Interventions for improving sleep quality in people with chronic kidney disease

Patrizia Natale; Marinella Ruospo; Valeria M Saglimbene; Suetonia C Palmer; Giovanni FM Strippoli

doi:10.1002/14651858.CD012625.pub2

. 2019 May 26;2019(5):CD012625. doi: 10.1002/14651858.CD012625.pub2

Interventions for improving sleep quality in people with chronic kidney disease

Patrizia Natale ^1,², Marinella Ruospo ¹, Valeria M Saglimbene ^1,³, Suetonia C Palmer ⁴, Giovanni FM Strippoli ^1,^2,^3,^5,^6,^✉

Editor: Cochrane Kidney and Transplant Group

PMCID: PMC6535156 PMID: 31129916

Abstract

Background

Sleep disorders are commonly experienced by people with chronic kidney disease (CKD). Several approaches for improving sleep quality are used in clinical practice including relaxation techniques, exercise, acupressure, and medication.

Objectives

To assess the effectiveness and associated adverse events of interventions designed to improve sleep quality among adults and children with CKD including people with end‐stage kidney disease (ESKD) treated with dialysis or kidney transplantation.

Search methods

We searched the Cochrane Kidney and Transplant Register of Studies up to 8 October 2018 with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria

We included randomised controlled trials (RCTs) or quasi‐randomised RCTs of any intervention in which investigators reported effects on sleep quality. Two authors independently screened titles and abstracts of identified records.

Data collection and analysis

Two review authors independently extracted data and assessed the risk of bias for included studies. The primary outcomes were sleep quality, sleep onset latency, sleep duration, sleep interruption, and sleep efficiency. Risks of bias were assessed using the Cochrane tool. Evidence certainty was assessed using the GRADE approach. We calculated treatment estimates as risk ratios (RR) for dichotomous outcomes or mean difference (MD) or standardised MD (SMD) for continuous outcomes to account for heterogeneity in measures of sleep quality.

Main results

Sixty‐seven studies involving 3427 participants met the eligibility criteria. Thirty‐six studies involving 2239 participants were included in meta‐analyses. Follow‐up for clinical outcomes ranged between 0.3 and 52.8 weeks (median 5 weeks). Interventions included relaxation techniques, exercise, acupressure, cognitive‐behavioural therapy (CBT), educational interventions, benzodiazepine treatment, dopaminergic agonists, telephone support, melatonin, reflexology, light therapy, different forms of peritoneal dialysis, music, aromatherapy, and massage. Incomplete reporting of key methodological details resulted in uncertain risk of bias in many studies.

In very low certainty evidence relaxation techniques had uncertain effects on sleep quality and duration, health‐related quality of life (HRQoL), depression, anxiety, and fatigue. Studies were not designed to evaluate the effects of relaxation on sleep latency or hospitalisation. Exercise had uncertain effects on sleep quality (SMD ‐1.10, 95% CI ‐2.26 to 0.05; I² = 90%; 5 studies, 165 participants; very low certainty evidence). Exercise probably decreased depression (MD ‐9.05, 95% CI ‐13.72 to ‐4.39; I² = 0%; 2 studies, 46 participants; moderate certainty evidence) and fatigue (SMD ‐0.68, 95% CI ‐1.07 to ‐0.29; I² = 0%; 2 studies, 107 participants; moderate certainty evidence). Compared with no acupressure, acupressure had uncertain effects on sleep quality (Pittsburgh Sleep Quality Index (PSQI) scale 0 ‐ 21) (MD ‐1.27, 95% CI ‐2.13 to ‐0.40; I² = 89%; 6 studies, 367 participants: very low certainty evidence). Acupressure probably slightly improved sleep latency (scale 0 ‐ 3) (MD ‐0.59, 95% CI ‐0.92 to ‐0.27; I² = 0%; 3 studies, 173 participants; moderate certainty evidence) and sleep time (scale 0 ‐ 3) (MD ‐0.60, 95% CI ‐1.12 to ‐0.09; I² = 68%; 3 studies, 173 participants; moderate certainty evidence), although effects on sleep disturbance were uncertain as the evidence certainty was very low (scale 0 ‐ 3) (MD ‐0.49, 95% CI ‐1.16 to 0.19; I² = 97%). In moderate certainty evidence, acupressure probably decrease fatigue (MD ‐1.07, 95% CI ‐1.67 to ‐0.48; I² = 0%; 2 studies, 137 participants). Acupressure had uncertain effects on depression (MD ‐3.65, 95% CI ‐7.63 to 0.33; I² = 27%; 2 studies, 137 participants; very low certainty evidence) while studies were not designed to evaluate the effect of acupressure on HRQoL, anxiety, or hospitalisation. It was uncertain whether acupressure compared with sham acupressure improved sleep quality (PSQI scale 0 to 21) because the certainty of the evidence was very low (MD ‐2.25, 95% CI ‐6.33 to 1.82; I² = 96%; 2 studies, 129 participants), but total sleep time may have been improved (SMD ‐0.34, 95% CI ‐0.73 to 0.04; I² = 0%; 2 studies, 107 participants; low certainty evidence). ² =² =There were no studies designed to directly examine and/or correlate efficacy of any interventions aimed at improving sleep that may have been attempted for the spectrum of sleep disordered breathing. No studies reported treatment effects for children. Adverse effects of therapies were very uncertain.

Authors' conclusions

The evidence base for improving sleep quality and related outcomes for adults and children with CKD is sparse. Relaxation techniques and exercise had uncertain effects on sleep outcomes. Acupressure may improve sleep latency and duration, although these findings are based on few studies. The effects of acupressure were not confirmed in studies in which sham acupressure was used as the control. Given the very low certainly evidence, future research will very likely change the evidence base. Based on the importance of symptom management to patients, caregivers and clinicians, future studies of sleep interventions among people with CKD should be a priority.

Plain language summary

Interventions to improve sleep in adults and children with kidney disease

What is the issue?

People with kidney disease can have severe sleep problems related to use of medications, depression, anxiety, pain, and itch that impact on the quality of sleep itself, including the time it takes to get to sleep, staying asleep, and the total time spent sleeping. Kidney disease is linked to sleep disordered breathing that can decrease sleep quality. We looked at whether treatment could help improve the quality of sleep for people who have kidney disease. We looked for studies that included children and adults with kidney disease, including those who were treated with dialysis or a kidney transplant.

What did we do?

We looked at electronic databases to find research studies of any treatment that was designed to help with sleep problems. Studies needed to be randomised (in other words, patients needed to have an equal chance that they might receive one of the treatments in the study). We collected information from the studies and combined this to identify whether treatment was helpful or if there were important side‐effects. We looked at how certain we could be that the treatments had any effects based on how well the studies were conducted (quality). The information in this review is up to date as of October 2018.

What did we find?

We found 67 studies that involved 3427 adults. We found no studies for children. The treatments for sleep included relaxation, exercise, medicines, education, psychological support, acupressure, music, aromatherapy, and massage. Generally, the studies were small and most did not tell us about the benefits and safety of the treatments. We did not find good information about relaxation, exercise, or medicines. We found that acupressure may reduce the amount of time it takes to get to sleep and may increase the time spent asleep. But these effects on sleep were not seen when acupressure was compared against "pretend" or "sham" acupressure. There was not enough information to learn about side‐effects of treatments, or to know about treatments that are designed to help improve breathing when asleep.

Conclusions

Information about ways to help improve sleep for people with kidney disease is not ready to help patients directly. New research is very likely to change our knowledge about treatments for sleep among people with kidney disease.

Summary of findings

Background

Description of the condition

Sleep duration and quality is commonly decreased in people with chronic kidney disease (CKD) and sleep disorders are often present even in the early stages of CKD. The prevalence rate of any sleep disorder in CKD ranges from 45% to 80% in adults with end‐stage kidney disease (ESKD) and affects approximately half of patients with earlier stages of CKD (Iliescu 2004). The true prevalence is uncertain due to heterogeneous definitions of sleep quality including problems initiating or maintaining sleep, early or difficulty waking, restlessness, tiredness on waking, and daytime sleepiness (Murtagh 2010). Risk factors of sleep disturbance in the general population such as older age, male gender, obesity, smoking, increased neck circumference and diabetes are also prevalent in the CKD population (Roumelioti 2011). Dialysis treatment modality may impact sleep dysfunction. People treated with automated peritoneal dialysis (PD) appear to have less severe sleep‐related breathing disorders (SBD) compared to continuous ambulatory PD patients (Roumelioti 2016). Kidney transplantation is associated with a low rate of sleep disorders (Mavanur 2010).

Among people with CKD, sleep disorders have been associated with impaired neurocognition, including inattention, lower performance at school or productivity at work, and driving related accidents (Ezzat 2015; Stabouli 2016). CKD is associated with sleep apnoea (central and obstructive), in part due to altered ventilatory control and upper airway obstruction (Markou 2006; Sim 2009). Poor sleep quality is a source of patient stress and is linked to lower health‐related quality of life (HRQoL) (Iliescu 2003), depression and greater use of antidepressants, narcotics and hypnotic medications, and worse life expectancy in people with a range of kidney function (Elder 2008; Kumar 2010; Unruh 2006). Overall, impaired sleep is experienced by patients as changes in their sleep‐wake cycle (insomnia, excessive sleepiness or both) and sleep‐disordered breathing (Young 2004). Contributing factors include restless legs syndrome (RLS) or periodic leg movement, night‐time dialysis care, depressed mood and anxiety, increased prescribing of neuroactive medications and analgesia, pain and itch, and altered sleep hygiene including napping during the day (Ogna 2016). Sleep disorders have been associated with increased cardiovascular risk and may contribute to the morbidity and mortality of people with advanced (stages 4 to 5) CKD and those treated with dialysis (Roumelioti 2011). Some studies have shown that sleep disturbances are associated with increased cardiovascular risk and arterial hypertension (Gonçalves 2007), subclinical atherosclerosis (Drager 2009), coronary heart disease (Hung 1990), heart failure (Hedner 1990), arrhythmias (Hoffstein 1994), cerebrovascular disease (Munoz 2006), type 2 diabetes mellitus and dysglycaemia (Botros 2009; Shpirer 2011), metabolic syndrome and its components (Assoumou 2012; Kono 2007) and dyslipidaemia (Assoumou 2012;Drager 2010). The major causes for a disordered sleep in CKD derive from biological, psychological, and environmental factors (Ahmad 2013; Ezzat 2015). Putative determinants of sleep disorders in people with ESKD include serum concentrations of creatinine, urea, phosphorus, parathyroid hormone (PTH), anaemia, nocturnal hypoxaemia, blood pressure, disease intrusiveness, time on dialysis, and comorbidity. Psychological factors and treatment‐related factors (such as nocturnal dialysis) may cause alterations in sleep and insomnia in CKD patients (De Santo 2008).

Description of the intervention

Due to the variable causes of altered sleep quality in people with CKD, a range of interventions are used including behavioural therapy with or without medication. A suggested approach to management of sleep has been to identify and treat any specific cause including disordered breathing, restless leg syndrome, pruritus, depression and anxiety, or pain (Murtagh 2010). General approaches to sleep management include a range of behavioural therapies such as sleep hygiene, stimulus control, and avoidance of caffeine, alcohol, and daytime sleeping, short‐term hypnotics to re‐establish sleep patterns, exercise, and complementary therapies (Jespersen 2015). CKD may constrain the use of neuroactive medications, which can lead to dependence if used in the longer‐term.

How the intervention might work

Numerous interventions including behavioural therapy, exercise, pharmacological agents and complementary therapy in addition to specific treatments for conditions associated with sleep impairment have individual mechanisms of action. In general, the effectiveness and safety of treatments may differ in people with CKD due to the frequency of additional severe symptoms including fatigue, pain, and depression, inactivity and frailty, and the altered metabolism of commonly‐used medications that may cause over‐sedation or lead to interactions with other treatments.

Why it is important to do this review

People with CKD have identified the importance of research focused on developing better treatments to reduce symptoms of CKD (Manns 2014; Tong 2008). In this review, we aimed to summarise the current evidence for treatments to improve sleep quality in CKD. This review is required given the range of causes of impaired sleep, the heterogeneity in available treatments and their potential for adverse effects, the impact of sleep changes on quality of life and prognosis, and the relative priority placed on research to manage symptoms by patients and caregivers.

Objectives

To assess the effectiveness and associated adverse events of interventions designed to improve sleep quality among adults and children with CKD.

Methods

Criteria for considering studies for this review

Types of studies

Eligible studies were randomised controlled trials (RCTs) and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at interventions for improving sleep quality in adults and children with CKD. We excluded studies which did not report sleep outcomes. We included eligible cross‐over studies in the review as we deemed them a common method for assessing the effects of interventions to increase sleep quality.

Types of participants

Inclusion criteria

Adults and children with CKD (as defined by Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for evaluation and management of CKD (KDIGO 2013) including all stages of CKD. We included people treated with dialysis, those who had ESKD treated without dialysis, recipients of a kidney transplant, and those with earlier stages (1‐4) of CKD.

Exclusion criteria

None.

Types of interventions

We considered any educational, physical, psychological, behavioural, or pharmacological intervention including:

Behavioural intervention: sleep hygiene education, stimulus control, relaxation, sleep restriction, cognitive therapy, and cognitive‐behavioural therapy (CBT)
Pharmacological treatments: benzodiazepines, non‐benzodiazepine hypnotics, antidepressants, melatonin agonists, orexin receptor antagonists
Interventions for disordered breathing: patient education, weight loss, exercise, physiotherapy, sleep positioning, positive airway pressure, oral appliances, upper airway surgery, dialysis management
Exercise and other complementary interventions including music therapy, relaxation therapy, meditation, and hypnotherapy
Optimisation of renal replacement therapy (dialysis).

We considered any mode, frequency, and duration of therapy and interventions administered in any clinical setting.

Types of outcome measures

Primary outcomes

Sleep quality as measured by a sleep‐specific quality of life measure
Sleep onset latency
Total sleep time
Sleep interruption: number of awakenings and waking after sleep onset
Sleep efficiency: percent of time spent in bed asleep.

Secondary outcomes

Depression
Anxiety
HRQoL
Fatigue
Daytime sleepiness
Death
Hospital admission
Major cardiovascular event
Adverse events (as reported by investigators).

We included studies that measured outcomes using standardised questionnaires with established reliability and validity (e.g. Beck Depression Inventory (BDI), State‐Trait Anxiety Inventory (STAI), Short‐Form 36 (SF‐36)). We extracted endpoints as post‐intervention mean or change scores, together with standard deviations (SD), or the number of participants experiencing one or more events.

We considered the study period and follow‐up as described in the included studies. When assessing outcomes in relation to time points we grouped the data as (when possible): immediate post‐intervention, short‐term (post‐intervention to one month), medium‐term (between one and three months follow‐up), and long‐term (more than three months follow‐up) effects.

Due to the heterogeneity of sleep disorders, interventions and clinical outcomes, we categorised sleep disorders according to aetiology. We aimed to group results by outcomes (so that all information for each category of sleep disorder and associated interventions was grouped by the impact of the intervention on outcomes).

To maximize clinical utility, we aimed to separate studies according to clinical setting (CKD/dialysis/transplant and for adults and children). However, insufficient data observations precluded subgroup analysis.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Kidney and Transplant Register of Studies up to 8 October 2018 through contact with the Information Specialist using search terms relevant to this review. The Register contains studies identified from the following sources.

Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)
Weekly searches of MEDLINE OVID SP
Handsearching of kidney‐related journals and the proceedings of major kidney conferences
Searching of the current year of EMBASE OVID SP
Weekly current awareness alerts for selected kidney and transplant journals
Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Studies contained in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of search 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.

Searching other resources

Reference lists of review articles, relevant studies and clinical practice guidelines.
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 was used to obtain titles and abstracts of studies that may be relevant to the review. The titles and abstracts were screened independently by two review authors, who discarded studies that were not applicable. Studies and reviews that might have included relevant data or information on studies were retained initially. Two review authors independently assessed retrieved abstracts and, if necessary the full text, of these studies to determine which studies met the review inclusion criteria.

Data extraction and management

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

General information: author, year of publication, title, publication source, country, language
Study design: design (e.g. parallel or cross‐over), method of randomisation and concealment, nature of the control group, blinding of study assessments, washout period in cross‐over design, inclusion criteria exclusion criteria
Participants: total sample size, number in experimental group, number in control group, age, gender, stage of CKD, ethnicity, diagnosis, comorbidity, sleep quality and reason for impaired sleep, duration of sleep impairment, previous or additional treatments
Intervention: type of treatment employed, provider, setting, length and frequency of treatment, duration of intervention, implementation
Outcomes: methods of assessment, primary and secondary outcome measures, pre‐test means and post‐test means or change scores and SD for all groups for all outcomes specified, numbers of participants experiencing one or more event, number of participants at risk, follow‐up duration

We will report the results of our findings separately focusing on sleep disorder categories and based on different stages of CKD.

Assessment of risk of bias in included studies

The following items were independently assessed by two review authors using the risk of bias assessment tool (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?

Measures of treatment effect

For dichotomous outcomes (adverse events, death, major adverse cardiovascular event, fatigue, depression, anxiety) results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment (sleep assessments, HRQoL, daytime sleepiness, depression, anxiety, fatigue), the mean difference (MD) was used, or the standardised mean difference (SMD) if different scales were used.

Unit of analysis issues

Cluster‐randomised studies

We anticipated that studies using clustered randomisation would have controlled for clustering effects. In case of doubt, we planned to contact the authors to ask for individual participant data to calculate an estimate of the intra cluster correlation coefficient (ICC). If this was not possible, we planned to obtain external estimates of the ICC from a similar study or from a study of a similar population as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). When the ICC was established, we planned to re‐analyse the study data. If ICCs from other sources were used, we planned to report this and to conduct sensitivity analyses to investigate the effect of variation in the ICC.

Cross‐over studies

Cross‐over studies were analysed using combined data from all study periods, or using first period data if combined data was not available.

Studies with more than two treatment arms

If more than one of the interventions was a sleep intervention, and there was sufficient information in the study to assess the similarity of the interventions, we planned to combine similar interventions to allow for a single pair‐wise comparison.

Dealing with missing data

Any further information required from the original authors was requested by written correspondence (e.g. emailing corresponding author) and any relevant information obtained in this manner was 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 was carefully performed. Attrition rates, for example drop‐outs, losses to follow‐up and withdrawals were investigated. Issues of missing data and imputation methods (for example, last‐observation‐carried‐forward) were critically appraised (Higgins 2011).

Assessment of heterogeneity

We assessed for evidence of statistical heterogeneity by visual inspection of the forest plot. We quantified 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 was 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 were planned to assess for the potential existence of small study effects (Higgins 2011).

Data synthesis

We assessed study outcomes using a variety of assessment tools and reported in various metrics. We calculated mean differences (MD) when all studies reported the same sleep outcome measure. We calculated standardised mean differences (SMD) to account for variable outcome measures) for each comparison, using the generic inverse variance method in a random‐effect meta‐analysis model. We selected end of treatment values for inclusion in meta‐analysis, to maximise the number of studies that could be pooled.

We calculated treatment effects were using random‐effects meta‐analysis. We planned to explore treatment effects using a fixed‐effect model to ensure robustness of the model chosen and susceptibility to outliers. Adverse effects were tabulated and assessed with descriptive techniques, as they were likely to be different for the various interventions used.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis were planned a priori to explore possible sources of heterogeneity (e.g. participants, interventions and study quality such as age, stage of CKD, country, duration of treatment or follow‐up, study quality). As the range of sleep disorders is complex and the pathobiologies of each are sufficiently different, we planned a framework for sleep disorder categories to be used as a framework for analysis.

We planned the following sleep disorder categories to construct the review and analyse data.

Insomnias: insomnia and short sleeper
Hypersomnias: narcolepsy; idiopathic hypersomnia; insufficient sleep syndrome; long sleeper; excessive daytime sleepiness
SBD: mild‐moderate‐severe obstructive sleep apnoea; central sleep apnoea; child sleep apnoea; snoring
Circadian rhythm sleep‐wake disorders: irregular sleep‐wake rhythm; delayed sleep‐wake phase; advanced sleep‐wake phase
Parasomnias: confusional arousals; sleep walking; sleep terrors; nightmares; sleep eating disorder; sleep talking; night awakening
Sleep movement disorders: RLS; periodic limb movements; sleep leg cramps; bruxism; rapid eye movement behaviour disorders; limb pains; pruritus; itch.

However, there were few data available in included studies, and reporting of the results by this framework was not possible. We planned to report the treatment comparisons by sleep disorder and as a total including all studies when there was no evidence of substantial heterogeneity between groups. We planned a priori to report the results of our findings separately for people with earlier stages of CKD, those with ESKD and recipients of a kidney transplant. However, there were too few data to enable these subgroup analyses to be conducted.

Sensitivity analysis

Where possible, we planned sensitivity analyses 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 presented 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; GRADE 2011). 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. We used methods and recommendations described in Section 8.5 and Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), using GRADEpro software (gradepro.org/). 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 justified all decisions to downgrade the quality of studies using footnotes, and made comments to aid the reader's understanding of the review where necessary. Two review authors, working independently, judged the quality of the evidence, with disagreements resolved by discussion or by involving a third review author (SP). We justified, documented and incorporated the judgements into the reporting of results for each outcome. We extracted study data, formatted our comparisons in data tables, and prepared a 'Summary of findings' table before writing the results and conclusions of our review.

We presented the following outcomes in the 'Summary of findings' tables.

Sleep quality
Sleep latency
HRQoL
Depression
Anxiety
Fatigue
Hospitalisation

We have produced three 'Summary of Findings' tables, one for each of the following treatment comparisons.

Relaxation techniques compared to no intervention control
Exercise interventions compared to no intervention control
Acupressure compared to no intervention control.

Results

Description of studies

Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification; Characteristics of ongoing studies

Results of the search

The electronic search strategy of the Cochrane Kidney and Transplant Specialised Register (8 October 2018) identified 127 records (Figure 1). After duplicates were removed we screened the titles and abstracts and 10 records were excluded (not RCTs). The full text of the remaining 114 records was evaluated. We included 67 studies (92 records) and excluded 3 studies (10 records). We also identified 11 ongoing studies and one study is completed but with no published results ‐ these studies will be assessed in a future update of this review.

Included studies

Sixty‐seven studies (3427 participants) reported in 92 publications were included in the systematic review (Afshar 2011; Amini 2016; Aoike 2018; Arab 2016; Bro 1999; Burkhalter 2015; Champagne 2008; Chen 2008a; Chen 2011a; Cho 2018; Chow 2010; Dai 2007a; Dashti‐Khavidaki 2011; Dauvilliers 2016; Duarte 2009; Edalat‐Nejad 2013; EMSCAP 2009; Farrokian 2016; Ghavami 2016; Giannaki 2013; Giannaki 2013a; Hanna 2013; Hou 2014; IRCT2013021212448N1; IRCT2014061717237N3; IRCT2015051122218N1; Jean 1995; Kolner 1989; Li 2014b; MELODY 2013; Micozkadioglu 2004; Momennasab 2018; Muz 2017; Nasiri 2011; Natarajan 2003; NCT02825589; Parker 2007; Pellecchia 2004; Pellizzaro 2013; Pieta 1998; Pooranfar 2014; Rambod 2013; Razazian 2015; Reilly‐Spong 2015; Ren 2017a; Sabbatini 2003; Saeedi 2014; Shariati 2012; SIESTA 2017; Silva 2017; Sklar 1998; Solak 2012; Soleimani 2016; Soreide 1991; Sun 2017; Tol 2010; Trenkwalder 1995; Tsai 2015; Tsay 2003a; Tsay 2004; Turk 2010; Unal 2016; Walker 1996; Williams 2017; Yurtkuran 2007; Zhao 2011; Zou 2015). Thirty‐six studies involving 2239 participants were included in meta‐analysis. Thirty‐one studies were not included in meta‐analyses as outcome data were not reported in a format that could be extracted for analysis (Aoike 2018; Champagne 2008; Chen 2008a; Edalat‐Nejad 2013; EMSCAP 2009; Ghavami 2016; Hanna 2013; IRCT2013021212448N1; IRCT2014061717237N3; IRCT2015051122218N1; Jean 1995; Kolner 1989; Micozkadioglu 2004; Nasiri 2011; NCT02825589; Parker 2007; Pellecchia 2004; Pellizzaro 2013; Pieta 1998; Pooranfar 2014; Ren 2017a; Sabbatini 2003; Silva 2017; Sklar 1998; Solak 2012; Soreide 1991; Tol 2010; Trenkwalder 1995; Turk 2010; Walker 1996; Williams 2017).

Studies were published between 1989 and 2018. Thirty‐seven studies received funding from governmental or healthcare organisations, and thirty studies did not report a funding source. Sixty‐one studies enrolled 3201 people treated with long‐term dialysis. Of these, 57 studies involved participants on haemodialysis and four studies involved participants treated with peritoneal dialysis (Bro 1999; Chen 2008a; Chow 2010; Li 2014b). One study reported 14 patients treated with either haemodialysis and peritoneal dialysis (Pieta 1998), one study involved 63 kidney transplant candidates who were treated with haemodialysis, or peritoneal dialysis or who were pre‐dialysis (Reilly‐Spong 2015). Three studies enrolled 104 kidney transplant recipients (Burkhalter 2015; Hanna 2013; Pooranfar 2014) and one study enrolled 45 people with CKD stages 3 and 4 (Aoike 2018).

Studies were conducted in Australia (SIESTA 2017), Brazil (Aoike 2018; Duarte 2009; Pellizzaro 2013; Silva 2017), Canada (Champagne 2008; Pieta 1998; Walker 1996), China (Chow 2010; Dai 2007a; Hou 2014; Li 2014b; Ren 2017a; Sun 2017; Zhao 2011; Zou 2015), Denmark (Bro 1999), France (Jean 1995), Germany (Trenkwalder 1995), Greece (Giannaki 2013; Giannaki 2013a), Iran (Afshar 2011; Amini 2016; Arab 2016; Dashti‐Khavidaki 2011; Edalat‐Nejad 2013; Farrokian 2016; Ghavami 2016; IRCT2013021212448N1; IRCT2014061717237N3; IRCT2015051122218N1; Momennasab 2018; Nasiri 2011; Pooranfar 2014; Rambod 2013; Razazian 2015; Saeedi 2014; Shariati 2012; Soleimani 2016), Italy (Pellecchia 2004; Sabbatini 2003), Korea (Cho 2018), Slovakia (Tol 2010), Switzerland (Burkhalter 2015; Hanna 2013), Taiwan (Chen 2008a; Chen 2011a; Tsai 2015; Tsay 2003a; Tsay 2004), Thailand (NCT02825589), The Netherlands (EMSCAP 2009; MELODY 2013; Parker 2007), Turkey (Micozkadioglu 2004; Muz 2017; Solak 2012; Turk 2010; Unal 2016; Yurtkuran 2007), and the USA (Kolner 1989; Natarajan 2003; Reilly‐Spong 2015; Sklar 1998; Soreide 1991; Williams 2017). One study was conducted both in the USA and Europe (Dauvilliers 2016).

The mean age of participants in the 36 studies contributing outcome data was 54.3 years. Follow‐up for clinical outcomes ranged between 0.3 and 52.8 weeks (median 5 weeks).

Sleep interventions

The methods for implementation, tailoring, and measurement of adherence of interventions are provided in Table 4 using a TIDIeR (Template for Intervention Description and Replication) checklist (Hoffmann 2014).

1. TIDieR framework of intervention descriptions for included studies.

Study ID	Intervention	Control	Materials	Sleep intervention				Adherence
Study ID	Intervention	Control	Why	What	How	Who provided, where and when	Tailoring/modification	How well: Planned	How well: Actual
Afshar 2011	Exercise	Control	To determine the effects of aerobic training on sleep quality, serum leptin, and inflammatory status	People in the intervention group cycled during the 1st two hours of each dialysis  session in a recumbent position	Regular aerobic training which consisted  of 5 minutes of warm‐up and 10 to 30 minutes of  stationary cycling	3 sessions per week, for 3 weeks in the clinic	Patients were asked to cycle at an intensity of 12 to 15 of 20 at the rate of perceived exertion of Borg scale, of an individual’s maximal capacity	Blood pressure and heart rate of the participants  were monitored each 5 minutes, during the exercise	The number of patients who completed the study interventions was not reported
Amini 2016	Relaxation	Control 1: Exercise Control 2: Control	Investigate aerobic exercise and progressive muscle relaxation on anxiety, fatigue, and sleep disorders	Explained to patients while undergoing HD. Recording about muscle relaxation shown	Recording shown to patients. Patients were corrected on technique. Patients then did exercises at home using recording	There was the supervision of a researcher. The intervention was performed daily in the clinic or at home, for 60 days for 8 weeks	‐	Researcher followed up every two weeks to encourage exercise program or exclude patients who did not adhere	The number of patients who completed the study interventions was not reported
Aoike 2018	Exercise	Control 1: Exercise Control 2: Control	To test if home‐based  aerobic exercise program provides similar benefits  as a centre‐based program	The patients included in the exercise  groups were submitted to a moderate aerobic exercise program	The home‐based performed exercise at home, the others at an exercise centre	A physiologist provided the intervention. Exercises were performed in the centre or at home for 30 min for 8 weeks	The exercise training intensity was prescribed according to  each patient’s ventilatory threshold	‐	40 patients completed the study
Arab 2016	Acupressure	Control 1: Sham Control 2: Control	To investigate the effect of acupressure on the sleep and quality of life	The intervention group received acupressure in the bilateral Shenmen points. The others received either sham acupressure or no treatment	Acupressure was applied using a circular movement. The sham was performed on points at 0.5 cm from the true points	A trained researcher provided the intervention in the clinic for 8 minutes, 3 times a week for 8 weeks	‐	To establish consistency of performance, the amount of pressure applied was measured using a scale; 30 measurements were recorded	93 patients completed the study
Bro 1999	CAPD	APD	To test if there should be a difference between the effects of APD compared to CAPD on quality of life and clinical outcomes	17 patients were  allocated to APD treatment and 17 patients to CAPD treatment	CAPD and APD devices	Skilled PD nurses provided the intervention in the clinic. APD and CAPD were delivered for 26.4 weeks	One patient on CAPD needed an additional exchange to achieve the target dialysis dose	During the study, patients were seen at monthly controls in the CAPD unit. Adequacy tests were performed every 3 months	25 patients completed  the study
Burkhalter 2015	Light	Control	To evaluate the feasibility of the intervention and to assess its efficacy for improving sleep	To receive the appropriate dosage, at a time determined by individual chronotype	The patient sited 30–50 cm from the light box lamp, which produced light at eye level	The principal investigator instructed participants on the light box’s use to perform at home, 30 min daily for 3 weeks	We allowed for a 1.5 h deviation from the optimum starting time	‐	28 patients completed  the study
Champagne 2008	HDF	HD	To compare sleep apnoea severity in HD and HDF	Polysomnography was used to assess the efficacy of the intervention	After the prescribed period, these treatments were inverted	Thrice‐weekly schedules for 13.2 weeks (first phase) in the clinic	‐	‐	At the end of phases II, 6 patients completed  the study
Chen 2008a	CBT	Education	To investigate the effectiveness  of intervention in patients with insomnia and to investigated the association with cytokine levels	To assist participants in identifying, challenging, and changing misconceptions about sleep	Participants were instructed to relieve muscular tension and perform rhythmic breathing	Research staff (psychiatrist, nephrologist, nurse) provided the intervention at home, 1 hour weekly for 4 weeks	‐	‐	24 patients completed  the study
Chen 2011a	CBT	Education	To validate the efficacy of  intervention for sleep disorders and fatigue, depression and anxiety	To assist participants in identifying, challenging,  and changing the misconceptions about sleep	The intervention included a psychiatrist‐oriented, video assisted  program and group discussion  and education	2 psychiatrists  and a psychologist provided the intervention in the clinic, 30‐min tri‐weekly for 6 weeks	‐	‐	All patients who received the treatment completed the study
Cho 2018	Exercise (aerobic exercise)	Control 1: Exercise (resistance exercise) Control 2: Exercise (combination exercise) Control 3: Control	To investigate the effect of intra dialytic exercise on daily physical activity and sleep quality, measured by an accelerometer	To perform recumbent stationary  cycling or exercises, involving muscles of both the lower and upper body	A stationary bike or Coloured elastic resistive bands and soft weights were used. All the exercises were performed in a supine or a sitting position	A researcher provided the intervention in the clinic: 5‐min warm‐up and maximum of 30 min for 12 weeks	According to patients’ performance, training loads were adjusted	Participants were encouraged to perform each exercise to optimise movement speed and muscle power	46 patients completed  the study
Chow 2010	Education	Control	To examine the effectiveness of a  nurse‐led case management programme in improving the  quality of life	Patients received a comprehensive discharge planning protocol and a standardized  telephone follow‐up regimen	All calls focused on health‐related behaviours and were  audio taped for documentation	A nurse provided the training program of 24 hours in the clinic. A nurse contacted patients by telephone weekly for 6 weeks	Patients could referral to the community nurse, the renal team or to  the emergency department. The duration of follow‐up calls varied, depending on patients’ specific	Realistic action plan and participation of family members in  discussing to assess the patient’s needs	85 patients completed  the study
Dai 2007a	Acupressure	Estazolam	To study the effect of lower extremity point massage for improving quality of sleep	1 mg of estazolam tablets orally half an hour before sleep or acupressure	‐	Intervention was performed in the clinic or at home once a day, 20 to 30 seconds each time for 4 weeks	‐	‐	The number of patients who completed the study was not reported
Dashti‐Khavidaki 2011	Benzodiazepine (zolpidem)	Benzodiazepine (clonazepam)	To compare zolpidem with clonazepam in terms of on sleep quality	5 to 10 mg of zolpidem or 1 mg of clonazepam, orally	After the prescribed period these treatments were inverted	Daily for 2 weeks (first phase) at home	‐	‐	All patients completed the  first phase of treatment
Dauvilliers 2016	Dopaminergic agonist (rotigotine)	Control	To investigate the efficacy on periodic legs movement, sleep, RLS and quality of life	Polysomnography was performed on the 2 consecutive nights	‐	Trained personnel provided the intervention that was performed at home (1 to 3 mg of rotigotine) for 6 weeks	‐	‐	25 patients completed the study
Duarte 2009	CBT	Control	To assess the effectiveness  of an intervention in patients with a  diagnosis of major depression	The patients attended sessions when they were  off HD	Educating on kidney disease, dialysis, depression and the therapeutic cognitive model. All sessions involved homework	2 psychologists provided the intervention in the clinic: 12 weekly sessions for 13.2 weeks	Individualized psychotherapy session for providing guidelines  about the treatment and emotional support	‐	74 patients completed the study
Edalat‐Nejad 2013	Melatonin	Control	Melatonin 3 mg	To assess the effect of the intervention on sleep quality	After the prescribed period these treatments were inverted	Melatonin 3 mg orally per day for 6 weeks (first phase) at home	‐	Compliance was confirmed by pill count	At the end of phases II, 68 patients completed the study
EMSCAP 2009	Melatonin	Control	To investigate the effects of exogenous melatonin on  sleep–wake rhythm	Actigraphy was used to assess the efficacy of the intervention	After the prescribed period these treatments were inverted	3 mg of melatonin orally per day for 6 weeks (first phase)	‐	‐	At the end of phases II, 20 patients completed the study
Farrokian 2016	Reflexology	Control	To determine the effect of reflexology massage on sleep quality	Massage will be done by nurse of the same sex of the patient	Slow and regular rhythm massage	Trained nurses provided the intervention in the clinic: 12 sessions of 30 minutes, 3 day a week for 4 weeks	The depth of the massage depended on the patient's tolerance	‐	All patients completed the study
Ghavami 2016	Massage	Control	To determine the effectiveness of hot stone massage therapy on sleep quality level	Massage compared with routine health care	‐	12 sessions	‐	‐	The number of patients who completed the study was not reported
Giannaki 2013	Exercise	Control 1: Dopaminergic agonist (ropinirole) Control 2: Control	To compare the changes across groups on RLS symptoms to evaluate quality of life	Cycling compared with ropinirole 0.25 mg orally	Exercise consisted of cycling in a recumbent cycle	A specialized neurologist provided exercises in the clinic 3 times per week, ropinirole was delivered 0.25 mg daily for 26.4 weeks	The exercise intensity was readjusted on a monthly base	‐	29 patients completed the study
Giannaki 2013a	Exercise	Control	To investigate the intervention that reduce RLS  severity	The exercise session in both groups included intra‐dialytic cycling for 45 min at 50 rpm	The exercise included aerobic exercise performed in a recumbent cycle	A neurologist provided the intervention in the clinic for 45 min, 3 times per week for 26.4 weeks	The exercise intensity was readjusted every 4 weeks to account for the patients’  improvement	‐	All patients completed the study
Hanna 2013	Light	Control	To evaluate the efficacy of the intervention in people with sleep‐wake disturbance and depressive symptomatology	Morning light was scheduled according to chronotype daily. The rest‐activity cycle was monitored with a wrist actimeter	‐	30 minutes daily for 3 weeks	‐	‐	The number of patients who completed the study was not reported
Hou 2014	CBT	Control	To verify the effects of sleep‐related behaviour modification in combination with progressive muscle relaxation on insomnia	During the interval of training, they did progressive  muscle relaxation with a magnetic tape of ‘‘self‐relaxation’’	The physician did the progressive muscle relaxation for the patients and guided the patients	A physician provided the intervention in the clinic for 20 minutes every 2 days, 3 times week. Relaxation was performed daily at home for 30 min for 13.2 weeks	‐	‐	98 patients completed the study
IRCT2013021212448N1	Collaborative care model	Control	To determine the effect of collaborative care model on the fatigue	Care model included motivation, preparation, and evaluation	Sessions about the illness and the proper behaviour to deal with	Researchers, doctors and nurses provide the intervention in the clinic, 2 hours per day for 12 weeks	Half‐hour meetings were held to deal with specific needed	‐	The number of patients who completed the study was not reported
IRCT2015051122218N1	Chamomile	Control	To determine the effect of camomile	The intervention group will take syrup of chamomile	‐	Chamomile 400 mg/day orally for 4 weeks at home	‐	‐	The number of patients who completed the study was not reported
IRCT2014061717237N3	Acupressure	Control 1: Sham Control 2: Control	To determine the relationship between anxiety and sleep quality	In intervention group will receive acupressure in true acupoint	Acupressure will be done using pressure with the thumb	2 trained practitioners provided the intervention in the clinic, 3 times a week for 4 weeks	‐	‐	The number of patients who completed the study was not reported
Jean 1995	Acetate dialysis	Bicarbonate dialysis	To assess the influence of buffer, acetate or bicarbonate, on sleep and ventilation	Polysomnography was used to assess the efficacy of the intervention	After the prescribed period these treatments were inverted.	The medical team provided the intervention in the clinic	‐	‐	At the end of phases II, all patients completed the study
Kolner 1989	Benzodiapine (triazolam)	Control	To test the efficacy of Triazolam in HD patients with sleep disorder	‐	‐	Daily for 1 week at home	‐	‐	The number of patients who completed the study was not reported
Li 2014b	Telephone support	Control	To develop an original telephone support model for  improving quality of life	Patients received a standardized nurse‐led  telephone support	Sessions to optimise health outcomes. After discharge started telephone call	A nurse provided the intervention in the clinic. Telephone‐  call contact with patients weekly for 12 weeks	The patient’s needs were assessed with an individualized program	Each telephone call was guided by the protocol and were audio taped to ensure consistency	135 patients had completed the follow‐up questionnaires
MELODY 2013	Melatonin	Control	To investigate the effects of drug on sleep and quality of life in patients with  sleep problems	Actigraphy was used to assess the efficacy of the intervention	The actiwatch was placed on the wrist of the arm without fistula	Physicians provided the intervention in the clinic or at home: 3 mg of melatonin daily for 52.4 weeks	‐	‐	42 patients completed the study
Micozkadioglu 2004	Levodopa	Gabapentin	To find the efficacy of gabapentin compared with levodopa in the treatment of RLS	125 mg/day of levodopa 2 hours before sleep. 200 mg of gabapentin after HD	After the prescribed period these treatments were inverted	4‐week management for each drug (first phase) in the clinic or at home	‐	‐	14 patients completed the study
Momennasab 2018	Music	Control 1: Music Control 2: Control	To compare the effectiveness  of music therapy during HD and at bedtime on sleep  quality	The music used was a 6‐pieces piano improvisation in  new age (relaxation) genre	Participants were exposed to music via  an MP3‐player using an occlusive headphone or  prerecorded music compact disc	Researchers provided the intervention that was performed in the clinic or at home for 4 weeks	The patient could stop or play the music whenever he/she liked or listen to it again	Patients were assessed about fulfilling the intervention  by weekly telephone follow‐up	102 patients completed the study
Muz 2017	Aromatherapy	Control	To determine the effect of aromatherapy on the sleep quality and fatigue	Aromatherapy group (sweet orange oil and lavender oil)  via inhalation	Lavender and sweet orange oils were dropped to a gauze bandage. Patients had to smell the aromatic mixture for 2 min	Researchers provided the intervention that was performed at home for one month for 2 min before sleeping	‐	Patients were called to report any problems. Answers were recorded, and support was provided	62 patients completed the study
Nasiri 2011	Acupressure	Control	To evaluate the effectiveness of acupressure on quality of sleep	4 points were pressured: this pressure was continuous with finger circularly for 1‐2 second	‐	Researcher and his cooperator provided the intervention in the clinic, 12 times for 5 min, 3 days per week for 4 weeks	‐	The force of pressure (consistency /reliability) were confirmed by using a scale	The number of patients who completed the study was not reported
Natarajan 2003	Melatonin	Control	To assess the effect of melatonin administration on sleep quality	Actigraphy was used to assess the efficacy of the intervention		Melatonin 3 mg orally per day, for 4 weeks (first phase) at home	‐	‐	At the end the first phase, all patients completed the study
NCT02825589	Bioelectrical impedance	Control	To assess the effect of bioelectrical impedance analysis on sleep	‐	‐	13.2 weeks	‐	‐	The number of patients who completed the study was not reported
Parker 2007	Dialysate 37°	Dialysate 35°	To test if cool dialysate would improve blood flow, heat dissipation and sleep	Subjects received HD in warm condition (37°C) or cool condition (35°C)	After the prescribed period these treatments were inverted	Trained nurses and nephrology co‐investigator provided the intervention in the clinic	‐	The personnel ensured the integrity and proper functioning of the equipment	The number of patients who completed the study was not reported
Pellecchia 2004	Levodopa	Ropinirole	To determine the efficacy and adverse event profile of ropinirole as compared with levodopa	Levodopa dosage was 100 to 200 mg/d and ropinirole dosage was 0.25 to 2 mg/d	After the prescribed period these treatments were inverted	Medications were performed orally for 6 weeks (first phase) in the clinic or at home	Doses could be doubled according to the investigators’ and patients’ opinions	‐	10 patients completed the study
Pellizzaro 2013	Respiratory muscle training	Control 1: Peripheral muscle training Control 2: Control	To assess the effects of interventions on functional parameters, inflammatory state, and quality of life	Spirometry was used to assess the efficacy of the intervention	Patients performed three sets of 15 inspirations and rested for 60 seconds	30 training sessions for 10 weeks in the clinic	The exercise load was changed throughout  the training according to 50% of PImax	‐	39 patients completed the study
Pieta 1998	Dopaminergic agonist (pergolide)	Control	To test the effect of pergolide on leg movements and sleep disturbance	Polysomnography was used to assess the efficacy of the intervention	After the prescribed period these treatments were inverted	Pergolide from 0.05 to 0.25 for 1.5 weeks (first phase) at home	‐	‐	At the end of phases II, 8 patients completed the study
Pooranfar 2014	Exercise	Control	To assess the effect of a period of exercise on sleep quality and quantity	Participants were acquainted with cycling method on bicycle ergometer,  treadmill and other exercises	The sessions  were divided into pre‐warming, main step (aerobic and resistive exercises using ergometer bicycle) and rest	A researcher provided the intervention: 3 days a week for 10 weeks in 60–90 minute exercise sessions	The exercise  program was designed in terms of type, intensity,  and frequency according to physical status of the patients	‐	The number of patients who completed the study was not reported
Rambod 2013	Relaxation	Control	To evaluate the effect of the intervention on the sleep quality	The intervention group listened to the audiotape of Benson’s  relaxation technique	The patients were instructed and were comfortably at rest in bed in a separate room	An expert provided the intervention that was performed twice a day for twenty minutes for 8 weeks, in the clinic or at home	‐	A CD on relaxation technique and research's number was given to the patients. Weekly Were provided  reinforcements	83 patients completed the study
Razazian 2015	Gabapentin	Dopaminergic agonist (levodopa/carbidopa)	To compare drugs in reducing symptoms and sleep problems	Gabapentin 200 mg orally compared to levodopa‐c 110 mg orally	‐	Gabapentin 200 mg (3 times weekly), levodopa‐c 110 mg in a single dose for 4 weeks at home	‐	‐	83 patients completed the study
Reilly‐Spong 2015	Relaxation	Control	To reduce symptoms and improve quality of life using a multi‐modal telephone‐adapted program	Intervention was a bookend program. Actigraphy was used to assess the efficacy of the intervention	Workshops and teleconferences that included discussions, homework and practice	Certified teachers and a psychologist provided the intervention at the University. Teleconferences were held from patients' home for 8 weeks	Teacher ensured that yoga poses could be modified for people with disabilities. Emails were also used to document any deviations from checklists	Teleconferences used standard guidelines and each group had a unique password.  Attendance was recorded	52 patients completed the study
Ren 2017a	Foot‐bath	Control	To explore the intervention effect of herb foot‐bath therapy to improve sleep quality and symptom  distress	Herbs packed by gauze bag were put into a footbath with  boiled water	Feet were put above the footbath in water  vapour. Until the water temperature was cooled to 38‐43°C, feet  were put in water	A course of treatment was four weeks; the  intervention time was 30‐40 min before nightly bedtime every day at home	Once uncomfortableness and problems occurred, patient should stop the intervention and reported symptoms	‐	The number of patients who completed the study was not reported
Sabbatini 2003	Benzodiazepine (zaleplon)	Control	To test the effects of  zaleplon on the sleep quality in patients affected by insomnia	5 to 10 mg of zaleplon	After the prescribed period these treatments were inverted	A nephrologist provided the intervention that was performed at home (5 to 10 mg of zaleplon) for 2 weeks (first phase)	‐	‐	At the end of phases II, 10 patients completed the study
Saeedi 2014	Education	Control	To investigate the effect of the intervention on the sleep quality for  improving quality of life and their  satisfaction	Patients in the intervention  group participated in sessions on sleep hygiene training program	Direct teaching methods, combination of face‐to‐face  methods, lectures and group discussions	A researcher provided the intervention: 6 weekly sessions of half‐hour for 4 weeks	‐	‐	76 patients completed the study
Shariati 2012	Acupressure	Control	To investigate the effects of acupressure on sleep quality	Acupressure applied consistent pressure on the correct acupoints with small rotational	The intervention group  received acupressure on hands and feet	The investigators provided the intervention in the clinic: 15 min, 3 times per week for 4 weeks	Three acupoints that could be used to enhance sleep were chosen for the subjects	The precision was confirmed if subjects  felt sore, numb, heavy, distended, and/or warm	40 patients completed the study
SIESTA 2017	Acupressure	Sham	To investigate the effect and safety of acupressure on the sleep quality	‐	All selected acupoints were stimulated bilaterally	An accredited practitioner provided the intervention in the clinic (3 min, 3 times a week) for 4 weeks	The intensity was adjusted according to the  patient’s level of tolerance	‐	41 patients completed the study
Silva 2017	Continuous Positive Airway Pressure	Compression stockings	To evaluate the short‐term impact of treatments on the severity of sleep apnoea	Polysomnography was used to assess the efficacy of the intervention	After the prescribed period these treatments were inverted	A technician provided the intervention in the clinic for 1 week (first phase)	The lowest pressure was initially applied to all patients and increased progressively as needed	‐	At the end of phases II, 14 patients completed the study
Sklar 1998	Dialyzer with cuprophan membrane	Dialyzer with poly‐methylmethacrylate membrane	To evaluate  the role for type of blood‐membrane interaction in postdialysis fatigue	Using two different types of membranes  and TNF‐alfa as a marker of their biocompatibility	After the prescribed period these treatments were inverted	The Medical team provided the intervention in the clinic thrice weekly, for 1 week (first phase)	‐	‐	At the end of phases II, 16 patients completed the study
Solak 2012	Gabapentin	Pregabalin	To compare the effects of drugs on sleep quality and depression	Electromyography was used to assess the efficacy of the intervention	After the prescribed period these treatments were inverted	A neurologist provided the intervention that was performed in the clinic or at home (gabapentin 300 mg thrice weekly, pregabalin 75 mg daily), for 6 weeks (first phase)	‐	‐	At the end of phases II, 48 patients completed the study
Soleimani 2016	Education	Control	To improve sleep quality through face‐to‐face sleep health education	Sleep hygiene education was performed. in two sections	The materials and a face‐to‐face session were provided	Researcher provided the intervention. This protocol was taught within an hour	‐	The participants asked questions and the materials were assessed	57 patients completed the study
Soreide 1991	Branch‐chain amino acid	Control	To assess the effect of the branch‐chain amino acid on sleep apnoea	Polysomnography was used to assess the efficacy of the intervention	After the prescribed period these treatments were inverted	For 2 study nights (first phase)	‐	‐	At the end of phases II, all patients completed the study
Sun 2017	Massage	Control	To assess if stimulating gastric activity improves relax and sleep	Abdominal massage, patient's education and training exercise	Massage to improve below contractility	Nurses provided the intervention in the clinic or at home for 4 weeks	‐	‐	Data were reported for all patients
Tol 2010	Gabapentin	Control	To determine changes on pruritus, quality of life, depression and sleep quality	Gabapentin 300 mg compared with placebo	After the prescribed period these treatments were inverted	Gabapentin 300 mg orally for 8 weeks (first phase) in the clinic or at home	‐	‐	At the end of phases II, all patients completed the study
Trenkwalder 1995	L‐dopa + benserazide	Control	To assess the effects of L‐dopa on sleep quality in restless leg syndrome	Polysomnography was used to assess the efficacy of the intervention	After the prescribed period these treatments were inverted	L‐dopa + benserazide (200mg + 50mg) orally for 4 weeks (first phase) at home	‐	Patients were monitored by phone calls	At the end of phases II, 28 patients completed the study
Tsai 2015	Relaxation	Control	To examine the efficacy of a nurse‐led,  in‐centre breathing training program in reducing depressive symptoms and improving sleep quality and  QoL	The dialysis nurse administered the audio device–guided breathing training in a quiet room	Patients listened to prerecorded  instructions on breathing technique and then practiced the breathing exercise	A trained nurse provided the intervention in the clinic: 8 sessions, twice weekly for 4 weeks	Each patient received an individual coaching session	The nurse supervised each practice session and evaluated  the breathing exercises to ensure that participants  performed them correctly	57 patients completed the study
Tsay 2003a	Acupressure	Control 1: Sham Control 2: Control	To test the effectiveness of acupressure on sleep quality and fatigue	The intervention group received acupressure. The  placebo group received a massage	Four acupoints were used to decrease fatigue	Researchers trained provided the intervention: 15 min, 3 times a week for 4 weeks	‐	The precision of acupressure was confirmed if  subjects felt sore, numb, heavy, distended	98 patients completed the study
Tsay 2004	Acupressure	Control 1: Acupressure (Transcutaneous Electrical Acupoint Stimulation) Control 2: Control	To test the effectiveness of the interventions on fatigue, sleep quality and depression	Acupressure compare with  transcutaneous electrical acupoint stimulation and control group	Four acupoints were used to decrease fatigue	Investigators provided the intervention: 15 minutes of treatment  3 times a week for 4 weeks	‐	The reliability of the pressure was assesses using a  protocol that was standardized before each treatment	106 patients completed the study
Turk 2010	Phosphodiesterase type 5 (sildenafil)	Phosphodiesterase type 5 (vardenafil)	To compare the  effects of drugs on depression  and sleep quality in male with erectile dysfunction	Sildenafil 50 mg orally compared with Vardenafil 10 mg orally	After the prescribed period these treatments were inverted	The drugs were administered  prior to sexual intercourse once per week for 4 weeks (first phase) at home	‐	‐	The number of patients who completed the study was not reported
Unal 2016	Reflexology	Control 1: Massage Control 2: Control	To examine the effectiveness the interventions on  sleep quality and fatigue	Foot reflexology compared with back massage and control group	3 drops of baby oil were applied at room temperature to facilitate the massage	A researcher provided the intervention in the clinic: 30 minutes, 2 days a week for 4 weeks	‐	‐	105 patients completed the study
Walker 1996	L‐dopa/carbidopa	Control	To determine if levodopa/carbidopa decreased leg movements and improved sleep	L‐dopa/carbidopa 100 mg + 25 mg compared with placebo	After the prescribed period these treatments were inverted	L‐dopa/carbidopa 100 mg + 25 mg daily for 1 week (first phase) at home	‐	‐	At the end of phases II, 5 patients completed the study
Williams 2017	Feedback group	Control	To determine if providing feedback  on activity will have an impact on physical activity levels	All participants were equipped with the tracking bracelet. Intervention group received feedback	Patients in the feedback group received their activity and sleep data at each dialysis treatment	Research coordinators provided the intervention in the clinic or at home. All participants wore the tracking bracelet at all times for 5 weeks	‐	‐	29 patients completed the study
Yurtkuran 2007	Exercise	Control	To assess if yoga exercise can improve pain, fatigue, sleep disorder and biochemical markers	Yoga‐based exercises were done in groups	Using some yogic postures and breathing exercises in the rehabilitation of dialysis patients	A yoga teacher provided the intervention. Exercises were performed in the clinic or at home, 30 min/day twice a week for 13.2 weeks	Some modifications to the program were done to increase patient compliance. The exercise has to be stopped if there is severe fatigue or pain	The exercises was explained to each patient until the physiotherapist was satisfied that all of them could do the exercises	37 patients completed the study
Zhao 2011	Acupressure	Control	To assess the efficacy of acupressure	4 auricular magnetic bead plaster points in fixed points	Take the side of each ear, 2 days later using another ear	Patient provided a self‐pressure twice daily for 56 days, for 8 weeks (at home)	‐	‐	The number of patients who completed the study was not reported
Zou 2015	Acupressure	Control	To assess the feasibility and  acceptability of acupressure treatment	Participants received acupressure on five active acupoints	Participants were instructed to press the beads until a slight soreness were felt	Trained nurse practitioner provided the intervention in the clinic for 8 weeks	If the plasters or beads detached, the patients came to hospital	Feasibility was assessed by the percentage of recruitment, retention,  attendance and adherence	58 patients completed the 8 weeks of treatment, 55 completed the 12 weeks of follow‐up

Relaxation versus control for sleep outcomes in people with CKD
Patient or population: people with CKD Intervention: relaxation¹ Comparison: without relaxation technique/training
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Without relaxation training/technique	Relaxation training/technique
Sleep quality PSQI (median follow‐up: 8 weeks)	The mean sleep quality index score ranged across control groups from 1.53 to 11.09	The mean sleep quality index score in the intervention groups was 1.62 lower (95% CI ‐5.03 to 1.79) A lower score is indicative of higher sleep quality	MD ‐1.62 (95% CI ‐5.03 to 1.79)	259 (4)	⊕⊝⊝⊝  Very low ^{2 3 4}	It is very uncertain whether relaxation makes any difference to sleep quality
Sleep latency PSQI (median follow‐up: 8 weeks)	Only one study reported sleep latency	Not estimable as only a single study reported this measure	Not estimable.	Insufficient data observations	Not estimable	Studies were not designed to measure effects of relaxation on sleep latency
Quality of life Quality of Life Index ‐ dialysis version and Medical Outcome Studies 36‐Item Short Form Health Survey (median follow‐up: 6 weeks)	The mean quality of life index score ranged across control groups from 17.73 to 43.08	The mean quality of life index score in the intervention groups was 0.47 higher (95% CI ‐0.09 to 1.04) A higher score is indicative of higher perceived of quality of life	SMD 0.47 (95% CI ‐0.09 to 1.04)	138 (2)	⊕⊕⊝⊝  Low ^{4 5}	It is uncertain whether relaxation makes any difference to quality of life
Depression Center for Epidemiologic Studies Depression Scale and The Beck Depression Inventory II (median follow‐up: 6 weeks)	The mean depression index score ranged across control groups from 9.1 to 9.56	The mean depression index score in the intervention groups was 0.04 higher (95% ‐1.27 to 1.35) A higher score is indicative of more depressive symptoms	SMD 0.04 (95% CI ‐1.27 to 1.35)	108 (2)	⊕⊝⊝⊝  Very low ^{4 6}	It is very uncertain whether relaxation makes any difference to depressive symptoms
Anxiety Beck Anxiety Inventory and Spielberger State‐Trait Anxiety Inventory (median follow‐up: 8 weeks)	The mean anxiety index score ranged across control groups from 31.61 to 34.9	The mean anxiety index score in the intervention groups was 0.11 higher (95% CI ‐0.55 to 0.77) A higher score is indicative of more anxiety symptoms	SMD 0.11 (95% CI ‐0.55 to 0.77)	119 (2)	⊕⊝⊝⊝  Very low ^{4 5 7}	It is very uncertain whether relaxation makes any difference to anxiety
Fatigue PROMIS‐Fatigue Short Form 1.0 and Rhoten and Piper fatigue (median follow‐up: 8 weeks)	The mean fatigue score ranged across control groups from 55.5 to 81.17	The mean fatigue score in the intervention groups was 0.61 lower (95% CI ‐2.09 to 0.87) A higher score is indicative of worse fatigue	SMD ‐0.61 (95% CI ‐2.09 to 0.87)	119 (2)	⊕⊝⊝⊝  Very low ^{4 6}	It is very uncertain whether relaxation makes any difference to fatigue
Hospitalisation (median follow‐up: 4 weeks)	Not estimable⁸	Not estimable	Not estimable.	Insufficient data observations	Not estimable	Studies were not designed to measure effects of relaxation on hospitalisation
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: Confidence interval; RR: Risk ratio; MD: mean difference; SMD: standardised mean difference; PSQI: Pittsburgh Sleep Quality Index
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Exercise compared to control for sleep outcomes in people with chronic kidney disease (CKD)
Patient or population: people with CKD Settings: CKD Intervention: exercise¹ Comparison: without exercise
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Without exercise	Exercise
Sleep quality PSQI, ESS and tri‐axial accelerometer (median follow‐up: 26.4 weeks)	The mean sleep quality score ranged across control groups from 8.85 to 43.6	The mean sleep quality index score in the intervention groups was 1.10 lower (95% CI ‐2.26 to 0.05). A lower score is indicative of higher sleep quality	SMD ‐1.10 (95% CI ‐2.26 to 0.05)	165 (5)	⊕⊝⊝⊝  Very low ^{2 3 4}	It is very uncertain whether exercise makes any difference to sleep quality
Sleep latency	No data observations	Not estimable	No observations	Insufficient data observations	Not estimable	Studies were not designed to measure effects of exercise on sleep latency
Quality of life	No data observations	Not estimable	No observations	Insufficient data observations	Not estimable	Studies were not designed to measure effects of exercise on quality of life
Depression Zung Self‐Rating Depression Scale (ZUNG) (median follow‐up: 26.4 weeks)	The mean depression index score ranged across control groups from 43.7 to 43.71	The mean depression index score in the intervention groups was 9.05 lower (95% CI ‐13.72 to ‐4.39) A higher score is indicative of worse depressive symptoms	MD ‐9.05 (95% CI ‐13.72 to ‐4.39)	46 (2)	⊕⊕⊕⊝  Moderate ⁵	Exercise probably decreases depressive symptoms
Anxiety Beck Anxiety Inventory (BECK) (median follow‐up: 8 weeks)	Only one study reported anxiety.	Not estimable as only a single study reported this measure	Not estimable.	Insufficient data observation	Not estimable	Studies were not designed to measure effects of exercise on anxiety
Fatigue PIPER Fatigue Scale (PFS) and Visual Analogue Scale (VAS) (median follow‐up: 13.2 weeks)	The mean fatigue index score ranged across control groups from 6.9 to 81.17	The mean fatigue index score in the intervention groups was 0.68 lower (95% CI ‐1.07 to ‐0.29). A higher score is indicative of worse fatigue	SMD ‐0.68 (95% CI ‐1.07 to ‐0.29)	107 (2)	⊕⊕⊕⊝  Moderate ⁶	Exercise probably improves fatigue
Hospitalisation	No data observations	Not estimable	No observations.	Insufficient data observations	Not estimable	Studies were not designed to measure effects of exercise on hospitalisation
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; SMD: standardised mean difference; MD: mean difference
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change the certainty in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on the certainty in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on the certainty in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Acupressure versus control for sleep outcomes in people with chronic kidney disease (CKD)
Patient or population: people with CKD Settings: CKD Intervention: acupressure Comparison: without acupressure (no treatment)
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect  (95% CI)	No. of participants  (studies)	Quality of the evidence  (GRADE)	Comments
	Assumed risk	Corresponding risk
	Without acupressure	Acupressure
Sleep quality PSQI (median follow‐up: 4 weeks)	The mean sleep quality index score ranged across control groups from 1.29 to 11	The mean sleep quality index score in the intervention groups was 1.27 lower (95% CI ‐2.13 to ‐0.40) A lower score is indicative of higher sleep quality	MD ‐1.27 (95% CI ‐2.13 to ‐0.40)	367 (6)	⊕⊝⊝⊝  Very low ^{1 2}	It is very uncertain whether acupressure makes any difference to sleep quality
Sleep latency PSQI (median follow‐up: 4 weeks)	The mean sleep latency index score ranged across control groups from 1.74 to 2.4	The mean sleep latency index score in the intervention groups was 0.59 lower (95% CI ‐0.92 to ‐0.27) A lower score is indicative of shorter sleep latency	MD ‐0.59 (95% CI ‐0.92 to ‐0.27)	173 (3)	⊕⊕⊕⊝  Moderate ¹	Accupressure may shorten sleep latency
Quality of life	No data observations.	Not estimable	No observations	Insufficient data observations	Not estimable.	Studies were not designed to measure effects of acupressure on quality of life
Depression Beck Depression Inventory (BECK) (median follow‐up: 4 weeks)	The mean depression index score ranged across control groups from 18.88 to 21.61	The mean depression index score in the intervention groups was 3.65 lower (95% CI ‐7.63 to 0.33) A higher score is indicative of worse depressive symptoms.	MD ‐3.65 (95% CI ‐7.63 to 0.33)	137 (2)	⊕⊝⊝⊝  Very low ^{3 4 5}	It is very uncertain whether acupressure makes any difference to depressive symptoms
Anxiety	No data observations	Not estimable	No observations	Insufficient data observations	Not estimable.	Studies were not designed to measure effects of acupressure on anxiety
Fatigue PIPER Fatigue Scale (PSF) (median follow‐up: 4 weeks)	The mean fatigue index score ranged across control groups from 5.7 to 5.71	The mean fatigue index score in the intervention groups was 1.07 lower (95% CI ‐1.67 to ‐0.48) A higher score is indicative of worse fatigue	MD ‐1.07 (95% CI ‐1.67 to ‐0.48)	137 (2)	⊕⊕⊕⊝  Moderate ³	Accupressure may reduce fatigue
Hospitalisation	No data observations	Not estimable	No observations	Insufficient data observations	Not estimable	Studies were not designed to measure effects of acupressure on hospitalisation
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; SMD: standardised mean difference; MD: mean difference
GRADE Working Group grades of evidence  High quality: Further research is very unlikely to change our confidence in the estimate of effect.  Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.  Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.  Very low quality: We are very uncertain about the estimate.

Study ID	Treatment	Control	Adverse events in treatment arm	Adverse events in control arm	Comment
Bro 1999	CAPD	APD	Peritonitis (2); exit‐site infection (1)	Peritonitis (1); exit‐site infection (1); tunnel infection (1); leakage (1); hernia (1); over‐hydration (2)	Quote: "No proper statistics could be applied due to the low numbers of patients and events."
Burkhalter 2015	Light	Control	No participants experienced an adverse event	No participants experienced an adverse event	Quote: "No adverse reactions or symptom complaints were registered."
Chen 2011a	CBT	Education	No participants experienced an adverse event	No participants experienced an adverse event	Quote: "No adverse events were reported during the intervention."
Cho 2018	Exercise (aerobic exercise)	Control 1: Exercise (resistance exercise) Control 2: Exercise (combination exercise) Control 3: Control	No participants experienced an adverse event	No participants experienced an adverse event	Quote: "There were no reported adverse events, such as musculoskeletal injuries, hypoglycaemic episodes, cardiovascular events, or hospitalizations, as result of the intervention."
Dai 2007a	Acupressure	Estazolam	No participants experienced an adverse event	No participants experienced an adverse event	This study was not in English Quote from the "Acupuncture and related interventions for symptoms of chronic kidney disease (Review)": "Whether adverse events related to administration of estazolam such as somnolence, dizziness, hypokinesia and abnormal coordination occurred was not reported in the control group. Potential adverse events of estazolam might have been regarded as one of outcomes (complaints of adverse reaction), not as adverse events."
Dashti‐Khavidaki 2011	Benzodiazepine (zolpidem)	Benzodiazepine (clonazepam)	No participants experienced an adverse event	No participants experienced an adverse event	Quote: "In this study, zolpidem was not associated with undesirable sleep side effects such as daytime drowsiness, headache, or amnesia, at least during the short‐term course of our study. [...] Meanwhile, the patients who received zolpidem did not complain of any particular side effects."
Dauvilliers 2016	Dopaminergic agonist (rotigotine)	Control	Application site reaction of mild pruritus(1); anxiety (1); foot fracture (1); abdominal pain (1); chest pain (1); dyspnoea (2); nausea (4); vomiting (3); diarrhoea (1); hypertension (2); headache (2)	Gastrointestinal infection (1); diarrhoea (2)	Quote: "AEs were reported by 12 (60%) patients receiving rotigotine and 5 (50%) patients receiving placebo (Table 4). Two patients had hypertension of moderate intensity while receiving rotigotine. Both patients were receiving medications for this condition prior to study start. One patient reported an application site reaction (MedDRA [Medical Dictionary for Regulatory Activities] high‐level term “application and instillation site reactions”) of mild pruritus while receiving 2 mg/24 h of rotigotine; no application site reactions were reported for placebo. Serious AEs were reported for 3 patients receiving rotigotine (foot fracture [n = 1]; anxiety, chest pain, and dyspnoea [n = 1]; and abdominal pain [n = 1]) and 1 patient receiving placebo (gastrointestinal infection)."
Duarte 2009	CBT	Control	Death (4)	Death (4)	Quote; "None of the patients in the intervention group were discontinued because of a CBT adverse effect. [...] Most of these losses were due to death, which is somewhat expected for ESRD patients after almost 1 year of follow‐up." Comment: Figure 1 showed the number of deaths for each group
Giannaki 2013	Exercise	Control 1: Dopaminergic agonist (ropinirole) Control 2: Control	No participants experienced an adverse event	No participants experienced an adverse event in both control groups	Quote: "Finally, none of the patients reported any drug adverse reactions or augmentation phenomena from the three interventions."
Giannaki 2013a	Exercise	Control	No participants experienced an adverse event	No participants experienced an adverse event	Quote: "All patients completed the exercise programme with no adverse effects."
MELODY 2013	Melatonin	Control	Death (3)	Death (3)	No adverse events were reported. However, Figure 2 showed the number of deaths for each group
Rambod 2013	Relaxation	Control	No participants experienced an adverse event	No participants experienced an adverse event	Quote: "In this study, no one reported any undesirable side effects or unintended harm sign, symptom, or disease related to participation in the study or the relaxation technique."
Razazian 2015	Gabapentin	Dopaminergic agonist (levodopa/carbidopa)	Somnolence and lethargy (2)	Allergy (1); death for myocardial infarction (1)	Quote: "During the course of the study period, two patients dropped out during the study secondary to somnolence and lethargy. These patients were administered gabapentin when the symptoms developed. One patient died because of myocardial infarction."
Reilly‐Spong 2015	Relaxation	Control	No participants experienced an adverse event	No participants experienced an adverse event	Quote from Gross 2017: "No intervention‐related adverse events occurred."
SIESTA 2017	Acupressure	Sham	Fluid overload (1); ocular haemorrhage (1)	Necrotizing fasciitis (1); physical trauma (1); chest muscle pain (1); arteriovenous graft failure (1)	Quote: "There were six adverse events (6 participants) recorded during the study (Table 4), all of which were rated as serious adverse events (SAEs) as they led to hospitalisation. Two SAEs occurred in the intervention group (fluid overload and ocular haemorrhage) and the remaining four SAEs occurred in the control group (necrotizing fasciitis, physical trauma, chest muscle pain, and arteriovenous graft failure). No adverse event was considered by investigators to be causally related to the study intervention. No local skin reaction (e.g., bruise) from repeated acupressure was reported during the study."
Zou 2015	Acupressure	Control	Death (3)	No participants experienced an adverse event	Quote: "Three participants died during the follow‐up period. No evidence supported their deaths were related to the AA intervention. No other adverse event was observed."

Database	Search terms
CENTRAL	MeSH descriptor: [Sleep] explode all trees MeSH descriptor: [Sleep Disorders] explode all trees MeSH descriptor: [Sleep Apnea Syndromes] explode all trees sleep:ti,ab,kw (Word variations have been searched) {or #1‐#4} MeSH descriptor: [Kidney Diseases] explode all trees MeSH descriptor: [Renal Replacement Therapy] explode all trees MeSH descriptor: [Renal Insufficiency] explode all trees MeSH descriptor: [Renal Insufficiency, Chronic] explode all trees dialysis:ti,ab,kw (Word variations have been searched) haemodialysis or haemodialysis:ti,ab,kw (Word variations have been searched) hemofiltration or haemofiltration:ti,ab,kw (Word variations have been searched) hemodiafiltration or haemodiafiltration:ti,ab,kw (Word variations have been searched) kidney disease or renal disease* or kidney failure or renal failure:ti,ab,kw (Word variations have been searched) ESRF or ESKF or ESRD or ESKD:ti,ab,kw (Word variations have been searched) CKF or CKD or CRF or CRD:ti,ab,kw (Word variations have been searched) CAPD or CCPD or APD:ti,ab,kw (Word variations have been searched) predialysis or pre‐dialysis:ti,ab,kw (Word variations have been searched) {or 6‐18} {and 5, 19}
MEDLINE	exp Sleep/ exp Sleep Disorders/ sleep$.tw. exp Sleep Apnea Syndromes/ or/1‐4 Kidney Diseases/ exp Renal Replacement Therapy/ Renal Insufficiency/ exp Renal Insufficiency, Chronic/ dialysis.tw. (haemodialysis or haemodialysis).tw. (hemofiltration or haemofiltration).tw. (hemodiafiltration or haemodiafiltration).tw. (kidney disease* or renal disease* or kidney failure or renal failure).tw. (ESRF or ESKF or ESRD or ESKD).tw. (CKF or CKD or CRF or CRD).tw. (CAPD or CCPD or APD).tw. (predialysis or pre‐dialysis).tw. or/6‐18 and/5,19
EMBASE	exp sleep disorder/ exp sleep/ sleep$.tw. or/1‐3 exp renal replacement therapy/ kidney disease/ chronic kidney disease/ kidney failure/ chronic kidney failure/ mild renal impairment/ stage 1 kidney disease/ moderate renal impairment/ severe renal impairment/ end stage renal disease/ renal replacement therapy‐dependent renal disease/ kidney transplantation/ (haemodialysis or haemodialysis).tw. (hemofiltration or haemofiltration).tw. (hemodiafiltration or haemodiafiltration).tw. dialysis.tw. (CAPD or CCPD or APD).tw. (kidney disease* or renal disease* or kidney failure or renal failure).tw. (CKF or CKD or CRF or CRD).tw. (ESRF or ESKF or ESRD or ESKD).tw. (predialysis or pre‐dialysis).tw. ((kidney or renal) adj (transplant* or graft* or allograft*)).tw. or/5‐26 and/4,27

Potential source of bias	Assessment criteria
Random sequence generation Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence	Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimisation (minimisation may be implemented without a random element, and this is considered to be equivalent to being random).
	High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
	Unclear: Insufficient information about the sequence generation process to permit judgement.
Allocation concealment Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment	Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web‐based, and pharmacy‐controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).
	High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
	Unclear: Randomisation stated but no information on method used is available.
Blinding of participants and personnel Performance bias due to knowledge of the allocated interventions by participants and personnel during the study	Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
	High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
	Unclear: Insufficient information to permit judgement
Blinding of outcome assessment Detection bias due to knowledge of the allocated interventions by outcome assessors.	Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
	High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.
	Unclear: Insufficient information to permit judgement
Incomplete outcome data Attrition bias due to amount, nature or handling of incomplete outcome data.	Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.
	High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.
	Unclear: Insufficient information to permit judgement
Selective reporting Reporting bias due to selective outcome reporting	Low risk of bias: The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon).
	High risk of bias: Not all of the study’s pre‐specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. sub‐scales) that were not pre‐specified; one or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.
	Unclear: Insufficient information to permit judgement
Other bias Bias due to problems not covered elsewhere in the table	Low risk of bias: The study appears to be free of other sources of bias.
	High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data‐dependent process (including a formal‐stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.
	Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sleep quality	4	259	Mean Difference (IV, Random, 95% CI)	‐1.62 [‐5.03, 1.79]
2 Sleep latency	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3 Total sleep time	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
4 Sleep disturbance	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5 Hospitalisation	1		Risk Ratio (IV, Random, 95% CI)	Totals not selected
6 Anxiety	2	119	Std. Mean Difference (IV, Random, 95% CI)	0.11 [‐0.55, 0.77]
7 Pain	3	189	Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.67, 0.15]
8 Fatigue	2	119	Std. Mean Difference (IV, Random, 95% CI)	‐0.61 [‐2.09, 0.87]
9 Quality of life	2	138	Std. Mean Difference (IV, Random, 95% CI)	0.47 [‐0.09, 1.04]
10 Depression	2	108	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐1.27, 1.35]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sleep quality	5	165	Std. Mean Difference (IV, Random, 95% CI)	‐1.10 [‐2.26, 0.05]
2 Total sleep time	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3 Sleep efficiency	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
4 Sleep disturbance	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5 Anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6 Pain	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
7 Fatigue	2	107	Std. Mean Difference (IV, Random, 95% CI)	‐0.68 [‐1.07, ‐0.29]
8 Depression	2	46	Mean Difference (IV, Random, 95% CI)	‐9.05 [‐13.72, ‐4.39]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sleep quality	6	367	Mean Difference (IV, Random, 95% CI)	‐1.27 [‐2.13, ‐0.40]
2 Sleep latency	3	173	Mean Difference (IV, Random, 95% CI)	‐0.59 [‐0.92, ‐0.27]
3 Total sleep time	3	173	Mean Difference (IV, Random, 95% CI)	‐0.60 [‐1.12, ‐0.09]
4 Sleep disturbance	3	173	Mean Difference (IV, Random, 95% CI)	‐0.49 [‐1.16, 0.19]
5 Sleep interruption	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6 Sleep efficiency	2	107	Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.39, 0.03]
7 Death (all causes)	1		Risk Ratio (IV, Random, 95% CI)	Totals not selected
8 Fatigue	2	137	Mean Difference (IV, Random, 95% CI)	‐1.07 [‐1.67, ‐0.48]
9 Depression	2	137	Mean Difference (IV, Random, 95% CI)	‐3.65 [‐7.63, 0.33]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sleep quality	2	129	Mean Difference (IV, Random, 95% CI)	‐2.25 [‐6.33, 1.82]
2 Sleep latency	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3 Sleep interruption	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
4 Total sleep time	2	107	Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐0.73, 0.04]
5 Sleep disturbance	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6 Hospitalisation	1		Risk Ratio (IV, Random, 95% CI)	Totals not selected
7 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
8 Depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sleep quality	2	183	Std. Mean Difference (IV, Random, 95% CI)	‐0.65 [‐1.03, ‐0.26]
2 Sleep latency	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
3 Total sleep time	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
4 Sleep efficiency	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5 Death (all causes)	1		Risk Ratio (IV, Random, 95% CI)	Totals not selected
6 Anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
7 Quality of life	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
8 Depression	2	183	Std. Mean Difference (IV, Random, 95% CI)	‐0.76 [‐1.06, ‐0.46]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sleep quality	3	220	Std. Mean Difference (IV, Random, 95% CI)	‐0.50 [‐0.77, ‐0.23]
2 Sleep latency	2	135	Mean Difference (IV, Random, 95% CI)	‐0.50 [‐0.76, ‐0.23]
3 Total sleep time	2	135	Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.59, 0.05]
4 Sleep efficiency	2	135	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.66, 0.06]
5 Sleep disturbance	2	135	Mean Difference (IV, Random, 95% CI)	‐0.38 [‐0.52, ‐0.24]
6 Pain	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
7 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
8 Quality of life	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sleep quality	2	132	Mean Difference (IV, Random, 95% CI)	‐5.90 [‐6.56, ‐5.23]
2 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
1 Sleep latency	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
2 Sleep efficiency	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3 Depression	1	Mean Difference (IV, Random, 95% CI)	Totals not selected

Methods	Study design: parallel RCT Duration of study: 2009 Duration of follow‐up: 8 weeks
Participants	Country: Iran Setting: Single centre People on maintenance HD for > 3 months, aged > 20 years, and good compliance with dialysis treatment (not missing more than 2 dialysis sessions in the prior month) and had sleep problems (in regular sleeping time at night) Number: treatment group (14); control group (14) Mean age ± SD (years): treatment group (21.06 ± 50.71); control group (19.40 ± 53.00) Sex (M/F): all males Exclusion criteria: active infection or inflammation; autoimmune disorders; malignancy; psychiatric diseases; severe musculoskeletal disorders; poor controlled diabetes; uncontrolled heart failure or pulmonary diseases; hospitalisation during the prior month; using drugs that influence serum cytokines levels; vascular access in the lower extremity; BMI > 25 kg/m²
Interventions	Treatment group Aerobic training: 5 minutes of warm‐up and 10 to 30 minutes of stationary cycling, 3 times/week Control group Not reported
Outcomes	Sleep quality (PSQI)
Notes	Funding source: not reported Trial registration number: not reported Quoting from the paper: "This is a descriptive cross‐sectional case control study that was performed in a haemodialysis unit in Tehran, Iran, in 2009." However, both in the abstract and in the main body the study was reporting as the following "The participants were randomly divided into the training group and the control group (n = 14 in each group)." It was not completely clear if the study should be included: we contacted the author to ask clarification about this issue. We will perform sensitivity analysis with and without this study
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "They were randomly assigned into control and training groups." Comment: Sequence generation methods were not reported in sufficient detail to permit judgement
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported in sufficient detail to permit judgement
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Blinding of participants and investigators was not reported in sufficient detail to permit judgement. However, due to physical differences between interventions, awareness of treatment allocation was likely
Blinding of outcome assessment (detection bias)   All outcomes	High risk	Quote: "The Pittsburgh Sleep Quality Index and the Baecke questionnaire on physical activity were filled out for all participants." Comment: Sleep quality was assessed using the PSQI which was self‐administered by participants who could be aware of treatment assignment
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Not reported in sufficient detail to permit judgement
Selective reporting (reporting bias)	Low risk	Quote: "The global Pittsburgh Sleep Quality Index (PSQI) score was calculated at baseline and at the end of the study (after the 8th week)." Comment: Sleep outcomes was measured by PSQI questionnaire in all participants at end of treatment in a format that was extractable for meta‐analysis
Other bias	Unclear risk	Quote: "The participants’ characteristics are shown in Table 1." Comment: The baseline characteristics and the co‐interventions were not provided in sufficient detail to perform assess comparability between groups, the study funding source was not described. There was insufficient information to permit judgement

Methods	Study design: cross‐over study Duration of study: not reported Duration of follow‐up: 13.2 weeks (first phase)
Participants	Country: Canada Setting: not reported HD patients with moderate sleep apnoea Number: 15 Mean age ± SD: 58 ± 14 years Sex (M/F): 8/1 had completed protocol Exclusion criteria: not reported
Interventions	Treatment group HDF Control group HD
Outcomes	Sleep apnoea (polysomnogram) 24 hour BP Sleep‐related QoL (SF‐36; FOSQ; Quebec Sleep Questionnaire) ESS
Notes	Abstract‐only publication Outcome data could not be meta‐analysed Funding source: Gambro. NCT0038084
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Sequence generation methods were not reported in sufficient detail to permit judgement
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported in sufficient detail to permit judgement
Blinding of participants and personnel (performance bias)   All outcomes	High risk	Not reported. However, patients were randomised to HD or HDF. As these treatments are physically different, blinding of participants and investigators to treatment assignment was unlikely
Blinding of outcome assessment (detection bias)   All outcomes	Unclear risk	Not reported in sufficient detail to permit judgement
Incomplete outcome data (attrition bias)   All outcomes	High risk	> 10% loss of participants: overall 6/15 have completed the protocol to date. However, it was not clear whether there was a differential rate loss to follow‐up between the two study groups
Selective reporting (reporting bias)	Unclear risk	Unclear whether outcome was assessed for both intervention and control groups. Data were not extractable for the meta‐analysis
Other bias	High risk	Cross‐over study in which investigators did not report outcome measures appropriately for the crossover study design. Sponsor could be involved into the analysis

Methods	Study design: parallel, open‐label RCT Duration of study: not reported Duration of follow‐up: 4weeks
Participants	Country: China Setting: single centre Patients with ESKD (NKF‐K/DOQI diagnostic criteria) with sleep disturbance and having ≥ 23 points in the Self‐Rating Scale of Sleep and no mental disorder; willingness to participate in the study Number: treatment group 1 (42); treatment group 2 (40) Mean age ± SD (years): treatment group 1 (53.0 ± 15.1); treatment group 2 (60.4 ± 18.2) Men: 47.6% Exclusion criteria: not reported
Interventions	Treatment group 1 Lower extremity point massage (manual acupressure): once/day, and 20 to 30 seconds each time Treatment group 2 Estazolam (oral): 1 mg/day
Outcomes	Sleep quality Adverse events
Notes	Not English Trial number registration: not reported
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "82 cases of patients with End Stage Kidney Disease with sleep disorders were randomly divided into observation group and control group." Comment: Sequence generation methods were not reported in sufficient detail to make an adjudication
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported in sufficient detail to permit judgement
Blinding of participants and personnel (performance bias)   All outcomes	High risk	The study was an open‐label study. An open‐label study is considered as high risk of bias, Both participants and therapists were aware of the treatments assignment
Blinding of outcome assessment (detection bias)   All outcomes	High risk	Not reported. However, patients were randomised to lower extremity point massage or Estrazolam. As these treatments are physically different, blinding of participants and investigators to treatment assignment was unlikely
Incomplete outcome data (attrition bias)   All outcomes	Unclear risk	Not reported in sufficient detail to permit judgement
Selective reporting (reporting bias)	Low risk	Quote: "Self‐Rating Scale of Sleep (SRSS) was used to evaluate sleep conditions." Comment: Sleep outcomes was measured by the Self‐Rating Scale of Sleep at end of treatment in all participants in a format that was extractable for meta‐analysis
Other bias	Low risk	Study appears free of other biases

Study	Reason for exclusion
ACTIVE Dialysis 2015	Outcomes of interest not reported: extended weekly HD hours (≥ 24 hours) versus standard hours HD (12 to 15 hours); sleep quality was not a reported outcome
Cooper 2004	Wrong population: nasal CPAP or usual care among people with uncontrolled hypertension (not stated whether patients had CKD)
Deng 2017	Outcomes of interest not reported: iron sucrose versus normal saline for RLS; sleep quality was not a reported outcome

Methods	As reported in the abstract "This study was designed for a nonequivalent control group repeated measures quasi‐experimental study." Comment: Not clear if the study is a RCT
Participants	43 HD patients, 21 for the experimental group and 22 for the control group
Interventions	2 weeks pruritus intervention program was given to the experimental group only
Outcomes	Not reported
Notes	Not in English

Trial name or title	Effectiveness of self care management support intervention on medication adherence, pruritus severity, sleep quality and quality of life in patients with chronic kidney disease associated pruritus
Methods	RCT evaluating the effectiveness of a self‐care management support intervention on medication adherence, pruritus severity, sleep quality, and quality of life in patients with CKD‐associated pruritus Sample size: 210 Phase 4 Estimated duration: 12 months Status: not yet recruiting
Participants	Country: India Male and female patients with CKD; aged 18 to 70 years Inclusion criteria 1.Have mild, moderate and severe pruritus 2.Are expected to continue treatment as out patient 3.Can read and comprehend Tamil, English, and Hindi 4.Give consent to participate in the study Exclusion criteria: cognitive, hearing and speech disabilities; serious illness and unable to follow the instructions; undergoing HD; history of dermatologic diseases such as psoriasis, various form of dermatitis, lichen simplex and dermatophytosis; unwilling to comply with the study protocol, mode of administration and duration of treatment; sick during the study period
Interventions	Treatment group Self‐care management support intervention Control group Standard care
Outcomes	Increase in medication adherence Reduction of pruritus severity Increase in sleep quality Improve in QoL
Starting date	02/01/2017. Described on the Clinical Trials Registry ‐ India as "not recruiting". The trial registration record has not been updated since 27 January 2016. Emailed investigator (Professor Anandha Ruby) at the College of Nursing, Christian Medical College, Vellore to request an update on the trial status on 17 April 2018. Reply not received.
Contact information	[email protected]
Notes	Funding source: Research institution and hospital

PERMALINK

Interventions for improving sleep quality in people with chronic kidney disease

Patrizia Natale

Marinella Ruospo

Valeria M Saglimbene

Suetonia C Palmer

Giovanni FM Strippoli

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Inclusion criteria

Exclusion criteria

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Cluster‐randomised studies

Cross‐over studies

Studies with more than two treatment arms

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

'Summary of Findings' tables

Results

Description of studies

Results of the search

1.

Included studies

Sleep interventions

1. TIDieR framework of intervention descriptions for included studies.

Excluded studies

Risk of bias in included studies

2.

3.

Allocation

Random sequence generation

Allocation concealment

Blinding

Performance bias

Detection bias

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Summary of findings for the main comparison. Summary of findings: relaxation versus control for sleep outcomes in people with chronic kidney disease (CKD).

Summary of findings 2. Summary of findings: exercise versus control.

Summary of findings 3. Summary of findings: acupressure versus control.

Relaxation versus control

1.1. Analysis.

1.2. Analysis.

1.3. Analysis.

Trial name or title	Cardiovascular risk and mortality in end‐stage renal disease patients undergoing dialysis: sleep study, pulmonary function, respiratory mechanics, upper airway collapsibility, autonomic nervous activity, depression, anxiety, stress and quality of life: a prospective, double blind, randomised controlled clinical trial
Methods	RCT Sample size: 57 Phase 4 Estimated duration: not reported Status of study: not yet recruiting
Participants	Setting: Brazil Male or female patients aged 18 to 80 years; CKD; candidate for kidney transplant with indication for dialysis; cognitive level sufficient for understanding the procedures and following the instructions; and agreement to participate by signing a statement of informed consent Exclusion criteria: craniofacial abnormalities; undergoing active treatment of sleep apnoea; active malignancy; active alcohol and/or drug abuse; and dementia or treatment‐refractory psychiatric diseases leading to an inability to provide informed consent
Interventions	Diurnal HD Nocturnal HD Control group
Outcomes	Sleep parameters Pulmonary function Respiratory mechanics Upper airway collapsibility Autonomic nervous activity Depression Anxiety Stress QoL
Starting date	2 April 2012
Contact information	[email protected]. Contacted the investigator by email on 17 April 2018 to request an update on the trial status. Update not received. The trial is reported as having commenced on 2 April 2012. Protocol published in 2013. No results found
Notes	Funding source: The Sleep Laboratory receives funding from the Nove de Julho University (Brazil) and research projects approved by the Brazilian fostering agencies Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo (local acronym FAPESP; protocol no. 2003/01810‐4) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (local acronym CNPq; Research Productivity modality; process no. 307618/2010‐2)

Trial name or title	Effects of cool dialysate on sleep quality in patients undergoing haemodialysis
Methods	As reported in the study protocol: "The study was a randomised single blind controlled clinical trial, done in the before and after treatment method"
Participants	Country: Iran The study will be done on 13 patients in the intervention group and 13 patients in the control group. Male and female patients; consent for participation in the study; age older than 18 years and maximum 75 years; suffering from vision, hearing loss; not suffering from clear mental disorders and severe emotional mood disorders, which prevent effective communication; patients with CKD (patients who 6 months have passed since their dialysis); patients receiving dialysis treatment three times a week and each session for 4 hours; not suffering from endocrine disorders (such as hypothyroidism, hyperparathyroidism); patients who have received score higher than 5 PSQI; patients with haemoglobin levels are greater than 8 mg/dl; lack of debilitating diseases and disorders such as severe chronic heart, respiratory, hepatic, history of seizures and severe neuropathy based on medical records and patient history; lack of psychiatric disorders (schizophrenia, anxiety, depression) or dementia or stay in psychiatric wards because of the items listed; no history of kidney transplant Exclusion criteria: develop acute complications during HD (disequilibrium syndrome, embolism, dysrhythmia, cardiac, respiratory arrest, coma); discontinued dialysis for any reason; referred for kidney transplants (patients who get kidney transplantation during the study); death; cannot tolerate cold dialysis; unwillingness to continue to participate in the study
Interventions	Treatment group HD with cold dialysis solution with temperature (35.5°C) for 4 weeks control group HD with dialysis solution with standard temperature (37°C), for 4 weeks
Outcomes	Not reported
Starting date	22 September 2016 (expected recruitment end date 21 November 2016)
Contact information	[email protected]
Notes	Contacted author team ([email protected]) to request an update on the trial status. Emailed 16 April 2018. No reply received

Trial name or title	Effects of transcranial direct‐current stimulation (tDCS) on the treatment of depressive and anxiety symptoms and improve quality of sleep in patients with chronic renal diseases on dialysis‐ a randomised double‐blind placebo controlled trial
Methods	RCT
Participants	Country: Iran Males and females of two "anxiety‐depression" and "sleep disorders" in HD Exclusion criteria: history of head trauma in patient; history of epilepsy in patients or their families; past history of bipolar or psychotic disease; acute suicidal ideas; consumption of neuroleptics during the study; addiction to drugs or alcohol; pregnancy; having metal prosthesis or implant; severe anorexia; past history of neurologic dx., serious medical illness
Interventions	tDCS.F3‐Fp2 protocol Placebo
Outcomes	Anxiety Depression Sleep quality
Starting date	20‐03‐2015
Contact information	[email protected]
Notes	Funding source: Mazandaran Research Center of Psychiatry and Behavioral Sciences

Trial name or title	Symptom management program for haemodialysis patients
Methods	RCT
Participants	Country: USA Males and females on HD; aged ≥ 18 years; on HD 3 times/week; received HD for ≥ 6 months; read and write English; have telephone service Exclusion criteria: history of dementia; AIDS; active cancer; inability to give informed consent
Interventions	Treatment group Self‐management strategies Control group Dietary information
Outcomes	Decrease symptom burden The study aims are: to compare the differences between the self‐management intervention and control group on the following outcomes: decreased symptoms: itching, tiredness, numbness, sleep disturbance (difficulty falling asleep & difficulty staying asleep); adherence to treatment diary Improved social functioning, physical functioning and emotional status Feasibility of implementing self‐management intervention To evaluate the feasibility of implementing the self‐management intervention for a larger randomised controlled study treatment delivered (number of interventions sessions delivered and strategies used); treatment receipts (understanding of strategies); and treatment enactment (reported perception of usefulness of the strategies)
Starting date	September 2011
Contact information	Francess Danquah, The University of Texas Health Science Center, Houston
Notes	Funding source: The University of Texas Health Science Center, Houston

Trial name or title	A randomised, prospective, double blind, placebo‐controlled trial of two different doses of oral melatonin supplements in chronic kidney disease (CKD)‐associated sleep disorders
Methods	RCT
Participants	Country: USA Males and females aged 18 to 85 years with CKD or SKD with eGFR < 30 mL/min; receiving HD for > 3 months; normal healthy controls must be without a known history of CKD and be willing to have formal polysomnography test and plasma melatonin measurements Exclusion criteria: outpatient HD for < 3 months; eGFR > 30 mL/min; receiving beta blocker therapy within one month of randomisation; receiving nifedipine therapy within one month randomisation; on PD; chronic home oxygen supplementation; receiving chronic home CPAP therapy; actively receiving outpatient sleep medications; diabetic gastroparesis unresponsive to medication; known pregnancy or unwilling to use contraception during the course of the study; functioning kidney allograft; currently receiving long‐term immunosuppressive therapy; receiving low dose prednisone (≤ 10 mg/day); unable to give informed consent
Interventions	Treatment group Melatonin (1mg or 3 mg daily) Control group Placebo
Outcomes	2 groups will be compared to see who group achieved a 25% reduction in sleep latency or 25% increase in total sleep time at the end of 60 days. Using the PSQI questionnaire as the index to measure quality of sleep and sleep patterns
Starting date	December 2012
Contact information	Southeast Renal Research Institute
Notes	Funding source: Southeast Renal Research Institute

Trial name or title	End‐stage renal disease intra‐dialysis lifestyle education study
Methods	RCT
Participants	Country: USA Males and females aged ≥ 18 years on maintenance HD for ≥ 3 months; adequately dialysed (Kt/V ≥ 1.2 measured within last 3 months); expected to remain in present HD shift for next 4 months and expected to remain on HD for at least 6 months Exclusion criteria: acute or chronic medical conditions that would make intra‐dialysis yoga potentially hazardous; unstable cardiac disease e.g. angina, life threatening arrhythmia; chronic lung disease that prevents gentle exercise or deep breathing exercises; active cerebrovascular disease; major depression; chronic symptoms of nausea, vomiting, or diarrhoea; current participation in exercise or mind body program/practice; cognitive impairment (MMSE ≤ 24) measured at baseline testing visit
Interventions	Intradialysis‐yoga Educational program
Outcomes	QoL Fatigue Emotional states Depression Patient satisfaction Sleep quality Self‐efficacy for self‐management Physical performance Blood pressure Endothelial function Arterial stiffness Cardiovagal and sympathoneural functioning including baroreflex and heart rate variability
Starting date	July 2015
Contact information	Gurjeet Birdee, Vanderbilt University Medical Center
Notes	Funding source. Vanderbilt University Medical Center

Trial name or title	Treatment of obstructive sleep apnoea in chronic kidney disease
Methods	RCT
Participants	Country: Canada Males and females with CKD stage 3 or 4; OSA (RDI > 15) and nocturnal hypoxaemia (SaO₂ < 90% for > 12% of night) Exclusion criteria: failure to meet inclusion criteria; current therapy with CPAP or supplemental oxygen; severe daytime sleepiness reflected by an ESS > 15; any driver who holds a commercial drivers' license or who reports a recent history (past 6 months) of a road traffic accident; severe nocturnal hypoxaemia reflected by mean SaO₂ < 80% during level 3 sleep testing; daytime hypoxaemia reflected by partial pressure of PaO₂ < 60 mmHg during wakefulness; hypoventilation reflected by PaCO₂ > 45 mmHg during wakefulness; central sleep apnoea that accounts for > 50% of the estimated RDI; unable to provide informed consent
Interventions	CPAP therapy Placebo
Outcomes	eGFR ACR
Starting date	June 2015
Contact information	Patrick Hanly, University of Calgary
Notes	Funding source: University of Calgary

Trial name or title	Effect of continuous positive airway pressure on albuminuria in patients with diabetic nephropathy and obstructive sleep apnoea
Methods	RCT
Participants	Country: Spain Males and females aged 18 to 80 years; Overweight or obesity (BMI ≥25 kg/m²); previous diagnosis of type 2 diabetes, fulfilling at least one of the following criteria: 1) current treatment with oral antidiabetic drugs and/or insulin; 2) a fasting glucose value above 126 mg/dl on at least 2 occasions; 3) blood glucose level at 2 hours after an oral glucose tolerance test is equal to or more than 200 mg/dL; or 4) a HbA1c level > 6.5%; clinical diagnosis of diabetic kidney disease, with a urinary ACR > 30 mg/g and an eGFR > 20 mL/min/1.73 m²; treatment with stable doses of ACEi, ARB or anti‐aldosterone agents in the last 4 weeks Exclusion criteria: nondiabetic kidney disease (confirmed by biopsy); dialysis for AKI within the 6 previous months; evidence in the clinic history of relevant bilateral stenosis of renal artery (> 75%); Urinary ACR > 3000 mg/g, at the baseline visit; SBP ≥ 180 mmHg or DBP ≥ 110 mmHg at the baseline visit; stroke, transient Ischaemic attack, acute coronary syndrome, or hospitalisation for heart failure worsening, within the previous 30 days; professional drivers, risk profession or respiratory failure; severe daytime sleepiness (ESS > 18); concomitant treatment with high doses of acetylsalicylic acid (> 500 mg/day) or continuous treatment with NSAIDs; previous treatment with CPAP; participation in another clinical study within the 30 days prior to randomisation
Interventions	CPAP therapy Pharmacological treatment
Outcomes	Albuminuria levels HbA1c HOMA index QUICKI index Cholesterol levels (total cholesterol, LDL‐cholesterol, HDL‐cholesterol and triglycerides) C‐reactive protein HRQoL assessed by the SF‐12 questionnaire HRQoL assessed by the EuroQoL questionnaire Physical activity of patients with diabetic kidney disease and OSA Plasma levels of biomarker of inflammation (interleukin (IL)‐1beta, IL‐6, IL‐8 and tumour necrosis factor‐alpha) Plasma levels of 8‐isoprostane Plasma levels of endothelin, intercellular adhesion molecule‐1 (ICAM‐1) and vascular cell adhesion molecule‐1 Plasma levels of appetite‐regulating hormones (leptin and adiponectin) Identify the CPAP‐responder subgroup of OSA patients with diabetic kidney disease in those the CPAP treatment achieve an albuminuria reduction > 20% from baseline
Starting date	June 2016
Contact information	Francisco Garcia‐Rio, Hospital Universitario La Paz
Notes	Funding source: Hospital Universitario La Paz

Trial name or title	A cross‐sectional, randomised‐controlled study to investigate the effect of HDF in sleep apnoea
Methods	Cross‐over study
Participants	Males and females aged ≥ 18 years receiving maintenance HD for > 3 months; able to provide informed consent; satisfactory written and spoken English language skills Exclusion criteria: acute dialysis or acutely unwell patients; home dialysis patients; unable to participate in the study in the opinion of the participant's primary Nephrologist or due to language barrier or cognitive impairment; already on treatment for sleep‐disordered breathing
Interventions	HD HDF
Outcomes	Objective sleep quality (total sleep time, sleep efficiency, types of sleep (% of non‐rapid eye movement (NREM) and rapid eye movement (REM)), arousal (episodes/hr), apnoea‐hypopnoea index (AHI), and oxygen saturation) Subjective sleep quality (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction) Overall QoL (physical and social functioning, physical and emotional role limitations, physical pain, mental health, vitality, general health perceptions plus the burden of kidney disease, and symptoms/problems commonly associated with kidney disease) The different concentration of inflammatory biomarker (CRP, β2M, TNF‐α, IL‐6 and IL‐8)
Starting date	October 2016
Contact information	Ginger Chu, John Hunter Hospital
Notes	Funding source: John Hunter Hospital

Trial name or title	Auricular acupressure for insomnia in haemodialysis patients: study protocol for a randomised controlled trial
Methods	RCT
Participants	Patients receiving regular HD treatment for more than 3 months and less than 10 years; gender: both; country: China Inclusion criteria: 1. Males and females aged 18 to 75 years on regular HD (two or three sessions every week, 4 h each session, total weekly dialysis period ≥10 h) for between 3 months and 10 years; insomnia diagnosed according to DSM‐5; baseline global PSQI score > 7; informed consent provided Exclusion criteria: presence of comorbidities including cancer, congestive heart failure, connective tissue disease and haematological diseases; inadequately dialyzed, indicated by Kt/V < 1.20; presence of severe physical symptoms, such as bone pain, itchy skin, sleep apnoea and restless legs, which are obviously causative of insomnia; and exhaustion caused by severe anaemia (Hb < 60 g/L) or malnutrition (serum albumin < 30 g/L)
Interventions	Auricular acupressure on either active points Control points (points irrelevant to insomnia management)
Outcomes	Sleep quality Changes in PSQI scores (including global score and scores of each of the seven domains) at the end of treatment and at each follow‐up visit compared with baseline
Starting date	December 2016
Contact information	[email protected]; [email protected].
Notes	TCM Research Project of Guangdong Provincial Hospital of Chinese Medicine (YN2015MS25), and supported by MOST/SATCM of the People' s Republic of China grant 2013BAI02B04 and the State Administration of Traditional Chinese Medicine, P.R. China (No. 201007005). The sponsor will not have a role in the design, conduct or interpretation of the study, or in any decision to submit the manuscript for publication. NCT03015766