CLINICAL RESEARCH

A Randomized Trial of Postoperative

Handgrip Exercises for Fistula Maturation
in Patients With Newly Created Wrist
Radiocephalic Arteriovenous Fistulas
Jeng-Wei Chen1, Hsun-Yi Fu2, Ing-Heng Hii3, Hsien-Wei Tseng4, Po-Ya Chang5,
Chin-Hao Chang6, Yih-Sharng Chen1, Ron-Bin Hsu1, I-Hui Wu1, Yung-Ming Chen7,
Tzong-Shinn Chu7, Kuan-Yu Hung7, Shuei-Liong Lin7, Kwan-Dun Wu7 and Chih-Yang Chan1
1
Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; 2Division of
Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan;
3
Division of Cardiovascular Surgery, Department of Surgery, Dalin Tzu Chi General Hospital, Chiayi, Taiwan; 4Department of
Surgery, Taitung MacKay Memorial Hospital, Taitung, Taiwan; 5Department of Surgery, National Taiwan University Hospital,
Taipei, Taiwan; 6Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; and 7Renal Division,
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Introduction: We aimed to substantiate the benefit of postoperative handgrip exercises (HGEs) in

enhancing the maturation of an arteriovenous wrist fistula.
Methods: We randomly assigned 119 patients aged 20 to 80 years who had wrist arteriovenous fistulas
(AVFs) to undergo either a basic HGE program (group A), an advanced program (group B), or an advanced-
plus upper arm banding program (group C). Outcomes were assessed by ultrasonographic evaluation of
the diameter and flow at each follow-up. The attending nephrologist decided the clinical use of the fistula.
Results: We identified no significant differences among the HGE groups in the mean diameter and blood
flow 14, 30, 60, and 90 days after the creation of the wrist AVF (P ¼ 0.55, 0.88, 0.21, and 0.19 for the
diameter; 0.94, 0.81, 0.49, and 0.56 for the flow, respectively). The intent-to-treat analysis also found no
difference in the clinical use of fistulas for hemodialysis (HD) (P ¼ 0.997).
Conclusion: In patients with a newly created wrist AVF, advancing frequency, with or without adding in-
tensity using an upper arm tourniquet, of postoperative HGEs did not enhance the growth of the fistula or
increase the rate of clinical use over 3 months. (ClinicalTrials.gov ID: NCT03077815).
Kidney Int Rep (2023) 8, 566–574; https://doi.org/10.1016/j.ekir.2022.12.019
KEYWORDS: exercise; hemodialysis; surgical arteriovenous shunt
ª 2022 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BY-
NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

n AVF is the preferred method for HD access commonly prescribe HGE for the AVF arm to enhance
A because it provides the safest, most reliable, and
most durable route.1-4 Nevertheless, creating an AVF is
maturation. However, the evidence supporting this is
weak.7 The absence of robust evidence in support of
not without limitations. Challenges may include the the efficacy of HGE inspired this study.
variation in evaluating what constitutes “good veins”
and a patient’s suitability for an AVF, the timing of METHODS
placement, and the rate of failure to mature.4 In addi-
Trial Oversight and Study Design
tion, the maturation rate of AVF is suboptimal,5 We conducted a parallel-group, 3-arm randomized
and less than half of the patients with AVFs achieve
controlled trial (ClinicalTrials.gov ID: NCT03077815) of
unassisted maturation.6 Consequently, physicians HGE programs for radiocephalic AVF (RC-AVF) matu-
ration. The design of this trial followed the funda-
mental requirements of the consolidated standards of
Correspondence: Chih-Yang Chan, Division of Cardiovascular reporting trials (CONSORT).8,9 The Institutional Re-
Surgery, Department of Surgery, National Taiwan University view Board of the National Taiwan University Hospital
Hospital, No. 7, Zhongshan South Road, Taipei 100, Taiwan.
E-mail: [email protected] approved the trial (201701043RINC). Written informed
Received 1 September 2022; revised 16 December 2022; accepted consent was obtained from all the patients. All pro-
19 December 2022; published online 24 December 2022 cedures were performed in accordance with the ethical
566 Kidney International Reports (2023) 8, 566–574
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standards of the Declaration of Helsinki. Furthermore, the study blinded all the assessors, including all sur-
patient records and information were anonymized and geons, technicians, physicians, and nurses. The re-
de-identified before analysis. An independent party searchers were also blinded to the results and analyses
with academic affiliations, who had access to the pri- before reporting.
mary data, served as the analyst panel for the in-
vestigators. The authors vouch for completeness, data Study Patients
accuracy, statistics, and fidelity of this report in terms We included adult patients aged 20 to 80 years with
of the trial protocol. A survey estimated the sample stages 5 or 6 chronic kidney disease who needed new
volume by an analysis of variance test by assuming a HD RC-AVF (Figure 1). All patients underwent a
grouping of 3 with 1:1:1 allocation, the effective size of standardized preoperative duplex ultrasonographic
0.5, and a significance alpha of 0.05. With 14 partici- scan (DUS)10,11 (Supplementary Methods and
pants in each arm, we had >80% power to detect Supplementary Figure S1). The study used the Philips
minimal differences. We expected to lose 20% of the IE 33 (Andover, MA, USA) and a Philips L12-3
participants during the follow-up. Therefore, to pro- broadband linear array transducer for DUS. The in-
mote a more statistically rigorous method, we used a ternal diameter of each vessel was measured using a
larger sample size, with at least 30 participants in each transverse scan technique. We defined a qualified
study arm (90 in total). The researchers conducted this forearm cephalic vein as being patent, soft, and
study in a blinding manner. It included allocation compressible, with an average postaugmented cephalic
concealment after the surgery. Moreover, except for vein diameter of $2.0 mm. In addition, we defined a
the unique study assistant who maintained the follow- qualified radial artery with a postflow-mediated dila-
up visits and records according to the study protocol, tion12 internal diameter $ 2.0 mm, as one with

Figure 1. Flowchart of the study design. The flowchart shows the enrollment, randomization, and follow-up methods of the randomized trial of
the 3 parallel groups. Follow-up measures involved 4 clinical visits and ultrasonographic scans. Primary endpoints included the analysis of
ultrasonographic parameters, and secondary endpoints involved clinical outcomes.
Note. a Supplementary Table S1 enlists all the reasons for exclusion. b Supplementary Table S2 lists the intervals between the index surgery and
the missing data of the 24 participants with incomplete follow-up. HGE, handgrip exercise; PTA, percutaneous balloon angioplasty.

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CLINICAL RESEARCH J-W Chen et al.: Handgrip Exercises for Fistula Maturation

adequate inflow and no prominent calcification. To 50 repeated handgrips in 1 session). This study
measure the flow, the DUS technician adjusted the designed 3 levels of the HGE program as follows. Group
insonation angle to # 60 to reduce the error of ve- A consisted of a basic HGE program that included 2
locity measurement.13 The Philips IE 33 automatically daily exercise sessions (1 in the morning and 1 in the
calculated the volume flow from the time-averaged evening). Group B consisted of an advanced HGE
velocity and the cross-sectional surface area. We tar- program with 6 HGE sessions daily. Group C consisted
geted the brachial artery proximal to the elbow to es- of an advanced-plus program that involved placing a
timate the RC-AVF flow.14,15 Technicians performed standard upper arm tourniquet (provided by the study)
measurements according to the trial schedule, which at the commencement of the 6 HGE sessions.17 The
was before the RC-AVF and 14, 30, 60, and 90 days study assistant checked the tourniquet pressure using a
after the procedure. The survey excluded 102 patients matrix pressure sensor system (Uneo Inc. Taipei, ROC)
for the following reasons: those whose preoperative to achieve a 50 mmHg compression at the upper arm
DUSs indicated cephalic veins or radial arteries that and marked the tourniquet after confirming the bruit.
were suboptimal to create a convenient wrist RC-AVF; We advised each patient to carry out their isometric
patients with a deeply positioned cephalic vein, HGE exercise program at home. As noted in the
defined as a depth of 5 mm or more at each of the randomization, the study assistant provided each pa-
presumed cannulation targets; constitutional exclu- tient a pamphlet containing individualized exercise
sions included significant heart failure New York Heart instructions and record sheets. The study assistant
Association functional class III or above, conscious supervised each patient by repeating the exercise at
disturbance, hemiplegia, long-term bedridden patients, each follow-up visit, verified their agreement with each
immunosuppression, or immunodeficiency; inability to HGE program by examining the exercise record, and
participate in the exercise programs for any reason; or rechecked the upper arm tourniquet pressure for group
those who rejected the study. The study also excluded C patients.
patients for the following surgery-associated concerns:
(i) those in whom the surgeon failed to create an RC-
AVF, (ii) those in whom the surgeon decided to Study Outcome
establish another type of access other than a standard The primary end point was the comparison of ultra-
wrist RC-AVF, (iii) those who experienced any adverse sonographic parameters of RC-AVF maturation, as
events during the surgery that prevented the patient measured by both the average diameter of the body of
from commencing an exercise program. the cephalic vein and the estimated flow of RC-AVF
among the groups over 3 months. We arbitrarily
Study Randomization applied 2 basic requirements of ultrasonographic
The randomization sequence was a raffle-drawing maturity as follows: an RC-AVF diameter $4.0 mm
method using a ballot box. A study assistant then (average diameter of the body of the RC-AVF vein) and
blindly pulled out an envelope containing the indi- an RC-AVF flow $ 500 ml/min.18 The criteria were
vidual brochure and exercise program, opened it before considered appropriate for cannulation with 2 needles
the participant, and instructed them regarding the with the expectation of delivering sufficient blood flow
exercise program privately. Therefore, each participant throughout the HD.15,18,19 The researchers could use
could learn only 1 of the HGE programs without any the data to demonstrate the differences among groups
idea of the others. Moreover, the study assistant was through time-to-mature survival analysis. The sec-
the only study personnel who knew precisely the ondary end point was a comparison of clinical out-
grouping of every participant. comes among the groups over 3 months, as measured
by the proportion of participants with RC-AVFs suc-
Study Procedures cessfully used for the maintenance HD for at least 6
The study defined each HGE as a 5-second isometric contiguous sessions, delivered the prescribed blood
squeeze of a soft elastic ball (provided by the survey). flow throughout, and achieved adequate HD.15 The
We instructed each patient to commence a 5-minute attending nephrologists, blinded to the trial grouping,
HGE of the AVF arm for each session, beginning on decided the time for clinical use of the RC-AVF. They
the second day after RC-AVF creation. The study nurse also determined clinical RC-AVF dysfunction and
instructed participants to perform a standardized iso- percutaneous balloon angioplasty (PTA) referrals. In
metric HGE session, which included the following in- addition, the researchers recorded other adverse
structions: squeeze and hold the ball for 5 seconds events, including unexpected bleeding, acute throm-
(measured by counting to 5) for each grip and repeat bosis of the RC-AVF, wound complications, and
HGE over 5 minutes in each session16 (approximately infection.
568 Kidney International Reports (2023) 8, 566–574
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Statistical Analysis groups. The baseline characteristics were similar among

The study de-linked patients’ private data. A statisti- the groups.
cian collected, managed, and analyzed the data in
agreement with a protocol of predefined intention-to- Primary End Point
treat analysis. An independent academic statistical The results for the primary end point of the ultrasonic
team, blinded to the HGE grouping, replicated the measurements of the enrolled 119 participants are
analyses. Continuous variables were expressed in terms summarized in Table 2. There was no significant dif-
of their median and interquartile range (IQR, 25th–75th ference in any parameter among the treatment groups
quartiles), and categorical variables as frequency and at each period of DUS from 14 to 90 days after the
percentage. The nonparametric Kruskal–Wallis test was construction of the RC-AVF. The brachial artery flow,
used for analyses of continuous variables, and the c2 radial artery diameter, and average diameter of the
test for categorical variables (or Fisher exact test when cephalic vein were the 3 measures of changes. Dilation
the expected count was <5). In addition, the study of the median diameter of the cephalic vein in each
used the log-rank test of the Kaplan–Meier model to group was >4.0 mm at the postoperative day 14 scan. It
depict the cumulative success rates and compared them continued to grow gradually until day 90 in most of the
among groups. Statistical analysis was performed using measures. However, one exception should be noted: a
IBM SPSS Statistics software version 23 (IBM Corp. mild decrease in the average cephalic diameter in group
Armonk, NY, USA). Statistical significance was set at B was observed on day 60 compared with its 30-day
P < 0.05. value. However, the comparison still showed no sig-
nificant differences between the groups. As mentioned
in the Methods section, we used the brachial artery
RESULTS flow to estimate the RC-AVF flow.14,15 The median RC-
The study enrolled patients from March 1, 2017, to AVF flow was >500 ml/min on the first postoperative
July 31, 2018. We visited all the referrals and screened DUS on day 14 and continuously increased to >600 ml/
the arm vessels using standardized DUS. Of the 221 min by day 90 in every group. Although a dubiously
patients screened, 134 were eligible; 119 agreed to high value was noted on day 30 in group A, the re-
participate and were randomized into 3 groups. searchers still found no significant difference during
Consequently, groups A, B, and C had 40, 43, and 36 any period between the 3 groups. The ratio of each
randomly assigned patients, respectively, of which 32, parameter to its preoperative value demonstrates serial
33, and 30 completed the 3-month ultrasonographic change over time in the lower half of the table. For each
follow-up (Figure 1). The patients’ ineligibility and DUS measure of diameter or flow, there was a promi-
why eligible patients declined randomization are nent increment on the first postoperative scan on day
summarized in Supplementary Table S1. Table 1 shows 14, with a slow increment to a plateau by day 90.
the baseline demographic and clinical data of the 3 Again, there were no significant differences among

Table 1. Baseline characteristics of the patients (N ¼ 119)

Characteristics Group A (n [ 40) Group B (n [ 43) Group C (n [ 36) P valuea
Age, median (IQR) 64.50 (56.00–72.50) 67.00 (58.00–75.00) 69.00 (59.00–76.00) 0.651
Male, n (%) 20 (50.00) 28 (65.12) 20 (55.56) 0.370
Height, median (IQR) 162.00 (152.00–170.00) 160.00 (155.00–165.60) 161.35 (153.00–166.85) 0.973
Weight, median (IQR) 62.65 (57.05–71.85) 61.10 (56.30–69.20) 61.75 (56.00–72.20) 0.720
BMI (kg/m2), median (IQR) 24.50 (22.30–28.30) 24.10 (21.30–25.50) 24.70 (21.85–27.15) 0.519
Obesity, n (%) 7 (17.50) 2(4.65) 2(5.56) 0.115
Diabetes, n (%) 23(57.50) 19(44.19) 19(52.78) 0.468
Hypertension, n (%) 37 (92.50) 38 (88.37) 31 (86.11) 0.661
Hyperlipidemia, n (%) 13 (32.50) 16 (37.21) 13 (36.11) 0.898
Heart disease, n (%) 12 (30.00) 20 (46.51) 9 (25.00) 0.103
Preaugmentation averaged vein diameter 2.42 (2.10–2.96) 2.18 (1.80–2.71) 2.32 (2.08–2.69) 0.274
Postaugmentation averaged vein diameter 3.11 (2.76–3.50) 2.74 (2.33–3.28) 3.13 (2.72–3.53) 0.058
Pre-FMD brachial artery diameter 4.70 (4.30–5.19) 4.50 (4.13–4.90) 4.55 (3.95–5.00) 0.533
Post-FMD brachial artery diameter 5.03 (4.61–5.71) 4.97 (4.64–5.37) 4.93 (4.40–5.50) 0.618
Pre-FMD radial artery diameter 2.34 (2.20–2.88) 2.45 (2.12–2.80) 2.48 (2.20–2.80) 0.922
Post-FMD radial artery diameter 2.68 (2.32–2.90) 2.70 (2.48–3.10) 2.68 (2.40–2.99) 0.579

BMI, bodymass index; FMD, flow-mediated dilation; IQR, interquartile range.

a
Estimated by Kruskal–Wallis test, c2 test, or Fisher exact test.
IQR, Interquartile range; FMD, postflow-mediated dilation; Group A: 2 handgrip exercise sessions daily. Group B: 6 handgrip exercise sessions daily. Group C: 6 handgrip exercise
sessions with an upper arm tourniquet daily.

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CLINICAL RESEARCH J-W Chen et al.: Handgrip Exercises for Fistula Maturation

Table 2. The serial changes in the radiocephalic fistula diameters, flows, and the ratiosa over time of the 3 groups at 14, 30, 60, and 90 d after
the index surgical creation (N ¼ 119)
Parameters Group A (n [ 40) Group B (n [ 43) Group C (n [ 36) P valueb
Median (Q1–Q3)
Averaged diameter of cephalic vein, mm
14 d 4.15 (3.80–4.60) 4.05 (3.50–4.50) 4.25 (3.70–4.60) 0.555
30 d 4.20 (3.80–5.10) 4.30 (3.60–4.70) 4.30 (3.40–4.90) 0.880
60 d 4.65 (4.00–5.10) 4.05 (3.45–5.00) 4.50 (4.10–5.10) 0.214
90 d 4.75 (4.00–5.75) 4.30 (4.00–4.90) 4.70 (4.30–5.20) 0.193
Radial artery diameter, mm
14 d 3.40 (2.65–4.00) 3.50 (3.20–4.10) 3.65 (3.17–3.20) 0.258
30 d 3.80 (3.15–4.32) 3.40 (2.77–3.92) 3.80 (3.20–4.10) 0.076
60 d 4.00 (3.00–4.30) 3.80 (3.07–4.23) 4.00 (3.80–4.55) 0.128
90 d 3.70 (3.30–4.40) 3.75 (3.00–4.42) 3.80 (3.37–4.57) 0.360
Brachial artery diameter, mm
14 d 5.10 (4.70–5.75) 5.00 (4.80–5.60) 5.30 (4.60–5.80) 0.939
30 d 5.40 (4.60–5.80) 5.10 (4.60–5.80) 5.00 (4.80–5.50) 0.806
60 d 5.55 (4.80–5.90) 5.10 (4.85–5.80) 5.10 (4.65–5.70) 0.493
90 d 5.40 (4.85–5.80) 5.10 (4.60–5.60) 5.30 (4.70–6.00) 0.562
Fistula flow estimated by the brachial artery, ml/min
14 d 595.45 (464.20–744.00) 562.05 (399.40–772.30) 655.95 (406.60–925.70) 0.723
30 d 731.20 (436.70–1082.00) 505.95 (372.05–694.35) 620.00 (427.40–988.00) 0.082
60 d 689.90 (418.20–951.10) 526.20 (379.35–666.60) 650.30 (545.40–846.90) 0.086
90 d 633.85 (405.15–1031.40) 629.80 (445.60–756.90) 627.60 (421.20–999.30) 0.657
Ratio of diameter of cephalic vein
14 d 1.58 (1.33–2.26) 1.77 (1.43–2.26) 1.86 (1.52–2.11) 0.732
30 d 1.77 (1.32–2.29) 1.94 (1.39–2.51) 1.91 (1.45–2.07) 0.723
60 d 1.86 (1.35–2.40) 1.91 (1.53–2.33) 1.95 (1.48–2.33) 0.997
90 d 1.82 (1.46–2.65) 2.03 (1.40–2.39) 1.96 (1.65–2.36) 0.969
Ratio of diameter of radial artery
14 d 1.40 (1.13–1.60) 1.37 (1.16–1.68) 1.48 (1.19–1.78) 0.785
30 d 1.49 (1.33–1.78) 1.37 (1.10–1.64) 1.49 (1.27–1.76) 0.168
60 d 1.48 (1.29–1.90) 1.36 (1.18–1.84) 1.69 (1.32–1.90) 0.163
90 d 1.53 (1.38–1.87) 1.37 (1.15–1.72) 1.64 (1.24–1.92) 0.138
Ratio of diameter of brachial artery
14 d 1.09 (1.00–1.26) 1.15 (1.05–1.25) 1.19 (1.02–1.26) 0.555
30 d 1.13 (1.00–1.19) 1.12 (1.03–1.31) 1.11 (1.00–1.27) 0.714
60 d 1.13 (1.02–1.35) 1.16 (1.09–1.28) 1.14 (0.97–1.27) 0.694
90 d 1.11 (1.03–1.32) 1.11 (1.00–1.26) 1.17 (1.01–1.30) 0.611
Ratio of fistula flow
14 d 11.12 (6.03–17.18) 9.85 (5.19–15.52) 11.48 (6.82–24.12) 0.205
30 d 12.83 (7.83–17.19) 9.39 (6.00–14.16) 15.48 (7.56–18.19) 0.088
60 d 11.02 (6.06–21.25) 9.14 (6.06–16.16) 12.65 (7.93–21.29) 0.295
90 d 12.17 (4.80–15.19) 10.08 (6.95–16.08) 16.07 (9.91–23.04) 0.050
a
Ratio of each parameter at each time point is calculated by the number divided by its preoperative value.
b
Estimated by Kruskal–Wallis test.
Group A: 2 handgrip exercise sessions daily.
Group B: 6 handgrip exercise sessions daily.
Group C: 6 handgrip exercise sessions with an upper arm tourniquet daily.

groups in each component ratio for any ultrasono- period. The number-at-risk table in Figure 2 shows
graphic follow-up period. that, by 3 months, 56.2  8.8%, 60.6  8.7%, and
The Kaplan–Meier model was used to analyze the 95 53.3  9.1% of the 95 participants had achieved DUS-
participants who had completed serial DUS follow-ups maturation of RC-AVF in groups A, B, and C,
3 months after RC-AVF creation. The Kaplan–Meier respectively. Considering the diversity among the 24
curves comparing the accumulation of RC-AVF matu- participants who missed some ultrasonographic follow-
ration by DUS criteria (DUS-maturation, defined in the ups (Supplementary Table S2), the researchers also
Methods) is depicted in Figure 2. The researchers could performed an intention-to-treat analysis of the 119
not demonstrate any difference in time-to-maturity participants. In addition, we found no significant
among the 3 groups (log-rank P ¼ 0.875) in the pace difference among the groups by the third month for
and proportions of DUS-maturation during any study the 61.6  7.9%, 58.6  8.0%, and 54.4  8.5% of
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Figure 2. Comparison of the cumulative proportion of participants with DUS-maturationa over time. The figure compares the 3 groups’ cu-
mulative DUS-maturation, number-at-risk, and cumulative incidences. The Kaplan–Meier model analyzes the 95 participants who had completed
serial DUS follow-ups. The cumulative incidence values denote the Kaplan–Meier estimated fraction of participants with DUS-maturation at
each time point.
Note. aDUS-maturation: the average diameter and flow of the target radiocephalic arteriovenous fistula fulfilling the ultrasonographic matu-
ration criteria (see text); Group A: 2 handgrip exercise sessions daily. Group B: 6 handgrip exercise sessions daily. Group C: 6 handgrip exercise
sessions with an upper arm tourniquet daily.

the 119 participants who achieved DUS-maturation in analysis, Figure 1). Consequently, the researchers
groups A, B, and C, respectively (log-rank P ¼ 0.965, excluded their post-PTA data when comparing DUS-
Supplementary Figure S2). maturation (Table 2, Figure 2, and Supplementary
Figure S2). Apart from PTA, no other significant
adverse events such as thrombosis, bleeding, infection,
Secondary End Points
or wound complications were noted in any HGE group
By the end of the trial, the attending nephrologists
within the study period.
decided to use RC-AVF for HD in 20 of 40 (50.0%), 24
of 43 (55.8%), and 22 of 36 (61.1%) participants in
groups A, B, and C, respectively (c2 ¼ 0.950, the P
DISCUSSION
value ¼ 0.622 based on intention-to-treat analysis,
Figure 1, Supplementary Table S3). They also deter- This prospective randomized controlled trial, which
mined which participants had inadequately matured enrolled 119 patients with chronic kidney disease who
AVFs and referred them for PTAs to assist with received a newly created RC-AVF, revealed no clinical
maturation. Between the first and last follow-up, 1, 4, benefit in the added intensity of postoperative HGE
and 2 participants in groups A, B, and C, respectively, programs to promote the process of RC-AVF maturation.
underwent PTA for both clinical and DUS findings, Neither ultrasonographic nor clinical measures differed
suggesting early stenosis of the RC-AVF (1/40 in group substantially among the groups. Furthermore, for the 95
A, 4/43 in group B, and 2/36 in group C, P ¼ 0.419 as participants who had completed the serial DUS follow-
determined by c2 test based on intention-to-treat ups over 3 months, the trial identified no objective

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CLINICAL RESEARCH J-W Chen et al.: Handgrip Exercises for Fistula Maturation

benefit in the rate, process, or proportion of maturation reported that a 6 lb dumbbell exercise benefited the
by Kaplan–Meier analysis among the 3 groups. maintenance of AVF patency over HGE by 3 months.
Studies and guidelines15,20 have suggested that phy- However, they found no difference in outcome when
sicians recommend arm and hand exercises before16,21 they followed up with their patients over 6 months in a
and after creating a new AVF to accelerate the matura- subsequent study.29
tion or maintenance of the AVF. Several studies have On the other hand, a well-designed specific arm
described increased blood flow and acceleration of this exercise may still provide new insights and infer the
process resulting from exercise training programs.16,22-25 possibility of prescribing an efficient exercise pro-
Those programs comprised a variety of upper extremity gram.25,26,28 Recently, Nantakool et al.24 found that a
exercises, with the activities ranging from the using a specific degree of the isometric exercise program was
squeeze ball,16 to a particular degree of isometric exer- advantageous over isotonic exercise to enhance AVF
cise using a specific device,22,24 to highly structured arm maturation. However, there was a gap between study
and body exercises.25,26 These studies served as the findings and clinical practice. Instructing patients to
primary foundation for post-AVF arm exercises. How- perform HGE (with or without banding of the upper
ever, reviewers have questioned the validity of these arm using an elastic tourniquet) every day after AVF
randomized studies.27 Consequently, an updated creation is a simple and common prescription in clinical
guideline provided inadequate evidence to recommend practice. Nevertheless, because of the lack of consensus
the use of arm exercises to facilitate AVF maturation.7 on the type, intensity, frequency, timing, or duration
HGE was chosen as the basis for the study on post- of exercise, the attending nephrologists and surgeons
AVF arm exercises because of its standard prescription provide varied clinical suggestions after AVF con-
in clinical practice. Adding an upper arm tourniquet or struction to enhance AVF maturation. As a result, pa-
banding is a typical method to dilate the AVF vein.17 tients may get confused by different instructions from
Furthermore, the HGE prescription in this trial was physicians monitoring the HGE program, in addition to
considered an isometric exercise.16 Correspondingly, more complex instructions.
the researchers established the HGE programs equiva- Although this trial identified no benefit of HGE on
lent to the levels described in articles16,17,22,25,26 and RC-AVF maturation, we also found no disadvantage
clinical practice. In addition, the researchers chose related to the postoperative exercise of the RC-AVF
regimens focused on simplicity to maximize adherence. arm. A recent trial also found no adverse events asso-
Moreover, the accommodation of the variability of arm ciated with AVFarm exercise using a 6 lb dumbbell.23
exercises within the standard instructions enhances the Therefore, evidence in support of restricting the mo-
generalizability of the findings. In contrast, particular tion of the AVFarm is lacking. A patient’s misconcep-
exercise instructions or the use of specific devices tion of AVF arm restriction may also gradually lead to
could help the study interest at the expense of gener- overprotection and a reduction in muscle strength.29
alizability.8,9 We aimed to report a robust comparison
and to have a substantial outcome from this study. Study Limitation
Therefore, the researchers diligently adhered to the This trial did not explore the effect of preoperative
CONSORT checklist items and facilitated the clarity, exercise.16,21 In addition, it did not include a non-
completeness, and transparency of our reporting.8 Ul- HGE group because HGE was a standard prescrip-
timately, we failed to show significant improvement in tion in most nephrology practices during the study
applying a higher frequency of HGE daily, with or period. Furthermore, not measuring the degree of
without using an upper arm tourniquet, compared isometric exercise could have limited our trial’s
with that of less frequent HGE daily. The results of our strength.24 Moreover, the researchers did not pre-
trial might seem to contradict the findings of a few scribe highly structured whole arm or body exercise
randomized trials.23-26,28 However, comparisons be- training programs.25,26 In addition, the researchers
tween reports seem unreasonable because the specific recognized the potential for participants to divulge
benefits of arm exercises varied among articles, the their programs that might interfere with clinical de-
programs were diverse,7,25,26,28 and the use of specific cisions. Finally, the 3-month follow-up time con-
devices differed. Besides, the researchers realized the strained our ability to study thrombotic events after
discrepancy between the 2 numbers of participants RC-AVF maturation and narrowed the study of
who achieved the primary end point of DUS- longer-term HGE effects.
maturation and those who attained the second end In summary, this study failed to demonstrate the
point of successful clinical use of the RC-AVF. In clinical benefit of advancing frequency, with or
addition, even the same study group may have re- without an upper arm tourniquet, of postoperative
ported different results. For example, Mo et al.23 HGE for RC-AVF maturation over 3 months. Therefore,
572 Kidney International Reports (2023) 8, 566–574
J-W Chen et al.: Handgrip Exercises for Fistula Maturation CLINICAL RESEARCH

we believe that the recommendation for HGE in such contributed to resources and supervision. C-YC contrib-
patients should be re-evaluated. In addition, we may uted to conceptualization, methodology, writing (review
best focus further studies on the generalizability of our and editing), visualization, project administration, and
findings by conducting a multicenter trial with a more funding acquisition.
extended study period.
SUPPLEMENTARY MATERIAL
DISCLOSURE Supplementary File (PDF)
All the authors declared no competing interests. Supplementary Methods. Protocol steps for the
ultrasonographic measurements of the arm vessels.
ACKNOWLEDGMENTS Figure S1. A sketch of the specifications of duplex
We thank the staff of the National Taiwan University Hos- ultrasonographic measurements of forearm vessels in
pital Statistical Consulting Unit for statistical consultation the study.
and analysis. We are also grateful to the renal team of the Figure S2. Comparison of the cumulative proportion of 119
National Taiwan University Hospital for supporting our participants with DUS-maturationa among groups.
trial and for sharing their pearls of wisdom with us during Table S1. Reasons for excluding patients from the study.
this research. The renal division colleagues included Yung- Table S2. Intervals between the index surgery and the last
Ming Chen, Tzong-Shinn Chu, Kuan-Yu Hung, Shuei-Liong response or first event of the 24 participants with
Lin, Kwan-Dun Wu (the 5 authors listed), Fan-Chi Chang, incomplete follow-up.
Chih-Kang Chiang, Wen-Chih Chiang, Yu-Hsiang Chou, Table S3. Intention-to-treat analysis of the clinical use of
Down-Ming Huang, Jeng-Wen Huang, Chun-Fu Lai, Tai- RC-AVFa by 3 months and the comparison between
Shuan Lai, Vin-Cent Wu, and Shao-Yu Yang. groups.
CONSORT 2010 Checklist.
Sources of support
This work was supported by the National Taiwan Univer- REFERENCES
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