The effects of exercise training interventions on depression in hemodialysis patients

Abstract

Purpose
Depression considerably influences the clinical outcomes, treatment compliance, quality of life, and mortality of hemodialysis patients. Exercise plays a beneficial role in depressive patients, but its quantitative effects remain elusive. This study aimed to summarize the effects of exercise training on depression in patients with end-stage renal disease undergoing hemodialysis.

Methods
The PUBMED, EMBASE, and Cochrane Library databases were systematically searched from inception to April 2023 to identify published articles reporting the effect of exercise training on the depression level of patients with End-Stage Renal Disease undergoing hemodialysis. Data were extracted from the included studies using predefined data fields by two independent researchers. The Cochrane Handbook for Systematic Reviews of Interventions and Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies were employed for quality evaluation.

Results
A total of 22 studies enrolling 1,059 patients who participated in exercise interventions were included. Hemodialysis patients exhibited superior outcomes with intradialytic exercise (SMD = −0.80, 95% CI: −1.10 to −0.49) and lower levels of depression following aerobic exercise (SMD = −0.93, 95%CI: −1.32 to −0.55) compared to combined exercise (c − 0.85, 95% CI: −1.29 to −0.41) and resistance exercise (SMD = −0.40, 95%CI: −0.96 to 0.17). Regarding exercise duration, patients manifested lower depression levels when engaging in exercise activities for a duration exceeding 6 months (SMD = −0.92, 95% CI: −1.67 to −0.17). Concerning the duration of a single exercise session, the most significant improvement was noted when the exercise duration exceeded 60 min (SMD = −1.47, 95% CI: −1.87 to −1.06).

Conclusion
Our study determined that exercise can alleviate depression symptoms in hemodialysis patients. This study established the varying impacts of different exercise parameters on the reduction of depression levels in hemodialysis patients and is anticipated to lay a theoretical reference for clinicians and nurses to devise tailored exercise strategies for interventions in patients with depression.

Systematic review registration
https://www.crd.york.ac.uk/prospero/, This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database, with registration number CRD42023434181.

Full text

Frontiers in Psychiatry 01 frontiersin.org
The eects of exercise training
interventions on depression in
hemodialysis patients
HuihuiYu
1,2†, MeiHuang
1†, YuxiuTao
1, ShanshanLi
1, JingWang
3,
PingLi
1, HonghongLv
4* and ChunpingNi
1
*
1 School of Nursing, Air Force Medical University, Xi'an, China, 2 The 1th Department of Gerontology,
the 960th Hospital of PLA Joint Logistics Support Force, Jinan, China, 3 School of Nursing, Shaanxi
University of Chinese Medicine, Xianyang, China, 4 Blood Purification Center, Tangdu Hospital, Air
Force Medical University, Xi'an, China
Purpose: Depression considerably influences the clinical outcomes, treatment
compliance, quality of life, and mortality of hemodialysis patients. Exercise plays
a beneficial role in depressive patients, but its quantitative eects remain elusive.
This study aimed to summarize the eects of exercise training on depression in
patients with end-stage renal disease undergoing hemodialysis.
Methods: The PUBMED, EMBASE, and Cochrane Library databases were
systematically searched from inception to April 2023 to identify published
articles reporting the eect of exercise training on the depression level of patients
with End-Stage Renal Disease undergoing hemodialysis. Data were extracted
from the included studies using predefined data fields by two independent
researchers. The Cochrane Handbook for Systematic Reviews of Interventions
and Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental
Studies were employed for quality evaluation.
Results: A total of 22 studies enrolling 1,059 patients who participated in
exercise interventions were included. Hemodialysis patients exhibited superior
outcomes with intradialytic exercise (SMD = −0.80, 95% CI: −1.10 to −0.49) and
lower levels of depression following aerobic exercise (SMD = −0.93, 95%CI:
−1.32 to −0.55) compared to combined exercise (c − 0.85, 95% CI: −1.29 to
−0.41) and resistance exercise (SMD = −0.40, 95%CI: −0.96 to 0.17). Regarding
exercise duration, patients manifested lower depression levels when engaging
in exercise activities for a duration exceeding 6 months (SMD = −0.92, 95%
CI: −1.67 to −0.17). Concerning the duration of a single exercise session, the
most significant improvement was noted when the exercise duration exceeded
60 min (SMD = −1.47, 95% CI: −1.87 to −1.06).
Conclusion: Our study determined that exercise can alleviate depression
symptoms in hemodialysis patients. This study established the varying impacts
of dierent exercise parameters on the reduction of depression levels in
hemodialysis patients and is anticipated to lay a theoretical reference for
clinicians and nurses to devise tailored exercise strategies for interventions in
patients with depression.
Systematic review registration: https://www.crd.york.ac.uk/prospero/, This
study was registered in the International Prospective Register of Systematic
Reviews (PROSPERO) database, with registration number CRD42023434181.
KEYWORDS
depression, exercise training, intradialytic exercise, hemodialysis, end-stage renal
disease
OPEN ACCESS
EDITED BY
Gustavo Hector Vazquez,
Queen's University, Canada
REVIEWED BY
Malahat Akbarfahimi,
Iran University of Medical Sciences, Iran
Bernard Canaud,
Université de Montpellier, France
*CORRESPONDENCE
Chunping Ni
pingchunni@163.com
Honghong Lv
283360153@qq.com
†These authors have contributed equally to
this work and share first authorship
RECEIVED 14 October 2023
ACCEPTED 19 December 2023
PUBLISHED 08 January 2024
CITATION
Yu H, Huang M, Tao Y, Li S, Wang J, Li P,
Lv H and Ni C (2024) The eects of exercise
training interventions on depression in
hemodialysis patients.
Front. Psychiatry 14:1321413.
doi: 10.3389/fpsyt.2023.1321413
COPYRIGHT
© 2024 Yu, Huang, Tao, Li, Wang, Li, Lv and
Ni. This is an open-access article distributed
under the terms of the Creative Commons
Attribution License (CC BY). The use,
distribution or reproduction in other forums is
permitted, provided the original author(s) and
the copyright owner(s) are credited and that
the original publication in this journal is cited,
in accordance with accepted academic
practice. No use, distribution or reproduction
is permitted which does not comply with
these terms.
TYPE Systematic Review
PUBLISHED 08 January 2024
DOI 10.3389/fpsyt.2023.1321413

Yu et al. 10.3389/fpsyt.2023.1321413
Frontiers in Psychiatry 02 frontiersin.org
1 Introduction
End-stage renal disease (ESRD), the h stage of chronic kidney
disease (CKD), arises from diverse etiologies and is characterized by low
quality of life and high mortality rates. As is well documented, the most
eective treatment modality for ESRD remains hemodialysis (HD) (1).
Recent clinical research estimated that nearly 5 million ESRD patients
will necessitate HD as a kidney replacement therapy worldwide by 2030
(2). While considerable advancements have been made in the treatment
and care of hemodialysis patients, the long-term prognosis of these
patients remains dismal (3).
e prevalence of depression in patients with HD is a particular
concern. Indeed, depressive symptoms aict approximately 74.58% of
patients undergoing HD and are associated with suicidal tendencies,
lower quality of life, reduced treatment compliance, medical
comorbidities, and elevated mortality rates (4–8). erefore, eective
nursing interventions are urgently warranted to aid patients in coping
with depression. At present, the primary approaches for the treatment
of depression involve a combination of pharmacological and
non-pharmacological interventions. Nonetheless, the majority of
antidepressants elicit adverse events, such as drug dependence,
addiction, and poor tolerance (9). A previous study demonstrated
promising outcomes for non-pharmacological interventions, specically
the incorporation of exercise training as a supplement to
pharmacotherapy (10).
e National Kidney Function Association recommends Exercise
training as a cornerstone for HD patients to eectively manage
complications (11). A recent study documented that exercise training
could assist HD patients in achieving a better quality of life and could
signicantly alleviate depressive symptoms (12). However, given that the
intervention is aected by specic training parameters, including the
type of exercise, the location of exercise, the duration and the frequency
of exercise, and so on, a comprehensive standard of exercise has not
been established so far. While earlier studies focused on the eects of
exercise on physical parameters such as blood pressure, motor function,
and hemoglobin levels in patients with ESRD (12, 13), those targeting
mental parameters are scarce, and the ndings are oen contradictory.
erefore, the purpose of this systematic review and meta-analysis was
to aggregate available evidence and systematically analyze the eects of
exercise on depression in HD patients to assess the eectiveness of
dierent exercise training parameters.
2 Methods
is study was performed in accordance with the PRISMA
guidelines for systematic reviews and meta-analyses. is systematic
review was conducted as a quantitative systematic review and meta-
analysis utilizing the xed-eects model (14). is study was registered
in the International Prospective Register of Systematic Reviews
(PROSPERO) database, with registration number CRD42023434181.
2.1 Data sources and searches
A systematic search was performed in the PUBMED, EMBASE, and
Cochrane Library databases to screen for published articles from
database inception to April 2023 with a combination of medical subject
headings (MeSH) terms and text keywords. Key words included in the
search were hemodialysis, mental disorder, depressive disorder, stress
disorders, and exercise (see details in Supplementary Methods 1). In
addition, the scope of our search was expanded to manually search the
reference list of original studies, as well as grey literature and records.
2.2 Inclusion and exclusion criteria
Inclusion criteria for this study were as follows: (1) population: adult
≥18 years of age with a diagnosis of ESRD requiring HD; (2) study
design: both quasi-randomized controlled trials and clinical randomized
controlled trials; (3) intervention and comparison: exercise training of
intervention group comprised aerobic training, resistance training, and
combined training, while the control group received usual care, sham
exercise, and no exercise. (4) Outcomes: the primary end-point was
depression. Assessment tools for depression included the Beck
Depression Inventory, the self-rating depression scale developed by
Zung, the Hospital Anxiety and Depressive Depression Scale, etc.
Exclusion criteria were as follows: (1) Inappropriate study types, such as
reviews, editorials, and case reports; (2) patients undergoing alternative
renal replacement therapies or those suering from acute kidney failure.
(3) Studies with incomplete data.
2.3 Quality assessment
e quality of all the included randomized controlled trial studies
was assessed following the guidelines outlined in the Cochrane
Handbook for Systematic Reviews of Interventions. Seven aspects were
considered, namely random generation, allocation concealment,
blinding of participants and outcome assessment, incomplete outcome
data, selective reporting, and other biases. All included trials were
independently assessed, and the risk of bias was classied as “low risk,”
“unclear,” or “high risk” (15). e Joanna Briggs Institute (JBI) Critical
Appraisal Checklist for Quasi-Experimental Studies was used for quality
evaluation of non-randomized experimental studies, which involved the
consideration of 9 aspects, with each item categorized as “Yes,” “No,”
“Unclear,” or “Not Applicable” (16). Disagreements between the 2
reviewers (HY and MH) were resolved by a third reviewer (YT).
2.4 Data extraction
e literature search, study selection, study appraisal, and data
extraction were pre-dened in the protocol and independently
conducted by two investigators (HY and MH). Data extracted for this
study included the following: rst author, publication year, country,
study design, sample size, male-to-female ratio, mean age, intervention
(exercise type, exercise location, total exercise duration, single exercise
duration, and outcome measurement tools). Discrepancies between the
two reviewers were resolved by discussion until reaching a consensus.
2.5 Data synthesis and statistical analysis
Statistical analyses were performed using Review Manager 5.3
(version 5.3.5, Copenhagen: e Nordic Cochrane Center, e

Yu et al. 10.3389/fpsyt.2023.1321413
Frontiers in Psychiatry 03 frontiersin.org
Cochrane Collaboration) and Comprehensive Meta-Analysis Version
3.0 soware (Biostat, Englewood, NJ), and p< 0.05 was considered
statistically signicant. Considering that the studies used dierent
measurement scales to measure depression levels, the standardized
dierences in mean (SMD), along with their 95% condence intervals
(CI), were used to estimate the intervention eect size. e Tau2 and I2
statistics were used to assess heterogeneity among studies. I
2
values
below 25% indicated low heterogeneity, values between 25 and 50%
suggested moderate heterogeneity and values exceeding 50% indicated
high heterogeneity. If the heterogeneity was high, subgroup analysis was
performed, and the random eects model was used. To assess the
potential presence of publication bias, the symmetry of the funnel chart
was examined. Sensitivity analyses were performed by excluding each
study one at a time and comparing the results with the original ndings.
3 Results
3.1 Search outcome
Two reviewers (H.Y. and M.H.) independently searched the titles and
abstracts of the aforementioned databases using a standardized form.
Discrepancies between the two reviewers were resolved by discussion
until a consensus was attained. e study selection process is illustrated
in the Preferred Reporting Items for Systematic Reviews and Meta-
Analyses ow diagram (shown in Figure.1). e database search yielded
a total of 695 original studies. Following the removal of duplicates, 648
studies remained. ese articles were screened by reviewers, which led to
the exclusion of studies with no relevant variables (n= 142), publications
in non-English languages (n= 14), incomplete data (n= 30), and those
lacking full-text information (n= 26). A total of 22 articles were retained
aer the full-text screening process and manual search of the reference list
of the full-text articles. A systematic review was performed, adhering to
Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA) guidelines (Supplementary Table 1).
3.2 Study selection and baseline
characteristics
According to the inclusion and exclusion criteria, a total of 22 studies
were included for analysis. e detailed characteristics of these studies
are listed in Table1. A total of 1,059 patients were included in this study.
Furthermore, all the studies were published in the English language from
1983 to 2023, and were conducted in China (n= 4) (17–20), UnitedStates
(n= 3) (21–23), Greece (n= 5) (24–28), Japan (n= 1) (29), Brazil (n= 1)
FIGURE1
PRISMA flow diagram for the meta-analysis. A flow diagram depicting the studies screened, assessed for eligibility, and included in the review, along
with reasons for exclusions.

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TABLE1 Characteristics of studies and patients included in the meta-analysis.
Author, year Country study
type
Sample size,n(male/total) Age, years, mean ± SD type duration Single
duration
timing Measuring
tools
intervention control intervention control
Liu etal. (17) China RCT 6/10 5/10 44.3 ± 6.7 33.2 ± 7.0 AE 12 weeks 30 min Intradialytic BDI-II
Tang etal. (18) China RCT 28/42 23/42 46.26 ± 15.61 43.90 ± 12.44 AE 12 weeks 20-30MIN non-
intradialytic HAD-D
Lin etal. (19) China RCT 22/32 19/32 62.0 ± 9.5 62.1 ± 12.3 AE 12 weeks 30MIN Intradialytic BDI
Zhou etal. (20) China nRCT 35/79 / 55.03 ± 10.69 / CE 12 weeks 30MIN Intradialytic HADS
Carney etal. (21) USA nRCT 4 4 38.75 ± 8.02 43.25 ± 7.14 AE 6 months /non-
intradialytic MAACL
Carney etal. (22) USA RCT 5/10 3/7 36.1 ± 3.2 40.7 ± 5.3 AE 6 months 45-60MIN Intradialytic BDI
Zhou etal. (23) USA nRCT 18/37 22/36 62.7 ± 6.8 66.5 ± 10.0 CE 4 weeks 30MIN Intradialytic CES-D
Kouidi etal. (24)Greece RCT 11/20 4/11 49.6 ± 12.1 52.8 ± 10.2 CE 6 months 90MIN non-
intradialytic BDI
Sakkas etal. (25)Greece RCT 5/7 5/7 48 ± 14 70 ± 11 AE 16 weeks 45MIN intradialytic Zung
Ouzouni etal. (26)Greece RCT 14/19 13/14 47.4 ± 15.7 50.5 ± 11.7 CE 10 months 60-90 min Intradialytic BDI
Kouidi etal. (27)Greece RCT 14/24 12/20 46.3 ± 11.2 45.8 ± 10.9 CE 12 months 60-90MIN Intradialytic BDI; HADS
Giannaki etal. (28)Greece RCT 11/15 5/7 56.4 ± 12.5 56.8 ± 16.5 AE 6 months 45MIN non-
intradialytic Zung
Yabe etal. (29)Japa n RCT 14/27 15/19 75.3 ± 4.4 74.3 ± 5.8 CE 12 months 30MIN Intradialytic GDS
Deus etal. (30) Brazilian RCT 46/81 40/76 67.27 ± 3.24 66.33 ± 3.88 RT 6 months 60MIN Predialysis BDI
Ortega-Pérez de Villar
etal. (31)Spain RCT 15/24 14/22 62.2 ± 15.0 59.3 ± 16.1 AE 16 weeks 20-40MIN Predialysis CES-D
Dziubek etal. (32)Poland RCT 9/20 5/8 66.3 ± 13.1 56.4 ± 13.6 CE 6 months 50 min Predialysis BDI
Rezaei etal. (33)Iran nRCT 21/25 14/26 43.96 ± 7.86 42.61 ± 12.67 CE 10 weeks 35MIN non-
intradialytic BDI
Rahimimoghadam
etal. (34)Iran RCT 21/25 20/25 39.1 ± 2.2 38.4 ± 1.8 AE 8 weeks 45MIN non-
intradialytic GHQ-28
Rhee etal. (35)Korea nRCT 9/22 / 57.0 ± 12.4 / CE 6 m onths 40-50 min Intradialytic BDI
van Vilsteren etal.
(36)
e
Netherlands RCT 33/53 30/43 52 ± 15 58 ± 16 CE 12 weeks 40MIN Predialysis SDS
Cheema etal. (37)New Ze aland RCT 17/24 17/25 60.0 ± 15.3 65.0 ± 12.9 RT 12 weeks / Intradialytic GDS
Levendoğlu etal. (38)Tur ke y nRCT 8/14 / 33.1 ± 13.1 / AE 12 weeks 90MIN non-
intradialytic
BDI
AE, aerobic exercise; CE, combined exercise; RT, resistance training; BDI, Beck Depression Inventory; Zung, the self-rating depression scale developed by Zung; HADS, Hospital Anxiety and Depressive Depression Scale; CES-D, Center for Epidemiological Studies
Depression; GDS, Geriatric Depression Scale; SDS, e 20-item Self-rating Depression Scale; GHQ-28, general health questionnaire-28; MAACL, Multiple Aect Adjective Checklist; /, unclear information.

Yu et al. 10.3389/fpsyt.2023.1321413
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(30), Spain (n= 1) (31), Poland (n= 1) (32), Iran (n= 2) (33, 34), Korea
(n= 1) (35), Netherlands (n= 2) (36), New Zealand (n= 1) (37) and
Turkey (n= 1) (38). Sixteen studies were randomized controlled trials,
and 6 studies were quasi-experimental trials.
Of the 22 studies, 11 involved intradialytic exercises, 11 examined
non-intradialytic exercises, and four explored pre-dialytic exercises. All
interventions were delivered on a regular basis, with the intervention
duration ranging from 1 month to 12 months. e majority of exercise
interventions consisted of combining 2 or 3 types of training (n= 6); the
remaining studies primarily focused on aerobic exercise (n = 9) and
resistance exercise (n= 1). In addition, exercise frequency was largely 3
times a week (n = 14), with two studies employing a twice-weekly
regimen. Single exercise duration ranged from 20 min to 90 min. e
intensity of exercise was typically moderate, with parameters such as
55 ~ 70% of the peak power or a rating of perceived exertion on the Borg
scale ranging between 11 ~ 15.
3.3 Assessment of risks of bias
e risk of bias was principally high or uncertain due to
incomplete descriptions of the methodology.
Out of 7 RCT checklist items, every study reported the use of
randomization; notwithstanding, merely 7 (43.75%) studies provided
details on the generation of random sequencing, and 2 studies
demonstrated proper allocation concealment. Considering that
blinding both participants and investigators in an exercise intervention
is challenging, only 3 studies blinded participants, and 2 studies
employed blinding for outcome assessment. Most trials (87.5%)
reported attrition. All 16 studies had complete data (Figure 2;
Supplementary Table 2).
Out of 9 checklist items for the 6 quasi-experimental studies, a
control group was established in 3 of the 6 studies. For the remaining
8 checklist items, the answers were all “yes” (Table2).
FIGURE2
Risk of bias summary for the included studies. The methodological quality of included studies was assessed using the Cochrane Handbook for
Systematic Reviews of Interventions, considering 7 aspects, namely random generation, allocation concealment, blinding of participants and outcome
assessment, incomplete outcome data, selective reporting, and other biases.

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TABLE2 Quality assessment of quasi-experimental studies using the Joanna Briggs Institute (JBI) Appraisal Checklist.
Study 1. Is it
clear in
the study
what is
the
‘cause’
and what
is the
‘eect’
2. Were the
participants
included in any
comparisons
similar?
3. Were the
participants
included in any
comparisons
receiving similar
treatment/care,
other than the
exposure or
intervention of
interest?
4. Was
there a
control
group?
5. Were there
multiple
measurements of
the outcome both
pre and post the
intervention/
exposure?
6. Was follow
up complete
and if not,
were
dierences
between
groups in
terms of their
follow up
adequately
described and
analyzed?
7. Were the
outcomes of
participants
included in any
comparisons
measured in the
same way?
8. Were
outcomes
measured in
a reliable
way?
9. Was
appropriate
statistical
analysis used?
Levendoğlu
2004 yes yes yes no yes yes yes yes yes
Rhee 2019 yes yes yes no yes yes yes yes yes
Zhou 2023 yes yes yes no yes yes yes yes yes
Zhou 2020 yes yes yes yes yes yes yes yes yes
Carney 1987 yes yes yes yes yes yes yes yes yes
Rezaei 2015 yes yes yes yes yes yes yes yes yes
3.4 Eect of exercise on depression in HD
patients
Total eect on depression: Among the 22 studies, the results
indicated that the intervention group had a 0.61 lower risk of
experiencing depression compared with the comparison group (SMD,
−0.61; 95% CI, −0.73 to −0.50; Figure3) e analysis revealed high
heterogeneity among the 22 studies (Tau2= 0.15, df= 22; I2= 63.38%;
Z = 10.13; p < 0.001). Overall, interventions in HD patients
signicantly decreased depression levels. Of note, sensitivity analysis
yielded similar results even when each study was removed one by one.
(Supplementary Figure 1).
Exercise training location: A total of 11 studies used
intradialytic exercise interventions, and 11 studies used
non-intradialytic exercise interventions. Both intradialytic
exercise and non-intradialytic exercise intervention decreased the
level of depression (SMD −0.80, 95%CI −1.10 to −0.49; SMD
−0.67, 95%CI −0.98 to −0.37; respectively); nevertheless,
heterogeneity was identified to be high (Tau
2
 = 0.17, df = 11,
I2= 63.40%, Z= −5.17, p< 0.001; Tau2= 0.15, df= 10, I2= 64.45%,
Z = −4.31, p < 0.001; respectively). Thus, the random effects
model was adopted (Figure4).
Exercise training types: e data revealed that exercise
interventions yielded a decrease in the depression level of all four
subgroups, with aerobic exercise displaying superior outcomes (SMD
−0.93, 95%CI −1.32 to −0.55). Nevertheless, heterogeneity was high
in the combined exercise group (Tau
2
 = 0.25, df = 6; I
2
 = 76.07%,
Z = −3.79, p< 0.001), but all 7 studies had a total SMD < 0, and the 95%
CI for SMD did not cross the equivalence line, showing a signicant
and positive eect. e SMD of a study administering resistance
exercise intervention was −0.40, but the 95% CI crossed the
equivalence line; hence, the result was not statistically signicant
(Figure5).
Exercise training duration: e eect of intradialytic exercise on
depressive symptoms exhibited a U-shape pattern, improving with
prolonged follow-up, with the optimal eect observed aer more than
6 months (SMD −0.81, 95%CI −1.26 to −0.36; SMD −0.67, 95%CI
−1.17 to −0.17; SMD −0.92, 95%CI −1.67 to −0.17; respectively).
Given that subgroup analysis comparing durations <3 months
and > 6 months revealing high heterogeneity (Tau
2
 = 0.22, df = 5,
I
2
 = 74.41%, Z = −3.53, p < 0.001; Tau
2
 = 0.34, df = 2, I
2
 = 76.64%,
Z= −2.39, p< 0.001; respectively), the random eects model was
applied (Figure6).
Single exercise training duration: The results of the subgroup
analysis demonstrated that all five subgroups with varying single
exercise training durations resulted in a decrease in the depression
levels of HD patients. Among them, the optimal single duration
of intradialytic exercise was more than 60 min (SMD −1.47,
95%CI −1.87 to −1.06). There was a high heterogeneity in the
group of less than 30 min (Tau
2
 = 0.16, df = 2, I
2
 = 62.72%,
Z = −2.52, p = 0.01), and thus the random effect model was
adopted (Figure7).
3.5 Publication bias
e funnel plots for all studies are depicted in Figure 8. No
evidence of publication bias was identied.

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4 Discussion
is review and meta-analysis incorporated data from 1,059 HD
patients and validated the benets of intradialytic exercise to reduce
the depression level of patients. is is consistent with the ndings of
previous studies that evinced that exercise training exerts a positive
eect on depressive symptoms in HD patients (39). In this large-scale
meta-analysis, in addition to calculating the total eect size of exercise
training on depression levels of HD patients, the impact of dierent
exercise parameters, including exercise location, exercise type, total
exercise duration, and single exercise duration, was also assessed.
e location of exercise in HD treatment is a key factor aecting
the improvement of depression in HD patients. Our meta-analysis
showed that intradialytic exercise was better than non-intradialytic
exercise in reducing depression levels in patients. Indeed,
intradialytic exercise has been shown to improve safety and peak
oxygen consumption, hemoglobin levels, and the physical
component of the quality of life (40). It is typically supervised and
guided by medical sta to enhance patient compliance and clinical
outcomes (41). Moreover, intradialytic exercise is an eective
method for utilizing the available time during hemodialysis in
various countries. However, intradialytic exercise requires additional
investments in equipment (such as bicycles) and increased attention
from medical sta. Identifying the optimal balance between cost and
cost-eectiveness warrants further exploration in future multi-
center, large-scale clinical trials comparing intradialytic exercise
with non-intradialytic exercise. Our study comprehensively included
studies from various countries, including ve from developed
countries (United States, Greece, Japan, and South Korea) and two
from developing countries (China). is inclusiveness partially
compensates for the lack of standards and geographical dierences
that may result in deviations.
Regarding exercise type, comparisons between intradialytic
aerobic exercise, intradialytic resistance exercise, and intradialytic
combined exercise uncovered that aerobic exercise was superior
in reducing depression levels compared to combined exercise and
resistance exercise. A recent review pointed out that aerobic
exercise could effectively enhance the cardiopulmonary function
of patients with chronic kidney disease (42). The positive
emotions and the well-being of patients with depression could
be reinforced by good physical function (43), which is in
agreement with our research results. This finding also signals that
FIGURE3
Forest plot of the eect of exercise on depression in HD patients. CI, confidence intervals.

Yu et al. 10.3389/fpsyt.2023.1321413
Frontiers in Psychiatry 08 frontiersin.org
promoting intradialytic aerobic exercise could bring additional
benefits to hemodialysis patients. In addition, studies have shown
that simple resistance exercise is also effective in reducing the
level of depression in patients. However, only one study in the
subgroup of resistance exercise analysis met the inclusion criteria
for our meta-analysis, and thus, the conclusions should
beinterpreted with caution.
e results of our analysis showed that the eectiveness of
intradialytic exercise in reducing depression levels decreased
between 3 and 6 months but subsequently became most signicant
aer more than 6 months. is is inconsistent with the conclusions
of previous studies that found that exercise interventions reduced
depression in patients, but the eectiveness of exercise decreased
over time (44). is discrepancy may beascribed to the following
reasons: patient compliance may uctuate during the interventions.
A prior investigation described that as the intervention duration
increases, the exercise compliance of patients decreases (45).
Notwithstanding, the compliance rate was consistently high during
HD, owing to the supervision of the nursing sta. Secondly, given
that participants were not blinded to exercise training and
participants expected improvement in symptoms, the expected eect
may wane over longer periods of time aer experiencing short-term
improvements. Although the eect of exercise on reducing
depression levels varies, it remains eective overall. us, long-term
exercise is recommended.
Furthermore, the duration of a single exercise session is also a
crucial indicator correlated with the eectiveness of exercise (46). e
duration of exercise ranged from 20 to 90 min in the included studies.
Our subgroup analysis exposed that the duration of exercise in all
subgroups signicantly lowered the depression level in hemodialysis
patients, with intradialytic exercise durations exceeding 60 min being
the most eective. Paul T. Williams (47) conducted a study on the
dose–response relationship between physical activity and mortality
and highlighted the signicant health benets associated with
exceeding the current exercise recommendations for optimal health
(≥750 MET minutes per week or ≥ 1.8 MET-hours/d) as opposed to
meeting them (450 to 750 MET minutes per week). erefore,
weadvocate for a duration of exercise exceeding 60 min.
FIGURE4
Forest plot of the eect of dierent exercise types on depression in HD patients. CI, confidence intervals.

Yu et al. 10.3389/fpsyt.2023.1321413
Frontiers in Psychiatry 09 frontiersin.org
FIGURE6
Forest plot of the eect of dierent total exercise duration on depression in HD patients. CI, confidence intervals.
FIGURE5
Forest plot of the eect of dierent exercise locations on depression in HD patients. CI, confidence intervals.

Yu et al. 10.3389/fpsyt.2023.1321413
Frontiers in Psychiatry 10 frontiersin.org
5 Study limitations
e current analysis has some limitations that merit
acknowledgment. To begin, the number of studies included in each
category of the exercise training group was limited. Nevertheless,
publication bias assessment and sensitivity analysis showed that our
results are credible. Secondly, the majority of trials on exercise
interventions in patients with ESRD undergoing HD were excluded
from this study during the screening phase on account that they did
not fulll the predened inclusion criteria. is underscores the
need for future RCTs to enable high-quality comparisons in order to
establish the eects of exercise interventions in this patient
population. Lastly, there is a paucity of eligible studies with long-
term intervention durations, especially those exceeding 6 months.
erefore, the eects of long-term exercise interventions necessitate
further investigation.
6 Conclusion
is systematic review determined that exercise training can reduce
depression levels in HD patients. Clinical sta can administer extended
intradialytic aerobic exercise training to ESRD patients undergoing HD
and control the duration of individual exercise interventions to facilitate
the recovery of patients from depression. Briey, werecommend that
HD patients with depression perform intradialytic aerobic exercise for
at least 60 min in a single session and continue at least 6 months.
Additionally, the desired exercise intervention team consists of
multidisciplinary sta members, including clinicians, nurses,
physiotherapists and occupational therapists. Nurses play a crucial role
in the eld of exercise prescription by assessing and monitoring patients’
physical and mental health status, collaborating with physiotherapists
and occupational therapists, ensuring patient safety during exercise
sessions, coordinating various aspects of patient care, providing
education to patients on the importance of exercise and encouraging
patients to participate in exercise actively. Cooperation among nurses,
physiotherapists and occupational therapists helps to ensure that
patients receive the best possible treatment and speed up the recovery
FIGURE7
Forest plot of the eect of dierent single exercise durations on depression in HD patients. CI, confidence intervals.
FIGURE8
Funnel plot assessing publication bias. Data points represent
individual studies. The y-axis represents the measurement of study
precision (plotted as the standard error of eect size), while the
x-axis represents the Std dierence in means for each study. Dashed
triangular lines represent the region in which 95% of studies are
expected to fall in the absence of bias and heterogeneity.

Yu et al. 10.3389/fpsyt.2023.1321413
Frontiers in Psychiatry 11 frontiersin.org
process. e favorable outcomes resulting from exercise intervention on
depression, physical ability, and quality of life in dialysis patients may
play a positive role in elevating survival rates and concurrently
decreasing hospitalization rates (48). is hypothesis necessitates
further validation in future clinical trials. Furthermore, for the
establishment of a patient exercise system, future studies should
prioritize high-quality evidence and diversify available strategies to
tailor to the specic needs of individual patients.
Data availability statement
e raw data supporting the conclusions of this article will
bemade available by the authors, without undue reservation.
Author contributions
HY: Writing – original dra, Data curation, Methodology,
Conceptualization. MH: Writing – review & editing, Formal analysis,
Soware. YT: Data curation, Writing – review & editing. SL: Data
curation, Writing – review & editing. JW: Writing – review & editing,
Data curation. PL: Formal analysis, Writing – review & editing. HL:
Resources, Supervision, Writing – review & editing. CN:
Conceptualization, Funding acquisition, Resources, Supervision,
Writing – review & editing.
Funding
e author(s) declare nancial support was received for the
research, authorship, and/or publication of this article. is study was
supported by the National Key Research and Development Program
of China (2017YFC0907800); the grants from Shaanxi Provincial Key
Research and Development Program General Project (2021SF-278).
Acknowledgments
We thank Home for Researchers editorial team (www.home-for-
researchers.com) for language editing service.
Conflict of interest
e authors declare that the research was conducted in the
absence of any commercial or nancial relationships that could
beconstrued as a potential conict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their aliated organizations,
or those of the publisher, the editors and the reviewers. Any product
that may be evaluated in this article, or claim that may be made by its
manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
e Supplementary material for this article can befound online
at: https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1321413/
full#supplementary-material
References
1. Robinson BM, Akizawa T, Jager KJ, Kerr PG, Saran R, Pisoni RL. Factors
aecting outcomes in patients reaching end-stage kidney disease worldwide:
dierences in access to renal replacement therapy, modality use, and haemodialysis
practices. Lancet (London, England). (2016) 388:294–306. doi: 10.1016/
S0140-6736(16)30448-2
2. urlow JS, Joshi M, Yan G, Norris KC, Agodoa LY, Yuan CM, et al. Global
epidemiology of end-stage kidney disease and disparities in kidney replacement
therapy. Am J Nephrol. (2021) 52:98–107. doi: 10.1159/000514550
3. Pallone JM, Santos D, Oliveira Dias AL, Ferreira LGS, Costa da Silva C, Orlandi
FS. Loneliness level and its associated factors in patients with hemodialysis. Clin Nurs
Res. (2022) 31:1164–71. doi: 10.1177/10547738211061447
4. Albuhayri AH, Alshaman AR, Alanazi MN, Aljuaid RM, Albalawi RIM, Albalawi
SS, et al. A cross-sectional study on assessing depression among hemodialysis
patients. J Adv Pharm Technol Res. (2022) 13:266–70. doi: 10.4103/japtr.japtr_322_22
5. Korkut S. Evaluation of psychopathological symptoms, death anxiety,
coronavirus anxiety, suicide risk, and associated risk factors among hemodialysis
patients in the COVID-19 pandemic. erapeutic apheresis and dialysis: ocial peer-
reviewed journal of the International Society for Apheresis, the Japanese Society for
Apheresis, Japanese Society for Dialysis erapy. (2022) 26:941–9. doi:
10.1111/1744-9987.13905
6. Khoury R, Ghantous Z, Ibrahim R, Ghossoub E, Madaghjian P, Karam E, et al.
Anxiety, depression and post-traumatic stress disorder in patients on hemodialysis
in the setting of the pandemic, ination, and the Beirut blast: a cross-sectional study.
BMC Psychiatry. (2023) 23:284. doi: 10.1186/s12888-023-04798-6
7. Huang CW, Wee PH, Low LL, Koong YLA, Htay H, Fan Q, et al. Prevalence and
risk factors for elevated anxiety symptoms and anxiety disorders in chronic kidney
disease: a systematic review and meta-analysis. Gen Hosp Psychiatry. (2021) 69:27–40.
doi: 10.1016/j.genhosppsych.2020.12.003
8. Palmer S, Oppler SH, Graham ML. Behavioral management as a coping strategy
for managing stressors in Primates: the inuence of temperament and species.
Biology. (2022) 11:423. doi: 10.3390/biology11030423
9. Lee M, Choi H, Shin J, Suh HS. e eects of adding art therapy to ongoing
antidepressant treatment in moderate-to-severe major depressive disorder: a
randomized controlled study. Int J Environ Res Public Health. (2022) 20:91. doi:
10.3390/ijerph20010091
10. Ashby D, Borman N, Burton J, Corbett R, Davenport A, Farrington K, et al. Renal
association clinical practice guideline on Haemodialysis. BMC Nephrol. (2019) 20:379.
doi: 10.1186/s12882-019-1527-3
11. National Kidney Foundation. KDOQI clinical practice guideline for hemodialysis
adequacy: 2015 update. American J Kidney Dis: Ocial J National Kidney Foundation.
(2015) 66:884–930. doi: 10.1053/j.ajkd.2015.07.015
12. Sheshadri A, Kittiskulnam P, Lazar AA, Johansen KL. A walking intervention to
increase weekly steps in Dialysis patients: a pilot randomized controlled trial. American
J Kidney Dis: Ocial J National Kidney Foundation. (2020) 75:488–96. doi: 10.1053/j.
ajkd.2019.07.026
13. Clarkson MJ, Bennett PN, Fraser SF, Warmington SA. Exercise interventions for
improving objective physical function in patients with end-stage kidney disease on
dialysis: a systematic review and meta-analysis. Am J Physiol Renal Physiol. (2019)
316:F856–72. doi: 10.1152/ajprenal.00317.2018
14. Liberati A, Altman DG, Tetzla J, Mulrow C, Gotzsche PC, Ioannidis JPA, et al.
e PRISMA statement for reporting systematic reviews and meta-analyses of studies
that evaluate heal thcare interventions: explanation and elaboration. BMJ. (2009)
339:b2700. doi: 10.1136/bmj.b2700
15. Higgins JPT, omas J, Cumpston M, Li T, Page MJ, Welch V. Cochrane handbook
for systematic reviews of interventions version 6.3 (updated February 2022): Cochrane;
(2022). Available from: www.training.cochrane.org/handbook.

Yu et al. 10.3389/fpsyt.2023.1321413
Frontiers in Psychiatry 12 frontiersin.org
16. Aromataris E, Munn Z. JBI manual for evidence synthesis: JBI; (2020). Available
from: https://synthesismanual.jbi.global.
17. Liu YM, Chung YC, Chang JS, Yeh ML. Eects of aerobic exercise during
hemodialysis on physical functional performance and depression. Biol Res Nurs. (2015)
17:214–21. doi: 10.1177/1099800414539548
18. Tang Q, Yang B, Fan F, Li P, Yang L, Guo Y. Eects of individualized exercise
program on physical function, psychological dimensions, and health-related quality of
life in patients with chronic kidney disease: a randomized controlled trial in China. Int
J Nurs Pract. (2017) 23:e12519. doi: 10.1111/ijn.12519
19. Lin CH, Hsu YJ, Hsu PH, Lee YL, Lin CH, Lee MS, et al. Eects of intradialytic
exercise on dialytic parameters, health-related quality of life, and depression status in
hemodialysis patients: a randomized controlled trial. Int J Environ Res Public Health.
(2021) 18:9205. doi: 10.3390/ijerph18179205
20. Zhou L, Shi D, Zhang L, Wang Q, Chen L, Chen H. Does intradialytic group
exercise Programme inuence patient-reported outcomes, laboratory parameters, and
anthropometric parameters in maintenance hemodialysis patients? A single-group
repeated-measures trial. Patient Prefer Adherence. (2023) 17:491–501. doi: 10.2147/PPA.
S400005
21. Carney RM, McKevitt PM, Goldberg AP, Hagberg J, Delmez JA, Harter HR.
Psychological eects of exercise training in hemodialysis patients. Nephron. (1983)
33:179–81. doi: 10.1159/000182938
22. Carney RM, Templeton B, Hong BA, Harter HR, Hagberg JM, Schechtman KB,
et al. Exercise training reduces depression and increases the performance of pleasant
activities in hemodialysis patients. Nephron. (1987) 47:194–8. doi:
10.1159/000184490
23. Zhou H, Al-Ali F, Kang GE, Hamad AI, Ibrahim RA, Talal TK, et al. Application
of wearables to facilitate virtually supervised intradialytic exercise for reducing
depression symptoms. Sensors (Basel, Switzerland). (2020) 20:1571. doi: 10.3390/
s20061571
24. Kouidi E, Iacovides A, Iordanidis P, Vassiliou S, Deligiannis A, Ierodiakonou C,
et al. Exercise renal rehabilitation program: psychosocial eects. Nephron. (1997)
77:152–8. doi: 10.1159/000190266
25. Sakkas GK, Hadjigeorgiou GM, Karatzaferi C, Maridaki MD, Giannaki CD,
Mertens PR, et al. Intradialytic aerobic exercise training ameliorates symptoms of
restless legs syndrome and improves functional capacity in patients on hemodialysis: a
pilot study. ASAIO J (American Society for Articial Internal Organs: 1992). (2008)
54:185–90. doi: 10.1097/MAT.0b013e3181641b07
26. Ouzouni S, Kouidi E, Sioulis A, Grekas D, Deligiannis A. Eects of intradialytic
exercise training on health-related quality of life indices in haemodialysis patients. Clin
Rehabil. (2009) 23:53–63. doi: 10.1177/0269215508096760
27. Kouidi E, Karagiannis V, Grekas D, Iakovides A, Kaprinis G, Tourkantonis A, et al.
Depression, heart rate variability, and exercise training in dialysis patients. European
journal of cardiovascular prevention and rehabilitation: ocial journal of the European
Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac
Rehabilitation and Exercise Physiology. (2010) 17:160–7. doi: 10.1097/
HJR.0b013e32833188c4
28. Giannaki CD, Sakkas GK, Karatzaferi C, Hadjigeorgiou GM, Lavdas E, Kyriakides
T, et al. Eect of exercise training and dopamine agonists in patients with uremic restless
legs syndrome: a six-month randomized, partially double-blind, placebo-controlled
comparative study. BMC Nephrol. (2013) 14:194. doi: 10.1186/1471-2369-14-194
29. Yabe H, Kono K, Yamaguchi T, Yamada N, Ishikawa Y, Yamaguchi Y, et al. Eect
of intradialytic exercise on geriatric issues in older patients undergoing hemodialysis: a
single-center non-randomized controlled study. Int Urol Nephrol. (2022) 54:2939–48.
doi: 10.1007/s11255-022-03205-5
30. Deus LA, Corrêa HL, Neves RVP, Reis AL, Honorato FS, Silva VL, et al. Are
resistance training-induced BDNF in hemodialysis patients associated with depressive
symptoms, quality of life, antioxidant capacity, and muscle strength? An insight for the
muscle-brain-renal Axis. Int J Environ Res Public Health. (2021) 18:11299. doi: 10.3390/
ijerph182111299
31. Ortega-Pérez de Villar L, Martínez-Olmos FJ, Pérez-Domínguez FB, Benavent-
Caballer V, Montañez-Aguilera FJ, Mercer T, et al. Comparison of intradialytic versus
home-based exercise programs on physical functioning, physical activity level,
adherence, and health-related quality of life: pilot study. Sci Rep. (2020) 10:8302. doi:
10.1038/s41598-020-64372-y
32. Dziubek W, Kowalska J, Kusztal M, Rogowski Ł, Gołębiowski T, Nikifur M, et al.
e level of anxiety and depression in Dialysis patients undertaking regular physical
exercise training- a preliminary study. Kidney Blood Press Res. (2016) 41:86–98. doi:
10.1159/000368548
33. Rezaei J, Abdi A, Rezaei M, Heydarnezhadian J, Jalali R. Eect of regular exercise
program on depression in hemodialysis patients. Int Scholarly Res Notices. (2015)
2015:182030:1–6. doi: 10.1155/2015/182030
34. Rahimimoghadam Z, Rahemi Z, Mirbagher Ajorpaz N, Sadat Z. Eects of Pilates
exercise on general health of hemodialysis patients. J Bodyw Mov er. (2017) 21:86–92.
doi: 10.1016/j.jbmt.2016.05.012
35. Rhee SY, Song JK, Hong SC, Choi JW, Jeon HJ, Shin DH, et al. Intradialytic exercise
improves physical function and reduces intradialytic hypotension and depression in
hemodialysis patients. Korean J Intern Med. (2019) 34:588–98. doi: 10.3904/
kjim.2017.020
36. van Vilsteren MC, de Greef MH, Huisman RM. e eects of a low-to-moderate
intensity pre-conditioning exercise programme linked with exercise counselling for
sedentary haemodialysis patients in the Netherlands: results of a randomized clinical
trial. Nephrology, dialysis, transplantation: ocial publication of the European Dialysis
and Transplant Association- European Renal Association. (2005) 20:141–6. doi: 10.1093/
ndt/g560
37. Cheema B, Abas H, Smith B, O'Sullivan A, Chan M, Patwardhan A, et al.
Progressive exercise for anabolism in kidney disease (PEAK): a randomized, controlled
trial of resistance training during hemodialysis. J American Society of Nephrol: JASN.
(2007) 18:1594–601. doi: 10.1681/ASN.2006121329
38. Levendoğlu F, Altintepe L, Okudan N, Uğurlu H, Gökbel H, Tonbul Z, et al. A
twelve week exercise program improves the psychological status, quality of life and work
capacity in hemodialysis patients. J Nephrol. (2004) 17:826–32.
39. Amiri S. Exercise training and depression and anxiety in musculoskeletal pain
patients: a meta-analysis of randomized control trials. Neuropsychiatrie:
Klinik, Diagnostik, Therapie und Rehabilitation: Organ der Gesellschaft
Osterreichischer Nervenarzte und Psychiater. (2023) 37:88–100. doi: 10.1007/
s40211-022-00431-2
40. Chung YC, Yeh ML, Liu YM. Eects of intradialytic exercise on the physical
function, depression and quality of life for haemodialysis patients: a systematic review
and meta-analysis of randomised controlled trials. J Clin Nurs. (2017) 26:1801–13. doi:
10.1111/jocn.13514
41. Andrade FP, Rezende PS, Ferreira TS, Borba GC, Müller AM, Rovedder PME.
Eects of intradialytic exercise on cardiopulmonary capacity in chronic kidney disease:
systematic review and meta-analysis of randomized clinical trials. Sci Rep. (2019)
9:18470. doi: 10.1038/s41598-019-54953-x
42. Afsar B, Siriopol D, Aslan G, Eren OC, Dagel T, Kilic U, et al. e impact of
exercise on physical function, cardiovascular outcomes and quality of life in chronic
kidney disease patients: a systematic review. Int Urol Nephrol. (2018) 50:885–904. doi:
10.1007/s11255-018-1790-4
43. Zhang Q, Yang Y, Zhang GL. Inuence of life meaning on subjective well-being of
older people: serial multiple mediation of exercise identication and amount of exercise.
Front Public Health. (2021) 9:515484. doi: 10.3389/fpubh.2021.515484
44. Singh B, Olds T, Curtis R, Dumuid D, Virgara R, Watson A, et al. Eectiveness of
physical activity interventions for improving depression, anxiety and distress: an
overview of systematic reviews. Br J Sports Med. (2023) 57:1203–9. doi: 10.1136/
bjsports-2022-106195
45. Collado-Mateo D, Lavín-Pérez AM, Peñacoba C, Del Coso J, Leyton-Román M,
Luque-Casado A, et al. Key factors associated with adherence to physical exercise in
patients with chronic diseases and older adults. Umbrella Rev Int J Environ Res Public
Heal. (2021) 18:2023. doi: 10.3390/ijerph18042023
46. Cheng A, Zhao Z, Liu H, Yang J, Luo J. e physiological mechanism and eect of
resistance exercise on cognitive function in the elderly people. Front Public Health.
(2022) 10:1013734. doi: 10.3389/fpubh.2022.1013734
47. Williams PT. Dose-response relationship of physical activity to premature and total
all-cause and cardiovascular disease mortality in walkers. PloS One. (2013) 8:e78777.
doi: 10.1371/journal.pone.0078777
48. Hoshino J. Renal rehabilitation: exercise intervention and nutritional support in
Dialysis patients. Nutrients. (2021) 13:1444. doi: 10.3390/nu13051444