or home HD)).

Secondary outcomes

  • Technique survival (number of patients remaining on the initial mode of RRT at the end of study)

  • All‐cause mortality

  • Hospitalisation (average days spent in hospital and episodes of hospitalisation)

  • Pain/discomfort related to dialysis therapy

  • Adverse effects

  • Quality of life

  • Cost of dialysis treatment

Search methods for identification of studies

Electronic searches

Randomised controlled trials

We will search the Cochrane Kidney and Transplant Specialised Register through contact with the Information Specialist using search terms relevant to this review. The Register contains studies identified from the following sources.

  1. Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)

  2. Weekly searches of MEDLINE OVID SP

  3. Handsearching of kidney‐related journals and the proceedings of major kidney conferences

  4. Searching of the current year of EMBASE OVID SP

  5. Weekly current awareness alerts for selected kidney and transplant journals

  6. Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Studies contained in the Register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of these strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available in the "Specialised Register" section of information about Cochrane Kidney and Transplant.

See Appendix 1 for search terms used in strategies for this review.

Non‐randomised controlled trials

MEDLINE (OVID) and EMBASE (OVID) will be searched with the same terms used for identifying RCTs.

Searching other resources

  1. Reference lists of review articles, relevant studies and clinical practice guidelines.

  2. Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.

Data collection and analysis

Selection of studies

The search strategy described will be used to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts will be screened independently by two authors, who will discard studies that are not applicable; however studies and reviews that might include relevant data or information on studies will be retained initially. Two authors will independently assess retrieved abstracts and, if necessary the full text, of these studies to determine which studies satisfy the inclusion criteria.

Data extraction and management

Data extraction will be carried out independently by two authors using standard data extraction forms. Studies reported in non‐English language journals will be translated before assessment. Where more than one publication of one study exists, reports will be grouped together and the publication with the most complete data will be used in the analyses. Where relevant outcomes are only published in earlier versions these data will be used. Any discrepancy between published versions will be highlighted.

Assessment of risk of bias in included studies

Randomised controlled trials

The following items will be independently assessed by two authors using the risk of bias assessment tool for RCTs (Higgins 2011) (see Appendix 2).

  • Was there adequate sequence generation (selection bias)?

  • Was allocation adequately concealed (selection bias)?

  • Was knowledge of the allocated interventions adequately prevented during the study?

    • Participants and personnel (performance bias)

    • Outcome assessors (detection bias)

  • Were incomplete outcome data adequately addressed (attrition bias)?

  • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?

  • Was the study apparently free of other problems that could put it at a risk of bias?

Non‐randomised controlled trials

The Newcastle‐Ottawa Scale (NOS) (www.ohri.ca/programs/clinical_epidemiology/nosgen.pdf) for assessing quality of non‐randomised studies will be used.

  • For case control studies the following items will be evaluated.

    • Selection (adequacy of definition, representativeness of the cases, selection of controls, definition of controls)

    • Comparability (comparability of cases and controls on the basis of the design or analysis)

    • Exposure (ascertainment of exposure, same method of ascertainment for cases and controls, non‐response rate).

  • For cohort studies the following items will be evaluated.

    • Selection (representativeness of the exposed cohort, selection of the non‐exposed cohort, ascertainment of exposure, demonstration that outcome of interest was not present at start of study)

    • Comparability (comparability of cohorts on the basis of the design or analysis)

    • Outcome (assessment of outcome, adequacy of follow‐up and duration of follow‐up).

Measures of treatment effect

For dichotomous outcomes (e.g. death, mechanical complications within one month of commencement of PD) results will be expressed as risk ratio (RR) with 95% confidence intervals (CI). Where continuous scales of measurement are used to assess the effects of treatment (e.g. duration of hospitalisation, duration of PD training), the mean difference (MD) will be used, or the standardised mean difference (SMD) if different scales have been used. Outcomes from RCTs and non‐RCTs will be reported separately.

Unit of analysis issues

If the review is to include cluster RCTs, the unit of analysis will be at the same level as the allocation, using a summary measurements from each cluster. All data will be collected and analysed according to the type of measure (e.g. hazard ratios, odds ratio).

Dealing with missing data

Any further information required from the original author will be requested by written correspondence (e.g. emailing the corresponding author) and any relevant information obtained in this manner will be included in the review. Evaluation of important numerical data such as screened, randomised patients as well as intention‐to‐treat, as‐treated and per‐protocol population will be carefully performed. Attrition rates, for example drop‐outs, losses to follow‐up and withdrawals will be investigated. Issues of missing data and imputation methods (for example, last‐observation‐carried‐forward) will be critically appraised (Higgins 2011).

Assessment of heterogeneity

We will first assess the heterogeneity by visual inspection of the forest plot. We will quantify statistical heterogeneity using the I2 statistic, which describes the percentage of total variation across studies that is due to heterogeneity rather than sampling error (Higgins 2003). A guide to the interpretation of I2 values will be as follows.

  • 0% to 40%: might not be important

  • 30% to 60%: may represent moderate heterogeneity

  • 50% to 90%: may represent substantial heterogeneity

  • 75% to 100%: considerable heterogeneity.

The importance of the observed value of I2 depends on the magnitude and direction of treatment effects and the strength of evidence for heterogeneity (e.g. P‐value from the Chi2 test, or a confidence interval for I2) (Higgins 2011).

Assessment of reporting biases

If possible, funnel plots will be used to assess for the potential existence of small study bias (Higgins 2011).

Data synthesis

Data will be pooled using the random‐effects model but the fixed‐effect model will also be used to ensure robustness of the model chosen and susceptibility to outliers.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis will be used to explore possible sources of heterogeneity (e.g. participants, interventions and study quality including method of PD catheter insertion). Heterogeneity among participants could be related to age and renal pathology (e.g. paediatric versus adults). Heterogeneity in treatments could be related to prior agent(s) used and the agent, dose and duration of therapy (e.g. initial fill volume). Therefore, subgroup analysis will be conducted to evaluate the source of heterogeneity according to:

  • Participants

    • Adult versus paediatric patients

    • Incident versus prevalent patients

  • Setting

    • Single‐centre versus multi‐centre

  • Study design

    • RCT versus non‐RCT

  • Type of treatment utilised

    • According to initial fill volume

    • Days to PD commencement (e.g. within 24 hours versus 7 days)

  • Methodological quality

Adverse effects will be tabulated and assessed with descriptive techniques, as they are likely to be different for the various agents used. Where possible, the risk difference with 95% CI will be calculated for each adverse effect, either compared to no treatment or to another agent.

Sensitivity analysis

We will perform sensitivity analyses in order to explore the influence of the following factors on effect size.

  • Repeating the analysis excluding unpublished studies

  • Repeating the analysis taking account of risk of bias, as specified

  • Repeating the analysis excluding any very long or large studies to establish how much they dominate the results

  • Repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), and country.

'Summary of findings' tables

We will present the main results of the review in 'Summary of findings' tables. These tables present key information concerning the quality of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schünemann 2011a). The 'Summary of findings' tables also include an overall grading of the evidence related to each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach (GRADE 2008). The GRADE approach defines the quality of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The quality of a body of evidence involves consideration of within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, precision of effect estimates and risk of publication bias (Schünemann 2011b). We plan to present the following outcomes in the 'Summary of findings' tables.

  • Catheter‐related infectious complications within 30 and 90 days of commencement of dialysis

    • Bacteraemia

    • Peritonitis

    • Exit site or tunnel infections

  • Catheter‐related non‐infectious complications within 30 and 90 days of commencement

    • Exit site bleeding

    • Catheter malfunction

    • Catheter re‐adjustment

  • Technique survival

  • Home dialysis

  • All‐cause mortality

  • Duration of hospitalisation