此外,我們使用 Jada 量表評估了納入研究的質量,該量表包含以下四個條目:隨機序列的生成、隨機化隱藏的方法、盲法的實施,以及數據缺失和納入研究退出評估的原因。
證據整體品質的評估
我們通過 GRADE(推薦分級評估、制定與評價)系統中的 GRADE pro 工具評估了證據的整體質量。根據 GRADE 證據評級系統的特徵,如偏倚風險、不一致性、不精確性、間接性和發表偏倚等,將證據的整體質量分為高、中、低和極低四個等級。若五項指標中有一項被降級,則整體質量視為中等;若有兩項被降級則為低;若觀察到三項或以上降級則為極低。
數據綜合
使用 Review Manager 5.4.1 軟體進行統計分析。納入研究的相關結果指標表均進行統計,單位及測量方法相同,以均數±標準差表示,以均數差為效應量,效應量以 95%置信區間(CI)表示。採用 I²和 P 值評估研究間的異質性大小,當研究間無統計學異質性(I²<50%,P>0.1)時,採用固定效應模型進行 Meta 分析;若研究間存在異質性(I²≥50%),則採用隨機效應模型進行 Meta 分析,並以 Z 檢驗對總效應值進行檢驗,若 P<0.05則認為結果具有統計學意義。進一步分析異質性來源後若仍存在異質性,則採用隨機效應模型合併效應量,並採用敏感性分析檢驗Meta分析結果的穩健性。
Intensity of the intervention and the duration of each exercise session were not stated, and frequency of intervention was 3/week
8 weeks
(1)(5)(6)
2
Studies Country Years Sample Type of intervention Intensity, frequency Intervention duration Outcomes Literature quality score
I C I C
Chan et al. (2019) America 2019 15 RE Usual nursing 70-80% hazard ratio, Borg scale: 12-14 and 2-3/week, and 44 min 12 weeks (1)(2) 3
Zhang et al. (2020) China 2020 43 44 Progressive resistance training Usual nursing Borg scale: 10-13 and 2-3/week, 1-2 h 12 weeks (1)(2) 4
Cheema et al. (2007) Australia 2007 24 25 Resistance Training Usual nursing Borg scale: 15-17, 3/week, no indication of duration of each exercise 12 weeks (2)(6) 5
Song & Sohng (2012) Korea 2012 20 20 Progressive Resistance Training Usual nursing Borg scale 11-15, 3/week, 30 min 12 weeks (1)(7)8 2
Cai et al. (2022) China 2022 44 REs Usual nursing Exercise with heart rate no more than 60-70% of the maximum heart rate, three times a week, 3// week, 45 min 24 weeks (1)(3)(4)(5)(6)(9) 3
Zhu (2022) China 2022 36 35 REs Usual nursing Borg scale: 11-13; the frequency and duration of weekly exercise were not stated 24 weeks (1)(4) 3
" Dai \& Ma
(2021) " China 2020 20 30 REs Usual nursing Borg scale: 11-13, 3/week, 40 min 24 weeks (1)(4)(5)(6)(7)(8)(9) 4
Yan, Zha & Peng (2022) China 2022 47 47 Progressive RE Usual nursing Borg scale: 12-14, 3-4/week, 40-50 min 12 weeks (1)(4)(5) 3
"Tayebi,
Ramezani & Kashef (2018)" Iran 2018 17 17 Resistance training Usual nursing Intensity of the intervention and the duration of each exercise session were not stated, and frequency of intervention was 3/week 8 weeks (1)(5)(6) 2| Studies | Country | Years | Sample | | Type of intervention | | Intensity, frequency | Intervention duration | Outcomes | Literature quality score |
| :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: |
| | | | I | C | I | C | | | | |
| Chan et al. (2019) | America | 2019 | | 15 | RE | Usual nursing | 70-80% hazard ratio, Borg scale: 12-14 and 2-3/week, and 44 min | 12 weeks | (1)(2) | 3 |
| Zhang et al. (2020) | China | 2020 | 43 | 44 | Progressive resistance training | Usual nursing | Borg scale: 10-13 and 2-3/week, 1-2 h | 12 weeks | (1)(2) | 4 |
| Cheema et al. (2007) | Australia | 2007 | 24 | 25 | Resistance Training | Usual nursing | Borg scale: 15-17, 3/week, no indication of duration of each exercise | 12 weeks | (2)(6) | 5 |
| Song & Sohng (2012) | Korea | 2012 | 20 | 20 | Progressive Resistance Training | Usual nursing | Borg scale 11-15, 3/week, 30 min | 12 weeks | (1)(7)8 | 2 |
| Cai et al. (2022) | China | 2022 | | 44 | REs | Usual nursing | Exercise with heart rate no more than $60-70 \%$ of the maximum heart rate, three times a week, $3 /$ week, 45 min | 24 weeks | (1)(3)(4)(5)(6)(9) | 3 |
| Zhu (2022) | China | 2022 | 36 | 35 | REs | Usual nursing | Borg scale: 11-13; the frequency and duration of weekly exercise were not stated | 24 weeks | (1)(4) | 3 |
| $\begin{gathered} \text { Dai \& Ma } \\ \text { (2021) } \end{gathered}$ | China | 2020 | 20 | 30 | REs | Usual nursing | Borg scale: 11-13, 3/week, 40 min | 24 weeks | (1)(4)(5)(6)(7)(8)(9) | 4 |
| Yan, Zha & Peng (2022) | China | 2022 | 47 | 47 | Progressive RE | Usual nursing | Borg scale: 12-14, 3-4/week, 40-50 min | 12 weeks | (1)(4)(5) | 3 |
| Tayebi, <br> Ramezani & Kashef (2018) | Iran | 2018 | 17 | 17 | Resistance training | Usual nursing | Intensity of the intervention and the duration of each exercise session were not stated, and frequency of intervention was 3/week | 8 weeks | (1)(5)(6) | 2 |
Note:
(1) Grip strength; (2) 6 min walk test; (3) muscle tissue mass; (4) Hb; (5) ALB; (6) BMI; (7) cholesterol; (8) low density lipoprotein (LDL); (9) urea clear index.
Figure 2 Review authors judgments about each risk of bias item presented as percentages across all included studies.
Full-size DOI: 10.7717/peerj.16909/fig-2
unclear. Of the nine included studies, one had incomplete data results because its control group, one was rated as high risk because of the significant difference in the number of missed visits in its control and trial groups, and eight were rated as low risk. The risk of bias for each trial was assessed using the Cochrane risk-of-bias tool (Figs. 2 and 3). We also
Figure 3 Reviewer’ judgments about each risk of bias item for each included study.
Full-size DOI: 10.7717/peerj.16909/fig-3
Note: data input format theta se_theta assumed.
Egger’s test for small-study effects:
Regress standard normal deviate of intervention
effect estimate against its standard error
Test of H0: no small-study effects quad P=0.086\quad P=0.086
Figure 4 Egger’s test plot of grip strength.
Full-size DOI: 10.7717/peerj.16909/fig-4
used the Jada scale to assess the quality of the included literature. If the score was less than or equal to three, a study was considered of low quality; a score greater than or equal to four indicated a high quality. The scores are shown in Table 1.
Publication bias assessment
Egger’s test revealed no significant publication bias between studies (Fig. 4).
Results of GRADE evaluation of outcome indicators (Table 2)
META-ANALYSIS RESULTS
Indexes related to sarcopenia
Grip strength
Changes in grip strength were assessed in seven of nine studies (Tayebi, Ramezani & Kashef, 2018; Yan, Zha & Peng, 2022; Cai et al., 2022; Dai & Ma, 2021; Chan et al., 2019; Song & Sohng, 2012; Zhang et al., 2020) that included 421 patients. A total of 204 patients were assigned to the exercise group and 217 patients to the control group. They were analyzed using a fixed-effects model due to significant heterogeneity ( I^(2)=0%,P=0.77\mathrm{I}^{2}=0 \%, P=0.77 ). Meta-analysis showed that RE increased the grip strength of patients (MD =4.39,95%CI=4.39,95 \% \mathrm{CI} [3.14-5.64], P < 0.00001P<0.00001 ), with a statistically significant difference (Fig. 5A).
Six-min walk test
Among the nine studies, three (Chan et al., 2019; Zhang et al., 2020; Cheema et al., 2007) evaluated changes in the 6 min walk trial involving 164 patients. A total of 80 and 84 patients were assigned to the exercise and control groups, respectively. No heterogeneity was observed between studies ( I^(2)=42%,P=0.18\mathrm{I}^{2}=42 \%, P=0.18 ). Thus, a fixed-effects model was used for analysis. Meta-analysis showed that RE improved the patients’ ability to walk for 6 min (MD =40.71,95%CI[8.92-72.49],P=0.01=40.71,95 \% \mathrm{CI}[8.92-72.49], P=0.01 ), with a statistically significant difference (Fig. 5B).
Muscle mass
Two studies (Cai et al., 2022; Dai & Ma, 2021) reported the effect of RE on muscle mass of 138 patients, that is, 64 patients in the exercise group and 74 in the control group. The heterogeneity test yielded I^(2)=0%\mathrm{I}^{2}=0 \% and P=0.97P=0.97, and thus, a fixed-effects model was used for the analysis. The meta-analysis showed that RE increased the muscle mass of patients (MD =4.50,95%CI[2.01-6.99],P=0.0004=4.50,95 \% \mathrm{CI}[2.01-6.99], P=0.0004 ), with a statistically significant difference (Fig. 5C).
營養指標
血紅蛋白
Exactly four of the nine studies (Zhu, 2022; Yan, Zha & Peng, 2022; Cai et al., 2022; Dai & Ma , 2021) reported changes in Hb levels caused by RE in 303 patients, in which 147 patients were assigned to the exercise group and 156 to the control group. Given the
Certainty assessment № of patients Effect Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations RE Usual care Relative (95% CI) Absolute (95% CI)
Grip strength
7 RCTs Serious Not serious Not serious Not serious None 204 217 - "MD 4.39 higher
(3.14 higher to 5.64 higher)" "o+o+o+◯
Moderate"
The 6-min walk test
3 RCTs Serious Not serious Not serious Not serious None 80 84 - "MD 40.71 higher
(8.92 higher to 72.49 higher)" "o+o+bigoplus◯
Moderate"
Muscle mass
2 RCTs Serious Not serious Not serious Not serious None 64 74 - "MD 4.5 higher
(2.01 higher to 6.99 higher)" "o+o+bigoplus◯
Moderate"
Hb
4 RCTs Serious Serious Not serious Serious None 147 156 - "MD 1.69 higher
(1.49 lower to 4.87 higher)" "o+◯◯◯
Very low"
ALB
4 RCTs Serious Serious Not serious Not serious None 128 138 - "MD 3.16 higher
(1.13 higher to 5.19 higher)" "o+o+◯◯
Low"
Urea clearance index
2 RCTs Serious Not serious Not serious Serious None 44 55 - "MD 0.08 lower
( 0.23 lower to 0.07 higher)" "o+o+◯◯
Low"
LDL
2 RCTs Serious Not serious Not serious Serious None 40 50 - "MD 1.33 higher
(4.12 lower to 6.77 higher)" "o+o+◯◯
Low"
BMI
3 RCTs Serious Very serious Not serious Not serious None 88 99 - "MD 1.46 higher
( 0.24 lower to 2.67 higher)" "bigoplus◯◯◯
Very low"
Cholesterol
2 RCTs Serious Not serious Not serious Serious None 40 50 - "MD 2.33 higher
(5 lower to 9.65 higher)" "o+o+◯◯
Low" | Certainty assessment | | | | | | | № of patients | | Effect | | Certainty | Importance |
| :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: | :---: |
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | RE | Usual care | Relative (95% CI) | Absolute (95% CI) | | |
| Grip strength | | | | | | | | | | | | |
| 7 | RCTs | Serious | Not serious | Not serious | Not serious | None | 204 | 217 | - | MD 4.39 higher <br> (3.14 higher to 5.64 higher) | $\oplus \oplus \oplus \bigcirc$ <br> Moderate | |
| The 6-min walk test | | | | | | | | | | | | |
| 3 | RCTs | Serious | Not serious | Not serious | Not serious | None | 80 | 84 | - | MD 40.71 higher <br> (8.92 higher to 72.49 higher) | $\oplus \oplus \bigoplus \bigcirc$ <br> Moderate | |
| Muscle mass | | | | | | | | | | | | |
| 2 | RCTs | Serious | Not serious | Not serious | Not serious | None | 64 | 74 | - | MD 4.5 higher <br> (2.01 higher to 6.99 higher) | $\oplus \oplus \bigoplus \bigcirc$ <br> Moderate | |
| Hb | | | | | | | | | | | | |
| 4 | RCTs | Serious | Serious | Not serious | Serious | None | 147 | 156 | - | MD 1.69 higher <br> (1.49 lower to 4.87 higher) | $\oplus \bigcirc \bigcirc \bigcirc$ <br> Very low | |
| ALB | | | | | | | | | | | | |
| 4 | RCTs | Serious | Serious | Not serious | Not serious | None | 128 | 138 | - | MD 3.16 higher <br> (1.13 higher to 5.19 higher) | $\oplus \oplus \bigcirc \bigcirc$ <br> Low | |
| Urea clearance index | | | | | | | | | | | | |
| $2$ | RCTs | Serious | Not serious | Not serious | Serious | None | 44 | 55 | - | MD 0.08 lower <br> ( 0.23 lower to 0.07 higher) | $\oplus \oplus \bigcirc \bigcirc$ <br> Low | |
| LDL | | | | | | | | | | | | |
| 2 | RCTs | Serious | Not serious | Not serious | Serious | None | 40 | 50 | - | MD 1.33 higher <br> (4.12 lower to 6.77 higher) | $\oplus \oplus \bigcirc \bigcirc$ <br> Low | |
| BMI | | | | | | | | | | | | |
| $3$ | RCTs | Serious | Very serious | Not serious | Not serious | None | 88 | 99 | - | MD 1.46 higher <br> ( 0.24 lower to 2.67 higher) | $\bigoplus \bigcirc \bigcirc \bigcirc$ <br> Very low | |
| Cholesterol | | | | | | | | | | | | |
| 2 | RCTs | Serious | Not serious | Not serious | Serious | None | 40 | 50 | - | MD 2.33 higher <br> (5 lower to 9.65 higher) | $\oplus \oplus \bigcirc \bigcirc$ <br> Low | |
註:
CI,信賴區間;MD,平均差;SMD,標準化平均差。
存在顯著異質性( I^(2)=69%,P=0.02\mathrm{I}^{2}=69 \%, P=0.02 ),因此採用隨機效應模型進行分析。統合分析顯示 RE 並未改善患者的 Hb 水平( MD=1.69\mathrm{MD}=1.69 , 95%95 \% CI [-1.49 至 4.87], P=0.30P=0.30 ),且差異無統計學意義(圖 6A)。敏感性分析後,通過逐一排除納入研究,結果未觀察到顯著變化。
A
C
圖 5 肌肉減少症相關指標的統合分析結果。(A)握力。(B)六分鐘步行測試。(C)肌肉質量。
Full-size DOI: 10.7717/peerj.16909/fig-5
白蛋白(ALB)
A total of four of nine studies (Tayebi, Ramezani & Kashef, 2018; Yan, Zha & Peng, 2022; Cai et al., 2022; Dai & MaM a, 2021) evaluated the effect of RE on ALB in 266 patients. A total of 128 patients were assigned to the exercise group, and 138 were assigned to the control group. A random-effects model was used for the analysis because a significant heterogeneity was observed across studies ( I^(2)=68%,P=0.02\mathrm{I}^{2}=68 \%, P=0.02 ). Meta-analysis showed that RE improved ALB levels in patients ( MD=3.16,95%CI[1.13-5.19],P=0.002\mathrm{MD}=3.16,95 \% \mathrm{CI}[1.13-5.19], P=0.002 ), and the difference was statistically significant (Fig. 6B). After sensitivity analysis and exclusion of one study (Dai & Ma, 2021), heterogeneity was reduced ( I^(2)=4%,P=0.35\mathrm{I}^{2}=4 \%, P=0.35 ), and homogeneity among studies was analyzed using a fixed effects model, which showed that ( MD=4.04,95%CI[2.44-5.65],P < 0.00001\mathrm{MD}=4.04,95 \% \mathrm{CI}[2.44-5.65], P<0.00001 ). The meta-analysis results did not change significantly, which indicates their robustness.
身體質量指數(BMI)
A total of three out of nine studies (Cai et al., 2022; Dai & Ma, 2021; Cheema et al., 2007) evaluated the changes caused by RE on patients’ BMI; the results of the heterogeneity test were I^(2)=82%\mathrm{I}^{2}=82 \% and P=0.0004P=0.0004, and thus, a random-effects model was used for the analysis.
A
Two articles (Dai & Ma, 2021; Song & Sohng, 2012) reported the effect of RE on cholesterol. No heterogeneity was observed across studies ( I^(2)=0%,P=0.67\mathrm{I}^{2}=0 \%, P=0.67 ), and thus, a fixed-effects model was used for the analysis. The meta-analysis showed that RE did not improve patients’ cholesterol ( MD=2.33,95%CI[-5.00\mathrm{MD}=2.33,95 \% \mathrm{CI}[-5.00 to 9.65],P=0.53], P=0.53 ), with a non-statistically significant difference (Fig. 6E).
尿素清除指數
Two articles (Dai & Ma, 2021; Cheema et al., 2007) reported the effect of RE on the urea clearance index, and no heterogeneity was observed between them ( I^(2)=0%,P=0.66\mathrm{I}^{2}=0 \%, P=0.66 ). Therefore, a fixed-effects model was used for the analysis. Meta-analysis showed that RE did not improve dialysis adequacy in patients ( MD=-0.08,95%CI[-0.23\mathrm{MD}=-0.08,95 \% \mathrm{CI}[-0.23 to 0.07]], P=0.29P=0.29 ). In addition, the difference was not statistically significant (Fig. 6F).
本研究探討抗阻運動對維持性血液透析(MHD)患者肌肉減少症及營養狀態的影響。首先,我們整合了相關臨床結局指標,分析現有臨床試驗中應用抗阻運動的證據等級與不足之處,為臨床工作者制定更細緻全面的干預方案提供參考。在未來針對 MHD 患者的運動干預研究中,可考慮根據干預強度與頻率、患者性別、年齡及透析病史進行分層,並將干預週期延長至 48 週以上以觀察臨床結局指標變化,此外需通過採用恰當的隨機對照試驗方法及分配隱藏、盲法等措施提升臨床試驗質量,為未來制定運動處方指南提供高質量證據(Liu, Wang & Cao, 2022)。
CONCLUSION
在這項統合分析中,阻力訓練(RE)提升了維持性血液透析(MHD)患者的握力與 6 分鐘步行距離,改善了白蛋白(ALB)水平,增強了肌肉力量與功能,並增加了肌肉質量與營養狀態。然而,RE 對 MHD 患者血紅蛋白(Hb)水平、膽固醇水平及尿素清除指數的影響結果不一致。部分研究顯示 RE 對這些指標有正面效應,但亦有研究指出 RE 並未影響這些參數。因此,未來需要更多方法學嚴謹、高品質的研究與更嚴格的試驗設計來驗證 RE 對 MHD 患者營養指標的影響。
ABBREVIATIONS
CKD
慢性腎臟病
MHD
維持性血液透析
HD
血液透析
CNKI
中國國家知識基礎設施
RE
抗阻運動
INPLASY
國際註冊系統評價與薈萃分析平台
協議
LDL
低密度脂蛋白
MD
Mean difference
CI
Confidence interval
BMI
身體質量指數
CBM
中國醫藥信息查詢平台
GRADE
建議分級 評估、發展與評價
RE
抗阻運動
CHOLG
膽固醇
ALB
血清白蛋白
血紅蛋白
血紅素
Kt/V 值
透析有效性指標
ABBREVIATIONS
CKD Chronic kidney disease
MHD Maintenance hemodialysis
HD Hemodialysis
CNKI China National Knowledge Infrastructure
RE Resistance exercise
INPLASY International Platform of Registered Systematic Review and Meta-analysis
Protocols
LDL Low-density lipoprotein
MD Mean difference
CI Confidence interval
BMI Body mass index
CBM SinoMed
GRADE Grading of Recommendations Assessment, Development and Evaluation
RE Resistance exercise
CHOLG Cholesterol
ALB Serum albumin
Hb Hemoglobin
Kt/V Dialysis effectiveness index| ABBREVIATIONS | |
| :--- | :--- |
| CKD | Chronic kidney disease |
| MHD | Maintenance hemodialysis |
| HD | Hemodialysis |
| CNKI | China National Knowledge Infrastructure |
| RE | Resistance exercise |
| INPLASY | International Platform of Registered Systematic Review and Meta-analysis |
| | Protocols |
| LDL | Low-density lipoprotein |
| MD | Mean difference |
| CI | Confidence interval |
| BMI | Body mass index |
| CBM | SinoMed |
| GRADE | Grading of Recommendations Assessment, Development and Evaluation |
| RE | Resistance exercise |
| CHOLG | Cholesterol |
| ALB | Serum albumin |
| Hb | Hemoglobin |
| Kt/V | Dialysis effectiveness index |
作者披露了以下資助資訊:
Major Scientific and Technological Projects in Hunan Province: 2020SK2085.
新疆維吾爾自治區自然科學基金:2018D01C196。
利益競爭聲明
作者聲明他們沒有競爭利益。
作者貢獻
李麗構思並設計了實驗,執行了實驗,分析了數據,準備了圖表和/或表格,並核准了最終稿。
馬曉蘭構思並設計了實驗,執行了實驗,分析了數據,準備了圖表和/或表格,並核准了最終稿。
謝春燕進行實驗、分析數據、撰寫或審閱文章草稿,並核准最終版本。
李亞敏構思並設計實驗、撰寫或審閱文章草稿,並核准最終版本。
數據可用性
關於數據可用性,已提供以下資訊:
原始數據可在補充文件中獲取。
補充資訊
Supplemental information for this article can be found online at http://dx.doi.org/10.7717/ peerj.16909#supplemental-information.
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