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Evidence based practice
Original research
Prevalence of post-dialysis fatigue: a systematic review and meta-analysis
  1. Junkai Dou1,
  2. Huan Liu2,
  3. Yuan Ma3,
  4. Ying-ying Wu3,
  5. Xiu-bin Tao4
  1. 1School of Nursing, Anhui University of Traditional Chinese Medicine–East Campus, Hefei, China
  2. 2Department of Nephrology, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
  3. 3School of Nursing, Wannan Medical College, Wuhu, China
  4. 4Department of Nursing, The First Affiliated Hospital of Wannan Medical College, Wuhu, China
  1. Correspondence to Professor Xiu-bin Tao; yjstaoxiubin{at}126.com

Abstract

Objectives The purpose of this study was to synthesise data on the prevalence of post-dialysis fatigue (PDF) among haemodialysis (HD) patients.

Design Systematic review and meta-analysis.

Data sources China National Knowledge Infrastructure, Wanfang, Chinese Biological Medical Database, PubMed, EMBASE and Web of Science were searched from their inception to 1 April 2022.

Eligibility criteria We selected patients who must receive HD treatment for at least 3 months. Cross-sectional or cohort studies published in Chinese or English were eligible for inclusion. The main search terms used in the abstract were: “renal dialysis”, “hemodialysis” and “post-dialysis”, in combination with the word “fatigue”.

Data extraction and synthesis Two investigators independently performed data extraction and quality assessment. Data were pooled to estimate the overall prevalence of PDF among HD patients using the random-effects model. Cochran’s Q and I2 statistics were adopted to evaluate heterogeneity.

Result A total of 12 studies were included, with 2152 HD patients, of which 1215 were defined as having PDF. The overall prevalence of PDF in HD patients was 61.0% (95% CI: 53.6% to 68.3%, p<0.001, I2=90.0%). Subgroup analysis failed to explain the source of heterogeneity, but univariable meta-regression showed that a mean age of ≥50 years might be the source of heterogeneity. Egger’s test revealed no publication bias among the studies (p=0.144).

Conclusions PDF is highly prevalent among HD patients.

  • chronic renal failure
  • dialysis
  • end stage renal failure

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2022-064174

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    STRENGTHS AND LIMITATIONS OF THIS STUDY

    • We conducted a comprehensive search strategy to screen all eligible studies.

    • Subgroup analysis and univariable meta-regression were used to explore the source of heterogeneity.

    • We included only a limited number of high-quality articles.

    • Studies from America, Europe and other regions were lacking, challenging the representativeness of the included studies.

    • Subgroup analysis could not examine some critical factors such as dialysis flow rates, length of time on dialysis and dialysis vintage.

    Introduction

    Regular hemodialysis (HD) serves as the predominant treatment for end-stage renal disease.1 The Global Burden of Disease, Injuries and Risk Factors Study in 2017 estimated that approximately 3 million HD patients existed worldwide, with projections indicating this number will rise to 5.4 million by 2030.2 It is widely acknowledged that advancements in HD technology have substantially increased the life expectancy of HD patients3 and improved their overall quality of life. Nevertheless, common complications such as intradialytic hypertension,4 fatigue,5 frailty6 and sarcopenia7 persist as inevitable challenges.

    In recent years, post-dialysis fatigue (PDF), an intermittent fatigue experienced after dialysis sessions, has been frequently described as a feeling of being worn out, drained or exhausted.8 Some studies have also defined it as feeling tired and in need of rest or sleep.9 However, no specific recovery time points for patients with PDF have been identified through rest or sleep. Given that fatigue is an inherently subjective experience, there are currently no optimal quantitative measures to evaluate PDF and gauge its severity in clinical guidelines. Moreover, the underlying mechanisms of PDF remain to be elucidated, and advancements in HD technology do not seem to have reduced the prevalence of PDF among HD patients. Additionally, higher rates of fatigue (not specifically PDF) are often associated with sleep quality, depression, anxiety and poor quality of life,10 11 potentially increasing the risk of initial hospitalisation and mortality among HD patients.12

    At present, the prevalence of PDF varies between 50.5% and 85% across different countries.13 No systematic reviews or meta-analyses have been conducted on PDF prevalence among HD patients thus far. In light of the considerable variability in reported PDF prevalence, this study seeks to determine the pooled prevalence of PDF and explore the association between study characteristics and PDF prevalence in HD patients through univariable meta-regression.

    Methods

    This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines.14

    Data sources and search strategy

    We conducted a search of six electronic databases (China National Knowledge Infrastructure, Wanfang, Chinese Biological Medical Database, EMBASE, PubMed and Web of Science) up until 1 April 2022. The search terms and Medical Subject Headings included “fatigue” AND “renal dialysis” OR “dialysis” OR “hemodialysis” OR “maintenance dialysis” OR “post-dialysis”. Additionally, we handsearched the reference lists of relevant literature for additional articles. The detailed search strategy is provided in online supplemental file 1.

    Study selection

    Articles were qualified for inclusion if they met the following criteria: (1) observational studies, encompassing cohort and cross-sectional studies; (2) participants aged 18 years or older; and (3) dialysis duration exceeding 3 months. Studies published in Chinese or English were eligible for inclusion.

    Studies were excluded if they fulfilled any of the following criteria: (1) reviews, letters, conference abstracts or comments; (2) literature lacking original data and (3) studies containing duplicated data.

    Data extraction

    Two reviewers (Y-yW and YM) independently extracted data from eligible studies and cross-checked their findings. The extracted data encompassed the following items: (1) first author’s name, (2) publication year, (3) country, (4) study design, (5) measurement, (6) mean age, (7) sample size and (8) prevalence.

    Quality assessment

    The Newcastle–Ottawa Scale (NOS)15 was employed to assess the risk of bias and study quality in non-randomised studies, covering three main domains: sample selection, comparability and outcome assessment. The NOS scoring system ranges from 0 to 9 points, with the total points determining the study’s quality. Scores of 0–4, 5–6 and 7–9 points indicate high, moderate and low-risk bias, respectively. The Agency for Healthcare Research and Quality (AHRQ)16 was used to evaluate the risk of bias in cross-sectional studies. This tool consists of 11-item questions, where ‘no’ or ‘unclear’ is awarded 0 point and ‘yes’ receives 1 point. Studies with scores of 8–11 are considered high quality, 4–7 are moderate quality and 0–3 are low quality.

    Data analysis

    All analyses were conducted using Stata V.14.0 software. A random-effects model was selected to quantify the prevalence of PDF in HD patients, with the 95% CI calculated using the inverse variance method. The I2 statistic was used to quantify heterogeneity across studies. To investigate heterogeneity and identify differences in PDF prevalence between various groups, subgroup analysis was performed. Funnel plots and Egger’s test were applied to evaluate publication bias. Univariable meta-regression was conducted to examine the relationship between measured covariates and effect size.17 Furthermore, sensitivity analysis was carried out to determine the stability and robustness of the pooled prevalence. In all models, a p value less than 0.05 was deemed statistically significant.

    Patient and public involvement

    None.

    Result

    Search results

    From the initial search, we identified 4466 articles across six electronic databases, with 838 being duplicates. We excluded 3580 citations upon screening abstracts and titles due to the following reasons: 184 were reviews and meta-analyses and 3396 were not relevant to the topic. During the full-text evaluation, we removed 25 articles that did not provide information about the prevalence of PDF in HD patients. We excluded four studies for using the same data and seven studies for not being observational. Finally, we included 12 studies, comprising 2152 patients, in the meta-analysis (figure 1). Based on the AHRQ and NOS assessments, 11 studies8 18–27 were of moderate quality, while only 1 article28 was classified as high quality among the eligible studies.

    Figure 1
    Figure 1

    Preferred Reporting Items for Systematic Reviews and Meta-analyses flow diagram. PDF, post-dialysis fatigue.

    Characteristics of the included studies

    The characteristics of the 12 eligible studies,8 18–28 published between 1996 and 2021, originating from China as well as America and Europe, are presented in online supplemental table 1. Among these studies, eight were conducted in China,18–24 28 while four took place in America and Europe.8 25–27 A single study was a prospective cohort study,28 while the remaining studies were cross-sectional8 18–27 (n=11). The sample sizes varied from 45 to 626, encompassing a total of 2152 patients, out of which 1215 had experienced PDF. Seven studies employed a questionnaire designed by Sklar et al,8 whereas others used various fatigue scales (three used the Revised Piper Scale, one used the Chalder Scale and one used the Functional Assessment of Chronic Illness Threapy-Fatigue (FACIT-F) Scale). Furthermore, the mean age of HD patients ranged from 46.8 years to 69.72 years.

    Pooled prevalence of PDF in HD patients

    The prevalence of PDF in eligible studies ranged from 44.6% to 86.2%. The overall pooled estimate for the prevalence of PDF was 61.0% (1215 out of 2152 participants, 95% CI: 54.0% to 68.0%). When assessing the prevalence of PDF, substantial heterogeneity was observed between studies (I2=90%, p<0.001) (figure 2, forest plot).

    Figure 2
    Figure 2

    Forest plot of prevalence of post-dialysis fatigue among haemodialysis patients. Weights are from random-efforts model.

    Subgroup analysis

    The subgroup analysis could not pinpoint the source of heterogeneity. Furthermore, the subgroup analysis revealed that the pooled prevalence of PDF in HD patients was 57.0% (95% CI: 50.0% to 66.0%) for patients from China and 68.0% (95% CI: 52.0% to 83.0%) for patients from America and Europe. Studies with a mean age of ≥50 years had a pooled PDF prevalence of 64.0% (95% CI: 58.0% to 71.0%), while those with a mean age of <50 years reported a prevalence of 45.0% (95% CI: 41.0% to 49.0%). The pooled prevalence of PDF was 52.0% (95% CI: 44.0% to 60.0%) for articles published in 2021, 64.0% (95% CI: 48.0% to 80.0%) for those in 2020 and 64.0% (95% CI: 53.0% to 76.0%) for those published before 2019. Using questionnaire assessments yielded a PDF prevalence of 65.0% (95% CI: 57.0% to 73.0%), 63.0% (95% CI: 48.0% to 78.0%) with the Revised Piper Scale, 45.0% (95% CI: 39.0% to 51.0%) with the Chalder Fatigue Scale and 46.0% (95% CI: 39.0% to 52.0%) with the FACIT-F Scale. A sample size larger than 200 was considered a large sample size, and the pooled prevalence of PDF was 57% (95% CI: 45.0% to 59.0%), lower than the 66.0% (95% CI: 57.0% to 75.0%) found in smaller sample sizes (table 1).

    View this table:
    Table 1

    Subgroup analysis

    The univariable meta-regression was conducted on the country, mean age (<50 vs ≥50 years), publication year (2021 vs 2020 vs before 2019), measurement and sample size (<200 vs ≥200) in the subgroups. The results showed that the overall prevalence of PDF among HD patients was higher in studies with a mean age of ≥50 years. Additionally, it revealed that mean age significantly affected model heterogeneity (table 2).

    View this table:
    Table 2

    Univariable meta-regression analysis

    Assessment of publication bias and sensitivity analysis

    Figure 3 displays the funnel plot. The results of Egger’s test (t=1.59, p=0.144) revealed no substantial publication bias. The sensitivity analysis showed minor differences in prevalence after removing each study, indicating the finding’s stability (figure 4 and online supplemental file 2).

    Figure 3
    Figure 3

    Funnel plot.

    Figure 4
    Figure 4

    Sensitivity analysis.

    Discussion

    Clinicians have been aware of fatigue in HD patients for quite some time; however, research on PDF has only recently emerged as an intriguing area of study among HD patients. This is evident from the publication years of the studies included in this review. It is the first systematic review and meta-analysis summarised regarding the prevalence of PDF among HD patients. We identified 12 articles from six databases, involving 2152 HD patients, which provided 12 prevalence estimates. The pooled prevalence of PDF among HD patients was as high as 61.0% (95% CI: 53.6% to 68.3%, I2=90%, p<0.01), consistent with a previous study.29 This indicates that more than 6 in 10 HD patients are suffering from PDF. However, substantial heterogeneity exists between studies, and univariable meta-regression revealed no significant differences, except for mean age.

    Based on our subgroup analysis, we found a higher prevalence of HD patients with a mean age older than 50 years (64.0%) compared with those younger than 50 years (45.0%). It is well-known that physical function declines with age, especially for patients undergoing HD treatment. Previous studies have also indicated that age is strongly related to fatigue,30 31 and according to two recent studies,32 33 physical dysfunction and physical activity among HD patients are associated with fatigue. Considering that the incidence of PDF is linked to age, a higher prevalence rate can be expected in future research involving participants of older age undergoing HD treatment.

    Currently, there is no universally accepted measurement or definition for PDF. Nevertheless, there is a need for more agreed-upon definitions and measuring tools for PDF worldwide. This review included 12 eligible studies, with the most frequently employed measures being questionnaires and the Revised Piper Scale. The prevalence of PDF measured with the Revised Piper Scale (63.0%) closely aligned with that obtained using questionnaires (65.0%). We suggest that the Revised Piper Scale, a multidimensional scale,34 might be more appropriate for evaluating PDF, as fatigue in HD patients spans multiple dimensions such as physical, sensory and cognitive fatigue.35 Furthermore, a prior study has successfully employed the Revised Piper Scale in HD patients, yielding a Cronbach’s alpha coefficient of 0.96.36

    To date, there is no consensus on the prevalence of PDF among HD patients worldwide. The prevalence varies between countries, with a lower prevalence in China (57.0%) compared with America and Europe (68.0%). One possible reason for this discrepancy could be the differences in HD frequency.37 Three times a week HD is the standard treatment in developed countries like America and Europe, while in China, a quarter of HD patients undergo two times a week HD.38 This may lead to a lower dialysis adequacy (Kt/V), potentially increasing the severity of fatigue after dialysis.39 Moreover, ethnicity might be associated with fatigue, as non-white individuals have been reported to exhibit lower fatigue levels compared with their white counterparts.37 Our study also found that the average age of study participants from American and European countries was higher than that of the Chinese population, which may impact the results. In the future, large-scale, multicentre research on PDF should be conducted to further explore the differences in prevalence between various geographical regions.

    Subgroup analyses demonstrated that the prevalence of PDF in smaller sample groups (66.0%) was notably higher than in larger sample groups (57.0%). A smaller sample size may increase the risk of selection and publication bias, resulting in more extreme prevalence estimates.40 Consequently, it is crucial for researchers to carefully consider the optimal sample sizes for their future studies.

    Limitations

    This meta-analysis has several limitations. First, significant heterogeneity exists between studies. Apart from mean age, other factors fail to identify the source of heterogeneity. Second, the limited sample size and study quality may introduce bias to this review. We recommend conducting more high-quality, multicentre and large sample-sized studies for PDF among HD patients. Third, although we systematically searched six databases, including three authoritative Chinese databases, there remains a need for more observational studies about PDF in America, which may affect the overall representation of PDF prevalence worldwide. Finally, crucial factors such as dialysis flow rates, the length of time on dialysis and dialysis vintage could only be obtained from a limited number of studies.

    Conclusions

    In summary, this meta-analysis is the first to calculate the prevalence of PDF among HD patients and analyse its relationship with various covariates. The pooled prevalence was 61.0% (95% CI: 53.6% to 68.3%, I2=90%, p<0.01), and differences were observed among countries, mean age, measurement methods and sample sizes in the incidence of PDF. The high prevalence of PDF in HD patients suggests that clinicians should pay more attention to this issue and promote high-quality studies to explore risk factors for PDF worldwide. Furthermore, based on our results, it is crucial to give special consideration to elderly HD patients.

    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

    Ethics statements

    Patient consent for publication

    Ethics approval

    All analyses were based on previously published studies. As such, no ethical approval was required.

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    Supplementary materials

    Footnotes

    • Contributors JD acted as guarantor for the validity of the study report. XT and JD contributed to the study design, manuscript preparation, data analysis and interpretation. HL, YM, YW and XT carried out the literature search and data extraction. XT, JD and HL reviewed and granted final approval for the manuscript. All authors (JD, XT, HL, YM, YW) approved the final protocol.

    • Funding This study was funded by the Research of Anhui Provincial Department of Education (grant/award number: SK2020ZD34).

    • Competing interests None declared.

    • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.