Upper limb exercise for arteriovenous fistula maturation in people requiring permanent haemodialysis access
Abstract
Background
The failure of arteriovenous fistulas (AVF) to mature is a major problem in patients with kidney failure who require haemodialysis (HD). Preoperative planning is an important factor in increasing functional AVF. Upper limb exercise has been recommended to gain AVF maturation. Studies of pre‐ and post‐operative upper limb exercises in patients with kidney failure patients have been reported; however, the optimal program for this population is unknown due to inconsistent results among these programs.
Objectives
We aimed to determine if upper limb exercise would be beneficial for AVF maturation (prior to and post AVF creation) in patients with kidney failure and to improve AVF outcomes. This review also aimed to identify adverse events related to upper limb exercise.
Search methods
We searched the Cochrane Kidney and Transplant Register of Studies up to 15 March 2022 through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov, and other resources (e.g. reference list, contacting relevant individuals, and grey literature).
Selection criteria
We included randomised controlled trials (RCTs) and quasi‐RCTs, comparing upper limb exercise training programs with no intervention or other control programs before or after AVF creation in patients with kidney failure. Outcome measures included time to mature, ultrasound and clinical maturation, venous diameter, blood flow in the inflow artery, dialysis efficacy indicator, vascular access function (functional AVF), vascular access complications, and adverse events.
Data collection and analysis
Study selection and data extraction were taken by four independent authors. Bias assessment and quality assessment were undertaken independently by two authors. The effect estimate was analysed using risk ratio (RR) with 95% confidence intervals (CI) for dichotomous data, or mean difference (MD) or standardised mean difference (SMD) for continuous data. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
Main results
Nine studies (579 participants) were included, and seven studies (519 participants) conducting post‐operative exercise training could be meta‐analysed. Three comparisons were undertaken: (i) isotonic exercise training versus no intervention; (ii) isometric versus isotonic exercise training; and (iii) isotonic (high volume) versus isotonic exercise training (low volume). Due to insufficient data, we could not analyse pre‐operative exercise training. Overall, the risk of bias was low for selection and reporting bias, high for performance and attrition bias, and unclear for detection bias.
Compared to no intervention, isotonic exercise training may make little or no difference to ultrasound maturation (2 studies, 263 participants: RR 1.09, 95% CI 0.94 to 1.25; I² = 0%; low certainty evidence), but may improve clinical maturation (2 studies, 263 participants: RR 1.14, 95% CI 1.02 to 1.27; I² = 0%; low certainty evidence).
Compared to isotonic exercise training, isometric exercise training may improve both ultrasound maturation (3 studies, 160 participants: RR 1.56, 95% CI 1.21 to 2.00; I² = 22%; low certainty evidence) and clinical maturation (3 studies, 160 participants: RR 1.80, 95% CI 1.18 to 2.76; I² = 53%; low certainty evidence). Venous diameter (3 studies, 160 participants: MD 0.84 mm, 95% CI 0.45 to 1.23; I² = 0%; low certainty evidence) and blood flow in the inflow artery (3 studies, 160 participants: MD 140.62 mL/min, 95% CI 38.72 to 242.52; I² = 0%; low certainty evidence) may be greater with isometric exercise training. It is uncertain whether isometric exercise training reduces vascular access complications (2 studies, 110 participants: RR 2.54, 95% CI 0.38 to 17.08; I² = 47%; very low certainty evidence).
It is uncertain whether high volume isotonic exercise training improves venous diameter (2 studies, 93 participants: MD 0.19 mm, 95% CI ‐0.75 to 1.13; I² = 34%; very low certainty evidence) or blood flow in the inflow artery (1 study, 15 participants: MD ‐287.70 mL/min, 95% CI ‐625.99 to 60.59; very low certainty evidence) compared to low volume isotonic exercise training.
None of the included studies reported time to mature, dialysis efficacy indicator, vascular access function, or adverse events.
Authors' conclusions
Our findings suggest that the current research evidence examining upper limb exercise programs is of low quality, attributable to variability in the type of interventions used and the overall low number of studies and participants.
PICOs
Plain language summary
Do upper limb exercise programs work for arteriovenous fistula maturation in people with kidney failure?
What is this issue?
An arteriovenous fistula (AVF) is a special connection made between an artery and vein, creating a strong blood vessel which can then be accessed repeatedly during haemodialysis treatment. Once created, it usually takes six to eight weeks to develop (or mature) before it can be used. Maturation results in the joined vein becoming bigger and its walls becoming thicker and stronger due to the increased blood flow. Exercise programs may improve the time taken to mature both the AVF and its function, however, what type of exercise program and when the exercise program should be undertaken (before or after the creation of the AVF) remains unclear.
What did we do?
We searched the literature to find studies that described the use of upper limb exercise on AVF maturation in people with kidney failure. We collected information from the studies and combined this to identify if an intervention was helpful. We examined the quality of these interventions to judge how certain we could be that the effects we observed were reliable.
What did we find?
We found nine studies that involved 579 patients; two studies looked at performing exercise before the AVF was created, and seven studies looked at performing exercise after the creation of the AVF. Unfortunately, only the seven studies performing exercises after the creation of the AVF could be analysed. The types of exercise programs used were isotonic (exercises which put a constant amount of weight on your muscles while moving your joints) and isometric (contraction of the muscles without any movement in the surrounding joints).
Isotonic exercise may improve ultrasound maturation compared to no intervention, while isometric training may improve both ultrasound and clinical maturation compared to isotonic exercise. Isometric exercise may also increase vein size and artery blood flow compared to isotonic exercise. None of the included studies reported adverse events.
There was low confidence in the information about the effects of interventions as the studies were small and the types of interventions varied.
Conclusions
Our findings suggest that the current research evidence examining upper limb exercise programs is of low quality, attributable to variability in the type of interventions used and the overall low number of participants.
Authors' conclusions
Summary of findings
| Upper limb exercise training versus control (no intervention/usual care/isotonic exercise) for AVF maturation | ||||||
| Patient or population: CKD patients who underwent AVF creation Settings: any setting in which there is an AVF creation for CKD patients Intervention: any upper limb exercise training program Comparison: controls (no intervention/usual care/isotonic exercise) | ||||||
| Outcomes | Anticipated absolute effects (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no intervention, usual care/isotonic exercise | Risk with exercise training program | |||||
| Time to mature | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported time to mature |
| Ultrasound maturation (isotonic exercise training versus no intervention) | 717 per 1000 | 781 per 1000 (674 to 896) | RR 1.09 (0.94 to 1.25) | 263 (2) | ⊕⊕⊝⊝ Low1 | Isotonic exercise training may make little or no difference to ultrasound maturation when compared to no intervention |
| Ultrasound maturation (isometric versus isotonic exercise training) | 525 per 1000 | 819 per 1000 (635 to 1000) | RR 1.56 (1.21 to 2.00) | 160 (3) | ⊕⊕⊝⊝ Low2 | Isometric exercise training may improve ultrasound maturation as compared to isotonic exercise training. |
| Clinical maturation (isotonic exercise training versus no intervention) | 787 per 1000 | 898 per 1000 (803 to 1000) | RR 1.14 (1.02 to 1.27) | 263 (2) | ⊕⊕⊝⊝ Low1 | Isotonic exercise training may slightly improve clinical maturation as compared to no intervention. |
| Clinical maturation (isometric versus isotonic exercise training) | 413 per 1000 | 742 per 1000 (487 to 1000) | RR 1.80 (1.18 to 2.76) | 160 (3) | ⊕⊕⊝⊝ Low2 | Isometric exercise training may improve clinical maturation when compared to isotonic exercise training |
| Venous diameter (isometric versus isotonic exercise training) | Venous diameter was 0.84 mm greater (0.45 to 1.23 mm greater) with isometric compared to isotonic exercise training | ‐ | 160 (3) | ⊕⊕⊝⊝ Low2 | Venous diameter may be greater after isometric exercise training compared to isotonic exercise training | |
| Venous diameter (high volume versus low volume isotonic exercise training) | Venous diameter was 0.19 mm greater (0.75 mm lower to 1.13 mm higher) with high volume isotonic exercise training compared to low volume isotonic exercise training | ‐ | 93 (2) | ⊕⊝⊝⊝ Very low3 | It is uncertain whether isotonic exercise training with high volume improves venous diameter because the certainty of this evidence is very low. | |
| Blood flow in the inflow artery (isometric versus isotonic exercise training) | Blood flow in the inflow artery was 140.62 mL/min greater (38.72 to 242.52 greater) with isometric compared to isometric exercise training | ‐ | 160 (3) | ⊕⊕⊝⊝ Low4 | Blood flow in the inflow artery may be greater after isometric exercise training compared to isotonic exercise training | |
| Blood flow in the inflow artery (high volume versus low volume isotonic exercise training) | Blood flow in the inflow artery was 287.7 mL/min lower (625.99 lower to 60.59 higher) with high volume isotonic exercise training compared to low volume isotonic exercise training | ‐ | 15 (1) | ⊕⊝⊝⊝ Very low5 | It is uncertain whether isotonic exercise training with high volume improves blood flow in the inflow artery because the certainty of this evidence is very low. | |
| Dialysis efficacy indicator | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported dialysis efficacy indicators. |
| Vascular access function | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported vascular access function. |
| Vascular access complications (isometric versus isotonic exercise training) | ‐ | ‐ | RR 2.54 (0.38 to 17.08) | 110 (2) | ⊕⊝⊝⊝ Very low6 | It is uncertain whether isometric exercise training reduces vascular access complications because the certainty of this evidence is very low. |
| Adverse events | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported adverse events. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 2 levels due to very serious risk of bias; lack of participant blinding (2 studies), identifying in incomplete outcome data (1 study), and reporting other bias (1 study) 2 Downgraded 2 levels due to very serious risk of bias; lack of random sequence generation (1 study), lack of allocation concealment (1 study), lack of participant blinding (3 studies), and identifying in incomplete outcome data (2 studies). 3 Downgraded 2 levels due to very serious risk of bias; lack of participant blinding (2 studies) and identifying in incomplete outcome data (2 studies). Downgraded 1 level due to serious imprecision; wide range of CI (2 studies). 4 Downgraded 2 levels due to very serious risk of bias; lack of random sequence generation (1 study), lack of allocation concealment (1 study), lack of participant blinding (3 studies), and identifying in incomplete outcome data (2 studies). 5 Downgraded 2 levels due to very serious risk of bias; lack of participant blinding (1 study) and identifying in incomplete outcome data. Downgraded 1 level due to serious imprecision; wide range of CI (1 study). 6 Downgraded 1 level due to serious risk of bias; lack of participant blinding (2 studies) and identifying in incomplete outcome data (1 study). Downgraded 1 level due to serious imprecision; wide range of CI (2 studies). Downgraded 1 level due to much difference in events between 2 small studies. | ||||||
Background
Description of the condition
Chronic kidney disease (CKD) is a global health problem. On the whole, CKD can be classified into 5 stages (Lee 2011). The most severe stage (stage 5), so called kidney failure, is defined when the glomerular filtration rate (GFR) is < 15 mL/min/1.73 m². These patients need kidney replacement therapy (KRT). The prevalence of stage 5 is still unclear worldwide. Based on one registry, the adjusted rates for incidence and prevalence of patients with kidney failure are 351 and 1,699 cases per million respectively (USRDS 2010).
People with kidney failure need KRT to remove waste products from the blood. There are three modes: peritoneal dialysis, haemodialysis (HD), and kidney transplantation. HD via arteriovenous fistula (AVF) is an recommended option based on current standard guidelines (Schmidli 2018), whereas arteriovenous graft and central vein cannulation are secondary and tertiary options. AVF has durable patency and very low infection rate (Al‐Jaishi 2017; Kaufman 1995; Mehta 1991; Murad 2008; Pisoni 2002). It is surgically created by connection or anastomosis between an artery and a vein. AVF is created mostly in the upper limbs. However, it is impossible to use immediately after surgery. It may take weeks or months for walls to allow high blood flow and easy access to repeated needling during HD (Arer 2016; Kumar 2010; Parisotto 2014; Park 1999). However, the non‐maturation (failure to mature) of AVF is ranged from 10% to 33% (Polkinghorne 2011), especially for females, elderly patients or those with small arteries and veins used in the AVF creation (Jemcov 2013; Malovrh 2010; Patel 2003). Non‐maturation can be treated in up to 80% of cases by using surgical or endovascular mean (McLafferty 2007). The commonest causes of non‐maturation are stenosis of the artery, vein or anastomosis, a large branching vein, and marked depth from the skin (Allon 2001). Therefore, any patients with kidney failure with non‐maturation of AVF should be referred to appropriate surgeons or interventionists as soon as possible for investigation and treatment (Sands 2005).
The criteria for AVF maturation is the "rule of sixes" that is composed of a flow of approximately 600 mL/min, less than 0.6 cm below the surface of the skin, and has a minimum diameter of 6 mm at 6 weeks post‐creation (Gilmore 2006). However, currently this rule is being used less often. Based on the current guidelines, the criteria of maturation are classified into two ways: mature AVF and functional AVF. The mature AVF is defined as a suitable AVF for cannulation and delivers adequate blood flow through a HD machine, whereas the functional AVF is defined as an AVF has been cannulated successfully with two needles over a period of at least six HD sessions during a one‐month period, and delivers the determined blood flow and achieves adequate HD (usually at least 300 mL/min) (Schmidli 2018). On the whole, only half of AVFs are successfully matured and usable (Bashar 2015; Feldman 2003). Delay or failure in maturation of AVFs has shown to contribute to significant vascular access‐related morbidity (Stel 2009; USRDS 2010). The dialysis patient with a central venous catheter who waits for AVF maturation has a high risk for catheter infection. Preoperative planning and optimal surgical techniques are important factors to increase functional AVFs (Feldman 2003). The standard guidelines suggest many interventions that aim to improve AVF maturation. One of these interventions is upper limb exercise.
Description of the intervention
Upper limb exercise for fistula surgery is part of routine clinical practice, although there is no evidence that exercise has any benefit on AVF functioning or maturation. There are many types of upper limb exercises in patients with kidney failure, including hand exercise (Oder 2003; Kong 2014; Leaf 2003), and hand and arm exercise with or without arm tourniquet (Fontsere 2016; Salimi 2013). The exercise duration and frequency varies greatly in clinical practice. Hand exercises with a hand grip are more effective in increasing pinch strength, hand grip strength, and forearm circumference than hand exercises using a soft ball but does not produce any difference in vein diameter (Kong 2014). Hand exercise with tourniquet showed good efficacy, increases vein diameter and wall thickness, blood flow and maturation rate of AVF, but this study had a small sample size (Salimi 2013). Hand and arm exercise using elastic band resulted in no significant differences in vein diameter, artery flow, but provided a greater clinical maturation (Fontsere 2016). Taken together, previous studies presented inconsistent results of the effects of upper limb exercise on AVFs maturation outcomes in patients with kidney failure.
How the intervention might work
Upper limb exercise increases blood flow to the arm via arteries and also increases blood flow back to the heart via veins. Several mechanisms have been proposed on how hand exercise improves brachial artery blood flow (Green 2017). It may be due to increases of wall transmural pressure and shear stress on the endothelial cells, nitric oxide bioavailability, and/or a decrease of oxidative stress. Nitric oxide stimulates metalloproteinase‐2 (MMP‐2) and MMP‐9 that consequently induces vasodilation and promotes permanent outward vascular remodelling (Brahmbhatt 2016; Green 2005). Therefore, hand exercise may promote the positive effect on AVF maturation for those with kidney failure.
Why it is important to do this review
A functional AVF is very important for those with kidney failure for HD treatment. The upper limb exercise is routinely applied to these patients. Our objective was undertaken a systematic review and meta‐analysis to investigate whether upper limb exercise training program would be beneficial for AVF creation in clinical practice.
Objectives
This review aimed to determine whether upper extremity exercise would be beneficial for AVF maturation (prior to and post AVF creation) in patients with kidney failure and to improve AVF outcome. This review also aimed to identify adverse events related to the upper limb exercise.
Methods
Criteria for considering studies for this review
Types of studies
Randomised controlled trials (RCTs) and quasi‐RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth, or other predictable methods) that compared different types of exercises before or after AVF creation and that measured clinically relevant outcomes were eligible for inclusion.
Types of participants
Inclusion criteria
We considered studies that included all patients undergoing AVF creation in the upper limbs for HD access eligible for inclusion without any restriction on the type of AVF, age, or gender.
Exclusion criteria
We excluded studies with children or adults with acute kidney injury.
Types of interventions
We included studies comparing any upper limb exercise training intervention (prior to or post AVF creation) aiming to affect any of the below‐mentioned types of outcome measures. The inclusion of studies was influenced by the types of exercises, duration, frequency or intensity of the arm exercise training program. Studies with an upper arm exercise regimen versus control (i.e. no upper limb exercise training), or versus medical/surgical treatment were evaluated.
Types of outcome measures
The outcome measures selected as specified by the Standardised Outcomes in Nephrology (SONG) initiative (SONG 2017) included the relevant SONG core outcome sets, and the study collected data on the characteristics of the HD centres and nephrologists and nurses which could contribute to the study.
Primary outcomes
There were three primary outcomes relating to AVF maturation. The AVF maturation was defined as an adequate venous diameter and blood flow, sufficient venous length, and superficial vein enough for puncturing two needles and delivering sufficient blood flow through an HD machine. All primary outcomes are as follows.
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Time to AVF maturation (months): defined as a duration spent waiting for a mature AVF
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Ultrasound maturation: defined as a number of participants who have a mature AVF assessed using an ultrasound device
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Clinical maturation: defined as a number of participants who have a mature AVF measured using a palpation method by a clinician.
Secondary outcomes
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Venous diameter (mm)
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Blood flow in inflow artery (mL/min)
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Dialysis efficacy indicators (urea reduction ratio and Kt/V)
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Vascular access function (functional AVF): AVF that has been cannulated successfully with two needles over a period of at least six HD sessions during a one‐month period, delivers the determined blood flow and achieves adequate HD (usually, at least 300 mL/min)
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Vascular access complications: thrombosis, aneurysm, infection, bleeding
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Adverse events: fatigue, cardiovascular events, death due to vascular access.
Search methods for identification of studies
Electronic searches
We searched the Cochrane Kidney and Transplant Register of Studies up to 15 March 2022 through contact with the Information Specialist using search terms relevant to this review. The Register contains studies identified from the following sources.
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Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)
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Weekly searches of MEDLINE OVID SP
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Searches of kidney and transplant journals, and the proceedings and abstracts from major kidney and transplant conferences
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Searching the current year of EMBASE OVID SP
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Weekly current awareness alerts for selected kidney and transplant journals
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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
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Reference lists of review articles, relevant studies, and clinical practice guidelines.
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Contacting relevant individuals/organisations seeking information about unpublished or incomplete studies.
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Grey literature sources (e.g. abstracts, dissertations and theses), in addition to those already included in the Cochrane Kidney and Transplant Register of Studies, were searched.
Data collection and analysis
Selection of studies
Four authors independently collected data (SN, MP, TR, SP), including details of methods, participants, setting, and context, interventions. They independently screened the likely titles and review the abstracts from the electronic searches. If the information given in the title and abstract recommended that the study might be suitable for the inclusion criteria of the systematic review, the full paper was retrieved for further evaluation. From the full articles, the decision to remove a study was based on the discussion and agreement of all authors. In the matter of any disagreement among the four authors, a fifth author (KR) was involved in the discussion and decision. Studies that did not fit the inclusion criteria were excluded.
Data extraction and management
Data from each study were independently extracted by the four authors (SN, TR, MP, SP). They extracted details of the method of randomisation, blinding, outcome assessment, losses to follow‐up, cross‐overs, and exclusions after randomisation from the publications. We also compared patient characteristics and details of the operation between the treatment groups in each study. Variations in data extraction were resolved by consensus, referring back to the original data. Data were extracted using a data extraction form.
Assessment of risk of bias in included studies
Two authors (SN, SP) independently assessed the methodological quality of the included studies using the Cochrane risk of bias tool (Higgins 2020) (see Appendix 1). We resolved any disagreements in the methodological assessment by reaching a consensus through discussion.
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Was there adequate sequence generation (selection bias)?
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Was allocation adequately concealed (selection bias)?
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Was knowledge of the allocated interventions adequately prevented during the study?
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Participants and personnel (performance bias)
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Outcome assessors (detection bias)
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Were incomplete outcome data adequately addressed (attrition bias)?
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Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?
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Was the study free of other problems that could put it at risk of bias?
Measures of treatment effect
For dichotomous outcomes, we presented the results as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used, we used the mean difference (MD) or the standardized mean difference (SMD) if different scales had been used.
Unit of analysis issues
Cluster‐randomised studies
We anticipated that studies using clustered randomisation were controlled for clustering effects. In case of doubt, we would contact the authors to ask for individual participant data to calculate an estimate of the intra‐cluster correlation coefficient (ICC). If this was not possible, we planned to obtain external estimates of the ICC from a similar study or from a study of a similar population as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2020). When the ICC was established, we planned to use it to re‐analyse the study data. If ICCs from other sources were used, we planned to report this and conducted sensitivity analyses to investigate the effect of variation in the ICC. No cluster RCTs were identified.
Cross‐over studies
Cross‐over studies were to be analysed using combined data from all study periods or using the first period if combined data were not available. No cross‐over studies were identified.
Studies with more than two treatment arms
If more than one of the interventions was a sleep intervention, and there was sufficient information in the study to assess the similarity of the interventions, we planned to combine similar interventions to allow for a single pair‐wise comparison. No studies with more than two treatment arms were identified.
Dealing with missing data
Any study containing unclear data would be resolved by contacting the study authors for clarifying information. We also requested missing information from any eligible studies. When a paper contained missing data, the primary investigator was contacted to clarify the results. If the investigators’ current contact information could not be found, despite using all possible means, or the investigators were not able to provide the missing data, the result was excluded from the meta‐analysis and noted as missing data. All studies included in the review, along with any missing data obtained, are presented in the table Characteristics of included studies.
Assessment of heterogeneity
We firstly assessed the heterogeneity by visual inspection of the forest plot. We quantified statistical heterogeneity using the I² statistic, which describes the percentage of total variation across studies that is due to heterogeneity rather than sampling error (Higgins 2003). A guide to the interpretation of I² values was as follows.
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0% to 40%: may not be important
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30% to 60%: may represent moderate heterogeneity
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50% to 90%: may represent substantial heterogeneity
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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 I² test or a CI for I²) (Higgins 2020).
Assessment of reporting biases
If possible, funnel plots were to be used to assess the potential existence of small study bias (Higgins 2020) however, there were too few studies to do this.
Data synthesis
The random‐effect model with inverse variance was used to generate the different effect estimations between intervention and control groups. The effect estimates were presented as RR with 95% CI for dichotomous outcomes, while MD (or SMD) and standard deviation (SD) were used for continuous outcomes.
Subgroup analysis and investigation of heterogeneity
We undertook subgroup analyses to investigate heterogeneity > 75%. These included the different types of upper limb exercise training (duration, frequency, intensity), age, gender, and diabetes. We performed the length of intervention subgroup analyses for outcome measures when there was sufficient data for this.
Sensitivity analysis
When the decisions for the process undertaken in this systematic review were arbitrary or unclear, we applied sensitivity analyses. We ran sensitivity analyses to determine if the overall results were similar when only studies with a low risk of bias were included. If a sensitivity analysis did not substantially change the results, it strengthened the confidence in the interpretation of these results. If the results changed in a way that might result in different conclusions, this determined a need for critical caution in translating the results and drawing conclusions. Such differences could also enable investigators to clarify the origin of existing controversies about the effectiveness of an intervention or cause them to hypothesize which major factors might be linked to the effectiveness of the intervention and lead to further investigation.
Summary of findings and assessment of the certainty of the evidence
The main outcomes demonstrated in the 'Summary of Findings' tables are as follows.
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Time to AVF maturation
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Ultrasound maturation
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Clinical maturation
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Venous diameter
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Blood flow in the inflow artery
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Dialysis efficacy indicator
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Vascular access function
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Vascular access complication
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Adverse events
These tables presented 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 2020a). The 'Summary of Findings' tables also included 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). Two independent authors evaluated the GRADE approach, which defines the quality of a body of evidence as the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The quality of a body of evidence involves consideration of the within‐trial risk of bias (methodological quality), directness of evidence, heterogeneity, the precision of effect estimates, and the risk of publication bias (Schunemann 2020b).
Results
Description of studies
Results of the search
After searching the Specialised Register and other sources (contacting relevant individuals, reference lists in review articles, and relevant studies) a total of 1860 records were identified. After duplicates were removed, titles and abstracts screened, and full‐text review, nine studies (16 records) were included. Four ongoing studies were identified (6 records) (NCT03137680; PHYSICALFAV 2018; PINCH 2018; UMIN000033356). Five studies (6 records) appear to be complete however, no results are available for three studies (NCT01068314; RBR‐4P6fk2; Ribeiro 2021), and we awaiting further information for two studies (Junglee 2009; Lin 2005a). These nine studies will be assessed in a future update of this review (Figure 1).
PRISMA diagram
Included studies
See Characteristics of included studies
Nine studies (579 participants) were included. Two studies conducted an upper limb exercise training program before AVF surgery, while the other seven studies conducted an exercise training program after AVF creation. Studies of pre‐operative upper limb exercise training (Barbosa 2018; Katheraveloo 2020) involving 60 participants (26 males, aged 43.4 to 61.3 years) could not be meta‐analyses due to insufficient data. One study used an isotonic exercise type plus blood flow restriction technique as an intervention and isotonic exercise alone as a comparator (Barbosa 2018), while the other study utilized an isotonic exercise type as an intervention and no treatment as the control (Katheraveloo 2020). These two studies only reported venous diameter.
For the seven included studies of post‐operative upper limb exercise training programs, there were a total of 519 participants, 344 males, and an age range of 40 and 69.9 years. Of these, three studies used isometric exercise (Nantakool 2022; Salimi 2013; Tapia González 2020), and four studies used isotonic exercise (Fontseré 2016; Kong 2014; Manjunath 2021; Mo 2020). Two studies used no intervention (i.e. performed usual lifestyle and routine care teaching) as a control group (Fontseré 2016; Manjunath 2021), and the remaining five studies utilized an isotonic exercise (Kong 2014; Mo 2020; Nantakool 2022; Salimi 2013; Tapia González 2020). Training program durations varied from two to 12 weeks, with the majority only four weeks (Fontseré 2016; Kong 2014). Only five of nine pre‐determined outcomes were documented. These five outcomes consisted of ultrasound and clinical maturation (five studies) (Fontseré 2016; Manjunath 2021; Nantakool 2022; Salimi 2013; Tapia González 2020), venous diameter (six studies) (Fontseré 2016; Kong 2014; Mo 2020; Nantakool 2022; Salimi 2013; Tapia González 2020), blood flow in the inflow artery (six studies) (Fontseré 2016; Kong 2014; Mo 2020; Nantakool 2022; Salimi 2013; Tapia González 2020), and vascular access complications (three studies) (Mo 2020; Nantakool 2022; Tapia González 2020).
Studies awaiting classification
We have identified five studies awaiting classification (see Characteristics of studies awaiting classification). All of these studies focused on exercise programs for CKD patients but were unclear whether these programs investigated pre‐ or post‐operative exercise programs. We could not assess the eligibility of these studies because:
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Lack of available results despite the study being completed (NCT01068314)
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An abstract‐only publication (Ribeiro 2021)
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Only the protocol is currently available (RBR‐4P6fk2)
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No available study information (both protocol and results) (Junglee 2009; Lin 2005a).
Ongoing studies
Four studies were classified as ongoing studies. All studies were RCTs focusing on the effect of pre‐operative exercise programs in CKD patients who required AVF. Various exercise types include squeezing a soft ball (NCT03137680), isometric exercise (PHYSICALFAV 2018), structured forearm exercise (PINCH 2018), and handgrip exercise (UMIN000033356), were described (see Characteristics of ongoing studies).
Excluded studies
After initial screening of titles and abstracts no additional studies were excluded.
Risk of bias in included studies
See the risk of bias table in Characteristics of included studies and Figure 2.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
The risk of bias assessment for Nantakool 2022 was undertaken by the Editorial Office of Cochrane Kidney and Transplant.
Allocation
Random sequence generation
Seven studies using computer‐based randomisation systems were judged to be at low risk of bias (Barbosa 2018; Fontseré 2016; Katheraveloo 2020; Manjunath 2021; Mo 2020; Nantakool 2022; Tapia González 2020). Salimi 2013 randomised patients based on their file number and was judged to be at high risk of bias. Kong 2014 stated the patients were 'randomly allocated'; however, no further information was provided; this study was judged to have an unclear risk of bias.
Allocation concealment
Four studies were judged to be at low risk of bias for allocation concealment (Barbosa 2018; Katheraveloo 2020; Manjunath 2021; Nantakool 2022); one study was judged to be at high risk of bias (Salimi 2013); and four studies were judged to have an unclear risk of bias (Fontseré 2016; Kong 2014; Mo 2020; Tapia González 2020).
Blinding
Performance bias
The participants were not blinded as the intervention was an exercise program. Therefore, this domain was considered as a high risk of bias in all studies.
Detection bias
Four studies reported the outcome assessors were not aware of the intervention allocation and were judged to be at low risk of bias (Fontseré 2016; Kong 2014; Nantakool 2022; Salimi 2013). The remaining five studies were judged to have an unclear risk of bias (Barbosa 2018; Katheraveloo 2020; Manjunath 2021; Mo 2020; Tapia González 2020).
Incomplete outcome data
Six studies had an imbalance in missing data between intervention and control groups and were judged to be at high risk of bias (Fontseré 2016; Katheraveloo 2020; Kong 2014; Mo 2020; Salimi 2013; Tapia González 2020). The remaining three studies were judged to be at a low risk bias based on no missing data identified (Barbosa 2018; Nantakool 2022) and an equivalent number of missing data between the groups (Manjunath 2021).
Selective reporting
All pre‐specified outcomes of interest were reported in all nine studies and were judged to be at low risk of bias.
Other potential sources of bias
Three studies had an unequal number allocated to the groups, as well as an unequal number of males and females allocated, which might result in bias, and we judged these to be at high risk of bias (Barbosa 2018; Fontseré 2016; Katheraveloo 2020).
Effects of interventions
See summary of findings Table 1
Seven studies of post‐operative upper limb exercise training programs investigating ultrasound and clinical maturation number, venous diameter, blood flow in the inflow artery, and vascular access complications were able to be meta‐analyses. Three comparisons were undertaken.
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Isotonic exercise training versus no intervention
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Isometric exercise training versus isotonic exercise training
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Isotonic exercise training (high volume) versus isotonic exercise training (low volume).
1. Isotonic exercise training versus no intervention
Ultrasound maturation
Isotonic exercise training may make little or no difference to ultrasound maturation compared to no intervention (Analysis 1.1 (2 studies, 263 participants): RR 1.09, 95% CI 0.94 to 1.25; I² = 0%, low certainty evidence).
Clinical maturation
Isotonic exercise training may improve clinical maturation compared to no intervention (Analysis 1.2 (2 studies, 263 participants): RR 1.14, 95% CI 1.02 to 1.27; I² = 0%; low certainty evidence).
Other outcomes
No other primary or secondary outcomes were reported by the included studies.
2. Isometric exercise training versus isotonic exercise training
Ultrasound maturation
Isometric exercise training may improve ultrasound maturation when compared to isotonic exercise training (Analysis 2.1 (3 studies, 160 participants): RR 1.56, 95% CI 1.21 to 2.00; I² = 22%; low certainty evidence).
Clinical maturation
Isometric exercise training may improve clinical maturation when compared to isotonic exercise training (Analysis 2.2 (3 studies, 160 participants): RR 1.80, 95% CI 1.18 to 2.76; I² = 53%; low certainty evidence).
Venous diameter
Venous diameter may be greater after isometric exercise training compared to isotonic exercise training (Analysis 2.3 (3 studies, 160 participants): MD 0.84 mm, 95% CI 0.45 to 1.23; I² = 0%; low certainty evidence).
Blood flow in the inflow artery
Blood flow in the inflow artery may be greater after isometric exercise training compared to isotonic exercise training (Analysis 2.4 (3 studies, 160 participants): MD 140.62 mL/min, 95% CI 38.72 to 242.52; I² = 0%; low certainty evidence).
Vascular access complications
It is uncertain whether isometric exercise training reduces vascular access complications (Analysis 2.5 (2 studies, 110 participants): RR 2.54, 95% CI 0.38 to 17.08; I² = 47%; very low certainty evidence).
Other outcomes
No other primary or secondary outcomes were reported by the included studies.
3. High volume isotonic exercise training versus low volume isotonic exercise training
Venous diameter
It is uncertain whether isotonic exercise training with high volume improves venous diameter (Analysis 3.1 (2 studies, 93 participants): MD 0.19 mm, 95% CI ‐0.75 to 1.13; I² = 34%; very low certainty evidence)
Blood flow in inflow artery
It is uncertain whether isotonic exercise training with high volume improves blood flow in inflow artery (Analysis 3.2 (1 study, 15 participants): MD ‐282.70 mL/min, 95% CI ‐625.99 to 60.59; very low certainty evidence).
Other outcomes
No other primary or secondary outcomes were reported by the included studies.
Sensitivity analysis: low risk of selection bias (allocation concealment) (isotonic exercise training versus no intervention)
Ultrasound maturation
After excluding Fontseré 2016 due to unclear risk of selection bias (allocation concealment) (Analysis 4.1.1 (1 study, 194 participants): RR 1.08, 95%CI 0.91 to 1.28; low certainty evidence), the direction of the effect estimate and the certainty interpretation for ultrasound maturation were not altered.
Clinical maturation
After excluding Fontseré 2016 due to unclear risk of selection bias (allocation concealment) (Analysis 4.2.1 (1 study, 194 participants): RR 1.12, 95% CI 0.99 to 1.28; low certainty evidence), the certainty interpretation for clinical maturation was altered. Isotonic exercise training may make little or no difference to clinical maturation compared to no intervention.
Sensitivity analysis: low risk of detection bias (isotonic exercise training versus no intervention)
Ultrasound maturation
After excluding Manjunath 2021 due to unclear risk of detection bias (Analysis 5.1.1 (1 study, 69 participants): RR 1.10, 95% CI 0.85 to 1.42; low certainty evidence), the direction of the effect estimate and the certainty interpretation for ultrasound maturation were not altered.
Clinical maturation
A sensitivity analysis of the comparison between isotonic exercise training and no intervention based on removing Manjunath 2021 due to unclear risk of detection bias (Analysis 5.2.1 (1 study, 69 participants): RR 1.17, 95% CI 0.97 to 1.42; I²= not applicable; low‐certainty evidence), altered the certainty interpretation for clinical maturation. Isotonic exercise training may make little or no difference to clinical maturation compared to no intervention.
Sensitivity analysis: low risk of attrition bias (isotonic exercise training versus no intervention)
Ultrasound maturation
After excluding Fontseré 2016 due to high risk of attrition bias (Analysis 6.1.1 (1 study, 194 participants): RR 1.08, 95% CI 0.91 to 1.28; low certainty evidence), the direction of the effect estimate and the certainty interpretation for ultrasound maturation were not altered.
Clinical maturation
After excluding Fontseré 2016 due to high risk of attrition bias (Analysis 6.2.1 (1 study, 194 participants): RR 1.12, 95% CI 0.99 to 1.28; low certainty evidence), the certainty interpretation for clinical maturation was altered. Isotonic exercise training may make little or no difference to clinical maturation compared to no intervention.
Sensitivity analysis: low risk of other bias (isotonic exercise training versus no intervention)
Ultrasound maturation
A sensitivity analysis of the comparison between isotonic exercise training and no intervention based on excluding Fontseré 2016 due to high risk of other bias (Analysis 7.1.1 (1 study, 194 participants): RR 1.08, 95%CI 0.91 to 1.28; low certainty evidence) the direction of the effect estimate and the certainty interpretation for ultrasound maturation were not altered.
Clinical maturation
After excluding Fontseré 2016 due to high risk of other bias (Analysis 7.2.1 (1 study, 194 participants): RR 1.12, 95% CI 0.99 to 1.28; low certainty evidence), the certainty interpretation for clinical maturation was altered. Isotonic exercise training may make little or no difference to clinical maturation compared to no intervention.
Sensitivity analysis: low risk of selection bias (random sequence generation) (isometric exercise training versus isotonic exercise training)
Ultrasound maturation
After excluding Salimi 2013 due to high risk of selection bias (random sequence generation) (Analysis 8.1.1 (2 studies, 110 participants): RR 1.84, 95% CI 1.34 to 2.51; I² = 0%; low certainty evidence), the direction of the effect estimate and the certainty interpretation for ultrasound maturation were not altered.
Clinical maturation
After excluding Salimi 2013 due to high risk of selection bias (random sequence generation) (Analysis 8.2,1 (2 studies, 110 participants): RR 1.68, 95% CI 1.03 to 2.73; I² = 64%; low certainty evidence), ) the direction of the effect estimate and the certainty interpretation for clinical maturation were not altered.
Venous diameter
After excluding Salimi 2013 due to high risk of selection bias (random sequence generation) (Analysis 8.3.1 (2 studies, 110 participants): MD 0.77 mm, 95% CI 0.24 to 1.30; I² = 16%; low certainty evidence), the direction of the effect estimate and the certainty interpretation for venous diameter were not altered.
Blood flow in the inflow artery
After excluding Salimi 2013 due to high risk of selection bias (random sequence generation) (Analysis 8.41 (2 studies, 110 participants): MD 166.71 mL/min, 96% CI ‐129.84 to 463.26; I²= 39%; low certainty evidence), the certainty interpretation of the blood flow in the inflow artery was altered. Isometric exercise training may make little or no difference to blood flow in the inflow artery compared to isotonic exercise training.
Sensitivity analysis: low risk of selection bias (allocation concealment) (isometric exercise training versus isotonic exercise training)
Ultrasound maturation
After excluding Salimi 2013 and Tapia González 2020 due to high and unclear risk of selection bias (allocation concealment) (Analysis 9.1.1 (1 study, 50 participants): RR 1.75, 95%CI 1.12 to 2.72; low certainty evidence), the direction of the effect estimate or the certainty interpretation for ultrasound maturation were not altered.
Clinical maturation
After excluding Salimi 2013 and Tapia González 2020 due to high and unclear risk of selection bias (allocation concealment) (Analysis 9.2.1 (1 study, 50 participants): RR 1.38, 95%CI 1.07 to 1.77; low certainty evidence), did not alter the direction of the effect estimate or the certainty interpretation for clinical maturation.
Venous diameter
After excluding studies with high or unclear risk of selection bias (allocation concealment) (Salimi 2013; Tapia González 2020), a sensitivity analysis (Analysis 9.3.1 (1 study, 50 participants): RR 0.97, 95%CI 0.39 to 1.55; low certainty evidence) did not alter the direction of the effect estimate or the certainty interpretation for venous diameter.
Blood flow in the inflow artery
After excluding Salimi 2013 and Tapia González 2020 due to high and unclear risk of selection bias (allocation concealment) (Analysis 9.4 (1 study, 50 participants): RR 57.95, 95% CI ‐182.85 to 298.75; low certainty evidence), the certainty interpretation was altered. Isometric exercise training may make little or no difference to blood flow in the inflow artery compared to isotonic exercise training.
Vascular access complications
After excluding Tapia González 2020 due to unclear risk of selection bias (allocation concealment) (Analysis 9.5.1 (1 study, 50 participants): RR 1.00, 95% CI 0.15 to 6.55; very low certainty evidence), the direction of the effect estimate and the certainty interpretation were not altered.
Sensitivity analysis: low risk of detection bias (isometric exercise training versus isotonic exercise training)
Ultrasound maturation
After excluding Tapia González 2020 due to unclear detection bias (Analysis 10.1.1 (2 studies, 100 participants): RR 1.44, 95% CI 1.09 to 1.91; I²= 17%; low certainty evidence), the direction of the effect estimate and the certainty interpretation for clinical maturation were not altered.
Clinical maturation
After excluding Tapia González 2020 due to unclear risk of detection bias (Analysis 10.2.1 (2 studies, 100 participants): RR 1.64, 95% CI 0.94 to 2.86; I²= 47%; low certainty evidence), the direction of the effect estimate and the certainty interpretation for clinical maturation were altered. Isometric exercise training may make little or no difference to clinical maturation when compared to isotonic exercise training.
Venous diameter
After excluding Tapia González 2020 due to unclear risk of detection bias (Analysis 10.3.1 (2 studies, 100 participants): MD 0.96 mm, 95% CI 0.52 to 1.40; I² = 0%; low certainty evidence), the direction of the effect estimate and the certainty interpretation for venous diameter were not altered.
Blood flow in inflow artery
After excluding Tapia González 2020 due to unclear risk of detection bias (Analysis 10.4.1 (2 studies, 100 participants): MD 126.37 mL/min, 95% CI 21.44 to 231.29; I²= 0%; very low certainty evidence), the direction of the effect estimate and the certainty interpretation for the blood flow in inflow artery were not altered.
Vascular access complications
After excluding Tapia González 2020 due to unclear risk of detection bias (Analysis 10.5.1 (1 study, 50 participants): RR 1.00, 95% CI 0.15 to 6.55; very low certainty evidence), the direction of the effect estimate and the certainty interpretation for vascular access complications were not altered.
Sensitivity analysis: low risk of attrition bias (isometric exercise training versus isotonic exercise training)
Ultrasound maturation
After excluding Salimi 2013 and Tapia González 2020 due to high risk of attrition bias (Analysis 11.1.1 (1 study, 50 participants): RR 1.75, 95%CI 1.12 to 2.72; low certainty evidence), the direction of the effect estimate and certainty interpretation for ultrasound maturation were not altered.
Clinical maturation
After excluding Salimi 2013 and Tapia González 2020 due to high risk of attrition bias (Analysis 11.2.1 (1 study, 50 participants): RR 1.38, 95% CI 1.07 to 1.77; low certainty evidence), the direction of the effect estimate and certainty interpretation for clinical maturation were not altered.
Venous diameter
After excluding Salimi 2013 and Tapia González 2020 due to high risk of attrition bias (Analysis 11.3.1 (1 study, 50 participants): MD 0.97 mm, 95% CI 0.39 to 1.55; low certainty evidence), the direction of the effect estimate and the certainty interpretation for venous diameter were not altered.
Blood flow in inflow artery
After excluding Salimi 2013 and Tapia González 2020 due to high risk of attrition bias, the certainty interpretation of the blood flow in the inflow artery was altered (Analysis 11.4.1 (1 study, 50 participants): MD 57.95 mL/min, 95% CI ‐182.85 to 298.75; low certainty evidence). Isometric exercise training may make little or no difference to blood flow in the inflow artery compared to isotonic exercise training.
Vascular access complications
After excluding Tapia González 2020 due to high risk of attrition bias (Analysis 11.5 (1 study, 50 participants): RR 1.00, 95% CI 0.15 to 6.55; very low certainty evidence), the direction of the effect estimate and the certainty interpretation for vascular access complications were not altered.
Sensitivity analysis: low risk of selection bias (random sequence generation) (high versus low volume isotonic exercise training)
Venous diameter
After excluding Kong 2014 due to unclear risk of selection bias (random sequence generation) (Analysis 12.1.1 (1 study, 78 participants): MD 0.58 mm, 95%CI ‐0.33 to 1.49; very low certainty evidence), the direction of the effect estimate and the certainty interpretation for venous diameter were not altered.
Sensitivity analysis: low risk of detection bias (high versus low volume isotonic exercise training)
Venous diameter
After excluding Mo 2020 due to unclear risk of detection bias (Analysis 12.1 (1 study, 15 participants): MD ‐0.40 mm, 95% CI ‐1.67 to 0.87 very low certainty evidence), the direction of the effect estimate changed however, the certainty interpretation did not.
Discussion
See summary of findings Table 1 for an overall summary of the study findings.
Summary of main results
We identified nine studies (579 participants) comparing upper limb training exercises with no intervention or another training exercise. Of these, only seven studies (519 participants) reported outcomes relevant to AVF maturation and could be meta‐analysed. We found three different comparisons: isotonic exercise training versus no intervention, isometric exercise training versus isotonic exercise training, and isotonic exercise training (high volume) versus isotonic exercise training (low volume). In most of these studies, bias was unavoidable due to the five issues: lack of random sequence generation and allocation concealment (56%), lack of participant blinding (100%), uncertain blinding of outcome assessment (56%), reporting other biases (33%), and presenting incomplete outcome data (67%).
The main findings of this meta‐analysis were as follows: compared to no intervention, isotonic exercise training may make little or no difference to ultrasound maturation but may improve clinical maturation. Isometric exercise training may improve both ultrasound and clinical maturation, and venous diameter and blood flow in inflow artery may be greater when compared to isotonic exercise training. It is uncertain whether isometric exercise training reduces vascular access complications compared to isotonic exercise training. The effects of high‐volume isotonic exercise training on improving venous diameter and blood flow in the inflow artery are uncertain. No evidence reported the effect of upper limb exercise training on time to mature, dialysis efficacy indicator, vascular access function, and adverse events.
Overall completeness and applicability of evidence
Our meta‐analysis included studies focusing on the effect of upper limb exercise training on outcome measures relevant to AVF maturation in patients with kidney failure before and after AVF creation. We used three electronic databases along with other sources that contained published and unpublished evidence (i.e. contacting relevant individuals, reference lists in the review articles, and relevant studies) to achieve the most comprehensive search. Of these, we were unable to determine whether pre‐operative upper limb exercise training would improve AVF maturation due to the lack of study data. For the included post‐operative upper limb exercise training studies, there were various intervention programs, including structured isotonic exercise training, structured isometric exercise training, and isotonic exercise training with high volume. Based on the primary outcomes, most studies (75%) were interested in how exercise programs contributed to ultrasound and clinical AVF maturation rather than time to mature. Focusing on the number reaching maturation relied on intervention duration in each study. For the secondary outcomes, more than 50% of the studies reported changes in venous diameter and blood flow in the inflow artery, followed by vascular access complications (33%). The lack of reporting of other relevant outcomes, in particular, vascular access function, needs to be explored to help determine if AVF maturation is sufficient for patients to undergo HD. Only two studies (Kong 2014; Nantakool 2022) provided program components in terms of type, intensity, frequency, and time that could be available for implementation.
Quality of the evidence
The certainty of the evidence was overall low to very low for all comparisons and outcomes meta‐analysed. There were only seven studies that could be meta‐analysed, with very few participants and a wide variety of programs used. Most low certainty evidence was downgraded by two levels due to serious risk of bias, including lack of participant blinding and incomplete outcome data. We note that intervention awareness was unavoidable because the participants performed the exercise programs. Very low certainty evidence was additionally downgraded due to serious imprecision due to wide CIs and differences in the event rates in two small studies.
Compared to no intervention, low certainty evidence showed clinical maturation may improve with isotonic exercise but may make little or no difference to ultrasound maturation.
Compared to isotonic exercise, low certainty evidence showed isometric exercise may improve ultrasound and clinical maturation, and venous diameter and blood flow in the inflow may be greater. However, the effect on vascular access complications is uncertain. Moreover, it is uncertain whether high‐volume isotonic exercise training increases the venous diameter and blood flow because the certainty was very low.
Potential biases in the review process
We have attempted to reduce the potential biases by comprehensive searching not only from the electronic databases, including three databases and the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov, but also from other sources (contacting relevant individuals, searching reference lists of both review articles and relevant studies). We also sought additional information from the authors of ongoing studies; however, we were unable to obtain any data at this time. Furthermore, we collected the eligible studies based on the pre‐determined inclusion and exclusion criteria. The most essential method administered in our meta‐analysis was having four independent authors responsible for seeking, selecting, and deciding bias assessment of the articles. This process favoured a reduction of publication selection and article bias assessment, which could be overestimated.
Agreements and disagreements with other studies or reviews
Regardless of the type of exercise program, a potential beneficial effect of upper limb exercise in our study is similar to an intermittent pneumatic vein compression technique, which can induce AVF maturation. Recent evidence has revealed that the Fist‐Assist wearable device, an intermittent pneumatic vein compression resulted in vein dilation in people undergoing AVF surgery (Desai 2019; Sullivan 2019).
To the best of our knowledge, only two recent meta‐analyses involving the effectiveness of exercise programs on AVF maturation in patients with kidney failure have been undertaken. One study aimed to explore the effectiveness of post‐operative exercise training on AVF maturation in patients with kidney failure (Fuzari 2017). The other study purposed to investigate both pre‐and post‐operative exercise training on AVF maturation status in this population (Nantakool 2020).
For the effectiveness of pre‐operative exercise training, our findings are in line with (Nantakool 2020), demonstrating an inability to interpret whether or not the pre‐operative exercise training programs would benefit due to few data that would contribute to a meta‐analysis. Considering the effectiveness of post‐operative exercise training on outcomes relevant to AVF maturation, our findings were in contrast to the results of both Fuzari 2017 and Nantakool 2020. This previous evidence concluded that upper limb exercise training did not favour venous diameter and blood flow improvement. Our findings provide similar effects to the previous evidence (Nantakool 2020), reporting superior effects of isotonic exercise training on clinical maturation than no intervention and greater effects of the isometric exercise training program on both ultrasound and clinical maturation when compared to isotonic exercise. In addition, our meta‐analysis complements the findings of Nantakool 2020; isometric exercise training had a greater effect on venous diameter and blood flow in the inflow artery than isotonic exercise training. In our review, even though there are improvements in the reported outcomes, the low certainty evidence reduced our confidence in all the effect estimates. These points are in contrast to the previous evidence by Nantakool 2020, which did not grade the certainty of evidence.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1: Isotonic exercise training versus no intervention, Outcome 1: Ultrasound maturation
Comparison 1: Isotonic exercise training versus no intervention, Outcome 2: Clinical maturation
Comparison 2: Isometric versus isotonic exercise training, Outcome 1: Ultrasound maturation
Comparison 2: Isometric versus isotonic exercise training, Outcome 2: Clinical maturation
Comparison 2: Isometric versus isotonic exercise training, Outcome 3: Venous diameter
Comparison 2: Isometric versus isotonic exercise training, Outcome 4: Blood flow in the inflow artery
Comparison 2: Isometric versus isotonic exercise training, Outcome 5: Vascular access complications
Comparison 3: High versus low volume isotonic exercise training, Outcome 1: Venous diameter
Comparison 3: High versus low volume isotonic exercise training, Outcome 2: Blood flow in the inflow artery
Comparison 4: Sensitivity analysis: selection bias (allocation concealment) (isotonic exercise training versus no intervention), Outcome 1: Ultrasound maturation
Comparison 4: Sensitivity analysis: selection bias (allocation concealment) (isotonic exercise training versus no intervention), Outcome 2: Clinical maturation
Comparison 5: Sensitivity analysis: detection bias (isotonic exercise training versus no intervention), Outcome 1: Ultrasound maturation
Comparison 5: Sensitivity analysis: detection bias (isotonic exercise training versus no intervention), Outcome 2: Clinical maturation
Comparison 6: Sensitivity analysis: attrition bias (isotonic exercise training versus no intervention), Outcome 1: Ultrasound maturation
Comparison 6: Sensitivity analysis: attrition bias (isotonic exercise training versus no intervention), Outcome 2: Clinical maturation
Comparison 7: Sensitivity analysis: other bias (isotonic exercise training versus no intervention), Outcome 1: Ultrasound maturation
Comparison 7: Sensitivity analysis: other bias (isotonic exercise training versus no intervention), Outcome 2: Clinical maturation
Comparison 8: Sensitivity analysis: selection bias (random sequence generation) (isometric versus isotonic exercise training), Outcome 1: Ultrasound maturation
Comparison 8: Sensitivity analysis: selection bias (random sequence generation) (isometric versus isotonic exercise training), Outcome 2: Clinical maturation
Comparison 8: Sensitivity analysis: selection bias (random sequence generation) (isometric versus isotonic exercise training), Outcome 3: Venous diameter
Comparison 8: Sensitivity analysis: selection bias (random sequence generation) (isometric versus isotonic exercise training), Outcome 4: Blood flow in the inflow artery
Comparison 9: Sensitivity analysis: selection bias (allocation concealment) (isometric versus isotonic exercise training), Outcome 1: Ultrasound maturation
Comparison 9: Sensitivity analysis: selection bias (allocation concealment) (isometric versus isotonic exercise training), Outcome 2: Clinical maturation
Comparison 9: Sensitivity analysis: selection bias (allocation concealment) (isometric versus isotonic exercise training), Outcome 3: Venous diameter
Comparison 9: Sensitivity analysis: selection bias (allocation concealment) (isometric versus isotonic exercise training), Outcome 4: Blood flow in the inflow artery
Comparison 9: Sensitivity analysis: selection bias (allocation concealment) (isometric versus isotonic exercise training), Outcome 5: Vascular access complications
Comparison 10: Sensitivity analysis: detection bias (isometric versus isotonic exercise training), Outcome 1: Ultrasound maturation
Comparison 10: Sensitivity analysis: detection bias (isometric versus isotonic exercise training), Outcome 2: Clinical maturation
Comparison 10: Sensitivity analysis: detection bias (isometric versus isotonic exercise training), Outcome 3: Venous diameter
Comparison 10: Sensitivity analysis: detection bias (isometric versus isotonic exercise training), Outcome 4: Blood flow in the inflow artery
Comparison 10: Sensitivity analysis: detection bias (isometric versus isotonic exercise training), Outcome 5: Vascular access complications
Comparison 11: Sensitivity analysis: attrition bias (isometric versus isotonic exercise training), Outcome 1: Ultrasound maturation
Comparison 11: Sensitivity analysis: attrition bias (isometric versus isotonic exercise training), Outcome 2: Clinical maturation
Comparison 11: Sensitivity analysis: attrition bias (isometric versus isotonic exercise training), Outcome 3: Venous diameter
Comparison 11: Sensitivity analysis: attrition bias (isometric versus isotonic exercise training), Outcome 4: Blood flow in the inflow artery
Comparison 11: Sensitivity analysis: attrition bias (isometric versus isotonic exercise training), Outcome 5: Vascular access complications
Comparison 12: Sensitivity analysis: selection bias (random sequence generation) (high versus low volume isotonic exercise training), Outcome 1: Venous diameter
Comparison 13: Sensitivity analysis: detection bias (high versus low volume isotonic exercise training), Outcome 1: Venous diameter
| Upper limb exercise training versus control (no intervention/usual care/isotonic exercise) for AVF maturation | ||||||
| Patient or population: CKD patients who underwent AVF creation Settings: any setting in which there is an AVF creation for CKD patients Intervention: any upper limb exercise training program Comparison: controls (no intervention/usual care/isotonic exercise) | ||||||
| Outcomes | Anticipated absolute effects (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with no intervention, usual care/isotonic exercise | Risk with exercise training program | |||||
| Time to mature | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported time to mature |
| Ultrasound maturation (isotonic exercise training versus no intervention) | 717 per 1000 | 781 per 1000 (674 to 896) | RR 1.09 (0.94 to 1.25) | 263 (2) | ⊕⊕⊝⊝ Low1 | Isotonic exercise training may make little or no difference to ultrasound maturation when compared to no intervention |
| Ultrasound maturation (isometric versus isotonic exercise training) | 525 per 1000 | 819 per 1000 (635 to 1000) | RR 1.56 (1.21 to 2.00) | 160 (3) | ⊕⊕⊝⊝ Low2 | Isometric exercise training may improve ultrasound maturation as compared to isotonic exercise training. |
| Clinical maturation (isotonic exercise training versus no intervention) | 787 per 1000 | 898 per 1000 (803 to 1000) | RR 1.14 (1.02 to 1.27) | 263 (2) | ⊕⊕⊝⊝ Low1 | Isotonic exercise training may slightly improve clinical maturation as compared to no intervention. |
| Clinical maturation (isometric versus isotonic exercise training) | 413 per 1000 | 742 per 1000 (487 to 1000) | RR 1.80 (1.18 to 2.76) | 160 (3) | ⊕⊕⊝⊝ Low2 | Isometric exercise training may improve clinical maturation when compared to isotonic exercise training |
| Venous diameter (isometric versus isotonic exercise training) | Venous diameter was 0.84 mm greater (0.45 to 1.23 mm greater) with isometric compared to isotonic exercise training | ‐ | 160 (3) | ⊕⊕⊝⊝ Low2 | Venous diameter may be greater after isometric exercise training compared to isotonic exercise training | |
| Venous diameter (high volume versus low volume isotonic exercise training) | Venous diameter was 0.19 mm greater (0.75 mm lower to 1.13 mm higher) with high volume isotonic exercise training compared to low volume isotonic exercise training | ‐ | 93 (2) | ⊕⊝⊝⊝ Very low3 | It is uncertain whether isotonic exercise training with high volume improves venous diameter because the certainty of this evidence is very low. | |
| Blood flow in the inflow artery (isometric versus isotonic exercise training) | Blood flow in the inflow artery was 140.62 mL/min greater (38.72 to 242.52 greater) with isometric compared to isometric exercise training | ‐ | 160 (3) | ⊕⊕⊝⊝ Low4 | Blood flow in the inflow artery may be greater after isometric exercise training compared to isotonic exercise training | |
| Blood flow in the inflow artery (high volume versus low volume isotonic exercise training) | Blood flow in the inflow artery was 287.7 mL/min lower (625.99 lower to 60.59 higher) with high volume isotonic exercise training compared to low volume isotonic exercise training | ‐ | 15 (1) | ⊕⊝⊝⊝ Very low5 | It is uncertain whether isotonic exercise training with high volume improves blood flow in the inflow artery because the certainty of this evidence is very low. | |
| Dialysis efficacy indicator | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported dialysis efficacy indicators. |
| Vascular access function | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported vascular access function. |
| Vascular access complications (isometric versus isotonic exercise training) | ‐ | ‐ | RR 2.54 (0.38 to 17.08) | 110 (2) | ⊕⊝⊝⊝ Very low6 | It is uncertain whether isometric exercise training reduces vascular access complications because the certainty of this evidence is very low. |
| Adverse events | ‐ | ‐ | ‐ | ‐ | ‐ | No studies were found that reported adverse events. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Downgraded 2 levels due to very serious risk of bias; lack of participant blinding (2 studies), identifying in incomplete outcome data (1 study), and reporting other bias (1 study) 2 Downgraded 2 levels due to very serious risk of bias; lack of random sequence generation (1 study), lack of allocation concealment (1 study), lack of participant blinding (3 studies), and identifying in incomplete outcome data (2 studies). 3 Downgraded 2 levels due to very serious risk of bias; lack of participant blinding (2 studies) and identifying in incomplete outcome data (2 studies). Downgraded 1 level due to serious imprecision; wide range of CI (2 studies). 4 Downgraded 2 levels due to very serious risk of bias; lack of random sequence generation (1 study), lack of allocation concealment (1 study), lack of participant blinding (3 studies), and identifying in incomplete outcome data (2 studies). 5 Downgraded 2 levels due to very serious risk of bias; lack of participant blinding (1 study) and identifying in incomplete outcome data. Downgraded 1 level due to serious imprecision; wide range of CI (1 study). 6 Downgraded 1 level due to serious risk of bias; lack of participant blinding (2 studies) and identifying in incomplete outcome data (1 study). Downgraded 1 level due to serious imprecision; wide range of CI (2 studies). Downgraded 1 level due to much difference in events between 2 small studies. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Ultrasound maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.94, 1.25] |
| 1.2 Clinical maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.14 [1.02, 1.27] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Ultrasound maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.56 [1.21, 2.00] |
| 2.2 Clinical maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.80 [1.18, 2.76] |
| 2.3 Venous diameter Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 0.84 [0.45, 1.23] |
| 2.4 Blood flow in the inflow artery Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 140.62 [38.72, 242.52] |
| 2.5 Vascular access complications Show forest plot | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 2.54 [0.38, 17.08] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Venous diameter Show forest plot | 2 | 93 | Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.75, 1.13] |
| 3.2 Blood flow in the inflow artery Show forest plot | 1 | 15 | Mean Difference (IV, Random, 95% CI) | ‐282.70 [‐625.99, 60.59] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Ultrasound maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.94, 1.25] |
| 4.1.1 Low risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.91, 1.28] |
| 4.1.2 Unclear risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.85, 1.42] |
| 4.1.3 High risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.2 Clinical maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.14 [1.02, 1.27] |
| 4.2.1 Low risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.99, 1.28] |
| 4.2.2 Unclear risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.17 [0.97, 1.42] |
| 4.2.3 High risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Ultrasound maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.94, 1.25] |
| 5.1.1 Low risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.85, 1.42] |
| 5.1.2 Unclear risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.91, 1.28] |
| 5.1.3 High risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.2 Clinical maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.14 [1.02, 1.27] |
| 5.2.1 Low risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.17 [0.97, 1.42] |
| 5.2.2 Unclear risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.99, 1.28] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Ultrasound maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.94, 1.25] |
| 6.1.1 Low risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.91, 1.28] |
| 6.1.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.1.3 High risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.85, 1.42] |
| 6.2 Clinical maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.14 [1.02, 1.27] |
| 6.2.1 Low risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.99, 1.28] |
| 6.2.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.2.3 High risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.17 [0.97, 1.42] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Ultrasound maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.94, 1.25] |
| 7.1.1 Low risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.91, 1.28] |
| 7.1.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.1.3 High risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.85, 1.42] |
| 7.2 Clinical maturation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 1.14 [1.02, 1.27] |
| 7.2.1 Low risk | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.99, 1.28] |
| 7.2.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.2.3 High risk | 1 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.17 [0.97, 1.42] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Ultrasound maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.56 [1.21, 2.00] |
| 8.1.1 Low risk | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 1.84 [1.34, 2.51] |
| 8.1.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 8.1.3 High risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.29 [0.95, 1.76] |
| 8.2 Clinical maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.80 [1.18, 2.76] |
| 8.2.1 Low risk | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 1.68 [1.03, 2.73] |
| 8.2.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 8.2.3 High risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 2.60 [1.09, 6.20] |
| 8.3 Venous diameter Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 0.84 [0.45, 1.23] |
| 8.3.1 Low risk | 2 | 110 | Mean Difference (IV, Random, 95% CI) | 0.77 [0.24, 1.30] |
| 8.3.2 Unclear risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 8.3.3 High risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 0.95 [0.27, 1.63] |
| 8.4 Blood flow in the inflow artery Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 140.62 [38.72, 242.52] |
| 8.4.1 Low risk | 2 | 110 | Mean Difference (IV, Random, 95% CI) | 166.71 [‐129.84, 463.26] |
| 8.4.2 Unclear risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 8.4.3 High risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 142.40 [25.83, 258.97] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 9.1 Ultrasound maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.56 [1.21, 2.00] |
| 9.1.1 Low risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.75 [1.12, 2.72] |
| 9.1.2 Unclear risk | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 1.92 [1.24, 2.98] |
| 9.1.3 High risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.29 [0.95, 1.76] |
| 9.2 Clinical maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.80 [1.18, 2.76] |
| 9.2.1 Low risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.38 [1.07, 1.77] |
| 9.2.2 Unclear risk | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 2.30 [1.34, 3.96] |
| 9.2.3 High risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 2.60 [1.09, 6.20] |
| 9.3 Venous diameter Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 0.84 [0.45, 1.23] |
| 9.3.1 Low risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 0.97 [0.39, 1.55] |
| 9.3.2 Unclear risk | 1 | 60 | Mean Difference (IV, Random, 95% CI) | 0.40 [‐0.44, 1.24] |
| 9.3.3 High risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 0.95 [0.27, 1.63] |
| 9.4 Blood flow in the inflow artery Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 140.62 [38.72, 242.52] |
| 9.4.1 Low risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 57.95 [‐182.85, 298.75] |
| 9.4.2 Unclear risk | 1 | 60 | Mean Difference (IV, Random, 95% CI) | 377.20 [‐50.28, 804.68] |
| 9.4.3 High risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 142.40 [25.83, 258.97] |
| 9.5 Vascular access complications Show forest plot | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 2.54 [0.38, 17.08] |
| 9.5.1 Low risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.15, 6.55] |
| 9.5.2 Unclear risk | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 7.00 [0.92, 53.47] |
| 9.5.3 High risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 10.1 Ultrasound maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.56 [1.21, 2.00] |
| 10.1.1 Low risk | 2 | 100 | Risk Ratio (IV, Random, 95% CI) | 1.44 [1.09, 1.91] |
| 10.1.2 Unclear risk | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 1.92 [1.24, 2.98] |
| 10.1.3 High risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.2 Clinical maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.80 [1.18, 2.76] |
| 10.2.1 Low risk | 2 | 100 | Risk Ratio (IV, Random, 95% CI) | 1.64 [0.94, 2.86] |
| 10.2.2 Unclear risk | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 2.30 [1.34, 3.96] |
| 10.2.3 High risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.3 Venous diameter Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 0.84 [0.45, 1.23] |
| 10.3.1 Low risk | 2 | 100 | Mean Difference (IV, Random, 95% CI) | 0.96 [0.52, 1.40] |
| 10.3.2 Unclear risk | 1 | 60 | Mean Difference (IV, Random, 95% CI) | 0.40 [‐0.44, 1.24] |
| 10.3.3 High risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 10.4 Blood flow in the inflow artery Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 140.62 [38.72, 242.52] |
| 10.4.1 Low risk | 2 | 100 | Mean Difference (IV, Random, 95% CI) | 126.37 [21.44, 231.29] |
| 10.4.2 Unclear risk | 1 | 60 | Mean Difference (IV, Random, 95% CI) | 377.20 [‐50.28, 804.68] |
| 10.4.3 High risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 10.5 Vascular access complications Show forest plot | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 2.54 [0.38, 17.08] |
| 10.5.1 Low risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.15, 6.55] |
| 10.5.2 Unclear risk | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 7.00 [0.92, 53.47] |
| 10.5.3 High risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 11.1 Ultrasound maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.56 [1.21, 2.00] |
| 11.1.1 Low risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.75 [1.12, 2.72] |
| 11.1.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.1.3 High risk | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 1.53 [1.04, 2.24] |
| 11.2 Clinical maturation Show forest plot | 3 | 160 | Risk Ratio (IV, Random, 95% CI) | 1.80 [1.18, 2.76] |
| 11.2.1 Low risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.38 [1.07, 1.77] |
| 11.2.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.2.3 High risk | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 2.38 [1.50, 3.77] |
| 11.3 Venous diameter Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 0.84 [0.45, 1.23] |
| 11.3.1 Low risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 0.97 [0.39, 1.55] |
| 11.3.2 Unclear risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 11.3.3 High risk | 2 | 110 | Mean Difference (IV, Random, 95% CI) | 0.74 [0.21, 1.26] |
| 11.4 Blood flow in the inflow artery Show forest plot | 3 | 160 | Mean Difference (IV, Random, 95% CI) | 142.67 [40.77, 244.57] |
| 11.4.1 Low risk | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 57.95 [‐182.85, 298.75] |
| 11.4.2 Unclear risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 11.4.3 High risk | 2 | 110 | Mean Difference (IV, Random, 95% CI) | 166.29 [35.20, 297.38] |
| 11.5 Vascular access complications Show forest plot | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 2.54 [0.38, 17.08] |
| 11.5.1 Low risk | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.15, 6.55] |
| 11.5.2 Unclear risk | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.5.3 High risk | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 7.00 [0.92, 53.47] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 12.1 Venous diameter Show forest plot | 2 | 93 | Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.75, 1.13] |
| 12.1.1 Low risk | 1 | 78 | Mean Difference (IV, Random, 95% CI) | 0.58 [‐0.33, 1.49] |
| 12.1.2 Unclear risk | 1 | 15 | Mean Difference (IV, Random, 95% CI) | ‐0.40 [‐1.67, 0.87] |
| 12.1.3 High risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 13.1 Venous diameter Show forest plot | 2 | 93 | Mean Difference (IV, Random, 95% CI) | 0.19 [‐0.75, 1.13] |
| 13.1.1 Low volume | 1 | 15 | Mean Difference (IV, Random, 95% CI) | ‐0.40 [‐1.67, 0.87] |
| 13.1.2 Unclear risk | 1 | 78 | Mean Difference (IV, Random, 95% CI) | 0.58 [‐0.33, 1.49] |
| 13.1.3 High risk | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
