Interventions for fatigue in people with kidney failure requiring dialysis

Patrizia Natale; Angela Ju; Giovanni FM Strippoli; Jonathan C Craig; Valeria M Saglimbene; Mark L Unruh; Giovanni Stallone; Allison Jaure

doi:10.1002/14651858.CD013074.pub2

. 2023 Aug 31;2023(8):CD013074. doi: 10.1002/14651858.CD013074.pub2

Interventions for fatigue in people with kidney failure requiring dialysis

Patrizia Natale ^1,^2,^3,^✉, Angela Ju ², Giovanni FM Strippoli ^1,^2,⁴, Jonathan C Craig ^4,⁵, Valeria M Saglimbene ^2,⁶, Mark L Unruh ⁷, Giovanni Stallone ³, Allison Jaure ^2,⁸

Editor: Cochrane Kidney and Transplant Group

PMCID: PMC10468823 PMID: 37651553

Abstract

Background

Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD).

Objectives

We aimed to evaluate the effects of pharmacological and non‐pharmacological interventions on fatigue in people with kidney failure receiving dialysis, including HD and peritoneal dialysis (PD), including any setting and frequency of the dialysis treatment.

Search methods

We searched the Cochrane Kidney and Transplant Register of Studies up to 18 October 2022 through contact 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 Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria

Studies evaluating pharmacological and non‐pharmacological interventions affecting levels of fatigue or fatigue‐related outcomes in people receiving dialysis were included. Studies were eligible if fatigue or fatigue‐related outcomes were reported as a primary or secondary outcome. Any mode, frequency, prescription, and duration of therapy were considered.

Data collection and analysis

Three authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects meta‐analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI) or standardised MD (SMD) if different scales were used. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results

Ninety‐four studies involving 8191 randomised participants were eligible. Pharmacological and non‐pharmacological interventions were compared either to placebo or control, or to another pharmacological or non‐pharmacological intervention. In the majority of domains, risks of bias in the included studies were unclear or high.

In low certainty evidence, when compared to control, exercise may improve fatigue (4 studies, 217 participants (Iowa Fatigue Scale, Modified Fatigue Impact Scale, Piper Fatigue Scale (PFS), or Haemodialysis‐Related Fatigue scale score): SMD ‐1.18, 95% CI ‐2.04 to ‐0.31; I² = 87%) in HD.

In low certainty evidence, when compared to placebo or standard care, aromatherapy may improve fatigue (7 studies, 542 participants (Fatigue Severity Scale (FSS), Rhoten Fatigue Scale (RFS), PFS or Brief Fatigue Inventory score): SMD ‐1.23, 95% CI ‐1.96 to ‐0.50; I² = 93%) in HD.

In low certainty evidence, when compared to no intervention, massage may improve fatigue (7 studies, 657 participants (FSS, RFS, PFS or Visual Analogue Scale (VAS) score): SMD ‐1.06, 95% CI ‐1.47, ‐0.65; I² = 81%) and increase energy (2 studies, 152 participants (VAS score): MD 4.87, 95% CI 1.69 to 8.06, I² = 59%) in HD.

In low certainty evidence, when compared to placebo or control, acupressure may reduce fatigue (6 studies, 459 participants (PFS score, revised PFS, or Fatigue Index): SMD ‐0.64, 95% CI ‐1.03 to ‐0.25; I² = 75%) in HD.

A wide range of heterogenous interventions and fatigue‐related outcomes were reported for exercise, aromatherapy, massage and acupressure, preventing our capability to pool and analyse the data.

Due to the paucity of studies, the effects of pharmacological and other non‐pharmacological interventions on fatigue or fatigue‐related outcomes, including non‐physiological neutral amino acid, relaxation with or without music therapy, meditation, exercise with nandrolone, nutritional supplementation, cognitive‐behavioural therapy, ESAs, frequent HD sections, home blood pressure monitoring, blood flow rate reduction, serotonin reuptake inhibitor, beta‐blockers, anabolic steroids, glucose‐enriched dialysate, or light therapy, were very uncertain.

Authors' conclusions

Exercise, aromatherapy, massage and acupressure may improve fatigue compared to placebo, standard care or no intervention. Pharmacological and other non‐pharmacological interventions had uncertain effects on fatigue or fatigue‐related outcomes in people receiving dialysis. Future adequately powered, high‐quality studies are likely to change the estimated effects of interventions for fatigue and fatigue‐related outcomes in people receiving dialysis.

Keywords: Humans, Cardiovascular Diseases, Fatigue, Fatigue/etiology, Fatigue/therapy, Kidney, Quality of Life, Randomized Controlled Trials as Topic, Renal Dialysis, Renal Insufficiency

Plain language summary

Are interventions for fatigue effective among people with kidney failure requiring dialysis?

What is the issue?

Fatigue is a frequent and debilitating symptom that can limit life participation in people receiving dialysis. Fatigue is linked to impaired quality of life, cardiovascular disease, death and depression in people on dialysis. Several potential interventions, including drugs or other non‐pharmacological treatments (e.g. exercise, diet, massage, aromatherapy, acupressure), have been evaluated for their effect on fatigue in people on dialysis.

What did we do?

We evaluated whether drugs or other non‐pharmacological interventions are beneficial for adults and children receiving haemodialysis or peritoneal dialysis to manage fatigue. We evaluated all clinical studies available and summarised the results. We evaluated how certain we could be about the evidence related to interventions for fatigue using a system called "GRADE".

What did we find?

Ninety‐four studies involving 8191 randomised participants were available. Patients in the studies were given a drug, non‐pharmacological intervention, standard care or a sugar pill (placebo). The treatment they received was decided by random chance. The studies were generally short‐term (over a few months). There were no studies in children. Exercise, aromatherapy, massage and acupressure improve fatigue compared to placebo or standard care. Drugs or other non‐pharmacological interventions have uncertain effects on fatigue in people on dialysis.

Conclusions

Exercise, aromatherapy, massage and acupressure improve fatigue compared to placebo or standard care. It remains uncertain whether drugs or other non‐pharmacological interventions have any impact on fatigue in people on dialysis when compared to a sugar pill, standard care or other treatments for fatigue.

Summary of findings

Summary of findings 1. Exercise versus control for people receiving dialysis.

Exercise versus control for people receiving dialysis
Patient or population: people receiving dialysis Settings: multinational Intervention: exercise Comparison: control
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (RCTs)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Exercise
Fatigue (IFS, MFI, PIPER, or HD‐related fatigue scale) median follow‐up: 2.7 months	The mean score for fatigue ranged across control groups from 29.75 to 81.17 (IFS, MFI, PFS, or HD related fatigue scale)	The standardised mean of fatigue in the intervention group was 1.18 lower than the control group (95% CI 2.04 lower to 0.31lower)	‐‐	217 (4)	⊕⊕⊝⊝ low^1,2,3	Exercise may improve fatigue compared to control in people undergoing HD
Weakness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Energy	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Tiredness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Exhaustion	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Asthenia	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
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% CI) 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; IFS: Iowa Fatigue Scale; MFI: Multidimensional Fatigue Inventory; PFS: Piper Fatigue Scale; HD: haemodialysis.
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.

Aromatherapy versus placebo or standard care for people receiving dialysis
Patient or population: people receiving dialysis Settings: multinational Intervention: aromatherapy Comparison: placebo or standard care
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (RCTs)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo or standard care	Aromatherapy
Fatigue (PIPER, BFI, FSS, RFS) median follow‐up: 0.9 months	The mean score for fatigue ranged across control groups from 6.21 to 45.1 (PFS, BFI, FSS, RFS)	The mean fatigue in the intervention group was 1.23 lower than the control group (95% CI 1.96 lower to 0.50 lower)	‐‐	542 (7)	⊕⊕⊝⊝ low^1,2,3	Aromatherapy may improve fatigue compared to placebo or standard care in people undergoing HD
Weakness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Energy	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Tiredness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Exhaustion	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Asthenia	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
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% CI) 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; PFS: Piper Fatigue Scale; BFI: Brief Fatigue Inventory; FSS: Fatigue Severity Scale; RFS: Rhoten fatigue scale; HD: haemodialysis.
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.

Massage versus no intervention for people receiving dialysis
Patient or population: people receiving dialysis Settings: multinational Intervention: massage Comparison: no intervention
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (RCTs)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	No intervention	Massage
Fatigue (PFS, FSS, VAS) median follow‐up: 0.9 months	The mean score for fatigue ranged across control groups from 5.17 to 80.74 (PFS, FSS, or VAS scores)	The mean fatigue in the intervention group was 1.06 lower than the control group (95% CI 1.47 lower to 0.65 lower)	‐‐	657 (7)	⊕⊕⊝⊝ low^1,2,3	Massage may improve fatigue compared to not intervention in people undergoing HD
Weakness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Energy (VAS) median follow‐up: 0.9 months	The mean score for energy ranged across control groups from 18.93 to 21.97 (VAS)	The mean energy in the intervention group was 4.87 more than the control group (95% CI 1.69 more to 8.06more)	‐‐	152 (2)	⊕⊕⊝⊝ low^1,3	Massage may increase energy compared to not intervention in people undergoing HD
Tiredness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Exhaustion	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Asthenia	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
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% CI) 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; PFS: Piper Fatigue Scale; FSS: Fatigue Severity Scale; VAS: Visual Analogue Scale; HD: haemodialysis.
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.

Acupressure versus placebo or control for people receiving dialysis
Patient or population: people receiving dialysis Settings: multinational Intervention: acupressure Comparison: placebo or control
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No. of participants (RCTs)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Placebo or control	Acupressure
Fatigue [PFS, revised PFS, FI] median follow‐up: 1 month	The mean score for fatigue ranged across control groups from 4.7 to 125.1 (PFS, revised PFS, FI)	The standardised mean of fatigue in the intervention group was 0.64 lower than the control group (95% CI 1.03 lower to 0.25 lower)	‐‐	459 (6)	⊕⊕⊝⊝ low^1,2,3	Acupressure may reduce fatigue compared to placebo or control in people undergoing HD
Weakness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Energy	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Tiredness	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Exhaustion	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
Asthenia	Not reported	Not reported	‐‐	‐‐	‐‐	No studies reported this outcome
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% CI) 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; PFS: Piper Fatigue Scale; revised PFS: revised Piper Fatigue Scale; FI: Fatigue Index; HD: haemodialysis.
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.

Database	Search terms
CENTRAL	MeSH descriptor: [Mental Fatigue] this term only fatigue:ti,ab,kw (Word variations have been searched) "lassitude":ti,ab,kw (Word variations have been searched) tired or tiredness:ti,ab,kw (Word variations have been searched) weary or weariness:ti,ab,kw (Word variations have been searched) exhaustion:ti,ab,kw (Word variations have been searched) {or #1‐#6} MeSH descriptor: [Renal Dialysis] explode all trees MeSH descriptor: [Hemofiltration] explode all trees MeSH descriptor: [Kidney Failure, Chronic] this term only "dialysis":ti,ab,kw (Word variations have been searched) hemodialysis 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) "end‐stage kidney" or "end‐stage renal" or "endstage kidney" or "endstage renal":ti,ab,kw (Word variations have been searched) eskd or eskf or esrd or esrf:ti,ab,kw (Word variations have been searched) MeSH descriptor: [Peritoneal Dialysis] explode all trees peritoneal dialysis:ti.ab.kw (Word variations have been searched) (CAPD or CCPD or APD): ti,ab,kw (Word variations have been searched) {or #8‐#19} {and #7, #20}
MEDLINE	Fatigue/ fatigue.tw. lassitude.tw. (tiredness or tired).tw. (weary or weariness).tw. exhaustion.tw weakness.tw or/1‐7 Renal Replacement Therapy/ Renal Dialysis/ Hemodiafiltration/ Hemodialysis, home/ exp Hemofiltration/ dialysis.tw. (hemodialysis or haemodialysis).tw. (hemofiltration or haemofiltration).tw. (hemodiafiltration or haemodiafiltration).tw. exp Peritoneal Dialysis/ peritoneal dialysis.tw (CAPD or CCPD or APD).tw. or/9‐20 and/8,21
EMBASE	fatigue/ or exhaustion/ or lassitude/ fatigue.tw. lassitude.tw. (tiredness or tired).tw. (weary or weariness).tw. exhaustion.tw. weakness.tw. or/1‐7 exp renal replacement therapy/ extended daily dialysis/ hemodialysis/ home dialysis/ hemofiltration/ hemodiafiltration/ dialysis.tw. (hemodialysis or haemodialysis).tw. (hemofiltration or haemofiltration).tw. (hemodiafiltration or haemodiafiltration).tw. renal replacement therapy‐dependent renal disease/ Peritoneal Dialysis/ Continuous Ambulatory Peritoneal Dialysis/ peritoneal dialysis.tw. (CAPD or CCPD or APD).tw. peritoneal dialysis fluid/ peritoneal dialysis catheter/ or/9‐25 and/8,26

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	Definition
ADL: Activities of Daily Living	Eight questions: they range from 0, meaning they have no difficulty, to 2, which means they can not do it even with help
Asthenia	Scored as slight if fatigue appeared at less than 60 sec of exercise A and at less than 30 ascents and descents during exercise B, intense at less than 15 sec of exercise A and at less than 10 ascents and descents of exercise B. Moderate degree of asthenia was between the two extremes
BAI: Beck Anxiety Inventory	21 questions about how the subject has been feeling in the last week expressed as common symptoms of anxiety. Each question has the same set of four possible answer choices (0 (never) and 3 (critically)). The total score ranges from 0 to 63 points, with higher scores meaning more anxiety
BDI: Beck Depression Inventory	21‐question multiple‐choice self‐report inventory for measuring the severity of depression. The total score ranges from 0 to 63 points, with higher total scores indicating more severe depressive symptoms
BFI: Brief Fatigue Inventory	Checklist with 10 questions so that the first question asks if the respondents had felt fatigue over the last week. Other questions ask about level of fatigue felt by the respondent at the time, normal and highest level of fatigue over the past 24 h, and the effects of fatigue on their general activity, mood, ability to walk, communicate with others, and enjoying life. The questions are designed based on an 11‐point scale (0‐10) so that 'zero' is the best possible condition and 10 is the worst. Eventually, total fatigue level of the patient is calculated as the total score of the questions 2‐10 (9 questions) divided by nine
Bouchard's PAL	Activities are categorized into 9 levels, with 1 as the least intense (0.26 kcal/kg/15 min) and 9 as the highest intensity (1.96 kcal/kg/15 min
CES‐D: Center for Epidemiologic Studies Depression Scale	Scores ≥ 16 indicate clinically meaningful symptoms
COPM: Canadian Occupational Performance Measure	Individuals asked to rate, on a 10‐point Likert scale, his/her performance in each of three self‐selected priority activities of everyday living. Higher scores out of 10 indicate better performance/satisfaction with performance
Cramps	Frequency, severity, site, and duration of the cramps were recorded and scored as slight when they lasted less than 5 mm; moderate 5 to 10 mm; intense more than 10 mm
ENRICH questionnaire	One of these 10 items assessed sexual satisfaction. The total score was the sum of positive and negative items and ranged from 10 to 50
EQ‐5D: EuroQol‐5 dimension health questionnaire	Number 1 indicates the best state of health (perfect health) and 0 the worst state of health (death)
Fatigue Management Questionnaire	Individuals asked to rate various aspects of their fatigue management (e.g. overall impact on life participation; satisfaction; self‐efficacy), out of 10, on 5‐point Likert‐scale questions. Scores are then summed and averaged for each of two subscales (Performance Subscale and Satisfaction Subscale), with higher scores out of 10 indicating better fatigue management)
Fatigue score	HD patients fatigue scale developed by Chung and Kao: fatigue was measured on a five‐point rating scale inquiring about 25 essential symptoms of fatigue, with 5 indicating the most fatigue and 1 the least
FI: Fatigue Index questionnaire	Each domain rated from 1 to 5, recorded hourly during the entire study period on a fatigue intensity form as follows: 0, none; 1, mild (noticeable but without effect); 2, moderate (felt sluggish); 3, severe (required rest); or 4, overwhelming (slept). The maximal fatigue score recorded within 6 hours after dialysis or at similar time periods on non‐dialysis days (baseline) was used to rate the level of fatigue for the period in question
FSS: Fatigue Severity Score	Nine questions, which questions 1–4 and 6 focus on the quality of fatigue, questions 5–7 and 9 are about physical and mental fatigue and their effects on the social life of individuals, and question 8 measures the severity of fatigue. The score range for each question is between 1 and 7, with a score of 1 for absolute disagreement and a score of 7 for absolute agreement. The total score range of the questionnaire is between 7 and 63, so a score of 36 or higher is an indication of fatigue. Hence, higher scores are indicative of higher fatigue
GAD: Generalized Anxiety Disorder	Brief 7‐item self‐report scale on the basis of Diagnostic and Statistical Manual of Mental Disorders‐IV criteria for generalized anxiety disorder, with items scored from 0 (not at all) to 3 (nearly every day)
HADS: Hospital Anxiety and Depression Scale	14‐item self‐report screening scale that comprises 7 items for each of the Anxiety and Depression subscales. The questionnaire assesses symptoms over the preceding week. Each item is scored on a 4‐point Likert scale, giving maximum subscale scores of 21 for depression and anxiety
HFS: Haemodialysis Fatigue scale	26 items; it used a 4‐point scoring, from rarely or never happening) to often happening (3). A higher score means worse fatigue
HSS: Haemodialysis Stressor Scale	5‐point Likert‐type scale (always: 5,mostly: 4, sometimes: 3, rarely: 2, and never). The Physiological Hemodialysis Stressor subscale score ranges between 6 and 30, and the Psychosocial Hemodialysis Stressor subscale score varies between 23 and 115. The total HSS score can range from 29 to 145. The higher the scores, the higher the perceived stress levels are
Health Utilities Index	This is an interval scale that can vary in theory between 0 (death) and 1 (perfect health)
IFS: Iowa Fatigue Scale	Eleven questions determined the level of fatigue (four questions were in cognitive aspects, a pair of questions were about physical fatigue, three questions were about energy rate and pair of questions were about work output). Fatigue score range was from 11 to 55. Score indicated the minimum fatigue rate, and 55 was maximum rate
IPOS‐Renal: Integrated Palliative Outcome Scale‐Renal	All symptoms cores are reported on a 0 to 4 scale (0=not at all, 1=slightly, 2=moderately, 3=severely, 4=overwhelmingly bothered) and indicate the effect of the symptom on the respondent over the past week
ItchyQoL: QoL questionnaire fo patients with pruritus	Consists of 27 questions. The answers to each question consist of five levels: never, rarely, sometimes, often, and always, which are scored from 1 to 5, respectively
KDQ: Kidney Disease Questionnaire	Follows a 7‐point Likert‐type scale (7 = no problem, 1 = a severe problem) with higher scores indicating better health‐related quality of life. A clinically meaningful difference in KDQ score was a 0.5 point change, and a mean change of 1.0 represented a large clinical change
KDQOL‐SF: Kidney Disease Quality of Life‐Short Form	43 items related to the quality of life in relation to kidney patients, with 36 items related to general health. Specific dimensions of the questionnaire include: symptoms and the list of problems (12 items), the effect of kidney disease (8 items), the burden of kidney disease (4 items), job performance (2 items), cognitive function (3 items), the quality of social relationships (3 items), sexual function (2 items), sleep (4 items), social support (2 items), medical) staff support (2 items), and general health status (1 item). 22 Different questions have different answer options. As to scoring, each question is scored in a scale ranging from 0 (worst health) to 100 (best health)
LEVIL: London Evaluation of Illness	Subject responses were rated from 0 (worst symptoms) to 100 (no symptoms
MFI‐20: Multidimensional Fatigue Inventory	Each dimension includes four items, and responses are score based on a 5‐point Likert scale from strongly agree to strongly disagree. Higher scores indicate greater fatigue. Total score of each dimension ranges between 4 and 20, and the total fatigue score ranges between 20 and 100. Scores of 20‐41 indicate mild fatigue, scores of 48‐74 indicate moderate fatigue, and scores of 75‐100 indicate severe fatigue
MFIS: Modified Fatigue Impact Scale	A 21‐item Likert‐based scale that assesses the effects of fatigue on physical, cognitive and psychosocial functioning. Scores are summed to produce an overall score out of 84, with higher scores indicating worse fatigue impact
PHQ‐9: Patient Health Questionnaire‐9	Brief 9‐item self‐report scale on the basis of the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria for major depressive disorder, in which each item is scored from 0 (not at all) to 3 (nearly every day)
PFS: Piper Fatigue Scale	Includes a total of 27 items and evaluates subjective perception of the patients on fatigue under four subscales. Responses for each item were scored between 0‐10 points. The total fatigue score was obtained by summing the points of 22 items, then dividing the sum into the number of items. High scores signify a high level of perceived fatigue
PROMIS‐Fatique Short Form	Seven items about energy or exhaustion
PSQI: Pittsburgh Sleep Quality Index	Scale comprised 18 items and 7 component scores. Every component was evaluated from 0 to 3. The total of these component points yielded the total score of the scale, which ranged from 0 to 21. A high score (5 or above) indicated poor sleep quality. Sleep quality classified as good (0–4) and poor (5–21)
RNLI: Reintegration to Normal Living Index	Assesses the degree to which individuals who have experienced traumatic or incapacitating illness achieve reintegration into normal activities, using 11 declarative statements each accompanied by a 10‐point visual analogue scale. Scores are then added to produce an overall score out of 110, with higher scores indicating better reintegration to normal living
SF‐12: 12‐item Short Form Health Survey	Higher Mental Component Scores and Physical Component scores indicate better HRQoL
SF‐36: 36‐item Short Form Health Survey	Eight subscales include physical function, role limitation due to physical problems, social function, role limitation due to emotional problems, mental health, fitness/fatigue, pain, and understanding of general health. By calculating the scores obtained from the subscales, 2 main scale scores are obtained; physical and mental scales. Each subscale score ranges from 0 to 100. The physical and mental scale scores are also between 0 and 100. Zero indicates the worst and 100 indicates the best health condition
SMMT: Standardized Mini Mental Test	Covers five main areas and consists of 11 items, takes approximately 10 min to complete. The highest score obtainable from the SMMT is 30. In the SMMT, a score of 24–30 points is considered normal, 20–23 is considered to indicate light/mild dementia, 10–19 to indicate intermediate/mid‐stage dementia, and 0–9 to indicate advanced dementia
SNAG: Simplified Nutritional Appetite Questionnaire	Maximum score of 20 and a score < 14 indicates poor appetite
SONG‐HDF: Standardised Outcomes in Nephrology‐Haemodialysis Fatigue	Assesses the severity of fatigue, and its impact on daily living, in people on maintenance haemodialysis using 3 Likert‐style questions. Scores are summed to produce a total score out of 9, with higher scores indicating worse fatigue
STAI / STAI‐Y1: State‐Trait Anxiety Inventory	Composed of 20 items concerning state anxiety. 4‐point Likert scale: 1 = “not at all”; 2 = “a little”; 3 = “enough”; and 4 = “very much.” The final score is obtained by sum of the responses to the individual items and can vary from a minimum of 20 to a maximum of 80. A higher score indicates a greater level of anxiety in the subject) with scores ≥ 40 indicating elevated anxiety
Symptoms related to orthostatic hypotension questionnaire	Assessed using a 4‐point rating scale; severe (daily activities were greatly disturbed by the symptom), moderate (daily activities were disturbed by symptoms), mild (patients were aware of the symptoms, but daily activities were not disturbed), and asymptomatic (there was no symptom at all and patients were not bothered by any symptoms). The improvement for each symptom or the global improvement rating was assessed using a 6‐point rating scale (marked improvement (4 or higher), moderate improvement (3 or 2 and if patients have no new symptoms), slight improvement (2 or 1 and if patients have no new symptoms), no changes (±1, 0), aggravation (‐2 or less, or if patients develop new symptoms), asymptomatic (if patients have no new symptoms)
VAS: Visual Analogue Scale	Numbers were placed at equal intervals on a horizontal line. The presence of the worst value was rated the highest point (e.g. 10 on a 10‐point scale) Example: 1‐3 mild; 4‐6 moderate; 7‐10 severe
WHOQOL‐BREF: WHO Quality of Life ‐ brief form	26 items; it used a 5‐point Likert scale. Items 3, 4 and 26 are scored in reverse. A higher score represents better quality of life
World Health Adverse Reactions Terminology	Haemorrhage: epistaxis, gastric ulcer haemorrhagic, gastrointestinal haemorrhage, haematoma, haematuria, haemoptysis, nose haemorrhage, rectal haemorrhage, haemothorax, oral haemorrhage, peptic ulcer haemorrhagic, vaginal haemorrhage, and cystitis haemorrhagic Infection: fever, herpes zoster, infection, bacterial infection, fungal infection, influenza‐like symptoms, peritonitis, pneumonia, sinusitis, and tooth caries Vascular access problems: arteriovenous fistula loss or thrombosis, device‐related complications, permanent dialysis catheter loss, and thrombosis Surgical intervention Anaemia and related symptoms: anaemia, asthenia, fatigue, and malaise Cardiovascular: blood pressure fluctuation, cardiac failure, chest pain, coronary artery disorder, dizziness, hypertension, hypotension, myocardial infarction, non‐site‐specific vascular disorder, palpitations, pericarditis, peripheral gangrene, pulmonary oedema, and vascular disorder Respiratory: coughing, cyanosis, dyspnoea, and atrial fibrillation Gastrointestinal: abdominal pain, anorexia, ascites, ulcerative colitis, diarrhoea, gastric ulcer, hepatic cirrhosis, intestinal obstruction, nausea, oesophagitis, and vomiting Musculoskeletal: arthralgia, arthritis, arthropathy, back pain, bone disorder, fall, fracture pathologic, injury, leg pain, myalgia, skeletal pain, and ankylosing spondylitis Skin: folliculitis, pruritus, purpura, rash, skin disorder, and skin ulceration Neurologic: cerebellar infarction, cerebral atrophy, cerebrovascular disorder, coma, confusion, gait abnormal, headache, hearing decreased, insomnia, ischial neuralgia, somnolence, and abnormal vision Miscellaneous: acidosis, allergic reaction, anxiety, aggravated diabetes mellitus, dysuria, hydronephrosis, hyperkalaemia, hyperparathyroidism, hypoglycaemia, nail disorder, non‐site‐specific embolism, thrombosis, oedema, generalized oedema, peripheral oedema, pain, renal cyst, thrombocytopenia, thrombosis, transplant rejection, Wegener’s granulomatosis, weight decrease

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.2 Change in fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.2.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.3 Number with improvement of fatigue	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.3.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.4 Number with aggravation of fatigue	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.4.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.5 Death (any cause)	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.5.1 Haemodialysis	3	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
1.6 Cardiovascular death	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.6.1 Haemodialysis	2	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
1.7 Quality of life (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.7.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.8 Change in quality of life	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.8.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.9 Depresssion	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.9.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.10 Change in depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.10.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
1.11 Hypertension	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
1.11.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Fatigue	3		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
2.1.1 Haemodialysis	3	234	Std. Mean Difference (IV, Random, 95% CI)	‐1.51 [‐2.28, ‐0.73]
2.2 Death (any cause)	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
2.2.1 HD	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
2.3 Cardiovascular death	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
2.3.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
2.4 Anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.4.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.5 Sleep quality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.5.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
3.1 Fatigue	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3.1.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3.2 Anxiety	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3.2.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3.3 Sleep quality	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
3.3.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
4.1 Death (any cause)	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
4.1.1 Haemodialysis	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
4.2 Cardiovascular death	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
4.2.1 Haemodialysis	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Study ID	Intervention	Control	Adverse events in the intervention arm	Adverse events in the control arm	Comments
Akizawa 2002	L‐DOPS (400 or 200 mg)	Placebo	Overall, 5/100 patients in the treatment group reported headache, increased blood pressure, urinary retention, facial hot flushed, bad feeling, drug eruption, but number of patients who reported each adverse event was not reported	Feeling irritated (1), insomnia (1)	Quote: "Adverse events occurred in 3/51 patients in the 400 mg group (5.9%; i.e.,headache, increased blood pressure, urinary retention), 2/49 patients in the 200 mg group (4.1%; i.e., headache, increased blood pressure, facial hot flushed, bad feeling, drug eruption), and 1/49 patients in the placebo group (2.0%; i.e., feeling irritated, insomnia)."
ASCEND 2016	Sertraline	CBT	Death 0/60, hospitalisation/other 9/60, major bleeding 1/60, cardiac 3/60, gastrointestinal 1/60, infection 2/60, other 2/60	Death 2/60, hospitalisation/other 14/60, major bleeding 2/60, cardiac 4/60, gastrointestinal 1/60, infection 2/60, other 8/60	Quote: "Serious adverse events occurred in both treatment groups: 13 in 11 patients in the CBT group and 18 in 14 patients in the sertraline group. Nonserious adverse events were more frequent in the sertraline (56 events in 25 patients) than the CBT (17 events in 12 patients) group."
ASSertID 2015	Sertraline	Placebo	Adverse events and/or serious adverse events (9/15); cardiovascular death (1/15)	Adverse events and/or serious adverse events (9/15); cardiovascular death (0/15)	Quote: "Eighteen patients experienced adverse events (24) and/ or SAEs (13), nine in each randomized group. Infections (8) and nausea (4) were the most commonly reported adverse events. With regard to the SAEs, there was one death that was possibly related to the study medication as mentioned above, six SAEs that were unlikely to be related, and six SAEs that were not related to the study medication." "In the sertraline group, there were six dropouts within the first 2 months. One patient died of cardiac arrest having taken one tablet. Three patients withdrew because of adverse events (one after 3 days with nausea, another after 12 days with headaches and dizziness, and the third due to insomnia after 23 days). The fifth patient withdrew because of concern about side effects, having taken no study medication. The sixth patient was admitted for a prolonged hospital stay with leg ulcers shortly after randomisation and subsequently withdrawn without having taken any study medication. At 3 months, a seventh patient withdrew because of sweating and palpitations. In the placebo group, one patient withdrew after the baseline interview because of concern about taking additional medication, and a second decided against continuing after 3 months."
BA16285 2007	C.E.R.A. (once/week)	C.E.R.A. (once every 2 weeks)	Adverse events were reported for all study participants without distinction between groups (fatigue, anaemia, headache, vomiting, dizziness, diarrhoea, upper respiratory tract infection, nausea, dyspnoea, kidney transplantation, chest pain, muscle cramp or spasm, pyrexia, constipation, pruritus, rectal cancer, accelerated hypertension, cerebrovascular accident, death, acute myocardial infarction and multiple organ failure, chronic renal failure)	Adverse events were reported for all study participants without distinction between groups (fatigue, anaemia, headache, vomiting, dizziness, diarrhoea, upper respiratory tract infection, nausea, dyspnoea, kidney transplantation, chest pain, muscle cramp or spasm, pyrexia, constipation, pruritus, rectal cancer, accelerated hypertension, cerebrovascular accident, death, acute myocardial infarction and multiple organ failure, chronic renal failure)	Quote: "During the core study period, 4 AEs led to premature withdrawal (worsening anaemia [2 patients in group A and 1 in group C] and kidney transplant [1 in group A]). All cases of anaemia were considered to be related to study medication, whereas the kidney transplant was not. There were 5 withdrawals because of AEs in the extension period (pruritus, chest pain, rectal cancer, accelerated hypertension, and cerebrovascular accident [1 patient each]). In addition, dialysis was discontinued in 1 patient (at the request of her family), who was subsequently withdrawn from the study. The investigator classified this as an AE of chronic renal failure. All AEs leading to withdrawal in the extension period were considered to be unrelated to the study medication with the exception of accelerated hypertension (1 patient), which was classified as an SAE. Nineteen patients experienced an SAE during the core period, and 22, during the extension period. Two patients died during the extension period of the study (acute myocardial infarction and multiple organ failure); these deaths were deemed as SAEs. Neither death was considered related to treatment."
Barre 1988	Low dialysate sodium	High dialysate sodium	In general, adverse events were reported for all study participants without clear distinction between groups (fatigue, thirst, cramps, back pain, stomach‐ache, irritability, nausea, vomiting, headache, weakness, restlessness, itchiness, or any other symptoms)	In general, adverse events were reported for all study participants without clear distinction between groups (fatigue, thirst, cramps, back pain, stomach‐ache, irritability, nausea, vomiting, headache, weakness, restlessness, itchiness, or any other symptoms)	Quote: "One patients accounted for 52% of symptoms during dialysis and 58% of symptoms between dialyses. As noted, thirst was significantly less frequent with a sodium dialysate of 150 mEq/L, whereas headache was more frequent with the same dialysate. Fatigue during dialysis was more frequent with sodium dialysate of 145 mEq/L, whereas other symptoms, including cramps, back pain, stomachache, and irritability, were less frequent with a sodium dialysate of 155 mEq/L. Symptoms between dialyses, including thirst and headache, were more frequent with dialysate sodium of 155 mEq/L but were only present in two patients."
Bicer 2022	Acupressure	Placebo	70.1% of the patients in the intervention group experienced hypotension	0.9% of the patients in the placebo group experienced hypotension	Quote:" The procedure‐related side effects did not develop in all the patients included in the study and no patients felt unwell during or after the procedure."
BOLD 2020	Home SBP	Pre‐dialysis SBP	Post‐dialysis SBP<90 mmHg 2/25, post‐dialysis SBP>200 mmHg 3/25, syncope 1/25, fall 3/25, flash pulmonary oedema 0/25, cramping 13/25, dizziness 10/25, light‐headedness 14/25, hypotension 21/25.	Post‐dialysis SBP<90 mmHg 0/25, post‐dialysis SBP>200 mmHg 2/25, syncope 1/25, fall 6/25, flash pulmonary oedema 0/25, cramping 18/25, dizziness 14/25, light‐headedness 12/25, hypotension 18/25.	Quote: "The proportion of dialysis treatments with either excessively low or high pre or post dialysis SBP was small and similar in the two treatment groups. The rates of syncope, falls and flash pulmonary edema were also comparable between treatment groups."
Brass 2001	L‐carnitine	Placebo	In general, adverse events were reported for all study participants without clear distinction between groups (flu syndrome, injection‐site reaction, pain, pharyngitis, headache, hypertension). The intervention group reported serious adverse events (data included study A and B): body injection site reaction (4/130), infection (2/130), chest pain (3/130), abdominal pain (2/130), fever (1/130), accidental injury (1/130), neck pain (1/130), tachycardia (3/130), atrial fibrillation (1/130), hypertension (1/130), hypotension (1/130), aortic stenosis (1/130), colitis (1/130), vomiting (2/130), parathyroid disease (1/130), hyperkalaemia (2/130), hypervolaemia (1/130), lung oedema (1/130), pneumonia (1/130), skin carcinoma (1/130), amblyopia (1/130), urogenital kidney failure (8/130)	In general, adverse events were reported for all study participants without clear distinction between groups (flu syndrome, injection‐site reaction, pain, pharyngitis, headache, hypertension). The control group reported serious adverse events (data included study A and B): body injection site reaction (6/63), infection (4/63), chest pain (0/63), abdominal pain (0/63), fever (0/63), accidental injury (0/63), neck pain (0/63), tachycardia (0/63), atrial fibrillation (0/63), hypertension (0/63), hypotension (0/63), aortic stenosis (0/63), colitis (0/63), vomiting (0/63), parathyroid disease (0/63), hyperkalaemia (0/63), hypervolaemia (0/63), lung oedema (0/63), pneumonia (0/63), skin carcinoma (0/63), amblyopia (0/63), urogenital kidney failure (3/63)	Quote: "The most commonly reported adverse events were flu syndrome, injection‐site reaction, pain, pharyngitis, headache, and hypertension and showed no difference in frequency between L‐carnitine and placebo. Several serious adverse events occurred during the course of the study, with no differences between active and placebo groups. No serious adverse event was believed by the investigators to be certainly or probably drug related and they were consistent with the population's underlying disease and maintenance haemodialysis treatment." Table 7 reported "events that occurred only in placebo groups were not listed".
Canadian EPO 1990	EPO alfa	Placebo	Adverse events for both intervention groups were reported: seizure (2/78), clotting of vascular access (11/78), clotting of tubing in dialysis machine (8/78), pain in chest (13/78), epistaxis or haemorrhage (10/78), abnormal sense of taste (11/78), headache (26/78), redness of eyes (5/78), flu‐like symptoms (18/78), aches in bone or muscle (20/78).	Adverse events in the control group were reported: seizure (1/40), clotting of vascular access (1/40), clotting of tubing in dialysis machine (4/40), pain in chest (6/40), epistaxis or haemorrhage (7/40), abnormal sense of taste (6/40), headache (19/40), redness of eyes (0/40), flu‐like symptoms (12/40), aches in bone or muscle (9/40).	Table V reported in the Canadian EPO 1990.
Chang 2010	Exercise	Control	Adverse events were not reported in the intervention group	All adverse events were not reported in the control group. However, authors reported that a muscle/joint pain (1/35) led to early termination	Quote: "There were three early terminations due to a Borg score of 15 (1), muscle/joint pain (1), and unsteady pedal speed (1). All occurred among the sedentary subjects."
Chen 2008a	CBT	Education	One participant with underlying stable major depression experienced a minor episode, but it was not reported in which treatment group he was allocated. 1/13 participants in the intervention group experienced morning dyspnoea	One participant with underlying stable major depression experienced a minor episode, but it was not reported in which treatment group he was allocated. Other adverse events were not reported in the control group	Quote: "One participant with underlying stable major depression experienced a minor episode because of cessation of antidepressant therapy. One participant in the CBT group experienced 1 episode of morning dyspnoea after a large meal during the last week of this 4‐week trial."
Chen 2011a	CBT	Education	There were no adverse events in the intervention group	There were no adverse events in the control group	Quote: "No adverse events were reported during the intervention."
Eroglu 2022	Relaxation + music	Control	No information was reported in detail	No information was reported in detail	Quote: "Moreover, no participants dropped out owing to unexpected adverse effects of BRT combined with music therapy."
Fatouros 2010	L‐carnitine	Placebo	No adverse events were reported in the intervention group	No adverse events were reported in the control group	Quote: "No adverse clinical effect related to L‐carnitine supplementation was reported."
FHN DAILY 2007	Frequent HD	Conventional HD	Death 5/125, all hospitalisation 109/125, all interventions related to vascular access 95/125, hypokalaemia 13/125, hyperphosphataemia 15/125	Death 9/120, all hospitalisation 114/120, all interventions related to vascular access 65/120, hypokalaemia 6/120, hyperphosphataemia 9/120	Quote from FHN trial 2010: "Adverse events were reported in table 4."
Foley 2000	EPO alpha (Hb target 9.5‐10.6 g/dL)	EPO alpha (Hb target 13‐14 g/dL)	Arteriovenous access thrombosis and cardiac events were reported in the low target Hb group but the number of patients was not reported. During the study period 3/73 participants died in the low target Hb group	Arteriovenous access thrombosis and cardiac events were reported in the high target Hb group but the number of patients was not reported. During the study period 4/73 participants died in the high target Hb group	Quote: "The comparative incidence of arteriovenous access thrombosis, cardiac events, and death."
Fukuda 2015	Nutritional supplementation	Placebo	Adverse events in the intervention group were reported: increased blood pressure (1/103), dizziness (1/103), insomnia (1/103), nausea (1/103), diarrhoea (2/103), sudden hearing loss (1/103). One participant in each group had cramp in the lower leg	Adverse events in the control group were reported: increased glucose level (1/99), felt sick (2/99), stomach discomfort (1/99), hospitalisation (2/99). One participant in each group had cramp in the lower leg	Quote: "In the nutritional drink group, one participant reported increased blood pressure, one complained of dizziness, one complained of insomnia, one reported nausea, and two had diarrhoea. One participant in each group had cramp in the lower leg. In the placebo group, one participant reported increased glucose level, two felt sick, and one complained of stomach discomfort. One participant developed sudden hearing loss and was prescribed any vitamins. Two participants were hospitalised in the placebo group. The safety monitoring board confirmed no serious adverse events, and hospitalisation was determined relating to the study intervention."
Grigoriou 2021	Exercise	Control	Not reported in sufficient detail	Not reported in sufficient detail	Quote: "All participants completed both scenarios without any adverse effects or significant complaints."
HDPAL 2014	Atenolol	Lisinopril	A questionnaire assessed the following adverse events: fatigue or tiredness, chest pain, abdominal pain, cold hands or feet, dizziness on standing, muscle cramps, diarrhoea, nausea, vomiting, dry cough, upper respiratory infection or common cold, shortness of breath, headaches, persistent dizziness, numbness in hands or feet, decreased sex drive, decreased ability to have sex, drowsiness or sleepiness, depression or feeling sad and nightmares. However, data were not reported considering the treatment assigned (for only 133 patients who completed the questionnaire). Adverse events in the intervention group were reported: overall serious adverse events (58/100), all‐cause hospitalisation (37/100), infections (24/100), access‐related (17/100), central nervous system (3/100), cancer‐related complications (2/100), cardiovascular event (16/100), angina (0/100), arrhythmia (2/100), cardiac arrest (0/100), congestive heart failure (5/100), myocardial infarction (2/100), peripheral vascular disease (1/100), revascularization (3/100), stroke (2/100), valve replacement surgery (1/100), cardiovascular death (2/100), non‐cardiovascular death (2/100), fractures (7/100), parathyroidectomy (3/100), biliary‐related (1/100), bowel‐related (3/100), falls (6/100), gastrointestinal bleeding (2/100), hypertensive crisis (3/100), hyperglycaemia (1/100), hyperkalaemia (3/100), hypoglycaemia (2/100), hypotension with hospitalisation (6/100), miscellaneous (12/100)	A questionnaire assessed the following adverse events: fatigue or tiredness, chest pain, abdominal pain, cold hands or feet, dizziness on standing, muscle cramps, diarrhoea, nausea, vomiting, dry cough, upper respiratory infection or common cold, shortness of breath, headaches, persistent dizziness, numbness in hands or feet, decreased sex drive, decreased ability to have sex, drowsiness or sleepiness, depression or feeling sad and nightmares. However, data were not reported considering the treatment assigned (for only 133 patients who completed the questionnaire). Adverse events in the control group were reported: overall serious adverse events (70/100), all‐cause hospitalisation (59/100), infections (20/100), access‐related (19/100), central nervous system (3/100), cancer‐related complications (2/100), cardiovascular event (28/100), angina (2/100), arrhythmia (3/100), cardiac arrest (2/100), congestive heart failure (10/100), myocardial infarction (3/100), peripheral vascular disease (5/100), revascularization (4/100), stroke (2/100), valve replacement surgery (1/100), cardiovascular death (3/100), non‐cardiovascular death (1/100), fractures (1/100), parathyroidectomy (1/100), biliary‐related (2/100), bowel‐related (5/100), falls (3/100), gastrointestinal bleeding (5/100), hypertensive crisis (10/100), hyperglycaemia (3/100), hyperkalaemia (10/100), hypoglycaemia (4/100), hypotension with hospitalisation (5/100), miscellaneous (18/100)	Quote from Agarwal 2016: "The symptoms were as follows: fatigue or tiredness, chest pain, abdominal pain, cold hands or feet, dizziness on standing, muscle cramps, diarrhoea, nausea, vomiting, dry cough, upper respiratory infection or common cold, shortness of breath, headaches, persistent dizziness, numbness in hands or feet, decreased sex drive, decreased ability to have sex, drowsiness or sleepiness, depression or feeling sad and nightmares." Quote from Agarwal 2014;"Table 3 shows the serious adverse events between groups over the course of the trial."
Johansen 1999	Nandrolone decanoate	Placebo	Adverse events in the intervention group were reported: hematoma (1/14), reduction in testicular size (1/14), amenorrhoea (1/14), acne (1/14), hypertension (3/14)	Adverse events in the control group were reported: hematoma (1/15), skin rash (2/15), hypertension (3/15)	Quote:"Reason for inability to undergo treadmill included coronary artery disease (7 subjects), severe hypertension (2 subjects), hospitalisation (3 subjects), study drop‐out (2 subjects), valvular heart disease, amputation, arthritis, abdominal hernia, and diabetic foot ulcer (1 subject). [...] The study was generally well tolerated, but minor adverse events occurred. Two subject (one in each arm) developed hematoma. One nandrolone recipient complained of a reduction in testicular size that resolved with dose reduction.two men (both in the placebo group) complained of skin rash. Of the 3 women who received nandrolone, 2 required dose reduction for amenorrhoea and acne, respectively. [...] Six subjects (3 in each group) required increase in antihypertensive medication dosages."
Johansen 2006	Nandrolone decanoate with or without exercise	Placebo with or without exercise	Adverse events in both intervention groups were reported: interference with sexual function (1/39)	Adverse events in the both control groups were reported: death (1/40), not feeling well (1/40), abdominal pain (1/40), itchy reaction (1/40)	Quote: "Those who received placebo discontinued because of an itchy reaction at the injection site, a nonspecific feeling that the drug was having adverse effects, abdominal pain and liver function test abnormalities, and discovery of a history of prostate cancer. Those who received nandrolone discontinued because of interference with sexual function (after five doses) and fear of possible adverse effects (after three doses)."
Konstadinidou‐ND 2002	Exercise	Control	Adverse events in both intervention groups were reported: death (1/36)	Adverse events in the control group were reported: death (1/12)	Quote:"However, during the study 5 patients from Group A, 1 from Group B, 2 from C voluntarily withdrew, while 1 patient from Group B and 1 from D died of causes unrelated to exercise."
Krase 2022	Exercise	Control	No detailed information was reported	No detailed information was reported	Quote: "Exercise was well tolerated by all patients, and no adverse reactions were reported."
Leski 1979	Dialysate containing glucose	Dialysate without glucose	The study assessed fatigue, headache and leg cramps using a questionnaire: number of patients who reported these adverse events after dialysis was not reported. Hypotension was recorded but the author did not report information neither on the intervention group allocation nor on the number of cases	The study assessed fatigue, headache and leg cramps using a questionnaire: number of patients who reported these adverse events after dialysis was not reported. Hypotension was recorded but the author did not report information neither on the intervention group allocation nor on the number of cases	Quote: "Headache diminished in frequency during the sessions after the sessions. Fatigue during dialysis was not significantly altered, however post‐dialysis fatigue dropped significantly. The episodes of hypotension decreased in number, but not significantly. The same was the case for cramps."
Li 2014b	Nurse led telephone support	Control	As reported in figure 1, death was reported in the intervention group but the number of patients was not reported. No data were clearly reported for oedema, peritonitis, catheter infections, exit‐site condition in the intervention group	As reported in figure 1, death was reported in the control group but the number of patients was not reported. No data were clearly reported for oedema, peritonitis, catheter infections, exit‐site condition in the control group	Quote: "The presence of edema, existence of peritonitis, catheter infections, exit‐site condition and weight gain were observed as the complication control of the participants within 42 days (6 weeks) and 84 days (12 weeks) post‐discharge."
Lillevang 1990	EPO	Placebo	Adverse events in the intervention group were reported: skeletal pain (1/9), abdominal pain (1/10)	Adverse events in the control group were reported: bodily distress (1/9), leg cramps (1/10)	Quote:"During the study period, the following adverse effects was registered (defined as new complaints from the patients, independent of the patients perception of relationship with the treatment): in the treatment group, there was one case of skeletal pain and one case of abdominal pain; in the placebo group, there was one case of “bodily distress” and one case of leg cramps."
Linde 2001	EPO alpha to achieve normal‐Hb target	Subnormal‐Hb target with or without ESA	Overall, in the intervention group there were the following adverse events: death (25/180), adverse events (29/180). Specifically: HD: death (22/157), adverse events (26/157) PD: death (3/23), adverse events (3/23) 5 participants had sepsis Data related to predialysis patient were not reported because they were out of our scope	Overall, in the control group there were the following adverse events: death (26/164), adverse events (14/164). Specifically: HD: death (20/136), adverse events (14/136) PD: death (6/28), adverse events (0/28) 7 participants had sepsis Data related to predialysis patient were not reported because they were out of our scope	Quote from Furuland 2003: "In a multivariate logistic regression analysis of SAE the number of patients with at least one SAE was 110 and 97 in the N‐Hb and S‐Hb groups, respectively. [...] Five patients in the N‐Hb group and seven in the S‐Hb group had sepsis."
Mohammadpourhodki 2021	Aromatherapy	Placebo	None known	None known	Quote: "None of patients included in the intervention groups reported side effects or local or general complications."
Muz 2017	Aromatherapy	Control	As reported in figure 1, participants in the intervention group reported: nausea and vomiting (1/41), increase of blood pressure (2/41).	No adverse events were reported for the control group in figure 1.	No relevant quotations were reported
Parfrey 2005	ESA (normal Hb target)	ESA (high Hb target)	Adverse events in the intervention group 1 were reported: any (281/300), hypertension (110/300), hypotension (105/300), platelet/bleeding/clotting arteriovenous fistula thrombosis (23/300), hematoma (36/300), arteriovenous fistula loss (26/300), vomiting (52/300), diarrhoea (53/300), nausea (53/300), abdominal pain (46/300), upper respiratory tract infection (69/300), dyspnoea (42/300), cough (36/300), pharyngitis (31/300), myalgia (85/300), skeletal pain (64/300), arthralgia (43/300), headache (64/300), dizziness (40/300), skin disorder (39/300), pruritus (33/300), infection (32/300), urinary tract infection (27/300), hyperparathyroidism (30/300), pain (47/300), back pain (40/300), fever (42/300), influenza (37/300), device complication (27/300), surgery (39/300), arteriovenous fistula thrombosis (36/300), non‐site‐specific embolism thrombosis (12/300), permanent catheter thrombosis (9/300), cerebrovascular disorder (4/300), peripheral ischaemia (7/300), angina pectoris (8/300), myocardial infarction (4/300), chest pain (7/300), permanent catheter loss (6/300), arteriovenous fistula loss (27/300), arteriovenous graft loss (9/300), tachycardia (15/300), palpitations (9/300), atrial fibrillation (7/300), bradycardia (5/300), pulmonary oedema (16/300), cardiac failure (6/300), pulmonary oedema or heart failure (19/300), death (20/300)	Adverse events in the intervention group 2 were reported: any (284/296), hypertension (120/296), hypotension (85/296), platelet/bleeding/clotting arteriovenous fistula thrombosis (30/296), hematoma (45/296), arteriovenous fistula loss (30/296), vomiting (54/296), diarrhoea (50/296), nausea (47/296), abdominal pain (45/296), upper respiratory tract infection (72/296), dyspnoea (35/296), cough (35/296), pharyngitis (29/296), myalgia (81/296), skeletal pain (39/296), arthralgia (36/296), headache (86/296), dizziness (16/296), skin disorder (41/296), pruritus (23/296), infection (34/296), urinary tract infection (29/296), hyperparathyroidism (19/296), pain (41/296), back pain (35/296), fever (30/296), influenza (30/296), device complication (42/296), surgery (20/296), arteriovenous fistula thrombosis (45/296), non‐site‐specific embolism thrombosis (14/296), permanent catheter thrombosis (8/296), cerebrovascular disorder (12/296), peripheral ischaemia (8/296), angina pectoris (9/296), myocardial infarction (7/296), chest pain (4/296), permanent catheter loss (7/296), arteriovenous fistula loss (30/296), arteriovenous graft loss (9/296), tachycardia (22/296), palpitations (6/296), atrial fibrillation (6/296), bradycardia (7/296), pulmonary oedema (9/296), cardiac failure (2/296), pulmonary oedema or heart failure (11/296), death (13/296)	Quote from Parfrey 2005: "Treatment‐emergent adverse events that occurred in at least 10% of patients; vascular, access loss, and cardiac events that occurred in at least 2% of patients; and death in lower and higher target groups. "
PEDAL 2020	Exercise	Control	Greenwood 2021 reported: serious adverse events 69/175, blood and lymphatic system disorders 2/175, cardiac disorders 9/175, congenital disorders 0/175, gastrointestinal disorders 10/175, hepatobiliary disorders 2/175, infections and infestations 29/175, injury 15/175, metabolism and nutritional disorders 13/175, musculoskeletal and connective tissue disorders 3/175, cancer 1/175, nervous system disorders 5/175, psychiatric disorders 3/175, renal and urinary disorders 0/175, respiratory disorders 10/175, reproductive disorders 1/175, skin and subcutaneous tissue disorders 1/175, surgical procedures 24/175, vascular disorders 4/175	Greenwood 2021 reported: serious adverse events 56/160, blood and lymphatic system disorders 0/160, cardiac disorders 6/160, congenital disorders 1/160, gastrointestinal disorders 4/160, hepatobiliary disorders 1/160, infections and infestations 18/160, injury 12/160, metabolism and nutritional disorders 4/160, musculoskeletal and connective tissue disorders 1/160, cancer 0/160, nervous system disorders 3/160, psychiatric disorders 1/160, renal and urinary disorders 1/160, respiratory disorders 3/160, reproductive disorders 1/160, skin and subcutaneous tissue disorders 0/160, surgical procedures 13/160, vascular disorders 6/160	Quote from Greenwood 2021: "The number of patients with harms (serious adverse events) was similar in the intervention group (n = 69) and control group (n = 56)."
Picariello 2018	CBT	Control	Admission to hospital 1/18	Admission to hospital 2/7	Quote: "No trial adverse events occurred."
Reilly‐Spong 2015	Meditation	Control	There were no adverse events in the intervention group	There were no adverse events in the control group	Quote from Reilly‐Spong 2015: "No adverse effects related to the interventions were reported."
Salehi 2020	Exercise	Control	None known	None known	Quote: "None of the patients suffered from such complications and all participated without interruption."
Sang 1997	Steady dialysate sodium	Linear sodium ramping Stepwise sodium ramping	Adverse events (hypotension, cramps, fatigue, thirsty and total symptoms) were recorded as score in all treatment groups. Other adverse events were not clearly stated	Adverse events (fatigue, thirsty and total symptoms) were recorded as score in all treatment groups. Other adverse events were not clearly stated	Quote: "The number of symptomatic or asymptomatic hypotensive episodes and the time of occurrence of a hypotensive episode were recorded. [...] It was noted when the patient complained of angina, cramps, nausea, or headaches, or vomited. [...] Thirst, fatigue, dizziness and total symptoms were also recorded."
Schardong 2021	Laser	Control	Not reported in sufficient detail	Not reported in sufficient detail	Quote: "Regarding the safety of this therapy, no changes were observed in patients’ vital signs and adverse effects during laser applications, as well as in the interval between them."
Schmitz 2016	Citrate dialysate	Standard citrate	Adverse events (including death) were not clearly reported per group in the first phase on the study period	Adverse events (including death) were not clearly reported per group in the first phase on the study period	Quote: "The events such as cramps and hypotension were more frequent with citrate dialysate. [...] The most common adverse events during standard dialysate use were infections and vascular disorders. During the citrate dialysate phase, the most frequent events were general disorders like fatigue, followed by infections and musculoskeletal disorders, e.g. muscle spasm or pain."
Semeniuk 2000	Nutritional supplementation	Placebo	Not reported in sufficient detail	Not reported in sufficient detail	Some adverse events were reported (gastrointestinal and cardiovascular adverse events, hypotension). However, no data were clearly reported for the first phase of the cross‐over study.
Singer 2010	Vitamin C	Placebo	Adverse events in the intervention group were reported: acute coronary syndrome (0/37). Other adverse events (including commence dialysis, bacteraemia and dialysis access thrombosis) were not clearly stated	Adverse events in the control group were reported: acute coronary syndrome (0/38). Other adverse events (including commence dialysis, bacteraemia and dialysis access thrombosis) were not clearly stated	Quote: "During the study, there were no episodes of acute coronary syndrome, and two subjects commenced dialysis, both to the PD modality. There were too few bacteraemia (two in ascorbate group and one in placebo group) and dialysis access thromboses (one in ascorbate group) to analyse differences between the groups."

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.2 Death (any cause)	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
5.2.1 Haemodialysis	2	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
5.3 Cardiovascular death	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
5.3.1 Haemodialysis	2	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
5.4 Depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.4.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.5 Change in depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.5.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.6 Anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.6.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.7 Change in anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.7.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.8 Sleep disturbance	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
5.8.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Fatigue	4		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
6.1.1 Haemodialysis	4	217	Std. Mean Difference (IV, Random, 95% CI)	‐1.18 [‐2.04, ‐0.31]
6.2 Number reporting fatigue	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
6.2.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
6.3 Change in fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.3.1 HD	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.4 General fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.4.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.5 Physical fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.5.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.6 Mental fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.6.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.7 Number with moderate fatigue	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
6.7.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
6.8 Number with severe fatigue	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
6.8.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
6.9 Vitality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.9.1 HD	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.10 Energy/fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.10.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.11 Death (any cause)	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.11.1 Haemodialysis	8	739	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.43, 1.76]
6.12 Cardiovascular death	5		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.12.1 Haemodialysis	5	587	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.10, 3.62]
6.13 Quality of life (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.13.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.14 General health	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.14.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.15 Anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.15.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
6.16 Cardiovascular events	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
6.16.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
7.1 Fatigue	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
7.1.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
7.2 Change in fatigue	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
7.2.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
7.3 Death (any cause)	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
7.3.1 Haemodialysis	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Death (any cause)	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
8.1.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Death (any cause)	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
9.1.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
10.1 Fatigue	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
10.1.1 Haemodialysis	2	117	Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.97, 0.52]
10.2 Remission of fatigue symptoms	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
10.2.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
10.3 Medium fatigue symptoms	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
10.3.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
10.4 Severe fatigue symptoms	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
10.4.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
10.5 Weakness	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
10.5.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
10.6 Energy/fatigue	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
10.6.1 Peritoneal dialysis	2	220	Mean Difference (IV, Random, 95% CI)	4.50 [‐0.55, 9.54]
10.7 Death (any cause)	5	314	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.25, 3.57]
10.7.1 Peritoneal dialysis	1	100	Risk Ratio (M‐H, Random, 95% CI)	3.00 [0.13, 71.92]
10.7.2 Haemodialysis	4	214	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.08, 4.74]
10.8 Cardiovascular death	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
10.8.1 Haemodialysis	2	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
10.9 Quality of life (overall)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
10.9.1 Peritoneal dialysis	2	220	Mean Difference (IV, Random, 95% CI)	1.86 [‐2.96, 6.69]
10.10 Sleep (overall)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
10.10.1 Peritoneal dialysis	2	220	Mean Difference (IV, Random, 95% CI)	7.46 [2.04, 12.87]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
11.1 Fatigue	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
11.1.1 Haemodialysis	2	230	Std. Mean Difference (IV, Random, 95% CI)	‐0.33 [‐1.16, 0.50]
11.2 Vitality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
11.2.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
11.3 General health	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
11.3.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
11.4 Death (any cause)	1	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
11.4.1 Haemodialysis	1	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
11.4.2 Peritoneal dialysis	1	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
11.5 Cardiovascular death	1	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
11.5.1 Haemodialysis	1	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
11.5.2 Peritoneal dialysis	1	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
11.6 Sleep problems	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
11.6.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	Statistical method	Effect size
12.1 Fatigue	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
12.1.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
12.2 Death (any cause)	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
12.2.1 Haemodialysis	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
12.3 Cardiovascular death	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
12.3.1 Haemodialysis	1	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
12.4 Depression	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
12.4.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
12.5 Anxiety	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
12.5.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
12.6 Sleep quality	1	Mean Difference (IV, Random, 95% CI)	Totals not selected
12.6.1 Haemodialysis	1	Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
13.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
13.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
13.2 Number with decline in fatigue	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
13.2.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
13.3 Death (any cause)	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
13.3.1 Haemodialysis	2	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
13.4 Cardiovascular death	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
13.4.1 Haemodialysis	2	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
13.5 Depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
13.5.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
13.6 Number with decline in depression	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
13.6.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
13.7 Anxiety	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
13.7.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
13.8 Number with decline in anxiety	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
13.8.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
13.9 Sleep (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
13.9.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
14.1 Death (any cause)	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
14.1.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

PERMALINK

Interventions for fatigue in people with kidney failure requiring dialysis

Patrizia Natale

Angela Ju

Giovanni FM Strippoli

Jonathan C Craig

Valeria M Saglimbene

Mark L Unruh

Giovanni Stallone

Allison Jaure

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Exercise versus control for people receiving dialysis.

Summary of findings 2. Aromatherapy versus placebo or standard care for people receiving dialysis.

Summary of findings 3. Massage versus no intervention for people receiving dialysis.

Summary of findings 4. Acupressure versus placebo or control for people receiving dialysis.

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 and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Study design, setting and characteristics

Study participants

Interventions

Non‐physiological neutral amino acids versus placebo

Serotonin reuptake inhibitor versus placebo

Beta‐blockers versus angiotensin‐converting enzyme inhibitors

Anabolic steroids versus placebo

Anabolic steroids versus exercise

Anabolic steroids alone versus anabolic steroids plus exercise

Anabolic steroids plus exercise versus exercise alone

Anabolic steroids plus exercise versus placebo

Iron replacement product versus placebo

Continuous erythropoietin receptor activation (C.E.R.A)

Erythropoietin stimulating agents versus placebo

Haemoglobin targets

Nutritional supplementation versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
15.1 Fatigue	7		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
15.1.1 Haemodialysis	7	542	Std. Mean Difference (IV, Random, 95% CI)	‐1.23 [‐1.96, ‐0.50]
15.2 Change in fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.2.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.3 Vitality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.3.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.4 Death (any cause)	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
15.4.1 Haemodialysis	6	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
15.5 Cardiovascular death	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
15.5.1 Haemodialysis	6	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
15.6 Quality of life (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.6.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.7 Global sleep quality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.7.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.8 Change in global sleep quality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.8.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.9 Sleep disturbance	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.9.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.10 Change in sleep disturbance	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
15.10.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
16.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
16.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
17.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
17.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
18.1 Fatigue	7		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
18.1.1 Haemodialysis	7	657	Std. Mean Difference (IV, Random, 95% CI)	‐1.06 [‐1.47, ‐0.65]
18.2 Change in fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
18.2.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
18.3 Number with severe fatigue	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
18.3.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
18.4 Energy	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
18.4.1 Haemodialysis	2	152	Mean Difference (IV, Random, 95% CI)	4.87 [1.69, 8.06]
18.5 Death (any cause)	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
18.5.1 Haemodialysis	3	404	Risk Ratio (M‐H, Random, 95% CI)	1.53 [0.06, 36.31]
18.6 Cardiovascular death	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
18.6.1 Haemodialysis	2	0	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
18.7 Quality of life (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
18.7.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
18.8 Change in quality of life	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
18.8.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
18.9 Sleep (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
18.9.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
19.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
19.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
20.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
20.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
21.1 Fatigue	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
21.1.1 Haemodialysis	2	160	Std. Mean Difference (IV, Random, 95% CI)	‐0.77 [‐1.10, ‐0.43]
21.2 Change in fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.2.1 HD	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.3 Energy	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.3.1 HD	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.4 All‐cause death	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
21.4.1 HD	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
21.5 Cardiovascular death	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
21.5.1 HD	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
21.6 Quality of life (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.6.1 HD	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.7 Change in quality of life	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.7.1 HD	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.8 Sleep (overall)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
21.8.1 HD	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
22.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.2 Weakness	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.2.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.3 Energy	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.3.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.4 Death (any cause)	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
22.4.1 Haemodialysis	2	137	Risk Ratio (M‐H, Random, 95% CI)	0.17 [0.01, 4.15]
22.5 Cardiovascular death	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
22.5.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
22.6 Depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.6.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
22.7 Clotting of vascular access	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
22.7.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
23.1 Fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.1.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.2 Change in fatigue	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.2.1 Haemoglobin	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.3 Vitality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.3.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.4 Change in vitality	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.4.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
23.5 Death (any cause)	3	1086	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.71, 1.56]
23.5.1 Haemodialysis	3	1035	Risk Ratio (M‐H, Random, 95% CI)	1.11 [0.73, 1.68]
23.5.2 Peritoneal dialysis	1	51	Risk Ratio (M‐H, Random, 95% CI)	0.61 [0.17, 2.17]
23.6 Cardiovascular death	1	344	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.68, 2.48]
23.6.1 Haemodialysis	1	293	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.75, 3.26]
23.6.2 Peritoneal dialysis	1	51	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.19, 2.74]
23.7 Cardiovascular events (angina pectoris, myocardial infarction, pulmonary oedema or cardiac failure)	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.7.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.8 Arteriovenous access thrombosis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.8.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.9 Hypertension	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.9.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.10 Myocardial infarction	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.10.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.11 Congestive heart failure	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.11.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.12 Permanent catheter thrombosis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.12.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.13 Arterious graft loss	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.13.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.14 Arterious fistula thrombosis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.14.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.15 Arterious fistula loss	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.15.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.16 Permanent catheter loss	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
23.16.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
24.1 Death (any cause)	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.1.1 Haemodialysis	2	332	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.25, 1.74]
24.2 Cardiovascular death	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
24.2.1 Haemodialysis	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
24.3 Depression	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
24.3.1 Haemodialysis	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
24.4 Vascular access outcomes (repair, loss, or access‐related hospitalisation)	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.4.1 Haemodialysis	2	332	Risk Ratio (M‐H, Random, 95% CI)	1.53 [1.13, 2.07]
24.5 Access loss	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.5.1 Haemodialysis	2	332	Risk Ratio (M‐H, Random, 95% CI)	1.21 [0.72, 2.03]
24.6 Access stenosis	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.6.1 Haemodialysis	2	332	Risk Ratio (M‐H, Random, 95% CI)	1.10 [0.37, 3.25]
24.7 Access thrombosis	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.7.1 Haemodialysis	2	332	Risk Ratio (M‐H, Random, 95% CI)	1.53 [0.28, 8.51]