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Cochrane Database of Systematic Reviews Review - Intervention

Exercise training for adults undergoing maintenance dialysis

Authors' declarations of interest

Version published: 12 January 2022 Version history

https://doi.org/10.1002/14651858.CD014653
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Background

Dialysis treatments weigh heavily on patients' physical and psychosocial health. Multiple studies have assessed the potential for exercise training to improve outcomes in adults undergoing dialysis. However, uncertainties exist in its relevance and sustainable benefits for patient‐important outcomes. This is an update of a review first published in 2011.

Objectives

To assess the benefits and safety of regular structured exercise training in adults undergoing dialysis on patient‐important outcomes including death, cardiovascular events, fatigue, functional capacity, pain, and depression. We also aimed to define the optimal prescription of exercise in adults undergoing dialysis.

Search methods

In this update, we conducted a systematic search of the Cochrane Kidney and Transplant Register of Studies up to 23 December 2020. The Register includes studies identified from CENTRAL, MEDLINE, EMBASE, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov as well as kidney‐related journals and the proceedings of major kidney conferences.

Selection criteria

Randomised controlled trials (RCTs) and quasi‐RCTs of any structured exercise programs of eight weeks or more in adults undergoing maintenance dialysis compared to no exercise or sham exercise.

Data collection and analysis

Two authors independently assessed the search results for eligibility, extracted the data and assessed the risk of bias using the Cochrane risk of bias tool. Whenever appropriate, we performed random‐effects meta‐analyses of the mean difference in outcomes. The primary outcomes were death (any cause), cardiovascular events and fatigue. Secondary outcomes were health‐related quality of life (HRQoL), depression, pain, functional capacity, blood pressure, adherence to the exercise program, and intervention‐related adverse events.

Main results

We identified 89 studies involving 4291 randomised participants, of which 77 studies (3846 participants) contributed to the meta‐analyses. Seven studies included adults undergoing peritoneal dialysis. Fifty‐six studies reported aerobic exercise interventions, 21 resistance exercise interventions and 19 combined aerobic and resistance training within the same study arm. The interventions lasted from eight weeks to two years and most often took place thrice weekly during dialysis treatments. A single study reported death and no study reported long‐term cardiovascular events. Five studies directly assessed fatigue, 46 reported HRQoL and 16 reported fatigue or pain through their assessment of HRQoL. Thirty‐five studies assessed functional capacity, and 21 reported resting peripheral blood pressure. Twelve studies reported adherence to exercise sessions, and nine reported exercise‐related adverse events. Overall, the quality of the included studies was low and blinding of the participants was generally not feasible due to the nature of the intervention.

Exercise had uncertain effects on death, cardiovascular events, and the mental component of HRQoL due to the very low certainty of evidence. Compared with sham or no exercise, exercise training for two to 12 months may improve fatigue in adults undergoing dialysis, however, a meta‐analysis could not be conducted. Any exercise training for two to 12 months may improve the physical component of HRQoL (17 studies, 656 participants: MD 4.12, 95% CI 1.88 to 6.37 points on 100 points‐scale; I² = 49%; low certainty evidence). Any exercise training for two to 12 months probably improves depressive symptoms (10 studies, 441 participants: SMD ‐0.65, 95% CI ‐1.07 to ‐0.22; I² = 77%; moderate certainty evidence) and the magnitude of the effect may be greater when maintaining the exercise beyond four months (6 studies, 311 participants: SMD ‐0.30, 95% CI 0.14 to ‐0.74; I² = 71%). Any exercise training for three to 12 months may improve pain (15 studies, 872 participants: MD 5.28 95% CI ‐0.12 to 10.69 points on 100 points‐scale; I² = 63%: low certainty evidence) however, the 95% CI indicates that exercise training may make little or no difference in the level of pain. Any exercise training for two to six months probably improves functional capacity as it increased the distance reached during six minutes of walking (19 studies, 827 participants: MD 49.91 metres, 95% CI 37.22 to 62.59; I² = 34%; moderate certainty evidence) and the number of sit‐to‐stand cycles performed in 30 seconds (MD 2.33 cycles, 95% CI 1.71 to 2.96; moderate certainty evidence). There was insufficient evidence to assess the safety of exercise training for adults undergoing maintenance dialysis. The results were similar for aerobic exercise, resistance exercise, and a combination of both aerobic and resistance exercise.

Authors' conclusions

It is uncertain whether exercise training improves death, cardiovascular events, or the mental component of HRQoL in adults undergoing maintenance dialysis. Exercise training probably improves depressive symptoms, particularly when the intervention is maintained beyond four months. Exercise training is also likely to improve functional capacity. Low certainty evidence suggested that exercise training may improve fatigue, the physical component of quality of life, and pain. The safety of exercise training for adults undergoing dialysis remains uncertain.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Exercise training for adults receiving dialysis treatments

What is the issue?

People undergoing dialysis treatments are at higher risk of cardiovascular disease and depression, have a lower quality of life and limited survival than the general population. Furthermore, many people undergoing dialysis have difficulty performing daily activities because they lack the physical capacity and strength to do so. Multiple trials have assessed the potential for exercise training to improve the condition of adults undergoing dialysis, but no consensus has been reached.

What did we do?

We searched the medical literature for all randomised trials that assessed structured exercise programs in people undergoing dialysis. We then assessed the quality of those studies and combined their results to draw conclusions regarding the effect of exercise training to improve aspects of physical and mental health that are important to patients undergoing dialysis.

What did we find?

We found 89 studies involving 4291 participants. The exercise training programs lasted from eight weeks to two years and most often took place three times a week during the dialysis treatment. We could not determine the impact of exercise training on death, cardiovascular events (such as a heart attack) or mental well‐being. Moderate certainty evidence suggested that exercise training of any type is likely to improve depressive symptoms in adults undergoing dialysis, particularly when the exercise was maintained for longer than four months. Moderate quality evidence also suggested that exercise training may improve people's capacity to perform activities and tasks through the improvement of their capacity to walk and the strength and endurance of their legs. Exercise training may also improve fatigue and the physical aspects of quality of life, but the quality of the evidence was low. We could not conclude on the effect of exercise training on a person's mental well‐being.

Conclusions
Exercise training for people undergoing maintenance dialysis is likely to improve depression and their capacity to perform activities and tasks. Exercise training may also improve fatigue and pain sightly. Exercise training may improve the physical aspects of quality of life, but it is unclear whether it improves a person's mental well‐being. It is unclear whether exercise training reduces the number of deaths or cardiovascular events.

Authors' conclusions

Implications for practice

  • Exercise training of any type for two to 12 months is likely to improve depressive symptoms in adults undergoing dialysis. Low certainty evidence suggests that extending the intervention for more than four months may provide additional benefits. There is no data as to whether the effect of exercise training on depressive symptoms persist beyond the duration of the intervention.

  • Exercise training of any type for two to 12 months may reduce fatigue and improve the physical component of QoL in adults undergoing maintenance dialysis.

  • Exercise training of any type for three to 12 months may reduce pain in adults undergoing maintenance dialysis slightly. However, the 95% CI indicates that exercise training might make little or no difference in the level of pain.

  • Exercise training of any type for two to six months may increase patient functional capacity.

  • Existing studies of exercise training in adults undergoing dialysis were not designed to assess long‐term outcomes such as death and cardiovascular events.

  • The level of certainty is very low for the effect of exercise training on mortality, the mental component of HR‐QoL and resting blood pressure.

  • There is little to no information on the effect of exercise training for adults undergoing PD.

  • There is little to no information regarding the sustained effects of exercise training beyond the duration of the exercise program.

  • Adverse effects of exercise training in adults undergoing dialysis are rarely reported and poorly defined. The evidence for the safety of exercise training in this population is therefore very uncertain.

Implications for research

  • Studies of exercise training for adults undergoing dialysis should prioritise outcomes that are important to patients, their caregivers and health professionals, including death, cardiovascular events, fatigue, and pain.

  • Long‐term studies with extended follow‐up periods are needed to assess critical outcomes, including death and cardiovascular disease, and to assess the persistence of the effect beyond the intervention. For long‐term studies of an exercise intervention to be successful, strategies to enhance adherence to the interventions should be sought.

  • Studies of exercise training for adults undergoing dialysis should put measures in place to minimise the effects of the lack of blinding in the participants, particularly for patient‐reported outcomes.

  • Studies should avoid convenience sampling and guide their recruitment on sample size and power calculations based on an estimate of a clinically relevant effect.

  • Dialysis patients that are frail or with a heavy burden of comorbidities are an important subpopulation for which dedicated studies of exercise intervention should be considered.

  • Studies of exercise training for adults undergoing dialysis must thoroughly assess and report adverse effects related to the intervention.

Summary of findings

Open in table viewer
Summary of findings 1. Any exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Any exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: any exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise

Risk with any exercise

Death (any cause
Follow up: 3 years

159 per 1,000

151 per 1,000
(89 to 257)

RR 0.95
(0.56 to 1.62)

296 (1)

⊕⊝⊝⊝
VERY LOW 1 2 3

‐

Cardiovascular
events

Not reported

Not reported

‐

‐

‐

‐

Fatigue
Follow up: range 2 to 12 months

See comment

See comment

‐

326 (6)

⊕⊕⊝⊝
LOW 4 7

A pooled estimate of the effect was not calculated because the included studies assessed different dimensions of fatigue. Based on the direction of the effect in the included studies, any exercise may reduce fatigue

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 34 to 74 points

The mean physical component score was 4.1 points higher with exercise

(1.9 to 6.4 higher)

‐

656 (17)

⊕⊕⊝⊝
LOW 4 5

Any exercise may improve the physical component score of HRQoL

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 38 to 76 points

The mean mental component score was 2.5 points higher with exercise

(0.4 lower to 5.5 higher)

‐

656 (17)

⊕⊝⊝⊝
VERY LOW 4 5 6

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 47 to 87 points

The mean pain score was 5.3 points higher with exercise

(0.1 lower to 10.7 higher)

‐

872 (15)

⊕⊕⊝⊝
LOW 4 5

Any exercise may reduce pain however, the 95% CI indicates that exercise training might make little or no difference in the level of pain

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 0.62 SD lower with exercise

(1.00 to 0.24 lower)

‐

490 (11)

⊕⊕⊕⊝
MODERATE5

A SD of 0.2 represents a small difference between groups^

Any exercise probably improves depression. The magnitude of the effect was greater after four months of exercise training (SMD ‐1.26, 95% CI ‐1.80 to ‐0.72)

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 290 to 495 metres

The mean 6MWT was 49.9 metres further with exercise

(37.2 to 62.6 further)

‐

827 (19)

⊕⊕⊕⊝
MODERATE 5

Any exercise probably improves functional capacity

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐minute walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 High risk of bias: significantly greater proportion of participants lost to follow‐up in the exercise group compared to the control group

2 Imprecision: based on a single study that was not powered for this outcome

3 Indirectness: the outcome was assessed 2.5 years after the completion of the intervention

4 Indirectness: short interventions and short‐term follow‐up

5 High risk of bias in the included studies

6 Inconsistency: significant unexplained heterogeneity

7 Imprecision: outcome reported in few participants

Open in table viewer
Summary of findings 2. Aerobic exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Aerobic exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: aerobic exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise

Risk with Aerobic exercise

Death (any cause)
Follow up: 3 years

159 per 1,000

151 per 1,000
(89 to 257)

RR 0.95
(0.56 to 1.62)

296 (1)

⊕⊝⊝⊝
VERY LOW 1 2 3

‐

Cardiovascular
events

Not reported

Not reported

‐

‐

‐

‐

Fatigue
Follow up: range 2 to 12 months

See comment

See comment

‐

221 (4)

⊕⊝⊝⊝
VERY LOW 1 4 5

A pooled estimate of the effect was not calculated because the included studies assessed different dimensions of fatigue

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 34 to 71 points

The mean physical component score was 6.0 points higher with aerobic exercise

(1.3 lower to 10.7 higher)

‐

306 (9)

⊕⊝⊝⊝
VERY LOW 4 5 6

‐

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 39 to 65 points

The mean mental component score was 3.3 points higher with aerobic exercise

(0.9 lower to 7.6 higher)

‐

306 (9)

⊕⊝⊝⊝
VERY LOW 4 5 6 7

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 47 to 87 points

The mean pain score was 2.3 points higher with aerobic exercise

(1.6 lower to 6.1 higher)

‐

570 (8)

⊕⊕⊝⊝
LOW 4 6

Aerobic exercise may result in little to no difference in pain

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 0.19 SD lower with aerobic exercise

(0.89 lower to 0.52 higher)

‐

127 (4)

⊕⊝⊝⊝
VERY LOW 5 6 7

A SD of 0.2 represents a small difference between groups^

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 290 to 454 metres

The mean 6MWT was 53.0 metres further with aerobic exercise

(33.8 to 72.2 further)

‐

515 (10)

⊕⊕⊕⊝
MODERATE 6

Aerobic exercise probably improves functional capacity.

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐minute walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 High risk of bias: significantly greater proportion of participants lost to follow‐up in the exercise group compared to the control group

2 Imprecision: based on a single study that was not powered for this outcome

3 Indirectness: the outcome was assessed 2.5 years after the completion of the intervention

4 Indirectness: short interventions and short follow‐up

5 Imprecision: outcome reported in few participants

6 High risk of bias in the included studies

7 Inconsistency: significant unexplained heterogeneity

Open in table viewer
Summary of findings 3. Resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: resistance exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise

Risk with resistance exercise

Death (any cause)

Not reported

Not reported

‐

‐

‐

‐

Cardiovascular events

Not reported

Not reported

‐

‐

‐

‐

Fatigue

Assessed: Profile of Mood States score
Follow up: 12 weeks

The mean fatigue score was 8.95 points

The mean fatigue score was 1.88 points lower with resistance exercise

(4.14 lower to 0.38 higher)

‐

68 (1)

⊕⊝⊝⊝
VERY LOW 1 2

‐

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 46 to 74 points

The mean physical component score was 2.5 points higher with resistance exercise

(1.3 lower to 6.3 higher)

‐

176 (5)

⊕⊝⊝⊝
VERY LOW 2 3 4

‐

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 38 to 76 points

the mean mental component score was 0.7 points lower with resistance exercise

(5.9 lower to 4.6 higher)

‐

176 (5)

⊕⊝⊝⊝
VERY LOW 2 3 4 5

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 60 to 82 points

The mean pain score was 10.7 points higher with resistance exercise

(6.5 lower to 28.0 higher)

‐

154 (5)

⊕⊝⊝⊝
VERY LOW 2 3 4

‐

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 0.52 SD lower with resistance exercise

(0.92 to 0.12 lower)

‐

99 (2)

⊕⊝⊝⊝
VERY LOW 2 3 4

A SD of 0.2 represents a small difference between groups^

The evidence is very uncertain about the effect of resistance exercise on depression

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 407 to 495 metres

The mean 6MWT was 44.7 metres further with resistance exercise

(27.0 to 62.4 further)

‐

216 (7)

⊕⊕⊕⊝
MODERATE 2

Resistance exercise probably improves functional capacity

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐minute walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Imprecision: based on a single study that was not powered for this outcome

2 High risk of bias in the included studies

3 Indirectness: short interventions and short follow‐up

4 Imprecision: outcome reported in few participants

5 Inconsistency: significant heterogeneity

Open in table viewer
Summary of findings 4. Combined aerobic and resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Combined aerobic and resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: combined aerobic and resistance exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise)

Risk with combined aerobic and resistance exercise

Death (any cause)

Not reported

Not reported

‐

‐

‐

‐

Cardiovascular events

Not reported

Not reported

‐

‐

‐

‐

Fatigue

Not reported

Not reported

‐

‐

‐

‐

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 38 to 51

The mean physical component score was 4.4 points higher with combined exercise
(1.9 higher to 6.8 higher)

‐

228 (6)

⊕⊝⊝⊝
VERY LOW 1 2 3

The evidence is very uncertain about the effect of combined aerobic and resistance exercise on the physical component of HRQoL

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 40 to 43

The mean mental component score was 2.6 points higher with combined exercise

(1.7 lower to 6.9 higher)

‐

228 (6)

⊕⊝⊝⊝
VERY LOW 1 2 3

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 68 to 83 points

The mean pain score was 4.0 points higher
with combined exercise

(2.5 lower to 10.5 higher)

‐

161 (3)

⊕⊝⊝⊝
VERY LOW 12 3

‐

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 1.0 SD lower with combined exercise
(1.7 lower to 0.3 lower)

‐

214 (4)

⊕⊝⊝⊝
VERY LOW 2 3

A SD of 0.2 represents a small difference between groups^

The evidence is very uncertain about the effect of combined aerobic and resistance exercise on depression

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 399 to 430 metres

The mean 6MWT was 53.6 metres further
(39.4 to 67.9 further)

‐

138 (6)

⊕⊕⊕⊝
MODERATE 1 2

Combined aerobic and resistance exercise probably improves functional capacity.

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐metre walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Indirectness: short interventions and short follow‐up

2 High risk of bias in the included studies

3 Imprecision: outcome reported in few participants

Background

Description of the condition

Kidney failure on dialysis is a debilitating condition weighing heavily on patients' physical and psychosocial health. Death is high, particularly in older age groups, with less than 50% surviving five years after initiation (ERA‐EDTA 2017; USRDS 2017; ANZDATA 2019). In addition to the time and commitment for the treatment itself, dialysis is often accompanied by debilitating symptoms such as fatigue, pain, pruritus, cramping, sleep disturbances and sexual dysfunction. As a result, quality of life (QoL) for individuals undergoing dialysis is among the lowest of any chronic diseases (Wyld 2012).

Neuromuscular complications of chronic kidney disease (CKD) have long been described (Serratrice 1967; Tyler 1975). Multiple uraemic, hormonal, immunologic, mechanical and myocellular changes are likely to contribute to skeletal muscle wasting in dialysis patients (Fahal 2014). Furthermore, the transfer of oxygen to the muscle cells is impaired despite the correction of anaemia (Stray‐Gundersen 2016). In consequence, people suffering from kidney failure have a severely impaired capacity to exercise, averaging 50% to 60% of the age‐expected norm (Kaysen 2011; Painter 2017) and low self‐reported physical functioning even amongst younger patients (DeOreo 1997; Painter 2005). Correspondingly, people with kidney failure have extremely low levels of physical activity and rank under the fifth percentile of healthy age‐matched individuals (Cupisti 2017; Johansen 2010). Of note, low exercise capacity, low physical functioning and low levels of physical activity have all been associated with a higher risk of death in this population (DeOreo 1997; Johansen 2013; Knight 2003; Sietsema 2004).

Description of the intervention

Physical activity varies in its nature, intensity, frequency, and duration. Aerobic or cardiovascular exercise implies an increase in heart and respiratory rate such as running, cycling, walking, or swimming. Resistance exercise relates to activities leading to increased muscle strength, tone and bulk, such as repeated movements of the upper and lower limbs against gravity with weights or against elastic bands. The World Health Organization recommends that adults aged 18 to 64 years old perform a minimum of 150 minutes of moderate‐intensity aerobic physical activity or 75 minutes of vigorous‐intensity aerobic physical activity throughout the week to improve cardiorespiratory and muscular fitness (WHO 2010). Based on evidence in the general population, the 2005 KDOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients recommend working towards 30 minutes of moderate exercise most days for adults on dialysis (KDOQI 2005).

How the intervention might work

Exercise training has the potential to improve many outcomes that are important to patients receiving dialysis treatments. In the general population, physical activity may reduce the risk of death (any cause), coronary heart disease, high blood pressure, stroke, type 2 diabetes, metabolic syndrome, and colon and breast cancer (WHO 2010). Fatigue, a debilitating symptom affecting 55% to 97% of people receiving dialysis (Chang 2001; Jacobson 2019; Jhamb 2008; Yngman‐Uhlin 2010), was improved after exercise training in people with cancer (Cramp 2012) and chronic fatigue syndrome (Larun 2019). Exercise can also improve depression (Cooney 2013), which affects 23% to 39% of adults undergoing dialysis (Palmer 2013). Finally, the previous version of this review demonstrated exercise training is likely to improve physical fitness, physical functioning and health‐related QoL (HRQoL) in adults with CKD (Heiwe 2011). Through better cardiorespiratory capacity and strength, exercise training may improve patients’ capacity to perform their daily activities and ease the burden of dialysis treatments.

Why it is important to do this review

Patients, caregivers, and health professionals alike believe lifestyle interventions, including exercise, should be a top priority for research in CKD (Manns 2014; Tong 2015). However, most randomised controlled trials (RCTs) do not address patients’ priorities or patient‐important outcomes (Tong 2018). The previous version of this review found exercise training improved physical fitness, HRQoL, and some cardiovascular and nutritional parameters. However, the certainty of the evidence was low, and many important outcomes such as death, cardiovascular events, and fatigue could not be assessed. Numerous studies have since been published, but no consensus has emerged concerning the effects and safety of exercise training for adults undergoing maintenance dialysis.

Differences with the previous Cochrane review

In its previous form, the Cochrane review for exercise training in adults with CKD included studies performed in individuals at all stages of CKD, including kidney transplantation and earlier stages of CKD (Heiwe 2011). As the exercise interventions in adults undergoing dialysis differed significantly from those in adults not receiving dialysis, and because these populations differ in their needs, risk factors and coexisting diseases, an editorial decision was taken to divide the previously published review into three separate reviews. The current review will focus on RCTs of exercise interventions in adults undergoing maintenance haemodialysis (HD) or peritoneal dialysis (PD), and separate reviews to be published at a later time will focus on adults with CKD not undergoing dialysis and kidney transplant recipients.

Objectives

To assess the benefits and safety of regular structured exercise training in adults undergoing dialysis on patient‐important outcomes including death, cardiovascular events, fatigue, functional capacity, pain, and depression. We also aimed to define the optimal prescription of exercise in adults undergoing dialysis.

Methods

Criteria for considering studies for this review

Types of studies

We included all RCTs and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) evaluating a structured program of regular physical exercise training in adults undergoing dialysis.

Types of participants

Inclusion criteria

We included studies involving adults receiving maintenance HD or PD treatments.

Exclusion criteria

We excluded studies involving children, kidney transplant recipients or adults with CKD not undergoing dialysis.

Types of interventions

We included interventions consisting of a structured program of regular physical exercise lasting a minimum of eight weeks to ensure the intervention consisted of regular ongoing exercise training. Interventions consisting solely of the recommendation or promotion of physical activity were excluded. Interventions targeting a single muscle group for purposes other than improvement of the general fitness, such as respiratory muscle training or hand‐forearm exercises for arteriovenous fistula maturation, were also excluded.

Eligible studies had to include a control group that did not partake in any significant exercise training. Sham exercises such as light stretching exercises were allowed. Co‐interventions with exercise training were allowed if the co‐interventions were also administered to the control group.

Types of outcome measures

While all outcomes were collected, this review focused on patient‐important outcomes, which we identified using the SONG core‐outcome set for adults undergoing HD (SONG‐HD 2017). When the outcomes were measured at multiple time points within the same study, we included the results corresponding to the end of the intervention period in the meta‐analyses. For long‐term outcomes such as death and cardiovascular events, we also recorded outcome results that were measured after the completion of the intervention.

Primary outcomes

  • Death (any cause)

  • Cardiovascular events

  • Fatigue

Secondary outcomes

  • HRQoL

  • Pain

  • Depression

  • Functional capacity

  • Resting blood pressure: systolic blood pressure (SBP) and diastolic blood pressure (DBP)

  • Adherence to the exercise program

  • Adverse events related to the exercise program

Other outcomes

We also assessed exploratory outcomes that were either reported in the previous version of this review (Heiwe 2011) or were commonly reported across the included studies.

  • Haemoglobin

  • Dialysis adequacy

  • Potassium

  • Physical fitness (aerobic capacity, muscular strength)

  • Measures from cardiac ultrasound (left ventricular ejection fraction, left ventricular mass index)

  • Body mass indices (body mass index, muscle mass, fat mass)

  • Nutritional measures (albumin, energy intake, protein intake)

  • Blood lipids (total cholesterol, low‐density lipoproteins (LDL), high‐density lipoproteins (HDL), triglycerides)

  • Bone health (calcium, phosphorus, parathyroid hormone)

  • Markers of inflammation (C‐reactive protein)

Search methods for identification of studies

Electronic searches

We searched the Cochrane Kidney and Transplant Register of Studies to 23 December 2020 through contact with the Information Specialist using search terms relevant to this review. The Cochrane Kidney and Transplant Specialised Register contains studies identified from the following sources.

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

  2. Weekly searches of MEDLINE OVID SP

  3. Searches of kidney and transplant journals, and the proceedings and abstracts from major kidney and transplant conferences

  4. Searching of the current year of EMBASE OVID SP

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

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

Studies contained in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on the scope of Cochrane Kidney and Transplant. Details of search strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available on the Cochrane Kidney and Transplant website under CKT Register of Studies.

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

Searching other resources

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

  2. Contacting relevant individuals/organisations seeking information about unpublished or incomplete studies.

Data collection and analysis

Selection of studies

Two authors independently screened the titles and abstracts from the electronic search and retained potentially eligible studies. Two authors then independently assessed the abstracts and, when necessary, the full published text and identified the studies to be included in the review.

Data extraction and management

Two authors independently extracted the data from each study using standardised data extraction forms. Studies in a non‐English language were translated into English. Results from multiple publications of the same study were grouped, and the primary study publication was used as the reference for the methods. One author performed the final data entry, and a second verified each entry using the independently collected extraction sheet. Disagreements were resolved by returning to the full published text, and a third author was available for persisting disagreements.

Assessment of risk of bias in included studies

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

  • Was there adequate sequence generation (selection bias)?

  • Was allocation adequately concealed (selection bias)?

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

  • Participants and personnel (performance bias)

  • Outcome assessors (detection bias)

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

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

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

Due to the nature of the intervention, we assumed that the studies that did not report whether the participants were blinded did not attempt to blind the participants.

Measures of treatment effect

We used the mean difference (MD) with 95% confidence intervals (CI) to measure the effect of exercise training on continuous outcomes. Where the included studies used different measuring scales, we used the standardised mean difference (SMD). For dichotomous outcomes, we used risk ratios (RR) with 95% CI to measure the effect of the intervention.

To assess whether the observed effect is clinically meaningful, we considered the following for each outcome measure.

  • Anchor‐based estimates of the minimal clinically important differences

  • Distribution methods such as the standardised mean difference

  • Definitions of a clinically meaningful effect that have been used in previous RCTs and systematic reviews of adults undergoing dialysis.

When an estimate of the minimal clinically important difference was not available for the kidney failure population, we used estimates established in populations with other debilitating chronic diseases.

Unit of analysis issues

This review included studies with non‐standard designs such as cross‐over RCTs, cluster RCTs, cluster step‐wedge RCTs, factorial RCTs and studies with two or more intervention arms.

Cross‐over RCTs

Cross‐over RCTs were eligible for inclusion in the review. However, the exercise intervention administered in the first study period was likely to have carry‐over effects into the subsequent study periods from long‐lasting effects and behaviour changes arising from the intervention. Therefore, we planned to only include outcome data following the first treatment period, where the intervention was randomly allocated analogous to a two‐arms parallel RCT. There was one cross‐over RCT eligible for inclusion in the review.

Cluster RCTs

Cluster RCTs were eligible for inclusion in the review. To correct for the correlation between the individuals within a cluster, we divided the effective sample size by the design effect defined as 1+ICC(M‐1), where M is the average cluster size and ICC the intra‐cluster correlation coefficient. Two cluster RCTs were eligible for inclusion in the review and their published article provided the ICC used for sample size calculation.

Step‐wedge RCTs

Step‐wedge RCTs were eligible for inclusion in the review. We collected and analysed the results at the latest time point before the last group initiated the intervention. The last group which had not yet initiated the intervention was used as the control group, analogous to a parallel RCT.

Factorial RCTs

Factorial RCTs were eligible for inclusion in the review. We pooled the results from the arm receiving exercise and the alternative intervention together with the results of the arm receiving exercise only under the exercise group and pooled the results from the arm receiving only the alternative intervention together with the results of the arm receiving no intervention under the control arm.

Multi‐arms RCTs

RCTs with more than two arms were eligible for inclusion in the review. One of the arms had to be a control group not undertaking any significant exercise training for the study to be included. We extracted the results from all arms meeting the inclusion criteria for the intervention. When two or more arms from the same study were relevant to a meta‐analysis (e.g. an aerobic exercise arm and a resistance exercise arm both eligible for a meta‐analysis of any exercise), we combined the results of each arm as if they were the same treatment arm. For subgroup analyses of continuous outcomes, if two or more arms from the same study were included in distinct subgroups but shared the same control group, we divided the sample size of the control group by the number of arms. At all times, we took special care not to include the same participants twice in either the treatment or the control group for all meta‐analyses.

Dealing with missing data

We contacted the study authors by written correspondence whenever data was missing from the publication. We also contacted the authors of abstracts for which we could not identify a full‐text publication. Whenever we suspected a report to be a secondary publication of another included study, we also contacted the authors for clarification.

When results were only provided in the form of graphs, we extracted, to the best of our abilities, the results from the graph and included them in meta‐analyses. For continuous outcomes, when only the median and the range or only the median and the interquartile range were reported, we estimated the mean and the standard deviation (SD) using the method described by Wan 2014. For continuous outcomes, when the SD was not reported, we imputed the missing SD using the highest SD from the other studies included in the meta‐analysis.

Assessment of heterogeneity

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

  • 0% to 40%: might not be important

  • 30% to 60%: may represent moderate heterogeneity

  • 50% to 90%: may represent substantial heterogeneity

  • 75% to 100%: considerable heterogeneity.

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

Assessment of reporting biases

In meta‐analyses of 10 studies or more and in the absence of statistical heterogeneity, we used funnel plots whenever possible to assess for the potential small study bias (Higgins 2011).

Data synthesis

In the meta‐analyses, we pooled the estimated effects of exercise training using the DerSimonian and Laird method for random effects (DerSimonian 1986).

Subgroup analysis and investigation of heterogeneity

We performed subgroup analyses to investigate the reasons behind heterogeneity. We performed the following subgroup analyse whenever there was evidence of significant heterogeneity in the effect of the intervention:

  • Type of exercise (aerobic versus resistance versus combined aerobic and resistance)

  • Duration of intervention (4 months or less versus longer)

  • Intensity of the exercise intervention (light to moderate versus moderate versus moderate to vigorous versus unclear)

  • Risk of bias (studies that blinded participants to treatment allocation versus those that didn't).

Sensitivity analysis

For each of the primary and secondary outcomes, we performed sensitivity analyses based on the risk of bias (study at higher risk of bias versus those at lower risk of bias).

Summary of findings and assessment of the certainty of the evidence

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

  • Death (any cause)

  • Cardiovascular events

  • Fatigue

  • HRQoL ‐ physical component score

  • HRQoL ‐ mental component score

  • Pain

  • Depression

  • Functional capacity ‐ 6MWT

Results

Description of studies

Results of the search

Figure 1 shows the number of studies screened and included in the 2011 review and in this current review.

Figure 1
Flow diagram showing study identification and selection

Flow diagram showing study identification and selection

2011 review

The original literature search for the 2011 review identified 2576 reports. Sixty‐one reports from 45 studies were included (Heiwe 2011). Studies were mainly excluded because they were not RCTs, did not involve an exercise intervention or did not involve a control group.

2021 update

The 2011 review has been divided into three independent reviews, one for adults undergoing dialysis, one for adults with CKD not undergoing dialysis and one for kidney transplant recipients. Of the 45 studies included in 2011, only studies involving participants undergoing dialysis were retained for this review update. We have confirmed with the authors that two studies were secondary publications of other already included studies, and have been combined for this update (Harter 1985; Kouidi 1997). There are 33 studies remaining from the 2011 review (Akiba 1995; Carmack 1995; Chen 2010; Deligiannis 1999; Deligiannis 1999a, DePaul 2002; Frey 1999; Goldberg 1983; Harter 1985; Johansen 2006; Koh 2009; Konstantinidou 2002; Kopple 2007; Koufaki 2002; Koufaki 2003; Kouidi 1997; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Kouidi 2008; Kouidi 2010; Lee 2001; Matsumoto 2007; Molsted 2004; Ouzouni 2009; Painter 2002a; Parsons 2004; PEAK 2006; Segura‐Orti 2009; Toussaint 2008; Tsuyuki 2003; van Vilsteren 2005; Yurtkuran 2007).

We searched the Cochrane Kidney and Transplantation up to December 2020 and identified 162 new potentially eligible reports. After reviewing abstracts and full‐text publications, we identified: 56 new included studies (93 reports); four reports of four previously included studies; 37 new excluded studies (48 reports); two reports of two previously excluded studies; and five ongoing studies (6 reports). Eight studies have been completed but are yet to publish results.

In total, for this 2021 update, we included 89 studies (143 reports) and excluded 41 studies (54 reports). There are five ongoing studies and eight studies awaiting classification which will be assessed in a future update of this review.

We contacted via email the authors of 25 studies (Abreu 2017; Abundis Mora 2017; Afshar 2010; Afshar 2011; Bennett 2013; Burrows 2018; Goldberg 1983, Harter 1985, IHOPE 2019; Kouidi 1997; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Kouidi 2008; Kouidi 2010; Ma 2018; Marinho 2016; Mitsiou 2015; Miura 2015; Paluchamy 2018; Reboredo 2010; Rouchon 2016; Sheshadri 2020; Wilund 2010; Zhao 2017) and received unpublished data from two (Paluchamy 2018; Rouchon 2016).

Included studies

Details of each included study are provided in Characteristics of included studies and Appendix 3.

We included 89 studies (143 reports; 4291 randomised participants). There was one cross‐over RCT (Toussaint 2008), one cluster RCT (CYCLE‐HD 2016), one step‐wedge cluster RCT (Bennett 2013), and three factorial RCTs (Johansen 2006; Mitsiou 2015; Painter 2002a). The remaining 83 studies were parallel‐group RCTs. Sixteen studies had three arms (Afshar 2010; Amini 2016; AVANTE‐HEMO 2020; Bennett 2013; Deligiannis 1999a; de Lima 2013; Dobsak 2012; Giannaki 2013a; IHOPE 2019; Koh 2009; McAdams‐DeMarco 2018; McGregor 2018; Miura 2015; Pellizzaro 2013; Suhardjono 2019; Zhao 2017) and seven had four arms (Cho 2018; DIALY‐SIZE 2016; Johansen 2006; Konstantinidou 2002; Kopple 2007, Mitsiou 2015; Painter 2002a). The remaining studies had two arms.

Nine studies were only published as abstracts (Abundis Mora 2017; Burrows 2018; CYCLE‐HD 2016; Koufaki 2003; Jong 2004; Ma 2018; Mitsiou 2015; Miura 2015; Rouchon 2016). Twelve studies could not contribute to the meta‐analyses (Abundis Mora 2017; Burrows 2018; Dashtidehkordi 2019; Harter 1985; Koufaki 2003; Kouidi 2003; Kouidi 2005; Ma 2018; McAdams‐DeMarco 2018; Mitsiou 2015; Miura 2015; Mortazavi 2013) because they either did not report the number of participants in which the outcome was measured or did not report outcomes that were relevant to this review. Therefore, 77 studies (3846 randomised participants) contributed to the meta‐analyses.

Twenty‐six studies were conducted in Europe/UK (ACTINUT 2013; CYCLE‐HD 2016; Deligiannis 1999; Deligiannis 1999a; Dobsak 2012; EXCITE 2014; Giannaki 2013a; Groussard 2015; Konstantinidou 2002; Koufaki 2002; Koufaki 2003; Kouidi 1997; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Kouidi 2008; Kouidi 2010; Marinho 2016; McGregor 2018; Mitsiou 2015; Molsted 2004; Ouzouni 2009; Rouchon 2016; Samara 2016; Segura‐Orti 2009; van Vilsteren 2005), 22 in North America (Abundis Mora 2017; AVANTE‐HEMO 2020; Burrows 2018; Carmack 1995; Chen 2010; Cooke 2018; DePaul 2002; DIALY‐SIZE 2016; Dong 2011; Frey 1999; Goldberg 1983; Harter 1985; IHOPE 2019; Johansen 2006; Kopple 2007; Martin‐Alemany 2016; McAdams‐DeMarco 2018; Olvera‐Soto 2016; Parsons 2004; Painter 2002a; Sheshadri 2020; Wilund 2010), 17 in Asia (Akiba 1995; CHAIR 2015; Chang 2010; Cho 2018; Jong 2004; Lee 2001; Liao 2016; Ma 2018; Matsumoto 2007; Miura 2015; Paluchamy 2018; Song 2012a; Suhardjono 2019; Tsuyuki 2003; Uchiyama 2019; Wu 2014d; Zhao 2017), 10 in the Middle East (Afshar 2010; Afshar 2011; Amini 2016; Dashtidehkordi 2019; Makhlough 2012; Momeni 2014; Mortazavi 2013; Rahimimoghadam 2017; Rezaei 2015; Yurtkuran 2007), eight in South America (Abreu 2017; de Lima 2013; Fernandes 2019; Marchesan 2016; Martins do Valle 2020; Pellizzaro 2013; Reboredo 2010; Rosa 2018), four in Oceania (Bennett 2013; Koh 2009; PEAK 2006; Toussaint 2008), and two in Africa (Frih 2017a; Soliman 2015).

Participants

Three studies exclusively included participants on PD (Jong 2004; Rouchon 2016; Uchiyama 2019), and four others included participants either on maintenance HD or PD (EXCITE 2014; Koufaki 2002; Koufaki 2003; Sheshadri 2020) for a total of 151 included participants receiving PD. The remaining studies included participants on HD only. Exclusion criteria were diverse but often included any medical condition or physical incapacities precluding the participant from undertaking the exercise intervention, cognitive limitations, medical instability, and significant cardiac events in the months leading to the trial. Many studies relied on a convenience sample of prevalent HD patients with only 15 studies reporting a power and sample size calculation (AVANTE‐HEMO 2020; Bennett 2013; Chang 2010; CYCLE‐HD 2016; Dong 2011; EXCITE 2014; Giannaki 2013a; IHOPE 2019; Koh 2009; Rahimimoghadam 2017; Rezaei 2015; Sheshadri 2020; Song 2012a; Suhardjono 2019; Uchiyama 2019).

The number of participants randomised ranged from 11 and 296 participants (median = 38) and 30 (34%) studies randomised less than 30 participants (Abundis Mora 2017; ACTINUT 2013; Afshar 2010; Afshar 2011; Akiba 1995; Burrows 2018; CHAIR 2015; Cooke 2018; Dobsak 2012; Frey 1999; Giannaki 2013a; Goldberg 1983; Groussard 2015; Harter 1985; Koufaki 2003; Kouidi 2004a; Marchesan 2016; Marinho 2016; Martins do Valle 2020; McAdams‐DeMarco 2018; Mortazavi 2013; Paluchamy 2018; Parsons 2004; Reboredo 2010; Rouchon 2016; Samara 2016; Segura‐Orti 2009; Toussaint 2008; Tsuyuki 2003; Wilund 2010). The rate of attrition ranged from 0 to 49% (median 13%).

The participants mean age ranged from 30 to 72 years. In 15 studies, the participants' mean age was lower than 40 years old (Akiba 1995; AVANTE‐HEMO 2020; CHAIR 2015; DIALY‐SIZE 2016; Goldberg 1983; Harter 1985; Marinho 2016; Martin‐Alemany 2016; Mortazavi 2013; Olvera‐Soto 2016; Rahimimoghadam 2017; Tsuyuki 2003; Wu 2014d; Yurtkuran 2007; Zhao 2017) and older than 60 years in 12 (ACTINUT 2013; Bennett 2013; Chen 2010; EXCITE 2014; Frih 2017a; Groussard 2015; Liao 2016; Marchesan 2016; Miura 2015; PEAK 2006; Rouchon 2016; Uchiyama 2019).

The included studies involved predominantly males (62% of all the included participants). Three studies included only men (Afshar 2010; Afshar 2011, Frih 2017a) and six included more than 75% men (DIALY‐SIZE 2016; EXCITE 2014; Rahimimoghadam 2017; Samara 2016; Sheshadri 2020; Wu 2014d). The average duration of dialysis across studies ranged from 1.8 to 6.0 years, and the average BMI across studies ranged from 20.1 to 31.2 kg/m². Eighteen studies had a mean participant's BMI above 25 (Chen 2010; Cooke 2018; de Lima 2013; Dobsak 2012; Dong 2011; EXCITE 2014; Giannaki 2013a; IHOPE 2019; Johansen 2006; Koh 2009; Koufaki 2002; Kouidi 1997; McAdams‐DeMarco 2018; McGregor 2018; PEAK 2006; Rouchon 2016; Soliman 2015; Toussaint 2008).

Study comparisons

Within the 89 published studies, there were 100 different eligible exercise interventions. The characteristics of the included exercise interventions are detailed in Table 1 and in Characteristics of included studies. The interventions lasted between eight weeks and two years. In 49 studies (55%), the intervention lasted three months or less (Abreu 2017; Afshar 2010; Afshar 2011; Akiba 1995; Amini 2016; AVANTE‐HEMO 2020; Bennett 2013; CHAIR 2015; Chang 2010; Cho 2018; Dashtidehkordi 2019; de Lima 2013; DePaul 2002; DIALY‐SIZE 2016; Fernandes 2019; Frey 1999; Johansen 2006; Jong 2004; Koufaki 2002; Koufaki 2003; Lee 2001; Liao 2016; Makhlough 2012; Marinho 2016; Martin‐Alemany 2016; Martins do Valle 2020; McAdams‐DeMarco 2018; McGregor 2018; Miura 2015; Momeni 2014; Olvera‐Soto 2016; Paluchamy 2018; Parsons 2004; PEAK 2006; Pellizzaro 2013; Rahimimoghadam 2017; Rezaei 2015; Reboredo 2010; Rosa 2018; Rouchon 2016; Sheshadri 2020; Soliman 2015; Song 2012a; Suhardjono 2019; Toussaint 2008; Uchiyama 2019; van Vilsteren 2005; Wu 2014d; Yurtkuran 2007) whilst only 10 interventions lasted more than six months (Abundis Mora 2017; Goldberg 1983; Harter 1985; IHOPE 2019; Kouidi 2003 ; Kouidi 2005; Kouidi 2010; Ma 2018; Matsumoto 2007; Ouzouni 2009).

Aerobic exercise

Aerobic training was assessed in 56 (63%) studies (Abundis Mora 2017; ACTINUT 2013; Afshar 2010 Afshar 2011; Akiba 1995; Amini 2016; AVANTE‐HEMO 2020; Carmack 1995; CHAIR 2015; Chang 2010; Cho 2018; Cooke 2018; CYCLE‐HD 2016; Dashtidehkordi 2019; Deligiannis 1999a; de Lima 2013; DIALY‐SIZE 2016; Dobsak 2012; EXCITE 2014; Fernandes 2019; Frey 1999; Giannaki 2013a; Goldberg 1983; Harter 1985; Groussard 2015; IHOPE 2019; Jong 2004; Koh 2009; Kopple 2007; Koufaki 2002; Koufaki 2003; Kouidi 1997; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Lee 2001; Liao 2016; Makhlough 2012; Matsumoto 2007; McAdams‐DeMarco 2018; McGregor 2018; Miura 2015; Momeni 2014; Mortazavi 2013; Painter 2002a; Paluchamy 2018; Parsons 2004; Reboredo 2010; Samara 2016; Sheshadri 2020; Suhardjono 2019; Toussaint 2008; Tsuyuki 2003; Wilund 2010; Wu 2014d; Zhao 2017).

The most common intervention consisted of stationary cycling on an ergometer in 46 studies (Abundis Mora 2017; ACTINUT 2013; Afshar 2010; Afshar 2011; Akiba 1995; AVANTE‐HEMO 2020; Carmack 1995; Chang 2010; Cho 2018; Cooke 2018; CYCLE‐HD 2016; Dashtidehkordi 2019; Deligiannis 1999a; de Lima 2013; DIALY‐SIZE 2016; Dobsak 2012; Fernandes 2019; Frey 1999; Giannaki 2013a; Goldberg 1983; Harter 1985; Groussard 2015; IHOPE 2019; Koh 2009; Kopple 2007; Koufaki 2003; Kouidi 1997; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Lee 2001; Liao 2016; Matsumoto 2007; McAdams‐DeMarco 2018; McGregor 2018; Miura 2015; Momeni 2014; Mortazavi 2013; Painter 2002a; Paluchamy 2018; Parsons 2004; Reboredo 2010; Suhardjono 2019; Toussaint 2008; Wilund 2010; Wu 2014d), but also included chair‐stand exercises (CHAIR 2015), walking (EXCITE 2014; Goldberg 1983; Harter 1985; Jong 2004; Koh 2009; Kouidi 1997; Lee 2001; Sheshadri 2020; Tsuyuki 2003), road cycling (Zhao 2017), and swimming (Samara 2016).

Duration of the aerobic training sessions varied between 10 and 90 minutes, with most intervention being between 20 and 40 minutes/sessions (ACTINUT 2013; Afshar 2010; Afshar 2011; Akiba 1995; AVANTE‐HEMO 2020; Carmack 1995; Chang 2010; Cho 2018; CYCLE‐HD 2016; Dashtidehkordi 2019; Deligiannis 1999a; Lee 2001; de Lima 2013; DIALY‐SIZE 2016; Dobsak 2012; Fernandes 2019; Frey 1999; Goldberg 1983; Groussard 2015; IHOPE 2019; Koh 2009; Koufaki 2003; Lee 2001; Liao 2016; Matsumoto 2007; Momeni 2014; Mortazavi 2013; Painter 2002a; Parsons 2004; Reboredo 2010; Samara 2016; Suhardjono 2019; Toussaint 2008; Tsuyuki 2003; Wilund 2010).

There was considerable heterogeneity on the method to assess the intensity of the exercise training: 19 studies used a version of the Borg scale of perceived exertion (ACTINUT 2013; Afshar 2011; Akiba 1995; AVANTE‐HEMO 2020; Chang 2010; Cooke 2018; CYCLE‐HD 2016; de Lima 2013; DIALY‐SIZE 2016; IHOPE 2019; Koh 2009; Lee 2001; Liao 2016; Miura 2015; Mortazavi 2013; Reboredo 2010; Samara 2016; Wilund 2010; Wu 2014d); six used a percentage of the maximum heart rate (Deligiannis 1999a; Fernandes 2019; Frey 1999; Matsumoto 2007; Suhardjono 2019; Tsuyuki 2003); four used a percentage of the maximum load (Dobsak 2012; Giannaki 2013a; Groussard 2015; Parsons 2004); four using a percentage of the maximum oxygen consumption (Goldberg 1983; Harter 1985; Kopple 2007; Koufaki 2003); three using a combination of methods (Kouidi 1997; McGregor 2018; Painter 2002a); and the remaining studies did not report the method they used. Using the interpretation of each scale we classified five studies as light to moderate intensity (perceived as light to somewhat hard) (de Lima 2013; Dobsak 2012; Miura 2015; Mortazavi 2013; Parsons 2004), 23 studies as moderate (perceived as somewhat hard) (Abundis Mora 2017; ACTINUT 2013; Akiba 1995; AVANTE‐HEMO 2020; Chang 2010; Deligiannis 1999; DIALY‐SIZE 2016; Fernandes 2019; Giannaki 2013a; Goldberg 1983; Harter 1985; Groussard 2015; IHOPE 2019; Koh 2009; Kopple 2007; Kouidi 1997; Lee 2001; Matsumoto 2007; McGregor 2018; Reboredo 2010; Samara 2016; Suhardjono 2019; Tsuyuki 2003; Wilund 2010), and nine studies as moderate to vigorous (perceived as somewhat hard to hard) (Afshar 2010; Afshar 2011; Cooke 2018; CYCLE‐HD 2016; Frey 1999; Koufaki 2002; Liao 2016; Painter 2002a; Wu 2014d).

Resistance exercise

Twenty‐one (24%) studies assessed resistance training (Abreu 2017; Afshar 2010; AVANTE‐HEMO 2020; Bennett 2013; Chen 2010; Cho 2018; de Lima 2013; DIALY‐SIZE 2016; Dong 2011; Johansen 2006; Kopple 2007; Marinho 2016; Martin‐Alemany 2016; Martins do Valle 2020; Olvera‐Soto 2016; PEAK 2006; Pellizzaro 2013; Rahimimoghadam 2017; Rosa 2018; Segura‐Orti 2009; Song 2012a).

Twelve exercise programs focused solely on the lower body (Abreu 2017; Afshar 2010; Bennett 2013; Chen 2010; de Lima 2013; DIALY‐SIZE 2016; Dong 2011; Johansen 2006; Kopple 2007; Marinho 2016; Pellizzaro 2013; Segura‐Orti 2009) and eight exercised both the upper and lower limbs (AVANTE‐HEMO 2020; Cho 2018; Martin‐Alemany 2016; Martins do Valle 2020; Olvera‐Soto 2016; PEAK 2006; Rosa 2018; Song 2012a). Eight studies used weights (Abreu 2017; Afshar 2010; Chen 2010; DIALY‐SIZE 2016; Johansen 2006; Martin‐Alemany 2016; Martins do Valle 2020; Pellizzaro 2013), three studies used resistance bands (AVANTE‐HEMO 2020; Bennett 2013; Cho 2018), six studies used both (DIALY‐SIZE 2016; Marinho 2016; Martin‐Alemany 2016; Olvera‐Soto 2016; Rosa 2018; Song 2012a) and two studies used a leg press machine (Dong 2011; Kopple 2007).

Eight studies defined the duration of the exercise session in terms of the time required to complete the prescribed number of repetitions (AVANTE‐HEMO 2020; Bennett 2013; DIALY‐SIZE 2016; Dong 2011; Johansen 2006; Marinho 2016; Martins do Valle 2020; Pellizzaro 2013). In 10 studies (Abreu 2017; Afshar 2010; AVANTE‐HEMO 2020; Martin‐Alemany 2016; Olvera‐Soto 2016; PEAK 2006; Rahimimoghadam 2017; Rosa 2018; Segura‐Orti 2009; Song 2012a), the duration of the training sessions varied between 10 and 50 minutes. and in four studies the duration was not reported or unclear (Chen 2010; Cho 2018; de Lima 2013; Kopple 2007).

Eight studies defined the target level of intensity on the Borg scale of perceived exertion (Afshar 2010; AVANTE‐HEMO 2020; DIALY‐SIZE 2016; Martin‐Alemany 2016; Martins do Valle 2020; PEAK 2006; Segura‐Orti 2009; Song 2012a), one on the Omni scale of perceived exertion (Chen 2010), six as a percentage of the one, three or five‐repetition maximum load (Abreu 2017; Dong 2011; Johansen 2006; Kopple 2007; Marinho 2016; Pellizzaro 2013), and six did not report the level of intensity (Bennett 2013; Cho 2018; de Lima 2013; Olvera‐Soto 2016; Rahimimoghadam 2017; Rosa 2018). Using the interpretation of each scale we classified 12 studies as moderate (perceived as somewhat hard) (Abreu 2017; AVANTE‐HEMO 2020; Chen 2010; DIALY‐SIZE 2016; Dong 2011; Johansen 2006; Kopple 2007; Marinho 2016; Martin‐Alemany 2016; Pellizzaro 2013; Segura‐Orti 2009; Song 2012a), and three studies as moderate to vigorous (perceived as somewhat hard to hard) (Afshar 2010; Martins do Valle 2020; PEAK 2006).

Combined aerobic and resistance exercise

Nineteen (22%) studies assessed interventions that combined aerobic and exercises within the same treatment arm (Burrows 2018; Cho 2018; Deligiannis 1999; Deligiannis 1999a; DePaul 2002; DIALY‐SIZE 2016; Frih 2017a; Konstantinidou 2002; Kopple 2007; Kouidi 2008; Kouidi 2010; Ma 2018; Marchesan 2016; Molsted 2004; Ouzouni 2009; Rouchon 2016; Suhardjono 2019; Uchiyama 2019; van Vilsteren 2005). These interventions consisted of a combination of the previously mentioned aerobic and resistance exercises in varying proportions. Cycling remained the most common aerobic exercise (14 studies: Burrows 2018; Cho 2018; Deligiannis 1999; Deligiannis 1999a; DePaul 2002; Frih 2017a; Konstantinidou 2002; Kopple 2007; Kouidi 2008; Kouidi 2010; Marchesan 2016; Ouzouni 2009; Rouchon 2016; Suhardjono 2019). The duration of the training sessions varied between 20 and 90 minutes. Five studies did not report a target intensity level (Cho 2018; Kouidi 2010; Ma 2018; Ouzouni 2009; Rouchon 2016), and the remaining studies used a combination of the previously mentioned scales. We classified one study as light to moderate intensity (perceived as light to somewhat hard) (Suhardjono 2019), 11 studies as moderate intensity (perceived as somewhat hard) (Burrows 2018; Deligiannis 1999; Deligiannis 1999a; DePaul 2002; DIALY‐SIZE 2016; Frih 2017a; Konstantinidou 2002; Kopple 2007; Marchesan 2016; Uchiyama 2019; van Vilsteren 2005), and three as moderate to vigorous (perceived as somewhat hard to hard) (Kouidi 2008; Konstantinidou 2002; Molsted 2004).

Other exercise training

One study assessed a yoga intervention (Yurtkuran 2007). The sessions lasted 30 minutes, two times/week and were progressive and supervised. Three studies assessed range of movement exercises (Makhlough 2012; Rezaei 2015; Soliman 2015) which consist of movements of the body articulations in their range of movement without resistance. The sessions lasted between 15 and 30 minutes, three times/week, and while the intensity was not specified, based on their description, we classified them as light exercises.

Timing of exercise training in relation to dialysis sessions

In the majority of studies (65 studies; 73%), exercise training took place during dialysis (Abreu 2017; Abundis Mora 2017; ACTINUT 2013; Afshar 2010; Afshar 2011; Akiba 1995; AVANTE‐HEMO 2020; Bennett 2013; Burrows 2018; Carmack 1995; Chang 2010; Chen 2010; Cho 2018; Cooke 2018; CYCLE‐HD 2016; Dashtidehkordi 2019; de Lima 2013; DePaul 2002; DIALY‐SIZE 2016; Dobsak 2012; Fernandes 2019; Frey 1999; Giannaki 2013a; Groussard 2015; IHOPE 2019; Johansen 2006; Koh 2009; Konstantinidou 2002; Kopple 2007; Koufaki 2002; Koufaki 2003; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Kouidi 2008; Kouidi 2010; Liao 2016; Ma 2018; Makhlough 2012; Marinho 2016; Martin‐Alemany 2016; Martins do Valle 2020; Marchesan 2016; McAdams‐DeMarco 2018; McGregor 2018; Mitsiou 2015; Miura 2015; Momeni 2014; Mortazavi 2013; Olvera‐Soto 2016; Ouzouni 2009; Painter 2002a; Paluchamy 2018; Parsons 2004; PEAK 2006; Pellizzaro 2013; Rosa 2018; Reboredo 2010; Segura‐Orti 2009; Soliman 2015; Suhardjono 2019; Toussaint 2008; van Vilsteren 2005; Wilund 2010; Wu 2014d).

Exercise training took place before or after the dialysis sessions in nine studies (CHAIR 2015; Dong 2011; Lee 2001; Matsumoto 2007; PEAK 2006; Rosa 2018; Song 2012a; van Vilsteren 2005; Zhao 2017), and on non‐dialysis days in eleven studies (Deligiannis 1999; Deligiannis 1999a; EXCITE 2014; Frih 2017a; Goldberg 1983; Harter 1985; Konstantinidou 2002; Kouidi 1997; Rahimimoghadam 2017; Samara 2016; Tsuyuki 2003). The timing of the exercise sessions was unclear in the remaining studies.

Supervision of exercise sessions

The exercise sessions were directly supervised by a physicians in 15 studies (ACTINUT 2013; Afshar 2010; CHAIR 2015; Deligiannis 1999; Deligiannis 1999a; Harter 1985; IHOPE 2019; Konstantinidou 2002; Kouidi 1997; Kouidi 2008; Kouidi 2010; Liao 2016; Ouzouni 2009; Suhardjono 2019; Tsuyuki 2003), by a kinesiologist or an exercise physiologist in 10 studies (Bennett 2013; Deligiannis 1999; DePaul 2002; DIALY‐SIZE 2016; Harter 1985; Kouidi 1997; McGregor 2018; Ouzouni 2009; PEAK 2006; Rosa 2018), by an investigator or research personnel in 10 studies (Amini 2016; Dong 2011; IHOPE 2019; Johansen 2006; Kopple 2007; Matsumoto 2007; McAdams‐DeMarco 2018; Painter 2002a; Song 2012a; Wilund 2010), by a physical education teacher in four studies (Deligiannis 1999; Deligiannis 1999a; Konstantinidou 2002; Marinho 2016), by a physiotherapist in four studies (Abreu 2017; Frih 2017a; Molsted 2004; Segura‐Orti 2009), by an exercise trainer in four studies (Kouidi 1997; Kouidi 2008; Kouidi 2010; Samara 2016), and by other professionals in two studies (EXCITE 2014; Groussard 2015). A further eight interventions were described as supervised without further information (Chen 2010; Koh 2009; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Martins do Valle 2020; Olvera‐Soto 2016; Reboredo 2010). The exercise sessions were unsupervised in six studies (Jong 2004; Koh 2009; Rezaei 2015; Sheshadri 2020; Toussaint 2008; Uchiyama 2019) and the remaining studies did not report whether the exercise intervention was supervised.

Tailoring

Twenty (22%) studies did not report tailoring of the intervention to the participant's physical capacity (Abreu 2017; Abundis Mora 2017; AVANTE‐HEMO 2020; Amini 2016; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Ma 2018; McAdams‐DeMarco 2018; Mitsiou 2015; Miura 2015; Momeni 2014; Olvera‐Soto 2016; Rahimimoghadam 2017; Rezaei 2015; Rouchon 2016; Segura‐Orti 2009; Soliman 2015; Toussaint 2008; Zhao 2017). In the remaining studies, the intervention was tailored to the participant's physical capacity through adjustment of the intensity level or adjustment of the duration of the exercise session or both.

Progression

In 50 (56%) studies, the intervention were progressive through time in term of either intensity, duration or the number of repetitions or steps to achieve (ACTINUT 2013; Afshar 2010; Akiba 1995; AVANTE‐HEMO 2020; Bennett 2013; Burrows 2018; Chang 2010; Chen 2010; Cho 2018; CYCLE‐HD 2016; Deligiannis 1999; Deligiannis 1999a; de Lima 2013; DePaul 2002; DIALY‐SIZE 2016; Dobsak 2012; Dong 2011; EXCITE 2014; Frey 1999; Frih 2017a; Giannaki 2013a; Goldberg 1983; Harter 1985; Groussard 2015; IHOPE 2019; Johansen 2006; Koh 2009; Konstantinidou 2002; Kopple 2007; Kouidi 1997; Kouidi 2008; Kouidi 2010; Lee 2001; Liao 2016; Marchesan 2016; Olvera‐Soto 2016; Ouzouni 2009; Painter 2002a; Parsons 2004; Pellizzaro 2013; Rosa 2018; Samara 2016; Segura‐Orti 2009; Sheshadri 2020; Song 2012a; Suhardjono 2019; Uchiyama 2019; Wilund 2010; Wu 2014d; Yurtkuran 2007). In the remaining studies, the intervention either remained unchanged throughout the study period or was not sufficiently described to assess progression.

Structured exercise intervention versus no exercise or placebo exercise were included in this review:

Co‐interventions reported were dietary counselling (ACTINUT 2013; AVANTE‐HEMO 2020), oral nutritional supplement (AVANTE‐HEMO 2020; Dong 2011; IHOPE 2019; Martin‐Alemany 2016), antidepressant medication (Zhao 2017), volume control (Burrows 2018), and erythropoietin (Konstantinidou 2002; Koufaki 2003; Kouidi 2005).

Study outcomes

The reported outcomes were numerous and disparate, which illustrate the broad spectrum of benefits that are expected from exercise training.

Death

One study reported death at the completion of the intervention which consisted of six months of home‐based walking sessions and at a post‐study follow‐up, three years after randomisation (EXCITE 2014). Death was a secondary endpoint for which the study was not powered.

Cardiovascular events

No study reported cardiovascular events.

Fatigue

Six studies directly measured fatigue, each using different instruments including the revised Piper Fatigue Scale and Rhoten Fatigue Scale (Amini 2016), the Hemodialysis Fatigue Scale (Chang 2010), the Profile of Mood States (Johansen 2006), the Iowa Fatigue Scale (Soliman 2015), and a poorly defined visual analogue scale (Yurtkuran 2007). One study reported the fatigue domain of the Dialysis Symptom Index (Sheshadri 2020). Because these scales assess different dimensions of fatigue, we did not conduct a meta‐analysis.

A further 16 studies reported the vitality domain of either the Medical Outcomes Study 36‐item Short‐Form Health Survey (SF‐36) or a version of the Kidney Disease Quality of Life (KDQOL) questionnaires (Abreu 2017; AVANTE‐HEMO 2020; Dobsak 2012; EXCITE 2014; Koh 2009; Martin‐Alemany 2016; Martins do Valle 2020; Matsumoto 2007; Paluchamy 2018; Parsons 2004; PEAK 2006; Pellizzaro 2013; Sheshadri 2020; van Vilsteren 2005; Wu 2014d; Zhao 2017). One study could not contribute to the meta‐analysis because its results were not rescaled from 0 to 100 points (Paluchamy 2018) and another did not provide sufficient information to be included in the meta‐analysis (Martins do Valle 2020).

Health‐Related Quality of Life

Forty‐six studies assessed HRQoL, 27 using the SF‐36 questionnaire (Abreu 2017; ACTINUT 2013; CHAIR 2015; Chen 2010; DePaul 2002; Dobsak 2012; Frih 2017a; Giannaki 2013a; IHOPE 2019; Jong 2004; Johansen 2006; Koh 2009; Martins do Valle 2020; Matsumoto 2007; Molsted 2004; Mortazavi 2013; Painter 2002a; Parsons 2004; PEAK 2006; Ouzouni 2009; Rosa 2018; Samara 2016; Segura‐Orti 2009; Sheshadri 2020; Song 2012a; van Vilsteren 2005; Zhao 2017), three using the KDQOL questionnaire (Bennett 2013; Burrows 2018; Sheshadri 2020), nine using the KDQOL‐Short Form (KDQOL‐SF) which includes the SF‐36 (AVANTE‐HEMO 2020; de Lima 2013; EXCITE 2014; Martin‐Alemany 2016; Paluchamy 2018; Pellizzaro 2013; Suhardjono 2019; Uchiyama 2019; Wu 2014d), one using the SF‐12 (IHOPE 2019), one using the KDQOL‐SF 36 which includes SF‐12 (DIALY‐SIZE 2016), two using the Spitzer Index (Kouidi 1997; Ouzouni 2009), one using the Scale of Life Satisfaction (Ouzouni 2009), one using questions from the Laupacis Kidney Disease Questionnaire (DePaul 2002) and one abstract that did not report the instrument (Kouidi 2005). Of the 39 that used either the SF‐36, the SF‐12 or a version of the KDQOL, 17 reported the summary physical and mental component scores (ACTINUT 2013; CHAIR 2015; Chen 2010; DIALY‐SIZE 2016; Dobsak 2012; Frih 2017a; Giannaki 2013a; IHOPE 2019; Koh 2009; Molsted 2004; Ouzouni 2009; Rosa 2018; Samara 2016; Segura‐Orti 2009; Song 2012a; Suhardjono 2019; Uchiyama 2019) and all could contribute to the meta‐analysis.

Twenty studies reported the scores for at least one individual domain of the SF‐36 questionnaire (Abreu 2017; AVANTE‐HEMO 2020; CHAIR 2015; Dobsak 2012; EXCITE 2014; Johansen 2006; Jong 2004; Koh 2009; Martin‐Alemany 2016; Martins do Valle 2020; Matsumoto 2007; Paluchamy 2018; Parsons 2004; PEAK 2006; Pellizzaro 2013; Sheshadri 2020; Uchiyama 2019; van Vilsteren 2005; Wu 2014d; Zhao 2017) and all but one (Paluchamy 2018), for which the results were not rescaled from 0 to 100 points, contributed to the meta‐analysis.

Pain

One study reported pain on a 0 to 10 visual analogue scale (Yurtkuran 2007). Sixteen studies reported pain as a domain of the SF‐36 questionnaire (Abreu 2017; AVANTE‐HEMO 2020; Dobsak 2012; EXCITE 2014; Koh 2009; Martin‐Alemany 2016; Martins do Valle 2020; Matsumoto 2007; Molsted 2004; Paluchamy 2018; Pellizzaro 2013; van Vilsteren 2005; Uchiyama 2019; Wu 2014d; Yurtkuran 2007; Zhao 2017)and all but one study (Paluchamy 2018), for which the results were not rescaled from 0 to 100 points, contributed to the meta‐analysis.

Depression

Seventeen studies assessed depression (Carmack 1995; CYCLE‐HD 2016; Frih 2017a; Giannaki 2013a; Goldberg 1983; Harter 1985; Johansen 2006; Kouidi 1997; Kouidi 2005; Kouidi 2010; Ma 2018; Ouzouni 2009; PEAK 2006; Rahimimoghadam 2017; Rezaei 2015;Sheshadri 2020; van Vilsteren 2005). Seven used the Beck Depression Index (Amini 2016; Goldberg 1983; Harter 1985; Kouidi 1997; Kouidi 2010; Ouzouni 2009; Rezaei 2015), three the Hospital Anxiety and Depression Scale (CYCLE‐HD 2016; Frih 2017a; Kouidi 2010), two the Center for Epidemiologic Studies Depression Scale (CES‐D) (Carmack 1995; Sheshadri 2020), two the Self‐rating Depression Scale (Giannaki 2013a; van Vilsteren 2005), four used other instruments (Amini 2016; Johansen 2006; PEAK 2006; Rahimimoghadam 2017) and two did not report their instrument (Kouidi 2005; Ma 2018). Ten studies (Carmack 1995; Frih 2017a; Giannaki 2013a; Kouidi 1997; Kouidi 2010; Ouzouni 2009; Rahimimoghadam 2017; Rezaei 2015; Sheshadri 2020; van Vilsteren 2005) provided sufficient information to contribute to the meta‐analysis using the standardised mean difference.

Functional capacity

Functional capacity was reported in 35 studies (ACTINUT 2013; AVANTE‐HEMO 2020; Bennett 2013; CHAIR 2015; Cho 2018; Cooke 2018; de Lima 2013; DePaul 2002; DIALY‐SIZE 2016; Dobsak 2012; EXCITE 2014; Fernandes 2019; Frih 2017a; Giannaki 2013a; Groussard 2015; IHOPE 2019; Johansen 2006; Koh 2009; Koufaki 2002; Liao 2016; Ma 2018; Martins do Valle 2020; Marchesan 2016; Mitsiou 2015; PEAK 2006; Pellizzaro 2013; Rosa 2018; Rouchon 2016; Samara 2016; Segura‐Orti 2009; Song 2012a; Suhardjono 2019; Uchiyama 2019; Wilund 2010; Wu 2014d). We meta‐analysed and reported the two most commonly reported tests.

Twenty‐three studies reported result for the 6MWT which measures the distance in metres covered over six minutes and reflects aerobic capacity and endurance (ACTINUT 2013; AVANTE‐HEMO 2020; CHAIR 2015; Cho 2018; DePaul 2002; DIALY‐SIZE 2016; EXCITE 2014; Fernandes 2019; Frih 2017a; Groussard 2015; Koh 2009; Liao 2016; Ma 2018; Martins do Valle 2020; Marchesan 2016; Mitsiou 2015; PEAK 2006; Pellizzaro 2013; Rosa 2018; Rouchon 2016; Samara 2016; Segura‐Orti 2009; Wu 2014d). Nineteen studies could be meta‐analysed (ACTINUT 2013; CHAIR 2015; Cho 2018; DePaul 2002; DIALY‐SIZE 2016; EXCITE 2014; Fernandes 2019; Frih 2017a; Koh 2009; Liao 2016; Martins do Valle 2020; Marchesan 2016; PEAK 2006; Pellizzaro 2013; Rosa 2018; Rouchon 2016; Samara 2016; Segura‐Orti 2009; Wu 2014d).

Sixteen studies reported results for the sit‐to‐stand test which measures leg strength and endurance (AVANTE‐HEMO 2020; Bennett 2013; Cho 2018; DIALY‐SIZE 2016; EXCITE 2014; Frih 2017a; Giannaki 2013a; IHOPE 2019; Johansen 2006; Koufaki 2002; Marchesan 2016; Rosa 2018; Samara 2016; Segura‐Orti 2009; Song 2012a; Wu 2014d). Eight reported the maximum number of sit‐to‐stand cycles executed within 30 seconds (Bennett 2013; Cho 2018; DIALY‐SIZE 2016; Giannaki 2013a; IHOPE 2019; Marchesan 2016; Rosa 2018; Song 2012a), and five reported the number of sit‐to‐stand cycles executed within 60 seconds (Frih 2017a; Giannaki 2013a; Koufaki 2002; Segura‐Orti 2009; Wu 2014d). To meta‐analyse the results conjointly, we approximated the number of cycles executed within 30 seconds by dividing the results of the last five studies by two. Five studies reported the time in seconds required to execute five sit‐to‐stand cycles (AVANTE‐HEMO 2020; EXCITE 2014; Giannaki 2013a; Johansen 2006; Koufaki 2002), and four studies reported the time in seconds required to execute 10 sit‐to‐stand cycles (Frih 2017a; Samara 2016; Segura‐Orti 2009; Wu 2014d). To combine these results within the same meta‐analysis, we approximated the time to execute five cycles by dividing the results of the later four studies by two. All but one study (AVANTE‐HEMO 2020) reported their results in a manner that was amenable to meta‐analysis.

Resting blood pressure

Twenty‐one studies assessed resting peripheral SBP and DBP (Cooke 2018; CYCLE‐HD 2016; Deligiannis 1999a; DePaul 2002; Fernandes 2019; Frih 2017a; Goldberg 1983; IHOPE 2019; Koh 2009; Kouidi 2008; Liao 2016; McGregor 2018; Miura 2015, Molsted 2004; Ouzouni 2009; Paluchamy 2018; Soliman 2015; Toussaint 2008; Tsuyuki 2003; van Vilsteren 2005; Wilund 2010) and all but one (Miura 2015) provided the results in a form amenable to meta‐analysis.

Adherence to the exercise intervention

Twelve (14%) studies reported the percentage of training sessions attended by the participants allocated to the intervention group (ACTINUT 2013; Chen 2010; Cooke 2018; IHOPE 2019; Kouidi 2008; Martins do Valle 2020; Molsted 2004; PEAK 2006; Reboredo 2010; Rosa 2018; Toussaint 2008; Uchiyama 2019).

Adverse events

Thirteen (15%) studies reported adverse events (AVANTE‐HEMO 2020; CHAIR 2015; Chen 2010; Cho 2018; DIALY‐SIZE 2016; EXCITE 2014; IHOPE 2019; Marinho 2016; McAdams‐DeMarco 2018; PEAK 2006; Sheshadri 2020; Uchiyama 2019; Wu 2014d) of which three reported severe adverse events separately (CHAIR 2015; DIALY‐SIZE 2016; EXCITE 2014). Nine studies specifically reported adverse events related to the intervention (AVANTE‐HEMO 2020; CHAIR 2015; Chen 2010; Cho 2018; DIALY‐SIZE 2016; IHOPE 2019; Sheshadri 2020; Uchiyama 2019; Wu 2014d) and were meta‐analysed.

Other outcomes

Outcomes that were frequently reported but not identified as important to patients included: aerobic capacity (VO2 max or peak); maximum heart rate; muscular strength; body mass index; body composition (fat and lean mass); haemoglobin; serum albumin; blood lipids; serum potassium; serum calcium; serum phosphate; parathyroid hormone levels; C‐reactive protein levels; left ventricular ejection fraction; and left ventricular mass index measured on cardiac ultrasonography. These outcomes were reported in Heiwe 2011 and have been retained for historical reference only.

Excluded studies

Forty‐one studies were excluded. The reasons for exclusion were no control group or active control (11 studies); no intervention group (6 studies); duration < eight weeks (22 studies); wrong population (1 study); and co‐interventions not the same in the control and intervention groups (1 study).

See Characteristics of excluded studies table.

Risk of bias in included studies

Figure 2 summarises the assessment of the risk of bias for the included studies, and Figure 3 provide the risk of bias assessment for individual studies.

Figure 2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Allocation

Random sequence generation

The random sequence generation method was at low risk of bias in 39 studies (44%) (ACTINUT 2013; AVANTE‐HEMO 2020; Bennett 2013; CHAIR 2015; Cho 2018; Cooke 2018; CYCLE‐HD 2016; de Lima 2013; DePaul 2002; DIALY‐SIZE 2016; Dong 2011; EXCITE 2014; Fernandes 2019; Frih 2017a; IHOPE 2019; Johansen 2006; Koh 2009; Kopple 2007; Koufaki 2002; Kouidi 2008; Makhlough 2012; Marinho 2016; Martin‐Alemany 2016; Martins do Valle 2020; McGregor 2018; Olvera‐Soto 2016; Painter 2002a; Parsons 2004; PEAK 2006; Rahimimoghadam 2017; Rosa 2018; Rouchon 2016; Samara 2016; Segura‐Orti 2009; Sheshadri 2020; Suhardjono 2019; Uchiyama 2019; Wu 2014d; Yurtkuran 2007), and not reported in the remaining 50 studies.

Allocation concealment

The method to conceal the treatment allocation was at low risk of bias in 24 studies (27%) (ACTINUT 2013; Bennett 2013; CHAIR 2015; Cho 2018; CYCLE‐HD 2016; Dashtidehkordi 2019; de Lima 2013; DIALY‐SIZE 2016; EXCITE 2014; Fernandes 2019; IHOPE 2019; Johansen 2006; Koh 2009; Koufaki 2002; Martins do Valle 2020; McGregor 2018; Molsted 2004; Painter 2002a; PEAK 2006; Rosa 2018; Sheshadri 2020; Toussaint 2008; Uchiyama 2019; Yurtkuran 2007) and not reported in the remaining 65 studies.

Blinding

Blinding of participants and investigators

While complete blinding of the participants to the exercise intervention is unlikely, we deemed the four studies that used a placebo or sham exercise were at low risk of bias (Chen 2010; DePaul 2002; Rosa 2018; Segura‐Orti 2009). One study was judged to be at unclear risk of bias (Dashtidehkordi 2019), and the remaining 84 studies were judged to be at high risk of bias.

Blinding of outcome assessment
Objective outcomes

We considered the 6MWT, the Sit‐To‐Stand test, the Time‐Up and Go test, muscular strength, blood pressure, heart rate, Kt/V, laboratory results, dietary intake, and cardiac ultrasound measures as objective outcomes that were less likely to be significantly affected by the lack of blinding of the assessors. With the exception of 10 abstracts (Abundis Mora 2017; Burrows 2018; Jong 2004; Koufaki 2003; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Ma 2018; Mitsiou 2015; Miura 2015) that we deemed at unclear risk; all studies were judged to be at low risk of bias.

Eight studies did not report any of the listed objective outcomes (Amini 2016; Chang 2010; Dashtidehkordi 2019; Matsumoto 2007; Mortazavi 2013; Rahimimoghadam 2017; Rezaei 2015; Wu 2014d).

Subjective outcomes

Fatigue, HRQoL, pain, and depression were considered subjective outcomes. Since the participants themselves assessed these outcomes, we deemed the four studies that used a placebo or sham exercise to be at low risk of bias for blinding of outcome assessment (Chen 2010; DePaul 2002; Rosa 2018; Segura‐Orti 2009) as well as the 34 studies that did not report any subjective outcomes (Abundis Mora 2017; Afshar 2011; Akiba 1995; Cho 2018; Cooke 2018; Deligiannis 1999; Deligiannis 1999a; de Lima 2013; Dong 2011; Fernandes 2019; Groussard 2015; Harter 1985; Konstantinidou 2002; Kopple 2007; Koufaki 2003; Kouidi 2003; Kouidi 2004a; Kouidi 2008; Lee 2001; Liao 2016; Makhlough 2012; Marchesan 2016; Marinho 2016; McAdams‐DeMarco 2018; McGregor 2018; Mitsiou 2015; Miura 2015; Momeni 2014; Olvera‐Soto 2016; Reboredo 2010; Rouchon 2016; Toussaint 2008; Tsuyuki 2003; Wilund 2010). One abstract was judged as unclear (Burrows 2018), and the remaining 50 studies were judged to be at high risk of bias since the participants reported the outcomes and the participants were not blinded to treatment allocation.

Incomplete outcome data

We judged 40 (45%) studies to be at low risk of bias for incomplete outcome data (ACTINUT 2013; AVANTE‐HEMO 2020; Chang 2010; Cho 2018; Dashtidehkordi 2019; de Lima 2013; DePaul 2002; DIALY‐SIZE 2016; Fernandes 2019; Groussard 2015; Johansen 2006; Konstantinidou 2002; Koufaki 2002; Kouidi 1997; Kouidi 2008; Kouidi 2010; Liao 2016; Marchesan 2016; Marinho 2016; Martin‐Alemany 2016; Martins do Valle 2020; Matsumoto 2007; Momeni 2014; Olvera‐Soto 2016; Ouzouni 2009; Painter 2002a; Parsons 2004; Rahimimoghadam 2017; Rosa 2018; Samara 2016; Segura‐Orti 2009; Sheshadri 2020; Song 2012a; Suhardjono 2019; Toussaint 2008; Uchiyama 2019; van Vilsteren 2005; Wilund 2010; Wu 2014d; Yurtkuran 2007) and 21 (23.5%) to be at high risk (Abreu 2017; Akiba 1995; Bennett 2013; Carmack 1995; CHAIR 2015; EXCITE 2014; Frey 1999; Frih 2017a; Harter 1985; IHOPE 2019; Koh 2009; Kopple 2007; Lee 2001; McAdams‐DeMarco 2018; McGregor 2018; Molsted 2004; Pellizzaro 2013; Reboredo 2010; Rezaei 2015; Rouchon 2016; Soliman 2015). The remaining 28 studies provided insufficient information to permit judgement.

Selective reporting

Eight (9%) studies were at high risk of bias from selective reporting of outcomes (Lee 2001; Liao 2016; McAdams‐DeMarco 2018; Olvera‐Soto 2016; Painter 2002a; PEAK 2006; Pellizzaro 2013; Rezaei 2015). Eighteen (20%) studies did not provide sufficient information to assess the risk of bias from selective reporting (Abundis Mora 2017; Afshar 2011; Akiba 1995; Burrows 2018; CYCLE‐HD 2016; Harter 1985; Jong 2004; Koufaki 2003; Kouidi 2003; Kouidi 2004a; Kouidi 2005; Ma 2018; Mitsiou 2015; Miura 2015; Momeni 2014; Paluchamy 2018; Rouchon 2016; Zhao 2017). The remaining 63 studies were at low risk of bias from selective reporting.

Other potential sources of bias

We judge seven (8%) studies at high risk of bias because they received private funding without specifying whether the funders were involved in the conduction of the study (DePaul 2002; Groussard 2015; Johansen 2006; Koufaki 2002; Molsted 2004; Painter 2002a; PEAK 2006). A further study was judged at high risk of bias for discrepancies in the number of participants across the published article (Makhlough 2012). We judge 31 studies (34%) at low risk of other sources of bias because they reported either no funding or public funding (Abreu 2017; ACTINUT 2013; AVANTE‐HEMO 2020; Bennett 2013; Chang 2010; Dashtidehkordi 2019; DIALY‐SIZE 2016; Dobsak 2012; Dong 2011; Fernandes 2019; Giannaki 2013a; Goldberg 1983; Harter 1985; IHOPE 2019; Koh 2009; Kopple 2007; Marinho 2016; Martins do Valle 2020; McAdams‐DeMarco 2018; McGregor 2018; Parsons 2004; Pellizzaro 2013; Rahimimoghadam 2017; Reboredo 2010; Rosa 2018; Segura‐Orti 2009; Sheshadri 2020; Suhardjono 2019; Toussaint 2008; Wilund 2010; Wu 2014d). The remaining 50 studies did not report their source of funding.

Effects of interventions

See: Summary of findings 1 Any exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis; Summary of findings 2 Aerobic exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis; Summary of findings 3 Resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis; Summary of findings 4 Combined aerobic and resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Primary outcomes

Death (any cause)

It is uncertain whether exercise training reduces the risk of death. EXCITE 2014 reported death three years after the intervention which consisted of six months of home‐based walking exercise. Deaths were similar across the two groups (Analysis 1.1 (1 study, 296 participants): RR 0.95; 95% CI 0.56 to 1.62; very low certainty evidence). This study was not powered to assess death and the report did not specify whether there was missing data for this outcome at the three‐year follow‐up assessment.

Studies reporting adverse events (CHAIR 2015; Chen 2010; Cho 2018; DIALY‐SIZE 2016; EXCITE 2014; Marinho 2016; McAdams‐DeMarco 2018; PEAK 2006; Wu 2014d) did not report any deaths related to the exercise intervention during the duration of the study (range two to six months).

Cardiovascular events

No study reported cardiovascular events.

Fatigue

Fatigue was reduced after the exercise intervention in three studies that used fatigue‐specific measures (Amini 2016; Soliman 2015; Yurtkuran 2007) and was reduced but did not reach statistical significance in two (Chang 2010; Johansen 2006). One study found similar results on the fatigue domain of the Dialysis Symptom Index across treatment groups after the exercise intervention (Sheshadri 2020) (Analysis 1.2). A sensitivity analysis based on the risk of bias could not be conducted due to the low number of studies. All the studies used aerobic training interventions and one used resistance training (Johansen 2006).

Exercise may improve vitality as assessed by the SF‐36 questionnaire (Analysis 1.4.7 (16 studies, 940 participants): MD 4.47, 95% CI 0.79 to 8.15 points on a 100‐point scale; I² = 46%; low certainty evidence) where higher scores signify greater vitality. Considering a minimal clinically important difference for the individual scales of the SF‐36 of two to five points (Eriksson 2016; Finkelstein 2018; Leaf 2009; Samsa 1999; Spinowitz 2019) or an SMD of 0.1 to 0.5 (Farivar 2004; Norman 2003; Samsa 1999), we judged the magnitude of the effect to be small. However, since vitality is an indirect measure of fatigue, the relevance of this result for the assessment of the outcome of fatigue is uncertain.

Health‐Related Quality of Life
Physical component score

Exercise training of any type may increase the physical component of HRQoL slightly (Analysis 1.3.1 (17 studies, 656 participants): MD 4.12, 95% CI 1.88 to 6.37 points on 100 points‐scale where higher scores signify a better QoL; I² = 49%; low certainty evidence). Considering a minimal clinically important difference for the physical component score of SF‐36 of two to five points (Eriksson 2016; Erez 2016; Finkelstein 2018; Leaf 2009; Samsa 1999; Spinowitz 2019) or an SMD of 0.1 to 0.5 (Farivar 2004; Norman 2003; Samsa 1999) we estimated the size of the effect to be small. A sensitivity analysis including only the studies at low risk of bias (ACTINUT 2013; DIALY‐SIZE 2016; Rosa 2018; Samara 2016; Segura‐Orti 2009; Suhardjono 2019; Uchiyama 2019) led to a similar pooled estimate of the effect (7 studies, 309 participants: MD 4.33 points on 100 points‐scale, 95% CI ‐0.11 to 8.76; I² = 67%).

It is uncertain whether aerobic, resistance, or combined aerobic and resistance exercise improved the physical component of QoL because the certainty of this evidence was very low (Analysis 2.3; Analysis 3.2; Analysis 4.1).

Mental component score

It is uncertain whether any exercise training improves the mental component of HR‐QoL (Analysis 1.3 (17 studies, 656 participants): MD 2.53, 95% CI ‐0.40 to 5.47 points on 100 points‐scale where higher scores signify a better QoL; I² = 73%; very low certainty evidence). There was evidence of significant heterogeneity in the effect of exercise training between studies that we could not explain with subgroups analyses based on the type, intensity or duration of exercise or based on the risk of bias. A sensitivity analysis including only the studies at low risk of bias (ACTINUT 2013; DIALY‐SIZE 2016; Rosa 2018; Samara 2016; Segura‐Orti 2009; Suhardjono 2019; Uchiyama 2019) led to a similar pooled estimate of the effect (7 studies, 309 participants: MD 3.04 points, 95% CI ‐2.91 to 8.98; I² = 67%).

It is also uncertain whether aerobic, resistance or combined aerobic and resistance exercise improves the mental component of HR‐QoL as the certainty of the evidence was very low (Analysis 2.3; Analysis 3.2; Analysis 4.1).

The results of the meta‐analyses for the individual domains of HR‐QoL are available in Analysis 1.4 for any exercise, Analysis 2.4 for aerobic exercise, Analysis 3.3 for resistance exercise, and Analysis 4.2 for combined aerobic and resistance exercise.

Pain

Exercise training of any type may lead to lesser pain as assessed by the SF‐36 or KDQOL questionnaires. However, the 95% CI indicates that exercise training might make little or no difference in the level of pain (Analysis 1.4.3 (15 studies, 872 participants): MD 5.28 95% CI ‐0.12 to 10.69 points on 100 points‐scale where higher scores signify less pain; I² = 63%; low certainty evidence). There was evidence of significant heterogeneity in the effect of exercise across studies. However, the heterogeneity was completely resolved by removing Pellizzaro 2013 which reported its results in figures only (pooled estimate after removing the study (14 studies. 844 participants): MD 2.80, 95% CI ‐0.30 to 5.91, I² = 0%). Considering a minimal clinically important difference for each scale of the SF‐36 of two to five points (Eriksson 2016; Finkelstein 2018; Leaf 2009; Samsa 1999; Spinowitz 2019) or an SMD of 0.1 to 0.5 (Farivar 2004; Norman 2003; Samsa 1999), we judged the magnitude of the effect to be small. A sensitivity analysis including only the studies at low risk of bias (AVANTE‐HEMO 2020; Martin‐Alemany 2016; Martins do Valle 2020; Parsons 2004; Uchiyama 2019; Wu 2014d) reported a similar pooled estimate of the effect (6 studies, 229 participants: MD 2.66 points on 100 points‐scale, 95% CI ‐2.02 to 7.34; I² = 0%).

Aerobic exercise training may make little or no difference to pain as assessed by the SF‐36 questionnaire (Analysis 2.4.3 (8 studies, 570 participants): MD 2.26 points 95% CI ‐1.61 to 6.12 on 100 points‐scale; I² = 0%; low certainty evidence).

It is uncertain whether resistance exercise training and combined aerobic and resistance exercise training improves pain in adults undergoing dialysis because the certainty of this evidence was very low (Analysis 3.3.3; Analysis 4.2.3).

Depression

Exercise training of any type likely improves depression in adults undergoing dialysis (Analysis 1.5 (10 studies, 441 participants): SMD ‐0.65, 95% CI ‐1.07 to ‐0.22 where lower scores signify improved depressive symptoms; I² = 77%; moderate certainty evidence). However, there was evidence of significant heterogeneity in the effect of exercise across studies. The heterogeneity was improved after stratifying the studies by the duration of the intervention (four months or less versus longer than four months). The magnitude of the effect was very large when the intervention lasted longer than four months (Analysis 1.5.2 (4 studies, 130 participants): SMD ‐1.26, 95% CI ‐0.72 to ‐1.80; I² = 45%), while the 95% CI indicated that exercise training for four months or less may make little or no difference on depression (Analysis 1.5.1 (6 studies, 311 participants): SMD ‐0.30, 95% CI 0.14 to ‐0.74; I² = 71%) (Test for subgroup differences: P = 0.007).

It is uncertain whether aerobic, resistance or combined aerobic and resistance exercise improves depressive symptoms because the certainty of this evidence is very low (Analysis 2.5; Analysis 3.4; Analysis 4.3). A sensitivity analysis based on the risk of bias could not be conducted due to the low number of studies.

Functional capacity
6‐Minute Walk Test

Exercise training of any type is likely to improve functional capacity as assessed by the 6MWT (Analysis 1.6 (19 studies, 827 participants): MD 49.91 metres, 95% CI 37.22 to 62.59; I² = 34%; moderate certainty evidence). Considering a previously reported minimal clinically important difference for the 6MWT ranging from 14.0 to 30.5 metres in patients with comorbidities and similar baseline results on the 6MWT (Bohannon 2017), we estimated the magnitude of the effect as moderate. A sensitivity analysis limited to the studies at low risk of bias (ACTINUT 2013; Cho 2018; DIALY‐SIZE 2016; Fernandes 2019; Martins do Valle 2020; Rosa 2018; Segura‐Orti 2009; Wu 2014d) did not significantly alter the pooled estimate of the effect (8 studies, 298 participants: MD 48.57 metres, 95% CI 34.23 to 62.92; I² = 0%).

Aerobic exercise (Analysis 2.6 (10 studies, 515 participants): MD 53.00 metres, 95% CI 33.84 to 72.17; I² = 47%; moderate certainty evidence), resistance exercise (Analysis 3.5 (7 studies, 216 participants): MD 44.71 metres, 95% CI 27.00 to 62.43; I² = 0%; moderate certainty evidence) or combined aerobic and resistance exercise (Analysis 4.4 (6 studies, 138 participants): MD 53.64 meters, 95% CI 39.36 to 67.91; I² = 0%; moderate certainty evidence) are all likely to increase functional capacity.

Sit‐To‐Stand test

Exercise training of any type is likely to improve functional capacity and lower extremities strength as assessed by the 30‐ or 60‐second STS test (Analysis 1.7 (12 studies, 478 participants): MD 2.36 repetitions in 30 seconds, 95% CI 1.73 to 2.98; I² = 0%; moderate certainty evidence). We found no reference in the literature of the minimal clinically important difference for this test in adults undergoing dialysis. Judging from the results in another population with similar baseline results (Wright 2011) and the SMD of 0.63 (95% CI 0.35 to 0.91) we judged the size of the effect to be moderate. A sensitivity analysis limited to the studies at low risk of bias (Cho 2018; DIALY‐SIZE 2016; Rosa 2018; Segura‐Orti 2009; Wu 2014d) did not significantly alter the pooled estimate of the effect (5 studies, 219 participants: 2.79 repetitions in 30 seconds, 95% CI 1.73 to 3.86; I² = 13%).

Exercise training is likely to improve functional lower extremities strength as assessed by the 5 to 10 repetitions STS test (Analysis 1.8 (8 studies, 508 participants) MD ‐1.74 seconds, 95% CI ‐2.25 to ‐1.22; I² = 0%; moderate certainty evidence). Using a minimal clinically important difference of 4.2 seconds in adults with CKD (Wilkinson 2019) not on dialysis and an SMD of 0.53 (95% CI 0.30 to 0.75) we judged the size of the effect to be small. A sensitivity analysis based on the risk of bias could not be conducted for the 5 to 10 repetitions STS test due to the low number of studies. Taken together, the pooled estimates for these two versions of the STS test point to a positive effect of exercise training on lower extremities strength and physical functioning.

Aerobic (Analysis 2.7 (6 studies, 227 participants): MD 1.81 repetitions in 30 seconds, 95% CI 0.86 to 2.76 ; I² = 0%; moderate certainty evidence) and resistance exercise (Analysis 3.6 (6 studies, 195 participants): MD 2.76 repetitions in 30 seconds, 95% CI 1.68 to 3.83; I² = 0%, moderate certainty evidence) are both likely to improve functional lower extremities strength as assessed by the 30‐ or 60‐second STS test. Combined aerobic and resistance training may improve performance on the 30 or 60 seconds STS test (Analysis 4.5 (4 studies, 97 participants): MD 2.63 repetitions in 30 seconds, 95% CI 1.49 to 3.77; I² = 9%; low certainty evidence). Aerobic exercise is likely to improve functional lower extremities strength as assessed by the 5 or 10 repetitions STS test (Analysis 2.8 (5 studies, 374 participants): MD ‐1.63 seconds, 95% CI ‐2.33 to ‐0.92, 2.33; I² = 8%; moderate certainty evidence). It is uncertain whether resistance exercise or combined aerobic and resistance exercise improves the results of the 5 to 10 repetitions STS test because the certainty of this evidence is very low.

Peripheral resting blood pressure

The effect of exercise training on SBP and DBP was different across types of exercise (Test for subgroup differences P < 0.001 for both SBP and DBP). We will, therefore, present the results for each type of exercise separately and will not provide a pooled estimate for any exercise training.

It is uncertain whether aerobic exercise reduces SBP because the certainty of this evidence is very low (Analysis 1.9.1 (13 studies, 394 participants): MD ‐3.99 mm Hg, 95% CI ‐9.78 to 1.80; I² = 45%; very low certainty evidence). No study assessed the impact of resistance training alone on SBP. The evidence is very uncertain on the effect of combined aerobic and resistance training on SBP (Analysis 1.9.2 (7 studies, 282 participants): MD ‐8.69 mm Hg, 95% CI ‐13.69 to ‐3.69; I² = 57%; very low certainty evidence). The heterogeneity was entirely resolved after excluding a single study (Frih 2017a) (pooled estimate after excluding the study: MD ‐5.84 95% CI ‐9.94 to ‐1.74 mm Hg; I² = 0%).

It is uncertain whether aerobic exercise reduces DBP because the certainty of this evidence is very low (Analysis 1.10.1 (13 studies, 394 participants): MD 0.72 mm Hg, 95% CI ‐2.24 to 3.69; I² = 31%, very low certainty evidence). No study assessed the impact of resistance training alone on DBP. The evidence is very uncertain about the effect of combined aerobic and resistance training on DBP (Analysis 1.10.2 (7 studies, 282 participants): MD ‐4.45 mm Hg, 95% CI ‐5.98 to ‐2.91; I² = 0%; very low certainty evidence).

Adherence to the exercise intervention

Of the eleven studies that reported the percentage of training sessions attended by the participants allocated to the intervention, the lowest adherence was reported as a median of 60% (Cooke 2018), and the highest was a mean adherence of 88% (Kouidi 2008).

Exercise‐related adverse events

It is uncertain whether exercise training is safe for adults undergoing maintenance dialysis because the certainty of this evidence is very low. Seven studies reported there were no exercise‐related adverse events (AVANTE‐HEMO 2020; Chen 2010; Cho 2018; DIALY‐SIZE 2016; IHOPE 2019; Uchiyama 2019; Wu 2014d) within a total of 171 participants assigned to the exercise intervention. One study reported 6/26 participants assigned to the intervention presented exercise‐related symptoms including shortness of breath, soreness, lower extremity pain, cramping and fatigue (Sheshadri 2020). Furthermore, two participants experienced chest pain during the intervention. One study reported that one of the six exercising participants presented with knee joint pain (CHAIR 2015).

Other outcomes

Meta‐analysis for the outcomes that were frequently reported but not identified as important to patients, or previously included are available as forest plots in Analysis 1.11 to Analysis 1.30 for any exercise training, Analysis 2.10 to Analysis 2.28 for aerobic training, Analysis 3.8 to Analysis 3.22 for resistance training, and Analysis 4.8 to Analysis 4.23 for combined aerobic and resistance training but will not be discussed further.

Discussion

Summary of main results

This review of the evidence supporting exercise training for adults undergoing maintenance dialysis included 89 studies involving randomising 4291 participants; 77 studies involving 3846 participants contributed to the meta‐analyses. The exercise programs, a complex intervention, were heterogeneous and varied in type, intensity, duration, frequency of sessions and timing in relation to dialysis treatments. Interventions within subtypes of exercises (aerobic, resistance or a combination of the two) were more comparable; however, the duration of the intervention remained highly variable. Only one study had long‐term follow‐up after the completion of the study.

A single study reported death but was not sufficiently powered to assess it and no study reported long‐term cardiovascular events. Compared to no or sham exercise, any exercise for two to 12 months may reduce fatigue in adults undergoing maintenance dialysis. Importantly, compared to no or sham exercise, any exercise training for two to 12 months is likely to significantly improve depression in adults undergoing maintenance dialysis, particularly when the intervention is sustained for longer than four months. Compared to no or sham exercise, any exercise training for two to six months is also likely to substantially improve functional capacity which has been associated with survival in people receiving dialysis treatments (DeOreo 1997; Knight 2003). Furthermore, compared to no or sham exercise, any exercise training for three to 12 months may increase the physical component of HRQoL. Compared to no or sham exercise, any exercise training for three to 12 months may lead to lesser pain. However, the 95% CI indicated that exercise training might make little or no difference in the level of pain. It is uncertain whether exercise training improves the mental component of HRQoL or resting blood pressure because the certainty of this evidence is very low.

Comparisons of one type of exercise to another were limited by the number of studies reporting patients‐important outcomes. We observed a differential effect of the type of exercise training on resting blood pressure, but the certainty of the evidence was very low.

Overall completeness and applicability of evidence

The current review is a comprehensive assessment of the effects of structured exercise training in adults undergoing maintenance dialysis. While it includes a vast number of studies covering aerobic, resistance and combined aerobic and resistance training, many uncertainties remain. Only seven studies included participants undergoing PD. We therefore cannot conclude on the impact of exercise training in this population. Secondly, the inclusion criteria were often stringent, excluding patients with extensive comorbidities. Furthermore, participants had to be able to perform some level of exercise from baseline, thereby excluding the frailest patients. The conclusions of the review therefore cannot be applied to the debilitated dialysis patient with a heavy burden of comorbidity, loss of autonomy, physical limitation, or cognitive decline.

Most exercise interventions were conducted during the dialysis treatments. While some patients might be fearful of exercising during dialysis, little is known about the effect and feasibility of home‐based exercise training for this population.

The interventions were overall of short duration, with only 10 interventions lasting longer than six months. We may have observed effects of greater magnitude where the interventions were more sustained.

Patients‐important outcomes were under‐represented, with many studies focusing on biomarkers and measures of exercise capacity. A single study reported long‐term outcomes and death but was insufficiently powered to do so. The long‐term impacts of exercise training in adults undergoing dialysis, therefore, remain unknown at this point.

Finally, the second objective of the review, which is to inform the design of exercise interventions that maximise the benefits for adults undergoing dialysis, could not be achieved due to the low number of studies reporting patient‐important outcomes. A network meta‐analysis, including the studies that compared one exercise intervention to another without necessarily including a no or sham exercise control group, would better address this aim.

Quality of the evidence

In general, the quality of evidence was low to very low due to the high risk of bias, the short duration of the interventions and follow‐up and the low number of participants in the included studies.

Regarding the internal validity of the included studies, a majority did not report the methods of randomisation and concealment of the allocation. Blinding of participants was generally not feasible in this review due to the nature of the intervention, and only four studies attempted to blind the participants using a sham intervention. Outcome assessors were also rarely blinded to treatment allocation, and a majority of the studies were at high or unclear risk of attrition bias. Overall, the quality of the included studies was low, and the certainty of the evidence for all the outcomes was downgraded by one level for the high risk of bias in the included studies.

The interventions were of short duration with more than half lasting three months or less. The reason behind the overall short duration of the interventions and the lack of long‐term outcomes may be the complexity of the intervention, a lack of adherence to the exercise intervention or costs. Furthermore, imprecision was a significant issue with most included studies relying on small convenience samples.

Potential biases in the review process

We searched the Cochrane Kidney and Transplant Specialised Register, which includes trial registries and hand‐searched conference abstracts (grey literature). However, some studies may have been reported only in exercise science conference proceedings or in conference proceedings in languages other than English and, therefore, missed by the Cochrane Kidney and Transplant Specialised Register. Despite our efforts to estimate means and SD from medians and ranges and impute missing SD, some studies still reported insufficient information for their results to be included in the meta‐analyses, which could lead to biases in the pooled estimates of effect. Finally, while the lack of blinding is likely to affect subjective outcomes more substantially than objective outcomes, the definition of objective versus subjective outcome is subject to interpretation, which could affect the level of certainty of the evidence presented in this review.

Agreements and disagreements with other studies or reviews

We have identified 17 systematic reviews of exercise training interventions relating to adults undergoing dialysis published in the past five years (Barcellos 2015; Bessa 2015; Chan 2016; Chung 2017; Clarkson 2019; Ferrari 2020; Gomes 2018; Heiwe 2014; Huang 2019; Pu 2019; Qiu 2017; Salhab 2019; Scapini 2019; Sheng 2014; Song 2018; Young 2018; Zhao 2019). They included between nine and 59 studies. The considerably larger number of studies included in the current review was probably due to broader inclusions criteria and our search of the grey literature. One review reported on fatigue and, like us, found an improvement with exercise training (Zhao 2019). Eleven reviews reported on the physical component of HRQoL, of which 10 found improvement with exercise (Barcellos 2015; Chan 2016; Chung 2017; Gomes 2018; Heiwe 2014; Huang 2019; Pu 2019; Salhab 2019; Thompson 1996; Zhao 2019) and one observed no effect (Young 2018). Ten reviews reported on the mental component of HRQoL, of which six found it unchanged by exercise training (Chan 2016; Chung 2017; Gomes 2018; Pu 2019; Sheng 2014; Young 2018) and three found it improved (Huang 2019; Salhab 2019; Zhao 2019). All of the five reviews that reported depression as an outcome found it improved with exercise training (Barcellos 2015; Gomes 2018; Pu 2019; Song 2018; Zhao 2019). Of the 10 reviews that reported the 6MWT, all but one that was focusing solely on resistance training (Chan 2016) concluded that exercise improved walking capacity (Chung 2017; Clarkson 2019; Ferrari 2020; Gomes 2018; Heiwe 2014; Huang 2019; Pu 2019; Sheng 2014; Young 2018). Two of the three studies that reported on the Sit‐To‐Stand test also concluded to improvement with exercise (Chan 2016; Clarkson 2019; Sheng 2014). Eight studies reported resting blood pressure, of which four observed improved SBP and DBP with exercise (Ferrari 2020; Pu 2019; Scapini 2019; Sheng 2014) and four did not observe a significant effect (Heiwe 2014; Huang 2019; Qiu 2017; Young 2018). No reviews reported death, cardiovascular events, or pain.

Flow diagram showing study identification and selection

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Figure 1

Flow diagram showing study identification and selection

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Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 1: Death

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Analysis 1.1

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 1: Death

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 2: Fatigue

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Analysis 1.2

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 2: Fatigue

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 3: HRQoL: Summary component scores

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Analysis 1.3

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 3: HRQoL: Summary component scores

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 4: HRQoL: Individual domains

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Analysis 1.4

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 4: HRQoL: Individual domains

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 5: Depression

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Analysis 1.5

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 5: Depression

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 6: 6MWT

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Analysis 1.6

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 6: 6MWT

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 7: Sit‐To‐Stand test [N reps/30 sec]

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Analysis 1.7

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 7: Sit‐To‐Stand test [N reps/30 sec]

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 8: Sit‐To‐Stand test [sit to 5 reps]

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Analysis 1.8

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 8: Sit‐To‐Stand test [sit to 5 reps]

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 9: Systolic blood pressure

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Analysis 1.9

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 9: Systolic blood pressure

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 10: Diastolic blood pressure

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Analysis 1.10

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 10: Diastolic blood pressure

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 11: Aerobic capacity (VO max or peak)

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Analysis 1.11

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 11: Aerobic capacity (VO max or peak)

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 12: Albumin

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Analysis 1.12

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 12: Albumin

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 13: Blood lipids

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Analysis 1.13

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 13: Blood lipids

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 14: Body composition

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Analysis 1.14

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 14: Body composition

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 15: Body mass index

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Analysis 1.15

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 15: Body mass index

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 16: Calcium

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Analysis 1.16

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 16: Calcium

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 17: C‐reactive protein

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Analysis 1.17

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 17: C‐reactive protein

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 18: Dialysis adequacy: Kt/V

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Analysis 1.18

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 18: Dialysis adequacy: Kt/V

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 19: Energy intake

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Analysis 1.19

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 19: Energy intake

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 20: Haemoglobin

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Analysis 1.20

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 20: Haemoglobin

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 21: Left ventricular ejection fraction

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Analysis 1.21

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 21: Left ventricular ejection fraction

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 22: Left ventricular mass index

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Analysis 1.22

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 22: Left ventricular mass index

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 23: Maximum heart rate

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Analysis 1.23

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 23: Maximum heart rate

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 24: Muscular strength

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Analysis 1.24

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 24: Muscular strength

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 25: Phosphate

Figures and Tables -
Analysis 1.25

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 25: Phosphate

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 26: Potassium

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Analysis 1.26

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 26: Potassium

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 27: Protein intake

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Analysis 1.27

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 27: Protein intake

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 28: Parathyroid hormone

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Analysis 1.28

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 28: Parathyroid hormone

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 29: Resting heart rate

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Analysis 1.29

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 29: Resting heart rate

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Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 30: Timed up‐and‐go test

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Analysis 1.30

Comparison 1: Any exercise versus control (no exercise/placebo exercise), Outcome 30: Timed up‐and‐go test

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 1: Death

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Analysis 2.1

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 1: Death

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 2: Fatigue

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Analysis 2.2

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 2: Fatigue

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 3: HRQoL: Summary component scores

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Analysis 2.3

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 3: HRQoL: Summary component scores

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 4: HRQoL: Individual domains

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Analysis 2.4

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 4: HRQoL: Individual domains

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 5: Depression

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Analysis 2.5

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 5: Depression

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 6: 6MWT

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Analysis 2.6

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 6: 6MWT

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 7: Sit‐To‐Stand test [N reps/30 sec]

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Analysis 2.7

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 7: Sit‐To‐Stand test [N reps/30 sec]

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 8: Sit‐To‐Stand test [sit to 5 reps]

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Analysis 2.8

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 8: Sit‐To‐Stand test [sit to 5 reps]

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 9: Resting blood pressure

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Analysis 2.9

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 9: Resting blood pressure

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 10: Aerobic capacity (VO2 max or peak)

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Analysis 2.10

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 10: Aerobic capacity (VO2 max or peak)

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 11: Albumin

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Analysis 2.11

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 11: Albumin

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 12: Blood lipids

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Analysis 2.12

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 12: Blood lipids

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 13: Body composition

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Analysis 2.13

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 13: Body composition

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 14: Body mass index

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Analysis 2.14

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 14: Body mass index

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 15: Calcium

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Analysis 2.15

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 15: Calcium

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 16: C‐reactive protein

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Analysis 2.16

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 16: C‐reactive protein

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 17: Dialysis adequacy: Kt/V

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Analysis 2.17

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 17: Dialysis adequacy: Kt/V

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 18: Energy intake

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Analysis 2.18

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 18: Energy intake

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 19: Haemoglobin

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Analysis 2.19

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 19: Haemoglobin

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 20: Heart rate

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Analysis 2.20

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 20: Heart rate

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 21: Left ventricular ejection fraction

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Analysis 2.21

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 21: Left ventricular ejection fraction

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 22: Left ventricular mass index

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Analysis 2.22

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 22: Left ventricular mass index

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 23: Muscular strength

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Analysis 2.23

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 23: Muscular strength

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 24: Phosphate

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Analysis 2.24

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 24: Phosphate

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 25: Potassium

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Analysis 2.25

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 25: Potassium

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 26: Protein intake

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Analysis 2.26

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 26: Protein intake

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 27: Parathyroid hormone

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Analysis 2.27

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 27: Parathyroid hormone

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Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 28: Timed up‐and‐go test

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Analysis 2.28

Comparison 2: Aerobic exercise versus control (no exercise/placebo exercise), Outcome 28: Timed up‐and‐go test

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 1: Fatigue

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Analysis 3.1

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 1: Fatigue

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 2: HRQoL: Summary component scores

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Analysis 3.2

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 2: HRQoL: Summary component scores

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 3: HR‐QoL: Individual domains

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Analysis 3.3

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 3: HR‐QoL: Individual domains

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 4: Depression

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Analysis 3.4

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 4: Depression

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 5: 6MWT

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Analysis 3.5

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 5: 6MWT

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 6: Sit‐To‐Stand test [N reps/30 sec]

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Analysis 3.6

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 6: Sit‐To‐Stand test [N reps/30 sec]

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 7: Sit‐To‐Stand test [N reps/30 sec]

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Analysis 3.7

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 7: Sit‐To‐Stand test [N reps/30 sec]

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 8: Albumin

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Analysis 3.8

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 8: Albumin

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 9: Blood lipids

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Analysis 3.9

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 9: Blood lipids

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 10: Body composition

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Analysis 3.10

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 10: Body composition

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 11: Body mass index

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Analysis 3.11

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 11: Body mass index

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 12: Calcium

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Analysis 3.12

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 12: Calcium

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 13: CRP

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Analysis 3.13

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 13: CRP

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 14: Dialysis adequacy: Kt/V

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Analysis 3.14

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 14: Dialysis adequacy: Kt/V

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 15: Energy intake

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Analysis 3.15

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 15: Energy intake

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 16: Haemoglobin

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Analysis 3.16

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 16: Haemoglobin

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 17: Muscular strength

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Analysis 3.17

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 17: Muscular strength

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 18: Phosphate

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Analysis 3.18

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 18: Phosphate

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 19: Potassium

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Analysis 3.19

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 19: Potassium

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 20: Protein intake

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Analysis 3.20

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 20: Protein intake

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 21: PTH

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Analysis 3.21

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 21: PTH

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Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 22: Timed up‐and‐go test

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Analysis 3.22

Comparison 3: Resistance exercise versus control (no exercise/placebo exercise), Outcome 22: Timed up‐and‐go test

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 1: HRQoL: Summary component scores

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Analysis 4.1

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 1: HRQoL: Summary component scores

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 2: HRQoL: Individual domains

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Analysis 4.2

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 2: HRQoL: Individual domains

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 3: Depression

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Analysis 4.3

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 3: Depression

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 4: 6MWT

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Analysis 4.4

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 4: 6MWT

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 5: Sit‐To‐Stand test [N reps/30 sec]

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Analysis 4.5

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 5: Sit‐To‐Stand test [N reps/30 sec]

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 6: Sit‐To‐Stand test [sit to 5 reps]

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Analysis 4.6

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 6: Sit‐To‐Stand test [sit to 5 reps]

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 7: Resting blood pressure

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Analysis 4.7

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 7: Resting blood pressure

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 8: Aerobic capacity (VO2 max or peak)

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Analysis 4.8

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 8: Aerobic capacity (VO2 max or peak)

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 9: Albumin

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Analysis 4.9

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 9: Albumin

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 10: Blood lipids

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Analysis 4.10

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 10: Blood lipids

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 11: Body composition

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Analysis 4.11

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 11: Body composition

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 12: Body mass index

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Analysis 4.12

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 12: Body mass index

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 13: Calcium

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Analysis 4.13

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 13: Calcium

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 14: CRP

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Analysis 4.14

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 14: CRP

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 15: Dialysis adequacy: Kt/V

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Analysis 4.15

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 15: Dialysis adequacy: Kt/V

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 16: Energy intake

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Analysis 4.16

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 16: Energy intake

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 17: Haemoglobin

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Analysis 4.17

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 17: Haemoglobin

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 18: Heart rate

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Analysis 4.18

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 18: Heart rate

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 19: Muscular strength

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Analysis 4.19

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 19: Muscular strength

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 20: Phosphate

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Analysis 4.20

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 20: Phosphate

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 21: Potassium

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Analysis 4.21

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 21: Potassium

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 22: Protein intake

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Analysis 4.22

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 22: Protein intake

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Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 23: Timed up‐and‐go test

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Analysis 4.23

Comparison 4: Combined aerobic and resistance exercise versus control (no exercise/placebo exercise), Outcome 23: Timed up‐and‐go test

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Summary of findings 1. Any exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Any exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: any exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise

Risk with any exercise

Death (any cause
Follow up: 3 years

159 per 1,000

151 per 1,000
(89 to 257)

RR 0.95
(0.56 to 1.62)

296 (1)

⊕⊝⊝⊝
VERY LOW 1 2 3

‐

Cardiovascular
events

Not reported

Not reported

‐

‐

‐

‐

Fatigue
Follow up: range 2 to 12 months

See comment

See comment

‐

326 (6)

⊕⊕⊝⊝
LOW 4 7

A pooled estimate of the effect was not calculated because the included studies assessed different dimensions of fatigue. Based on the direction of the effect in the included studies, any exercise may reduce fatigue

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 34 to 74 points

The mean physical component score was 4.1 points higher with exercise

(1.9 to 6.4 higher)

‐

656 (17)

⊕⊕⊝⊝
LOW 4 5

Any exercise may improve the physical component score of HRQoL

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 38 to 76 points

The mean mental component score was 2.5 points higher with exercise

(0.4 lower to 5.5 higher)

‐

656 (17)

⊕⊝⊝⊝
VERY LOW 4 5 6

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 47 to 87 points

The mean pain score was 5.3 points higher with exercise

(0.1 lower to 10.7 higher)

‐

872 (15)

⊕⊕⊝⊝
LOW 4 5

Any exercise may reduce pain however, the 95% CI indicates that exercise training might make little or no difference in the level of pain

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 0.62 SD lower with exercise

(1.00 to 0.24 lower)

‐

490 (11)

⊕⊕⊕⊝
MODERATE5

A SD of 0.2 represents a small difference between groups^

Any exercise probably improves depression. The magnitude of the effect was greater after four months of exercise training (SMD ‐1.26, 95% CI ‐1.80 to ‐0.72)

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 290 to 495 metres

The mean 6MWT was 49.9 metres further with exercise

(37.2 to 62.6 further)

‐

827 (19)

⊕⊕⊕⊝
MODERATE 5

Any exercise probably improves functional capacity

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐minute walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 High risk of bias: significantly greater proportion of participants lost to follow‐up in the exercise group compared to the control group

2 Imprecision: based on a single study that was not powered for this outcome

3 Indirectness: the outcome was assessed 2.5 years after the completion of the intervention

4 Indirectness: short interventions and short‐term follow‐up

5 High risk of bias in the included studies

6 Inconsistency: significant unexplained heterogeneity

7 Imprecision: outcome reported in few participants

Figures and Tables -
Summary of findings 1. Any exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis
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Summary of findings 2. Aerobic exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Aerobic exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: aerobic exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise

Risk with Aerobic exercise

Death (any cause)
Follow up: 3 years

159 per 1,000

151 per 1,000
(89 to 257)

RR 0.95
(0.56 to 1.62)

296 (1)

⊕⊝⊝⊝
VERY LOW 1 2 3

‐

Cardiovascular
events

Not reported

Not reported

‐

‐

‐

‐

Fatigue
Follow up: range 2 to 12 months

See comment

See comment

‐

221 (4)

⊕⊝⊝⊝
VERY LOW 1 4 5

A pooled estimate of the effect was not calculated because the included studies assessed different dimensions of fatigue

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 34 to 71 points

The mean physical component score was 6.0 points higher with aerobic exercise

(1.3 lower to 10.7 higher)

‐

306 (9)

⊕⊝⊝⊝
VERY LOW 4 5 6

‐

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 39 to 65 points

The mean mental component score was 3.3 points higher with aerobic exercise

(0.9 lower to 7.6 higher)

‐

306 (9)

⊕⊝⊝⊝
VERY LOW 4 5 6 7

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 47 to 87 points

The mean pain score was 2.3 points higher with aerobic exercise

(1.6 lower to 6.1 higher)

‐

570 (8)

⊕⊕⊝⊝
LOW 4 6

Aerobic exercise may result in little to no difference in pain

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 0.19 SD lower with aerobic exercise

(0.89 lower to 0.52 higher)

‐

127 (4)

⊕⊝⊝⊝
VERY LOW 5 6 7

A SD of 0.2 represents a small difference between groups^

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 290 to 454 metres

The mean 6MWT was 53.0 metres further with aerobic exercise

(33.8 to 72.2 further)

‐

515 (10)

⊕⊕⊕⊝
MODERATE 6

Aerobic exercise probably improves functional capacity.

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐minute walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 High risk of bias: significantly greater proportion of participants lost to follow‐up in the exercise group compared to the control group

2 Imprecision: based on a single study that was not powered for this outcome

3 Indirectness: the outcome was assessed 2.5 years after the completion of the intervention

4 Indirectness: short interventions and short follow‐up

5 Imprecision: outcome reported in few participants

6 High risk of bias in the included studies

7 Inconsistency: significant unexplained heterogeneity

Figures and Tables -
Summary of findings 2. Aerobic exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis
Navigate to table in Review
Summary of findings 3. Resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: resistance exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise

Risk with resistance exercise

Death (any cause)

Not reported

Not reported

‐

‐

‐

‐

Cardiovascular events

Not reported

Not reported

‐

‐

‐

‐

Fatigue

Assessed: Profile of Mood States score
Follow up: 12 weeks

The mean fatigue score was 8.95 points

The mean fatigue score was 1.88 points lower with resistance exercise

(4.14 lower to 0.38 higher)

‐

68 (1)

⊕⊝⊝⊝
VERY LOW 1 2

‐

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 46 to 74 points

The mean physical component score was 2.5 points higher with resistance exercise

(1.3 lower to 6.3 higher)

‐

176 (5)

⊕⊝⊝⊝
VERY LOW 2 3 4

‐

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 38 to 76 points

the mean mental component score was 0.7 points lower with resistance exercise

(5.9 lower to 4.6 higher)

‐

176 (5)

⊕⊝⊝⊝
VERY LOW 2 3 4 5

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 60 to 82 points

The mean pain score was 10.7 points higher with resistance exercise

(6.5 lower to 28.0 higher)

‐

154 (5)

⊕⊝⊝⊝
VERY LOW 2 3 4

‐

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 0.52 SD lower with resistance exercise

(0.92 to 0.12 lower)

‐

99 (2)

⊕⊝⊝⊝
VERY LOW 2 3 4

A SD of 0.2 represents a small difference between groups^

The evidence is very uncertain about the effect of resistance exercise on depression

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 407 to 495 metres

The mean 6MWT was 44.7 metres further with resistance exercise

(27.0 to 62.4 further)

‐

216 (7)

⊕⊕⊕⊝
MODERATE 2

Resistance exercise probably improves functional capacity

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐minute walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Imprecision: based on a single study that was not powered for this outcome

2 High risk of bias in the included studies

3 Indirectness: short interventions and short follow‐up

4 Imprecision: outcome reported in few participants

5 Inconsistency: significant heterogeneity

Figures and Tables -
Summary of findings 3. Resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis
Navigate to table in Review
Summary of findings 4. Combined aerobic and resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Combined aerobic and resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis

Patient or population: adults undergoing maintenance dialysis
Setting: all settings (e.g. during dialysis, pre‐ and post‐dialysis; home exercise)
Intervention: combined aerobic and resistance exercise
Comparison: no exercise or placebo exercise

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

No. of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with no exercise or placebo exercise)

Risk with combined aerobic and resistance exercise

Death (any cause)

Not reported

Not reported

‐

‐

‐

‐

Cardiovascular events

Not reported

Not reported

‐

‐

‐

‐

Fatigue

Not reported

Not reported

‐

‐

‐

‐

HRQoL: Physical component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean physical component score ranged from 38 to 51

The mean physical component score was 4.4 points higher with combined exercise
(1.9 higher to 6.8 higher)

‐

228 (6)

⊕⊝⊝⊝
VERY LOW 1 2 3

The evidence is very uncertain about the effect of combined aerobic and resistance exercise on the physical component of HRQoL

HRQoL: Mental component score
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 2 to 12 months

The mean mental component score ranged from 40 to 43

The mean mental component score was 2.6 points higher with combined exercise

(1.7 lower to 6.9 higher)

‐

228 (6)

⊕⊝⊝⊝
VERY LOW 1 2 3

‐

Pain
Assessed: SF‐36
Scale: 0 to 100
Follow up: range 3 to 12 months

The mean pain score ranged from 68 to 83 points

The mean pain score was 4.0 points higher
with combined exercise

(2.5 lower to 10.5 higher)

‐

161 (3)

⊕⊝⊝⊝
VERY LOW 12 3

‐

Depression
Assessed: multiple severity of depressive symptoms scales
Follow up: range 2 to 12 months

‐

The SMD for depression was 1.0 SD lower with combined exercise
(1.7 lower to 0.3 lower)

‐

214 (4)

⊕⊝⊝⊝
VERY LOW 2 3

A SD of 0.2 represents a small difference between groups^

The evidence is very uncertain about the effect of combined aerobic and resistance exercise on depression

Functional capacity
Assessed: 6MWT
Follow up: range 2 to 6 months

The mean 6MWT ranged from 399 to 430 metres

The mean 6MWT was 53.6 metres further
(39.4 to 67.9 further)

‐

138 (6)

⊕⊕⊕⊝
MODERATE 1 2

Combined aerobic and resistance exercise probably improves functional capacity.

*The risk in the intervention group (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).

^ Cohen's interpretation of effect size

CI: Confidence interval; RR: Risk ratio; 6MWT: 6‐metre walking test; SMD: standardised mean difference

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Indirectness: short interventions and short follow‐up

2 High risk of bias in the included studies

3 Imprecision: outcome reported in few participants

Figures and Tables -
Summary of findings 4. Combined aerobic and resistance exercise versus no exercise or placebo exercise for adults undergoing maintenance dialysis
Navigate to table in Review
Comparison 1. Any exercise versus control (no exercise/placebo exercise)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Death Show forest plot

1

296

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.56, 1.62]

1.2 Fatigue Show forest plot

6

Std. Mean Difference (IV, Random, 95% CI)

Totals not selected

1.3 HRQoL: Summary component scores Show forest plot

17

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.3.1 Physical Component Score

17

656

Mean Difference (IV, Random, 95% CI)

‐4.12 [‐6.37, ‐1.88]

1.3.2 Mental Component Score

17

656

Mean Difference (IV, Random, 95% CI)

‐2.53 [‐5.47, 0.40]

1.4 HRQoL: Individual domains Show forest plot

20

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.4.1 Physical Functioning

18

1040

Mean Difference (IV, Random, 95% CI)

‐4.70 [‐8.94, ‐0.47]

1.4.2 Role‐physical

13

809

Mean Difference (IV, Random, 95% CI)

‐3.75 [‐13.73, 6.23]

1.4.3 Pain

15

872

Mean Difference (IV, Random, 95% CI)

‐5.28 [‐10.69, 0.12]

1.4.4 General health perceptions

14

834

Mean Difference (IV, Random, 95% CI)

‐3.86 [‐7.39, ‐0.33]

1.4.5 Emotional well‐being

13

789

Mean Difference (IV, Random, 95% CI)

‐4.24 [‐8.00, ‐0.47]

1.4.6 Role‐emotional

14

833

Mean Difference (IV, Random, 95% CI)

‐8.08 [‐11.26, ‐4.90]

1.4.7 Vitality

16

940

Mean Difference (IV, Random, 95% CI)

‐4.47 [‐8.15, ‐0.79]

1.4.8 Social function

15

851

Mean Difference (IV, Random, 95% CI)

‐0.80 [‐4.56, 2.96]

1.4.9 Symptoms

7

533

Mean Difference (IV, Random, 95% CI)

‐6.07 [‐12.07, ‐0.08]

1.4.10 Effects of kidney disease

5

409

Mean Difference (IV, Random, 95% CI)

‐4.01 [‐6.47, ‐1.55]

1.4.11 Burden of kidney disease

5

409

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐2.64, 2.51]

1.4.12 Work status

4

362

Mean Difference (IV, Random, 95% CI)

‐0.36 [‐3.75, 3.03]

1.4.13 Cognitive function

5

409

Mean Difference (IV, Random, 95% CI)

‐2.66 [‐7.57, 2.25]

1.4.14 Quality of social interactions

5

409

Mean Difference (IV, Random, 95% CI)

‐4.92 [‐8.32, ‐1.51]

1.4.15 Sexual function

4

362

Mean Difference (IV, Random, 95% CI)

‐3.60 [‐11.16, 3.96]

1.4.16 Sleep

6

437

Mean Difference (IV, Random, 95% CI)

‐6.58 [‐12.57, ‐0.60]

1.4.17 Social support

5

409

Mean Difference (IV, Random, 95% CI)

‐3.98 [‐7.07, ‐0.89]

1.4.18 Dialysis staff encouragement

5

409

Mean Difference (IV, Random, 95% CI)

‐3.75 [‐8.40, 0.90]

1.4.19 Patient satisfaction

5

409

Mean Difference (IV, Random, 95% CI)

‐4.58 [‐10.23, 1.06]

1.5 Depression Show forest plot

10

441

Std. Mean Difference (IV, Random, 95% CI)

0.65 [0.22, 1.07]

1.5.1 4 months or less

6

311

Std. Mean Difference (IV, Random, 95% CI)

0.30 [‐0.14, 0.74]

1.5.2 More than 4 months

4

130

Std. Mean Difference (IV, Random, 95% CI)

1.26 [0.72, 1.80]

1.6 6MWT Show forest plot

19

827

Mean Difference (IV, Random, 95% CI)

‐49.91 [‐62.59, ‐37.22]

1.7 Sit‐To‐Stand test [N reps/30 sec] Show forest plot

12

478

Mean Difference (IV, Random, 95% CI)

‐2.36 [‐2.98, ‐1.73]

1.8 Sit‐To‐Stand test [sit to 5 reps] Show forest plot

8

508

Mean Difference (IV, Random, 95% CI)

1.74 [1.22, 2.25]

1.9 Systolic blood pressure Show forest plot

20

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.9.1 Aerobic

13

394

Mean Difference (IV, Random, 95% CI)

3.99 [‐1.80, 9.78]

1.9.2 Combined aerobic and resistance

7

282

Mean Difference (IV, Random, 95% CI)

8.69 [3.69, 13.69]

1.9.3 Others

1

30

Mean Difference (IV, Random, 95% CI)

25.55 [14.95, 36.15]

1.10 Diastolic blood pressure Show forest plot

20

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.10.1 Aerobic

13

394

Mean Difference (IV, Random, 95% CI)

‐0.72 [‐3.69, 2.24]

1.10.2 Combined aerobic and resistance

7

282

Mean Difference (IV, Random, 95% CI)

4.45 [2.91, 5.98]

1.10.3 Others

1

30

Mean Difference (IV, Random, 95% CI)

13.42 [7.46, 19.38]

1.11 Aerobic capacity (VO max or peak) Show forest plot

14

407

Mean Difference (IV, Random, 95% CI)

‐3.30 [‐4.33, ‐2.28]

1.12 Albumin Show forest plot

23

767

Mean Difference (IV, Random, 95% CI)

‐0.39 [‐1.25, 0.47]

1.13 Blood lipids Show forest plot

12

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.13.1 Total cholesterol [mmol/L]

12

439

Mean Difference (IV, Random, 95% CI)

0.22 [0.04, 0.39]

1.13.2 LDL cholesterol [mmol/L]

6

180

Mean Difference (IV, Random, 95% CI)

0.24 [‐0.02, 0.51]

1.13.3 HDL cholesterol [mmol/L]

8

264

Mean Difference (IV, Random, 95% CI)

‐0.07 [‐0.18, 0.04]

1.13.4 Triglycerides [mmol/L]

8

264

Mean Difference (IV, Random, 95% CI)

0.09 [‐0.25, 0.44]

1.14 Body composition Show forest plot

10

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.14.1 Fat mass [kg]

9

384

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.10, 0.02]

1.14.2 Lean mass [kg]

7

313

Mean Difference (IV, Random, 95% CI)

‐0.37 [‐2.74, 1.99]

1.15 Body mass index Show forest plot

16

590

Mean Difference (IV, Random, 95% CI)

‐0.12 [‐0.55, 0.31]

1.16 Calcium Show forest plot

17

592

Mean Difference (IV, Random, 95% CI)

0.03 [‐0.00, 0.06]

1.17 C‐reactive protein Show forest plot

14

421

Mean Difference (IV, Random, 95% CI)

0.31 [‐0.13, 0.74]

1.18 Dialysis adequacy: Kt/V Show forest plot

11

382

Mean Difference (IV, Random, 95% CI)

‐0.08 [‐0.16, 0.00]

1.19 Energy intake Show forest plot

7

316

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐1.58, 1.40]

1.20 Haemoglobin Show forest plot

29

975

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.18, 0.06]

1.21 Left ventricular ejection fraction Show forest plot

6

222

Mean Difference (IV, Random, 95% CI)

‐1.45 [‐3.60, 0.70]

1.22 Left ventricular mass index Show forest plot

6

215

Mean Difference (IV, Random, 95% CI)

‐9.85 [‐20.50, 0.80]

1.23 Maximum heart rate Show forest plot

8

275

Mean Difference (IV, Random, 95% CI)

‐6.14 [‐10.05, ‐2.24]

1.24 Muscular strength Show forest plot

16

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.24.1 Knee extension

8

316

Mean Difference (IV, Random, 95% CI)

‐5.06 [‐8.58, ‐1.54]

1.24.2 Handgrip

10

410

Mean Difference (IV, Random, 95% CI)

‐4.16 [‐6.61, ‐1.71]

1.25 Phosphate Show forest plot

20

672

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.07, 0.16]

1.26 Potassium Show forest plot

18

610

Mean Difference (IV, Random, 95% CI)

0.23 [‐0.06, 0.51]

1.27 Protein intake Show forest plot

7

316

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.10, 0.07]

1.28 Parathyroid hormone Show forest plot

5

129

Mean Difference (IV, Random, 95% CI)

0.39 [‐10.90, 11.68]

1.29 Resting heart rate Show forest plot

11

405

Mean Difference (IV, Random, 95% CI)

3.72 [1.89, 5.56]

1.30 Timed up‐and‐go test Show forest plot

6

285

Mean Difference (IV, Random, 95% CI)

1.63 [0.90, 2.36]
Figures and Tables -
Comparison 1. Any exercise versus control (no exercise/placebo exercise)
Navigate to table in Review
Comparison 2. Aerobic exercise versus control (no exercise/placebo exercise)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Death Show forest plot

1

296

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.56, 1.62]

2.2 Fatigue Show forest plot

4

Std. Mean Difference (IV, Random, 95% CI)

Totals not selected

2.3 HRQoL: Summary component scores Show forest plot

9

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.3.1 Physical Component Score

9

306

Mean Difference (IV, Random, 95% CI)

‐6.00 [‐10.71, ‐1.30]

2.3.2 Mental Component Score

9

306

Mean Difference (IV, Random, 95% CI)

‐3.33 [‐7.56, 0.90]

2.4 HRQoL: Individual domains Show forest plot

11

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.4.1 Physical Functioning

10

649

Mean Difference (IV, Random, 95% CI)

‐2.87 [‐10.12, 4.38]

2.4.2 Role‐physical

8

560

Mean Difference (IV, Random, 95% CI)

‐2.31 [‐17.29, 12.67]

2.4.3 Pain

8

570

Mean Difference (IV, Random, 95% CI)

‐2.26 [‐6.12, 1.61]

2.4.4 General health perceptions

8

560

Mean Difference (IV, Random, 95% CI)

‐5.38 [‐10.32, ‐0.43]

2.4.5 Emotional well‐being

7

515

Mean Difference (IV, Random, 95% CI)

‐5.63 [‐10.58, ‐0.67]

2.4.6 Role‐emotional

8

560

Mean Difference (IV, Random, 95% CI)

‐8.02 [‐11.45, ‐4.58]

2.4.7 Vitality

9

613

Mean Difference (IV, Random, 95% CI)

‐0.43 [‐6.45, 5.60]

2.4.8 Social function

9

577

Mean Difference (IV, Random, 95% CI)

0.94 [‐4.48, 6.37]

2.4.9 Symptoms

3

317

Mean Difference (IV, Random, 95% CI)

‐7.65 [‐20.65, 5.35]

2.4.10 Effects of kidney disease

3

317

Mean Difference (IV, Random, 95% CI)

‐4.27 [‐6.87, ‐1.66]

2.4.11 Burden of kidney disease

3

317

Mean Difference (IV, Random, 95% CI)

0.05 [‐2.63, 2.72]

2.4.12 Work status

3

317

Mean Difference (IV, Random, 95% CI)

‐0.44 [‐3.87, 2.99]

2.4.13 Cognitive function

3

317

Mean Difference (IV, Random, 95% CI)

‐6.36 [‐10.11, ‐2.60]

2.4.14 Quality of social interactions

3

317

Mean Difference (IV, Random, 95% CI)

‐6.96 [‐10.57, ‐3.36]

2.4.15 Sexual function

3

317

Mean Difference (IV, Random, 95% CI)

‐0.87 [‐7.23, 5.48]

2.4.16 Sleep

3

317

Mean Difference (IV, Random, 95% CI)

‐6.44 [‐13.46, 0.58]

2.4.17 Social support

3

317

Mean Difference (IV, Random, 95% CI)

‐4.35 [‐8.51, ‐0.19]

2.4.18 Dialysis staff encouragement

3

317

Mean Difference (IV, Random, 95% CI)

‐5.49 [‐11.11, 0.13]

2.4.19 Patient satisfaction

3

317

Mean Difference (IV, Random, 95% CI)

‐7.52 [‐13.12, ‐1.92]

2.5 Depression Show forest plot

4

127

Std. Mean Difference (IV, Random, 95% CI)

0.19 [‐0.52, 0.89]

2.6 6MWT Show forest plot

10

515

Mean Difference (IV, Random, 95% CI)

‐53.00 [‐72.17, ‐33.84]

2.7 Sit‐To‐Stand test [N reps/30 sec] Show forest plot

6

227

Mean Difference (IV, Random, 95% CI)

‐1.81 [‐2.76, ‐0.86]

2.8 Sit‐To‐Stand test [sit to 5 reps] Show forest plot

5

374

Mean Difference (IV, Random, 95% CI)

1.63 [0.92, 2.33]

2.9 Resting blood pressure Show forest plot

13

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.9.1 Systolic blood pressure

13

400

Mean Difference (IV, Random, 95% CI)

3.96 [‐1.78, 9.70]

2.9.2 Diastolic blood pressure

13

400

Mean Difference (IV, Random, 95% CI)

‐0.73 [‐3.68, 2.22]

2.10 Aerobic capacity (VO2 max or peak) Show forest plot

12

326

Mean Difference (IV, Random, 95% CI)

‐2.69 [‐4.55, ‐0.82]

2.11 Albumin Show forest plot

15

429

Mean Difference (IV, Random, 95% CI)

‐0.23 [‐1.45, 0.99]

2.12 Blood lipids Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.12.1 Total cholesterol [mmol/L]

5

129

Mean Difference (IV, Random, 95% CI)

0.30 [‐0.03, 0.63]

2.12.2 LDL cholesterol [mmol/L]

3

72

Mean Difference (IV, Random, 95% CI)

0.17 [‐0.08, 0.42]

2.12.3 HDL cholesterol [mmol/L]

3

72

Mean Difference (IV, Random, 95% CI)

0.05 [0.01, 0.09]

2.12.4 Triglycerides [mmol/L]

3

72

Mean Difference (IV, Random, 95% CI)

0.23 [‐0.59, 1.05]

2.13 Body composition Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.13.1 Fat mass [kg]

3

95

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.10, 0.02]

2.13.2 Lean mass [kg]

2

89

Mean Difference (IV, Random, 95% CI)

‐1.94 [‐6.32, 2.45]

2.14 Body mass index Show forest plot

9

291

Mean Difference (IV, Random, 95% CI)

‐0.17 [‐0.78, 0.45]

2.15 Calcium Show forest plot

8

208

Mean Difference (IV, Random, 95% CI)

0.01 [‐0.04, 0.06]

2.16 C‐reactive protein Show forest plot

9

206

Mean Difference (IV, Random, 95% CI)

0.60 [‐0.12, 1.32]

2.17 Dialysis adequacy: Kt/V Show forest plot

7

166

Mean Difference (IV, Random, 95% CI)

‐0.07 [‐0.20, 0.05]

2.18 Energy intake Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

‐1.84 [‐6.87, 3.20]

2.19 Haemoglobin Show forest plot

17

437

Mean Difference (IV, Random, 95% CI)

0.01 [‐0.18, 0.21]

2.20 Heart rate Show forest plot

10

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.20.1 Resting

7

218

Mean Difference (IV, Random, 95% CI)

4.07 [0.49, 7.65]

2.20.2 Maximum

6

179

Mean Difference (IV, Random, 95% CI)

‐6.54 [‐12.01, ‐1.07]

2.21 Left ventricular ejection fraction Show forest plot

5

141

Mean Difference (IV, Random, 95% CI)

‐1.65 [‐3.93, 0.62]

2.22 Left ventricular mass index Show forest plot

5

119

Mean Difference (IV, Random, 95% CI)

‐14.47 [‐26.25, ‐2.69]

2.23 Muscular strength Show forest plot

7

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.23.1 Knee extension

3

53

Mean Difference (IV, Random, 95% CI)

‐5.94 [‐13.95, 2.07]

2.23.2 handgrip

4

148

Mean Difference (IV, Random, 95% CI)

‐4.65 [‐9.44, 0.14]

2.24 Phosphate Show forest plot

9

214

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.07, 0.17]

2.25 Potassium Show forest plot

8

190

Mean Difference (IV, Random, 95% CI)

0.08 [‐0.08, 0.24]

2.26 Protein intake Show forest plot

4

118

Mean Difference (IV, Random, 95% CI)

0.04 [‐0.25, 0.33]

2.27 Parathyroid hormone Show forest plot

3

92

Mean Difference (IV, Random, 95% CI)

‐2.69 [‐20.31, 14.93]

2.28 Timed up‐and‐go test Show forest plot

4

204

Mean Difference (IV, Random, 95% CI)

1.38 [0.50, 2.26]
Figures and Tables -
Comparison 2. Aerobic exercise versus control (no exercise/placebo exercise)
Navigate to table in Review
Comparison 3. Resistance exercise versus control (no exercise/placebo exercise)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Fatigue Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

3.2 HRQoL: Summary component scores Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.2.1 Physical Component Score

5

176

Mean Difference (IV, Random, 95% CI)

‐2.52 [‐6.32, 1.29]

3.2.2 Mental Component Score

5

176

Mean Difference (IV, Random, 95% CI)

0.68 [‐4.57, 5.94]

3.3 HR‐QoL: Individual domains Show forest plot

7

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.3.1 Physical functioning

6

243

Mean Difference (IV, Random, 95% CI)

‐5.28 [‐10.09, ‐0.46]

3.3.2 Role‐physical

3

102

Mean Difference (IV, Random, 95% CI)

‐8.13 [‐21.33, 5.07]

3.3.3 Pain

5

154

Mean Difference (IV, Random, 95% CI)

‐10.74 [‐27.96, 6.47]

3.3.4 General health perceptions

4

126

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐6.43, 6.33]

3.3.5 Emotional well‐being

4

126

Mean Difference (IV, Random, 95% CI)

‐7.22 [‐13.98, ‐0.46]

3.3.6 Role‐emotional

4

126

Mean Difference (IV, Random, 95% CI)

‐4.25 [‐14.62, 6.12]

3.3.7 Vitality

5

179

Mean Difference (IV, Random, 95% CI)

‐5.17 [‐15.18, 4.85]

3.3.8 Social function

4

126

Mean Difference (IV, Random, 95% CI)

‐9.28 [‐17.08, ‐1.47]

3.3.9 Symptoms

3

86

Mean Difference (IV, Random, 95% CI)

‐9.25 [‐15.19, ‐3.30]

3.3.10 Effects of kidney disease

2

58

Mean Difference (IV, Random, 95% CI)

‐4.87 [‐16.82, 7.08]

3.3.11 Burden of kidney disease

2

58

Mean Difference (IV, Random, 95% CI)

3.35 [‐9.05, 15.75]

3.3.12 Work status

2

58

Mean Difference (IV, Random, 95% CI)

4.30 [‐14.99, 23.59]

3.3.13 Cognitive function

2

58

Mean Difference (IV, Random, 95% CI)

6.31 [‐6.73, 19.36]

3.3.14 Quality of social interactions

2

58

Mean Difference (IV, Random, 95% CI)

8.30 [‐3.74, 20.34]

3.3.15 Sexual function

2

58

Mean Difference (IV, Random, 95% CI)

‐14.16 [‐35.63, 7.31]

3.3.16 Sleep

3

86

Mean Difference (IV, Random, 95% CI)

‐10.70 [‐20.99, ‐0.40]

3.3.17 Social support

2

58

Mean Difference (IV, Random, 95% CI)

‐4.41 [‐13.92, 5.09]

3.3.18 Dialysis staff encouragement

2

58

Mean Difference (IV, Random, 95% CI)

‐1.10 [‐8.72, 6.52]

3.3.19 Patient satisfaction

2

58

Mean Difference (IV, Random, 95% CI)

‐1.07 [‐10.75, 8.60]

3.4 Depression Show forest plot

2

99

Std. Mean Difference (IV, Random, 95% CI)

0.52 [0.12, 0.92]

3.5 6MWT Show forest plot

7

216

Mean Difference (IV, Random, 95% CI)

‐44.71 [‐62.43, ‐27.00]

3.6 Sit‐To‐Stand test [N reps/30 sec] Show forest plot

6

196

Mean Difference (IV, Random, 95% CI)

‐2.76 [‐3.83, ‐1.68]

3.7 Sit‐To‐Stand test [N reps/30 sec] Show forest plot

2

93

Mean Difference (IV, Random, 95% CI)

1.56 [‐0.44, 3.57]

3.8 Albumin Show forest plot

9

268

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐1.59, 1.05]

3.9 Blood lipids Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.9.1 Total cholesterol [mmol/L]

3

76

Mean Difference (IV, Random, 95% CI)

0.26 [‐0.07, 0.58]

3.9.2 LDL cholesterol [mmol/L]

2

54

Mean Difference (IV, Random, 95% CI)

0.12 [‐0.17, 0.41]

3.9.3 HDL cholesterol [mmol/L]

2

54

Mean Difference (IV, Random, 95% CI)

0.02 [‐0.16, 0.19]

3.9.4 Triglycerides [mmol/L]

2

54

Mean Difference (IV, Random, 95% CI)

0.54 [‐0.00, 1.07]

3.10 Body composition Show forest plot

7

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.10.1 Fat mass [kg]

7

291

Mean Difference (IV, Random, 95% CI)

‐0.69 [‐2.94, 1.56]

3.10.2 Lean mass [kg]

5

224

Mean Difference (IV, Random, 95% CI)

0.16 [‐2.95, 3.28]

3.11 Body mass index Show forest plot

8

267

Mean Difference (IV, Random, 95% CI)

‐1.00 [‐1.98, ‐0.01]

3.12 Calcium Show forest plot

4

102

Mean Difference (IV, Random, 95% CI)

0.04 [‐0.08, 0.16]

3.13 CRP Show forest plot

6

153

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐0.58, 0.14]

3.14 Dialysis adequacy: Kt/V Show forest plot

2

73

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.23, 0.12]

3.15 Energy intake Show forest plot

5

208

Mean Difference (IV, Random, 95% CI)

0.17 [‐1.45, 1.80]

3.16 Haemoglobin Show forest plot

10

254

Mean Difference (IV, Random, 95% CI)

‐0.11 [‐0.29, 0.07]

3.17 Muscular strength Show forest plot

8

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.17.1 knee extension

6

238

Mean Difference (IV, Random, 95% CI)

‐6.09 [‐10.68, ‐1.50]

3.17.2 handgrip

3

137

Mean Difference (IV, Random, 95% CI)

‐2.01 [‐5.71, 1.69]

3.18 Phosphate Show forest plot

7

188

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.36, 0.24]

3.19 Potassium Show forest plot

7

188

Mean Difference (IV, Random, 95% CI)

0.32 [‐0.23, 0.86]

3.20 Protein intake Show forest plot

5

208

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.09, 0.07]

3.21 PTH Show forest plot

2

37

Mean Difference (IV, Random, 95% CI)

1.51 [‐30.38, 33.39]

3.22 Timed up‐and‐go test Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Figures and Tables -
Comparison 3. Resistance exercise versus control (no exercise/placebo exercise)
Navigate to table in Review
Comparison 4. Combined aerobic and resistance exercise versus control (no exercise/placebo exercise)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 HRQoL: Summary component scores Show forest plot

6

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.1.1 Physical Component Score

6

228

Mean Difference (IV, Random, 95% CI)

‐4.38 [‐6.82, ‐1.94]

4.1.2 Mental Component Score

6

228

Mean Difference (IV, Random, 95% CI)

‐2.58 [‐6.91, 1.74]

4.2 HRQoL: Individual domains Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.2.1 Physical Functioning

3

161

Mean Difference (IV, Random, 95% CI)

‐4.07 [‐10.60, 2.47]

4.2.2 Role‐physical

3

160

Mean Difference (IV, Random, 95% CI)

‐3.86 [‐14.38, 6.66]

4.2.3 Pain

3

161

Mean Difference (IV, Random, 95% CI)

‐3.98 [‐10.46, 2.49]

4.2.4 General health perceptions

3

161

Mean Difference (IV, Random, 95% CI)

‐3.67 [‐9.24, 1.90]

4.2.5 Emotional well‐being

3

161

Mean Difference (IV, Random, 95% CI)

1.29 [‐3.99, 6.57]

4.2.6 Role‐emotional

3

160

Mean Difference (IV, Random, 95% CI)

‐10.68 [‐20.92, ‐0.43]

4.2.7 Vitality

3

161

Mean Difference (IV, Random, 95% CI)

‐7.88 [‐13.48, ‐2.28]

4.2.8 Social function

3

161

Mean Difference (IV, Random, 95% CI)

1.83 [‐4.56, 8.22]

4.2.9 Symptoms

2

143

Mean Difference (IV, Random, 95% CI)

0.17 [‐3.20, 3.54]

4.2.10 Effects of kidney disease

1

47

Mean Difference (IV, Random, 95% CI)

‐1.70 [‐10.27, 6.87]

4.2.11 Burden of kidney disease

1

47

Mean Difference (IV, Random, 95% CI)

‐5.70 [‐17.40, 6.00]

4.2.12 Cognitive function

1

47

Mean Difference (IV, Random, 95% CI)

2.10 [‐3.68, 7.88]

4.2.13 Quality of social interactions

1

47

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐7.72, 7.12]

4.2.14 Sleep

1

47

Mean Difference (IV, Random, 95% CI)

4.30 [‐5.67, 14.27]

4.2.15 Social support

1

47

Mean Difference (IV, Random, 95% CI)

0.30 [‐9.88, 10.48]

4.2.16 Dialysis staff encouragement

1

47

Mean Difference (IV, Random, 95% CI)

2.40 [‐8.82, 13.62]

4.2.17 Patient satisfaction

1

47

Mean Difference (IV, Random, 95% CI)

2.80 [‐8.88, 14.48]

4.3 Depression Show forest plot

4

214

Std. Mean Difference (IV, Random, 95% CI)

0.97 [0.25, 1.68]

4.4 6MWT Show forest plot

6

138

Mean Difference (IV, Random, 95% CI)

‐53.64 [‐67.91, ‐39.36]

4.5 Sit‐To‐Stand test [N reps/30 sec] Show forest plot

4

97

Mean Difference (IV, Random, 95% CI)

‐2.63 [‐3.77, ‐1.49]

4.6 Sit‐To‐Stand test [sit to 5 reps] Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4.7 Resting blood pressure Show forest plot

7

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.7.1 Systolic blood pressure

7

288

Mean Difference (IV, Random, 95% CI)

8.69 [3.78, 13.59]

4.7.2 Diastolic blood pressure

7

288

Mean Difference (IV, Random, 95% CI)

4.42 [2.90, 5.94]

4.8 Aerobic capacity (VO2 max or peak) Show forest plot

3

93

Mean Difference (IV, Random, 95% CI)

‐4.29 [‐8.98, 0.39]

4.9 Albumin Show forest plot

3

116

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐1.61, 1.16]

4.10 Blood lipids Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.10.1 Total cholesterol [mmol/L]

4

204

Mean Difference (IV, Random, 95% CI)

0.03 [‐0.21, 0.27]

4.10.2 LDL cholesterol [mmol/L]

2

61

Mean Difference (IV, Random, 95% CI)

0.44 [‐0.09, 0.96]

4.10.3 HDL cholesterol [mmol/L]

3

108

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐0.44, ‐0.10]

4.10.4 Triglycerides [mmol/L]

3

108

Mean Difference (IV, Random, 95% CI)

‐0.11 [‐0.86, 0.64]

4.11 Body composition Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4.11.1 Fat mass [kg]

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4.12 Body mass index Show forest plot

2

73

Mean Difference (IV, Fixed, 95% CI)

‐0.42 [‐1.37, 0.53]

4.13 Calcium Show forest plot

4

190

Mean Difference (IV, Random, 95% CI)

0.06 [‐0.01, 0.12]

4.14 CRP Show forest plot

3

117

Mean Difference (IV, Random, 95% CI)

0.09 [‐0.27, 0.46]

4.15 Dialysis adequacy: Kt/V Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4.16 Energy intake Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4.17 Haemoglobin Show forest plot

5

266

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.24, 0.20]

4.18 Heart rate Show forest plot

5

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.18.1 Resting

4

179

Mean Difference (IV, Random, 95% CI)

3.05 [0.70, 5.40]

4.18.2 Maximum

3

90

Mean Difference (IV, Random, 95% CI)

‐5.37 [‐11.10, 0.35]

4.19 Muscular strength Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.19.1 Knee extension

2

63

Mean Difference (IV, Random, 95% CI)

1.60 [‐3.66, 6.87]

4.19.2 Handgrip

2

88

Mean Difference (IV, Random, 95% CI)

‐4.55 [‐10.23, 1.14]

4.20 Phosphate Show forest plot

4

190

Mean Difference (IV, Random, 95% CI)

‐0.04 [‐0.15, 0.08]

4.21 Potassium Show forest plot

4

190

Mean Difference (IV, Random, 95% CI)

‐0.15 [‐0.36, 0.06]

4.22 Protein intake Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4.23 Timed up‐and‐go test Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Figures and Tables -
Comparison 4. Combined aerobic and resistance exercise versus control (no exercise/placebo exercise)
Navigate to table in Review