Therapeutic effects of acupuncture therapy for kidney function and common symptoms in patients with chronic kidney disease: a systematic review and meta-analysis

Abstract

Purpose: The number of clinical reports of acupuncture therapy in chronic kidney disease (CKD) is gradually increasing. This systematic review and meta-analysis aim to examine the therapeutic role of acupuncture therapy in kidney function and common symptoms in CKD patients.

Methods: We searched Embase, PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, WanFang, and WeiPu for randomized controlled trials comparing acupuncture treatment with control or placebo groups. We assessed the effect of acupuncture therapy in CKD patients using a meta-analysis with the hartung-knapp-sidik-jonkman random effects model. In addition, we visualized keyword co-occurrence overlay visualization with the help of VOSviewer software to describe the research hotspots of acupuncture therapy and CKD.

Results: A total of 24 studies involving 1494 participants were included. Compared to the control group, acupuncture therapy reduced serum creatinine levels (standardized mean difference [SMD]: −0.57; 95% CI −1.05 to −0.09) and relieved pruritus (SMD: −2.20; 95% CI −3.84, −0.57) in patients with CKD, while the TSA showed that the included sample size did not exceed the required information size. The included studies did not report acupuncture-related adverse events.

Conclusions: Acupuncture is an effective and safe treatment for improving kidney function and relieving pruritic symptoms in patients with CKD, but the very low evidence may limit this conclusion. The TSA suggests that high-quality trials are needed to validate the efficacy of acupuncture therapy.

HIGHLIGHT

1. Acupuncture therapy may improve kidney function and relieve pruritus symptoms in CKD patients, but both are very low evidence.

2. Trial sequential analysis shows insufficient evidence for acupuncture therapy in CKD patients.

3. Future research could focus on the role of acupuncture for functional capacity, insomnia, and pain in CKD patients.

Keywords:

• Acupuncture
• chronic kidney disease
• systematic review
• meta-analysis

1. Introduction

Chronic kidney disease (CKD) is characterized by progressive loss of renal function over time, which can progress to end-stage renal disease (ESRD) and is one of the leading causes of increased cardiovascular morbidity and mortality [1]. ESRD requires renal replacement therapies such as peritoneal dialysis, hemodialysis, or kidney transplantation, which are associated with high healthcare costs and significantly burden patients [2]. Currently, CKD has become a growing public health problem [3].

Common symptoms of CKD include pruritus, sleep disturbances, depression, fatigue, sexual dysfunction, and gastrointestinal disorders that worsen with renal decompensation [4]. These symptoms are often under-treated or under-recognized, resulting in an increased symptom burden and reduced quality of life for CKD patients [5]. Given the overall negative impact of symptom distress, appropriate symptom management should be an essential component of high-quality care for patients with CKD [6,7].

Acupuncture is a non-pharmacological therapy originating in China, which involves the specific process of needling body points to provide adjunctive treatment of diseases [8]. With the advancement of science and technology, more studies have increasingly explored and confirmed the efficacy of acupuncture [9]. Some Cochrane evidence suggests the positive effects of acupuncture in the treatment of certain diseases and symptoms, such as overactive bladder [10], chronic nonspecific low back pain [11], and polycystic ovarian syndrome [12]. The popularity of acupuncture therapy and the patient’s need for integrative medicine and personalized treatment have prompted the broader practice of acupuncture in Western countries [13]. A survey of 278 Indian CKD patients showed that only 4.3% had experienced acupuncture treatment [14]. This result suggests that the use of acupuncture in CKD patients continues to be low.

Although previously published systematic reviews reported on the therapeutic effects of acupuncture in CKD [15,16]. However, regularly updated meta-analyses of trials with small sample sizes produce type I error rates, which can lead to an overestimation of acupuncture’s efficacy [17,18]. In addition, the small number of studies limits their meta-analysis. Thus, the effectiveness of acupuncture in CKD and the reliability of the available evidence remains questionable. Trial sequential analysis (TSA) is a methodology that combines cumulative information, i.e., required information sizes (RIS), and statistical monitoring to assess the statistical significance and reliability of trial data. TSA is designed to calculate the bounds on the cumulative z-value by considering the sample size, event rate, and expected effect size in a trial and to determine whether a reliable conclusion has been reached [19].

With this in mind, we used a systematic review and meta-analysis with TSA to assess the therapeutic role of acupuncture versus sham acupuncture or no acupuncture for CKD.

2. Methods

2.1. Registration

This systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [20] (supplemental Table S1). The protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023440233). The current study methodology is similar to the previously described protocol with a few modifications (supplemental Table S2). This review does not require ethical approval as the authors have retrieved and synthesized previously published literature.

2.2. Data sources and search strategies

We systematically searched four English databases (Embase, PubMed, Scopus, and Web of Science) and three Chinese databases (CNKI [China National Knowledge Infrastructure], WanFang, and WeiPu) using a combination of medical subject terms (MeSH) and keywords related to ‘acupuncture’ and ‘chronic kidney disease’, and search ClinicalTrials.gov (https://classic.clinicaltrials.gov/) and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/Default.aspx) for data from registered but unpublished studies. The timeline was from the inception to 30 June 2023, and was updated in November 2023. The search strategies for each database are shown in supplemental Table S3. In addition, we also manually searched for records in the reference lists of previous systematic reviews [15,16]. Literature downloaded from the databases was imported into EndNote 20 software for management.

2.3. Eligibility criteria

Eligibility criteria were based on PICOS (Population, Intervention, Comparator, Outcome, Study design) elements developed by potential randomized controlled trials (RCTs) should include (1) adult patients (age ≥18) diagnosed as CKD, including pre-dialysis, peritoneal dialysis, hemodialysis, kidney transplant recipients, (2) participants in the intervention group receiving acupuncture treatment, (3) participants in the control or placebo group receiving usual care or sham acupuncture, (4) outcomes of interest included kidney function, included serum creatinine (Scr) and blood urea nitrogen (BUN), and CKD-related common symptoms.

2.4. Selection process

Two authors (YB and SL) independently conducted the selection. The titles and abstracts were screened for relevance based on eligibility criteria, and potential full-text articles were reviewed. Disagreements were adjudicated by a third author (FZ).

2.5. Data extraction

Two independent reviewers (YB and SL) performed data extractions using an established form. The extracted information includes first authors, publication year, study locations (countries), mean age and gender of participants, acupoints, baseline, and endpoints for the intervention and control groups regarding the results. Any discrepancies were resolved through discussion.

Baseline and final outcomes were extracted when outcomes were measured more than twice. If multi-arm (≥2) trials were included, we extracted data only for the acupuncture treatment and control groups. If we encounter a study that presents results in the figure, we use GetData software to extract the mean and standard deviation (SD).

2.6. Risk of bias assessment

Two independent authors (YB and SL) assessed the risk of bias for each included RCT according to the Cochrane Collaboration’s risk of bias tool 2 (RoB-2) as having a low risk of bias, some concerns or a high risk of bias: bias arising from the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in measuring the outcome and bias in the selection of the reported result [21]. The Excel macro tool provided on the RoB-2 official website (https://www.riskofbias.info/welcome) was used to generate the risk of bias summary table. Any discrepancies were resolved through a third author (FZ).

2.7. Handling missing data

For missing data that cannot be obtained from the text, we attempted to contact the appropriate author for any incomplete or missing data. If no response was received within two weeks, it was considered a no response and included in the qualitative analysis.

In the case of studies reporting median, first, and third quartiles, we calculated mean and SD using the method of Luo et al. [22] and Wan et al. [23]. Calculation results are available on the web

(https://www.math.hkbu.edu.hk/∼tongt/papers/median2mean.html).

2.8. Data analysis

2.8.1. Data synthesis

We used the meta [24] packages in R software to include studies with continuous or dichotomous data for outcomes in the meta-analysis. A z-statistic with a p-value of 0.05 assessed the overall effect. The summary statistics for dichotomous data were odd ratio (OR) and 95% confidence intervals (95% CI). Considering the heterogeneity of populations and acupoint selection, continuous data analysis selected the standardized mean difference (SMD) to explain the effect size, and a random-effect model was applied to all analyses. The hartung-knapp-sidik-jonkman (HKSJ) method was used as the estimator for the meta-analysis because the results of this method are more robust [25]. The results were displayed through a forest plot, and the overall effect was checked using a z-test. In addition, we calculated 95% prediction intervals (95% PI) to predict the range of actual impacts [26].

Statistical heterogeneity between studies was assessed with I² and Cochrane Q-test, and the criteria are as follows: ≥25% (low heterogeneity), ≥50% (moderate heterogeneity), and ≥75% (high heterogeneity) [27]. We used the ‘leave-one-out’ method, i.e., deleting one study each time and repeating the analysis, to assess the robustness of the results.

2.8.2. Trial sequential analysis

The Lan-DeMets method was used for TSA to construct the O’Brien-Fleming monitoring boundary and the optimal amount of information, set to an alpha of 0.05 and a two-sided beta of 0.80 [18,28]. The expected intervention effect may reach the level of sufficient evidence when the cumulative Z-curve enters the null zone or crosses the trial sequential monitoring boundary. The evidence could not conclude if the Z-curve did not cross any boundary or reach the required information size. TSA was performed using TSA software (version 0.9.5.9 Beta).

2.8.3. Qualitative analysis

Although some of the results were reported in only one study, we drew forest maps to describe the effects of acupuncture more visually. For quality-of-life scores, we performed a qualitative analysis.

2.8.4. Grading of evidence assessment

We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to determine the certainty of the evidence for the following five domains [29]:

1. Risk of bias: we reduced the certainty of evidence if a sensitivity analysis shows significant differences between studies with low, medium, or high bias.

2. Indirectness: the evidence level was not downgraded if the research questions of the included studies were consistent with the PICO questions.

3. Inconsistency: unexplained heterogeneity was a reason for downgrading, i.e., I² > 50%.

4. Imprecision: whether the confidence interval corresponding to the effect estimate is narrow enough.

5. Other considerations: availability of adequate sample size (> 1000).

6. The certainty of evidence was rated as high, medium, low, and very low by the GRADE tool.

3. Results

3.1. Description of studies

A total of 1917 articles was found in the database, and after screening, we finally included 24 studies [30–53] with 1494 participants (774 males; 554 females [two studies did not report gender]). The screening process is shown in Figure 1. Reasons for full-text exclusion were documented (supplemental Table S4). Supplemental Table S5 summarizes the details of several ongoing randomized trials.

Figure 1. PRISMA flow diagram of literature search and study selection. CNKI, China National Knowledge Infrastructure; RCT, randomized control trial.

Supplemental Table S6 shows the main characteristics of the included RCTs. The included studies were conducted in only three countries (China, Portugal, and Iran). Three articles corresponding to one study reported different results [32–34]. Thus, 15 RCTs included hemodialysis-dependent CKD patients, four studies had pre-dialysis patients, one RCT included peritoneal dialysis-dependent CKD patients, one included kidney transplant recipients, and one RCT included both peritoneal dialysis and hemodialysis patients. The proportion of males was 58.3%, and the mean age ranged from 32.3 to 78.36 years. The assessment of bias for inclusion in the RCT is shown in supplemental Figure S1.

3.2. Kidney function

3.2.1. Serum creatinine (Scr)

The meta-analysis pooled six articles (nine trials) that reported Scr in 516 patients (Figure 2(A)). Compared to the control group, acupuncture treatment can significantly reduce Scr in CKD patients (SMD: −0.57; 95% CI −1.05 to −0.09), with moderate heterogeneity (I² = 74%, p < 0.01). 95% PI values ranged from −2.01 to 0.88, suggesting that acupuncture treatment may not significantly reduce Scr relative to a control group in future studies. Sensitivity analyses confirmed the result was reliable (supplemental Figure S2A), with very low-GRADE evidence (supplemental Table S7).

Figure 2. Meta-analysis (A) and TSA (B) of acupuncture vs. control group for serum creatinine. TSA, trial sequential analysis; Scr, serum creatinine; SD, standard deviation; SMD, standardized mean difference; 95% CI, 95% confidence interval. The blue curve represents the Z-curve, the red curves above and below represent trial sequential monitoring boundaries, the dashed red dotted line represents the traditional level of statistical significance, and the red vertical line represents RIS value; the red lines on the sides closest to the horizontal line are boundaries for futility.

The TSA showed that the cumulative Z-curves did not cross trial sequential monitoring boundaries, and the included sample size did not exceed the RIS (n = 1694, Figure 2(B)), suggesting that there is a lack of evidence to substantiate a significant difference between acupuncture and control in reducing Scr.

3.2.2. Blood urea nitrogen (BUN)

A meta-analysis of five articles (six trials) measuring BUN in 369 patients was performed (Figure 3(A)). Compared to the control group, acupuncture treatment did not show an advantage in decreasing BUN in patients with CKD (SMD: −0.34; 95% CI −0.77 to 0.09), with moderate heterogeny (I² = 60%, p = 0.03). 95% PI values ranged from −1.37 to 0.69, suggesting that acupuncture treatment in future studies may decrease BUN. Sensitivity analyses confirmed that the results were reliable (supplemental Figure S2B), with very low-GRADE evidence (supplemental Table S7).

Figure 3. Meta-analysis (A) and TSA (B) of acupuncture vs. control group for blood urea nitrogen. TSA, trial sequential analysis; BUN, blood urea nitrogen; SD, standard deviation; SMD, standardized mean difference; 95% CI, 95% confidence interval. The blue curve represents the Z-curve, the red curves above and below represent trial sequential monitoring boundaries, the dashed red dotted line represents the traditional level of statistical significance, and the red vertical line represents RIS value; the red lines on the sides closest to the horizontal line are boundaries for futility.

TSA showed that the cumulative Z curves did not cross trial sequential monitoring boundaries, and the sample size did not reach the RIS (n = 1671, Figure 3(B)), suggesting no conclusive evidence to support a statistically significant difference in reducing BUN with acupuncture.

3.3. CKD-related common symptoms

3.3.1. Pruritus (continuous data)

Six trials measuring pruritus in 226 participants were included in the meta-analysis (Figure 4(A)). Three trials used pruritus scores [30,51,52], and three used the visual analog scale [40,45,53]. Acupuncture treatment significantly reduced ­pruritus symptoms in CKD patients compared to controls (SMD: −2.20; 95% CI −3.84, −0.57), with considerable heterogeneity (I² = 91%; p < 0.01). 95% PI values ranged from −6.68 to 2.28, suggesting that acupuncture treatment in future studies may not decrease pruritus symptoms. Sensitivity analyses confirmed the results were reliable (supplemental Figure S2C), with very low-GRADE evidence (supplemental Table S7).

Figure 4. Meta-analysis (A) and TSA (B) of acupuncture vs. control group for pruritus (continuous data). TSA: trial sequential analysis; SD: standard deviation; SMD: standardized mean difference; 95% CI: 95% confidence interval. The blue curve represents the Z-curve, the red curves above and below represent trial sequential monitoring boundaries, the dashed red dotted line represents the traditional level of statistical significance, and the red vertical line represents RIS value; the red lines on the sides closest to the horizontal line are boundaries for futility.

TSA showed that the cumulative Z-curve did not cross trial sequential monitoring boundaries, and the sample size included did not reach the RIS (n = 543, Figure 4(B)), suggesting that there is still a lack of evidence to support a statistically significant difference in the reduction of pruritus symptoms with acupuncture.

3.3.2. Pruritus (dichotomous data)

Five studies reported outcomes for pruritus using an efficiency method. Meta-analysis showed that, although not statistically significant, patients in the acupuncture-treated group had a 3.22-fold increase in efficiency compared with the control group (OR: 3.22; 95% CI 0.91–11.45), with a low heterogeneity (I² = 47%; p = 0.11) (Figure 5). The 95% PI values ranged from 0.16 to 64.38, suggesting that acupuncture’s role in adjuvant pruritus treatment in future studies is unclear. Sensitivity analyses confirmed the results were reliable (supplemental Figure S2D), with very low-GRADE evidence (supplemental Table S7). TSA indicates the same conclusion (supplemental Figure S3).

Figure 5. Meta-analysis of acupuncture vs. control group for pruritus (dichotomous data).

3.2.3. Impaired physical function

Three studies reported the adjunctive therapeutic role of acupuncture in CKD patients with impaired physical function. Three trials measuring handgrip strength in 168 participants were included in the meta-analysis (supplemental Figure S4A). Acupuncture treatment did not improve handgrip strength in patients with CKD compared to controls (SMD: 0.70; 95% CI −0.40 to 1.80), with moderate heterogeneity (I² = 58.4%; p = 0.09). 95% PI values ranged from −4.86 to 6.26, suggesting that acupuncture has an unclear adjunctive therapeutic role for handgrip strength in future studies. Sensitivity analyses confirmed the results were reliable (supplemental Figure S2E), with very low-GRADE evidence (supplemental Table S7). TSA indicates the same conclusion (supplemental Figure S4B).

In addition, a meta-analysis of three individual outcomes demonstrated the superiority of acupuncture treatment relative to controls in improving physical functioning in CKD patients, including mobility assessed by gait speed, cardiorespiratory fitness assessed by a 6-min walk test, and lower extremity muscle strength assessed by a 30-s sit-to-stand test (supplemental Figure S5).

3.2.4. Other

A few separate studies have reported the role of acupuncture treatment in common symptoms in patients with CKD, including intradialytic hypotension on dialysis, poor sleep quality, anxiety, depression, muscle cramps, and dialysis imbalance syndrome (supplemental Figure S6). Each study reported an active effect of acupuncture treatment, but these results must be interpreted cautiously considering the small samples and high risk of bias.

4. Discussion

4.1. Summary of main results

The results of this systematic review and meta-analysis, which included 24 RCTs involving 1494 patients with CKD, showed an association between acupuncture and improvement in kidney function and a reduction in pruritus in patients with CKD compared with sham acupuncture or conventional treatment. However, most studies measured the short-term effects of acupuncture treatment, spanning less than two months. Notably, no acupuncture-related adverse events were reported.

Unexpectedly, we did not find studies on applying acupuncture to alleviate pain symptoms in CKD patients in this systematic review. Pain is a common but easily overlooked symptom in patients with CKD [54]. Similar to the general population, pharmacological therapies for pain control usually follow the World Health Organization’s ‘analgesic ladder’. However, CKD patients have a shortage of approved medications, especially for severe pain [55]. In such cases, patients are often treated with opioids, which can expose them to side effects such as nausea, anorexia, constipation, fatigue, impaired cognitive function, and risk of addiction [56]. Acupuncture has been shown to reduce pain in various populations [57–59], and these findings warrant consideration of extending this evidence to CKD. Consequently, there is a need for future research to explore the use of acupuncture in this population.

4.2. Discussion of main findings

Pooled analyses showed that acupuncture treatment has a significant benefit in reducing Scr levels in CKD patients. Several studies have elaborated on this mechanism. First, promoting blood circulation [60]: acupuncture can stimulate the nerves and tissues around acupoints, thus increasing blood flow and microcirculation, which helps to improve the blood supply to the kidneys. Second, regulating the immune system [61]: acupuncture is believed to regulate immune system function and reduce inflammatory response in CKD, which may help reduce further damage to kidney tissues and promote repair and regeneration processes. Third, regulating the neuroendocrine system [62]: acupuncture stimulation of specific acupoints may affect the regulation of the neuroendocrine system, including the secretion of adrenocorticotropic hormone. This may help balance the metabolism of body fluids and electrolytes, thereby improving kidney function.

From the current systematic review, acupuncture therapy may help symptom management and improve CKD patients’ quality of life. Pruritus is one of the symptoms with high incidence and frequency in CKD, especially end-stage renal disease, which interferes with sleep, reduces the quality of life, and causes severe distress to patients [63,64]. Since uremic pruritus is closely related to kidney function [65], acupuncture treatment improves kidney function and reduces pruritus to some extent. In addition, CKD-associated pruritus has been associated with inflammatory responses [66]. Acupuncture can alleviate the inflammatory response and relieve itching symptoms by regulating release of inflammatory mediators. It has also been suggested that acupuncture relieves pruritus by inhibiting afferent fibers by modulating the release of opioids [60].

It has been shown that physical function is impaired in CKD, even without any known heart disease or diabetes, and that its decline is proportional to the severity of kidney function [67]. Although acupuncture has shown advantages in improving handgrip strength and other dimensions of physical function in patients with CKD, there is insufficient evidence to support such a view. Similarly, the small amount of data and high risk of bias for other symptomatic outcomes make it impossible to draw definitive conclusions. Three studies reported positive results of acupuncture therapy for quality of life [34,48,52], which may be related to the prognosis of acupuncture for relief of CKD-related symptoms; after all, symptom distress is strongly and negatively associated with quality of life in CKD patients [4].

Given that most of the studies included were conducted in China, this may result in limited generalization of the findings across countries. Furthermore, in many studies, the participants were hemodialysis patients. It is well known that there are various stages of CKD, including pre-dialysis, dialysis, and kidney transplantation [1]. Due to the paucity of data, analyzing the studies based on CKD stages was impossible. In addition, the included studies used different acupoints, showing considerable clinical heterogeneity. However, due to the small number of studies, we could not perform subgroup analyses to clarify the source of heterogeneity; therefore, the impact of clinical heterogeneity on the pooled results remains unclear.

Given that CKD is a progressive disease, disease stages, such as nondialysis and dialysis, and acupuncture methods are likely factors contributing to differences in estimates. More studies in specific areas are needed to assess the role of these factors in heterogeneity fully.

It is important to note that most studies involving hemodialysis patients did not report the timing of acupuncture treatment (i.e., before, during, or after dialysis). Because hemodialysis requires patients to attend dialysis facilities regularly, allocating additional patient time and resources for acupuncture treatment may be challenging. The safety of intra- or post-dialysis acupuncture remains unclear, especially for patients who experience adverse events due to hemodynamic instability or post-dialysis fatigue [15]. Acupuncture interventions before starting a dialysis session may avoid such problems, but allocating the time and space needed for treatment in a busy dialysis schedule may not be possible. In conclusion, the acceptability of acupuncture for patients and dialysis staff and the optimal course of implementation in a given clinical setting remains uncertain.

Several randomized trials currently underway have the potential to confirm or refute our findings (supplemental Table S5). Two of these studies are being conducted outside of China, contributing to the generalizability of results. Unfortunately, these studies’ periodicity and target sample sizes are similarly small.

4.3. Future directions for research

Despite its origins in China, acupuncture therapy is now one of the most popular complementary and alternative therapies in many countries [68]. With this in mind, we used bibliometrics (see supplemental Table S8 for detailed methodology) to visualize the research hotspots of acupuncture applied to CKD. As shown in Figure 6, based on VOSviewer’s overlay visualization, keywords around restless legs syndrome, case reports, insomnia, functional capacity, and feasibility have been frequently mentioned in recent years. Based on this network mapping and the results of this systematic review, future research should focus on (1) The prevalence of restless legs syndrome is particularly prominent in hemodialysis patients, which is easily clinically neglected [69], and severely affects sleep and significantly reduces the quality of life of dialysis patients [70]. Currently, there is a lack of targeted drugs, and acupuncture seems to improve the severity of restless legs syndrome symptoms [71]. (2) according to traditional Chinese medicine theory, the premise of acupuncture is ‘dialectic’, which is based on the individual’s perspective and selects the appropriate acupoints for different symptoms or signs in the future. In future studies, case reports may be a form of publication on the efficacy of acupuncture. (3) As mentioned above, impaired physical function is a clinical problem that CKD patients and health providers must face, and the current treatment mainly consists of providing exercise guidance, but compliance is low [72]. Acupuncture, a non-pharmacological therapy, has the potential to improve functional capacity in CKD patients. (4) In the study by Correia de Carvalho et al. [32], the authors used safety (number of reported adverse events) and effectiveness (changes in functional capacity, peripheral muscle strength, and quality of life scores after treatment) to assess the feasibility of integrating acupuncture into dialysis centers. From the results, this outcome was recognized by hemodialysis patients, physicians, and nurses. Nevertheless, continued evaluation of the feasibility of acupuncture for CKD is needed in future studies.

Figure 6. Co-occurrence network mapping of author keywords.

From a clinical perspective, this study provides several directions for future research. Based on the above findings, future studies could include more populations of different races/ethnicities from other countries to increase the generalizability; a larger, statistically powerful multicenter, long-follow-up RCT study to further validate the efficacy of acupuncture on the prognosis of CKD; using standardized acupuncture protocols, as well as a consistent, validated renal function/symptom measure, would increase the consistency of future trials; a more rigorous design and clearer RCT reporting following the Consolidated Standards of Reporting Trials (CONSORT) guidelines [73] is necessary; in hemodialysis patients, it would make sense to conduct crossover trials to assess the effects of different acupoint prescriptions and times (pre-, intra-, post-dialysis). There is also value in designing pragmatic trials to explore the practical feasibility, costs, patient/provider acceptance, barriers to implementation, and scalability of incorporating acupuncture into routine care for CKD.

4.4. Strength and limitation

The strength of this study lies in the exhaustive search of Chinese and English databases, which adequately assessed the therapeutic role of acupuncture for CKD patients. However, the study still has unavoidable limitations. First, although acupuncture originated in China, it is now gradually becoming more popular worldwide, but we excluded non-Chinese and English literature, which may lead to language bias and have missed essential contributions written in other languages. Second, a higher heterogeneity was found in most meta-analyses, and all included studies were at high risk of bias, reducing the certainty of evidence. Third, most studies in China reported positive outcomes but lacked detailed reporting, making highlighting and replicating the critical factors behind treatment success difficult. Fourth, TSA has limitations, as its different estimates of effect sizes and additional assumptions about event proportions will lead to different RISs and influence whether the Z-curve will cross trial sequential monitoring boundaries [19]. Therefore, conclusions about TSA depend on our assumptions and the predefined variables in the models used. Fifth, the current meta-analysis included primarily Chinese (i.e., Asian) populations, and validation of the therapeutic effects on different races still requires high-quality studies. Sixth, because of the limited number of trials in each comparison in the meta-analysis, it was impossible to draw a funnel plot. Therefore, we were unable to assess publication bias fully.

5. Conclusions

This systematic review and meta-analysis demonstrated that acupuncture treatment was effective in improving renal function and decreasing pruritus in patients with CKD compared with sham acupuncture and/or no acupuncture, with a GRADE level of evidence of very low. The TSA demonstrated that a sufficient sample size is still needed to prove the therapeutic effect of acupuncture in CKD.

Authorship contributions

Conception and design: YFZ, Administrative support: YFZ and YL, Provision of study materials or subjects: All authors, collection and assembly of data: SL, YB, and FZ, Data analysis and interpretation: FZ and LYH, Manuscript writing: FZ and SL, Final approval of manuscript: All authors have read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data relevant to the study are included in the article and uploaded as supplementary material.

Additional information

Funding

This study was supported by Shanghai Hospital Development Center [SHDC2022CRD003], Shanghai University of Traditional Chinese Medicine [602059D], Shanghai Xuhui District Health Care Committee [XHLHGG202105], Demonstration-oriented Research Ward Construction Project of Shanghai Hospital Development Center [SHDC2022CRW006], and National Natural Science Foundation of China [82374589].