Skip to main content
NCBI home page
Tzu-Chi Medical Journal logoLink to Tzu-Chi Medical Journal
. 2024 Mar 26;36(2):195–202. doi: 10.4103/tcmj.tcmj_217_23

An Apriori algorithm-based association rule analysis to identify acupoint combinations for treating uremic pruritus

Ping-Hsun Lu a,b, Chien-Cheng Lai c, Ling-Ya Chiu d,e, I-Hsin Lin b, Chih-Chin Iou a, Po-Hsuan Lu d,f,*
PMCID: PMC11025587  PMID: 38645789

Abstract

Objective:

Uremic pruritus (UP) is a prevalent and troublesome condition affecting individuals with end-stage renal failure, which results in intense pruritus, depression, as well as poor quality of sleep, significantly impacting their quality of life. According to previous studies, acupuncture and acupoint stimulation have been shown to provide additional benefits in treating UP in dialysis patients. In addition, using acupoints combination may yield superior effectiveness compared to utilizing a singular acupoint. To investigate the potential correlations between acupoint combinations, an association-rule analysis was employed.

Materials and Methods:

Apriori algorithms stand out as highly potent techniques for identifying associations in databases; this study utilized an association rule mining to examine the association rules of key acupoint groupings that could be employed for treating UP.

Results:

The analysis utilized information derived from the meta-analysis encompassing 40 randomized controlled trials that used acupuncture to treat UP. In total, 64 acupoints were analyzed, and 71 association rules were found. The following acupoint combinations: Auricular shenmen (TF4), Quchi (LI11), and Geshu (BL17); Auricular heart (Extra14), Sanyinjiao (SP6), and Auricular lung (CO14); and Auricular heart (Extra14), Xuehai (SP10), and Auricular lung (CO14) showed the strongest associations.

Conclusion:

Acupoints involving Auricular shenmen (TF4), Quchi (LI11), Geshu (BL17), Auricular heart (Extra14), Sanyinjiao (SP6), Auricular lung (CO14), and Xuehai (SP10) can be regarded as the core combination of acupuncture points for managing UP.

KEYWORDS: Acupoints combinations, Acupuncture, Apriori association rule, Chronic kidney disease, Uremic pruritus

INTRODUCTION

Uremic pruritus (UP) presents a challenging dermatological issue that impacts around 40% of dialysis patients. UP has the potential to cause depression, impair sleep quality, and adversely affect the overall quality of life for dialytic individuals[1,2]. The pathogenetic mechanisms of UP remain vague, while it is known to involve a complicated interaction between several factors, such as skin pruritogens, the nervous system, and the immune system[3]. There are various treatment options available for UP, including topical treatments such as emollients, steroids, and capsaicin, as well as phototherapy and systemic treatments, including opioid antagonists and agonists, antihistamines, mast cell stabilizers, and leukotriene receptor antagonists[3,4]. However, side effects of the treatments for UP have been reported, including anticholinergic effects from antihistamines[5], skin atrophy resulting from topical steroid use[6], and dizziness and somnolence associated with gabapentin[7]. Therefore, finding a safe and effective complementary treatment for UP is imperative.

Complementary alternative medicines, including Chinese herbal bath therapy and acupuncture, have been shown to have fewer adverse drug reactions compared with Western medicine[8]. In previous systematic reviews and randomized controlled trials (RCTs), acupoint stimulation techniques, such as acupuncture, acupressure[9,10,11], auricular acupressure[12], and transcutaneous electrical acupoint stimulation (TEAS)[13], have been identified as safe and effective alternative therapies for reducing the itching sensation. A possible mechanism of alleviating pruritus involves regulating mast cell degranulation, reduction of histamine release, and endogenous opiate-like substance stimulation[8,12]. The studies mentioned above have provided evidence of the efficacy of acupoint stimulation in UP treatment. Nevertheless, there is a lack of agreement on the established acupuncture points to be used or the optimal combinations of acupoints for treating UP.

Data mining is a new approach used across multiple fields to enhance the generation of research findings from large datasets[14]. The data mining method has been gradually utilized in Chinese medicine to establish principles for selecting and combining acupoints to treat abundant conditions such as asthma[15], insulin resistance[16], and amyotrophic lateral sclerosis[17]. Although clinical practice relies on the combination of acupoints, there are currently no established criteria for determining the essential combinations. Hence, an association rule analysis could prove valuable and feasible in identifying the fundamental rules leading to effective acupoint combinations. Apriori, an algorithm belonging to the category of association rule mining techniques, functions by detecting the presence of item sets within extensive databases and subsequently formulates corresponding association rules utilizing metrics such as support, lift, and confidence[18]. Due to the lack of research on the use of acupoint combinations and standardized criteria, this study used an Apriori association rule analysis utilized data derived from the meta-analysis encompassing 40 RCTs to explore potential core acupoint combinations that were utilized in acupuncture and related techniques to treat UP[11].

MATERIALS AND METHODS

Sources of data and criteria for selection

The analysis stemmed from a previous meta-analysis conducted previously on 40 RCTs examining the efficacy of acupuncture in treating UP[11]. Acupoints for acupuncture and associated manipulation (acupressure, acupoint thermal therapy, auricular acupressure, acupoint sticking therapy TEAS, or acupoint injection) were extracted from the included RCTs published between 2002 and 2022. In total, 2735 patients with UP undergoing dialysis were involved in the meta-analysis. Inclusion criteria included the existence of UP, the application of acupuncture techniques, and the availability of quantitative data concerning itching intensity. Overlapping data with small populations were excluded from this study.

Risk of bias evaluation

The methodological quality of the trials included in the meta-analysis was assessed using the Cochrane tool for assessing the risk of bias (RoB), version 2.0[19]. The assessment conducted by the RoB 2.0 tool covered five aspects: randomization process, intended intervention, absence of outcome data, measurement of outcomes, and bias in selection. Overall bias was scored high, unclear, or low. A detailed description of this quality assessment has been provided previously[11].

Data analysis

An analysis using Apriori association rule was performed, and graphical representations were generated using R-Studio (Integrated Development Environment for R, version 1.2.5033, provided by RStudio, PBC, located in Boston, MA.)[20]. Previous data from the meta-analysis were classified into 40 columns, each representing a distinct acupuncture formula. The R package “arules” was employed to fit the data, and the R package “arulesViz” generated charts for visualization. Principally, the association rule generated by the Apriori algorithm consists of the antecedent and the consequent parts. The Apriori algorithm links the antecedent part of the items with the consequent part of the items by relying on the observation that these two parts tend to co-occur in the database.

Four prevalent metrics utilized to evaluate associations among items in an Apriori algorithm encompass support, confidence, expected confidence, and lift[14]. The frequency of a specific acupoint occurrence in different acupuncture formulas is defined as support. Confidence is the probability of the consequent item occurring, given the presence of the antecedent item. Expected confidence is a metric that calculates the probability of the consequent item appearing independently of the antecedent in a relationship. Expected confidence is determined by assessing the occurrences percentage where the consequent item is present. Lift is the value derived from dividing the confidence by the expected confidence. Lift indicates the probability of an upsurge in the consequent item when a specific antecedent item is present[14]. In this study, an analysis of the 71 association rules was performed, and the minimum criteria for inclusion were a support degree of at least 10% and a confidence level of at least 60%. The minimum criteria were applied to the metrics to filter out the less significant association rules, resulting in a dataset of 71 association rules. The association rules were arranged in descending order according to the values of the “lift” metric.

RESULTS

Characteristics of the study and assessment of risk of bias

Table 1 presents an overview of the characteristics and methodological features of the included studies. A detailed assessment of the RoB is provided in Supplementary Figure 1 (1.1MB, tif) . After the RoB analysis, 35, 2, and 3 RCTs were assessed as having a high, unclear, and low RoB, respectively. Possible reasons for the RoB results include only 7 trials mentioned blinding of the outcome measurement, and clear randomization processes were only mentioned in 11 trials.

Table 1.

Overview of the 40 randomized controlled trials incorporated in the meta-analysis assessing acupuncture interventions for uremic pruritus

Study (year) Study type Inclusion rule Acupoints Overall bias
Ardinata et al., 2021 [41] RCT HD LI11 Low
Juan, 2021 [42] RCT HD LI11 Unclear
Jiang et al., 2021 [43] RCT HD LI4, LI11, ST36, SP6, SP10 High
Zhang, 2020 [44] RCT HD LI11, SP10, SP6 High
Liu, 2018 [45] RCT HD LI11, SP6 High
Nahidi et al., 2018 [46] RCT HD LIV3, LI4, SP6, SP10 Low
Phan et al., 2018 [47] RCT HD Quchi, LI11 Low
Chu et al., 2018 [31] RCT HD DU20, LI4, LI11, SP6, SP10, ST36 High
Pu, 2017 [48] RCT HD LI4, LI11, LU5 ST36 High
Chang et al., 2017 [49] RCT HD BL17, GB31, LI11, ST36, SP10 High
Ono and Mukaino, 2015 [50] RCT HD BL65, BL67, GB38, GB43, HT7, HT9, KI1, KI7, LU5, LU9, LI2, LI11, LR2, LR8, PC7, PC9, SI3, SI8, SP2, SP5, ST41, ST45, TE3, TE10 High
Ma et al., 2014 [51] RCT HD SP10, LI4 High
Chang et al., 2011 [52] RCT HD BL17, LU5, LI4, LI11, SP10, ST36 High
Chou et al., 2005 [53] RCT HD LI11, ST36, SP6, SP10 High
Ruei et al., 2002 [54] RCT HD LI11, ST36, SP6, SP10 High
Kao et al., 2002 [55] RCT HD LI11, ST36 High
Mai, 2021 [56] RCT HD Endocrine, heart, lung, SF1.2i High
Yan et al., 2021 [57] RCT HD Endocrine, heart, lung, subcortical, shenmen High
Yu et al., 2021 [58] RCT HD Adrenal gland, endocrine, large intestine, lung, shenmen, occiput High
Zhai, 2021 [59] RCT HD Kidney, stomach, spleen, subcortical, sympathy, shenmen High
Chen et al., 2020 [60] RCT HD Kidney, stomach, spleen, subcortical, sympathy, shenmen High
Yan et al., 2020 [61] RCT HD Endocrine, heart, kidney, lung, shenmen, subcortical High
Ding et al., 2019 [32] RCT PD Endocrine, heart, kidney, lung, shenmen, subcortical High
He et al., 2018 [62] RCT HD Lung, endocrine, adrenal gland High
Lin, 2018 [63] RCT CKD Adrenal supracortical, endocrine, lung, spleen, stomach, sympathy, wheel area High
Li and Ma, 2017 [64] RCT HD AT2.3.4i, bladder, HX1, HX6.7i, kidney, lung, heart, liver, spleen, sanjiao, shenmen, SF1.2i High
Tao, 2016 [65] RCT HD Kidney, Spleen, Stomach, Sympathy, Subcortical, Shenmen High
Yan et al., 2015 [12] RCT HD Shenmen, Kidney, Lung, Endocrine, Subcortical High
Shr et al., 2012 [66] RCT HD Kidney, Lung, Heart, Liver, Spleen, Sanjiao
Bladder, Shenmen, HX1, HX6.7i, SF1.2i, AT2.3.4i		 High
Hsu et al., 2009 [67] RCT HD SP6 High
Wang et al., 2021 [68] RCT HD LI11, ST36 High
Deng, 2017 [69] RCT HD LI11, SP10, ST36 High
Wang et al., 2004 [70] RCT HD BL17, BI23, EM40, GB31, LI4, LI11, SP6, SP9, SP10, ST36 High
Chen et al., 2017 [71] RCT HD DU14, DU23, EM1, EM2, GB20, HT7, LI4, LI11, PC4, ST36, SP6, SP10 High
Yi and Zheng, 2018 [72] RCT HD LI11, SP6, SP10 High
Chen, 2021 [73] RCT High-flux HD LI11 High
Karjalian et al., 2020 [37] RCT HD LI11, ST36, SP6, SP10 Unclear
Kılıç Akça and Taşcı, 2016 [13] RCT HD LI11 High
Jedras et al., 2003 [74] RCT HD 140 acupoints (20 each on the head, hands, trunk, legs) High
Jiu et al., 2015 [75] RCT HD Umbilicus High
Open in a new tab

RCT: Randomized controlled trial, CKD: Chronic kidney disease, PD: Peritoneal dialysis, HD: Hemodialysis

Distribution of the acupoints

This analysis identified a total of 64 acupoints according to the previous meta-analysis articles. Figure 1 illustrates the distribution frequency of the acupoints. The ten most frequently used acupuncture acupoints for treating UP were Quchi (LI11), Zusanli (ST36), Xuehai (SP10), Auricular Shenmen (TF4), Sanyinjiao (SP6), Auricular lung (CO14), Auricular Neifenmi (CO18), Auricular Pizhixia (AT4), Auricular kidney (CO10), and Hegu (LI4).

Figure 1.

Figure 1

Open in a new tab

The frequency distribution of acupoints utilized in the meta-analysis encompassing 40 randomized controlled trials on acupuncture treatments for uremic pruritus

Association rule analysis of acupoint combinations’ item sets using the apriori algorithm

Based on data from 40 RCTs, this study analyzed 71 association rules. A scatter plot was formed to illustrate the association rules, featuring support values along the x-axis and confidence values along the y-axis. The lift value determined the color of each association rule on the plot, as shown in Figure 2. The results disclosed that each association rule exhibited a notably high lift, indicating a substantially increased likelihood of acupoint combinations co-occurring in association rules compared to the occurrence of a single acupoint. The association rules demonstrated a confidence value of one for all cases, indicating that whenever an antecedent acupoint was present in an acupuncture treatment, the consequent acupoint appeared together. Figure 2 illustrates overlaps among the 71 association rules, presented on both the left and right sides of the figure. However, based on the support values, the antecedent acupoint within each association rule exhibited limited frequency across the 71 formulas, indicating that each formula employed for UP treatment operated independently. Table 2 presents the top ten association rules of the acupoints generated using the Apriori algorithm, ordered based on their lift values.

Figure 2.

Figure 2

Open in a new tab

A scatter plot illustrating the 71 association rules derived from the meta-analysis of 40 randomized controlled trials on acupuncture treatments for uremic pruritus

Table 2.

Association rules based on the Apriori algorithm for the acupoints utilized in the 40 randomized controlled trials incorporated in the meta-analysis assessing acupuncture interventions for uremic pruritus

Number Association rules Support Confidence Expected confidence Lift
1 (CO14)≥(Extra14) 0.125 1.000000 0.125 8.0
2 (Extra14)≥(CO14) 0.125 1.000000 0.125 8.0
3 (BL17)≥(LI11) 0.125 1.000000 0.125 4.8
4 (AH6a)≥(LI11) 0.125 1.000000 0.125 4.8
5 (LU5)≥(LI4) 0.125 1.000000 0.125 4.8
6 (LU5)≥(LI11) 0.125 1.000000 0.125 4.8
7 (CO14)≥(SP6) 0.125 1.000000 0.125 4.8
8 (Extra14)≥(SP6) 0.125 1.000000 0.125 4.8
9 (TG2p)≥(TF4) 0.125 1.000000 0.125 4.0
10 (BL17)≥(TF4) 0.125 1.000000 0.125 4.0
Open in a new tab

Figure 3 displays a matrix diagram that depicts the distribution of grouped association rules. The diagram revealed that the association rules were grouped similarly into clusters. The 20 clusters are represented on the horizontal axis, and the items generated by these clusters are represented on the vertical axis. The intensity of color within individual circles corresponds to the magnitude of lift, with darker colors indicating higher lift degrees. The circle size represents the support degree, with larger circles indicating higher support degrees. The acupoint combinations (Auricular shenmen [TF4], Quchi [LI11]) ≥ (Geshu [BL17]), (Auricular heart [Extra14], Sanyinjiao [SP6]) ≥ (Auricular lung [CO14]), (Auricular lung [CO14], Sanyinjiao [SP6]) ≥ (Auricular heart [Extra14]), (Auricular heart [Extra14], Xuehai [SP10]) ≥ (Auricular lung [CO14]), and (Auricular lung [CO14], Xuehai [SP10]) ≥ (Auricular heart [Extra14]) were selected to pair with association rules, items range from the antecedent (left-hand side, LHS) to the consequent (right-hand side, RHS) item sets. The acupoint combinations corresponded with association rules #1 (Auricular lung [CO14]) ≥ (Auricular heart [Extra14]), #2 (Auricular heart [Extra14]) ≥ (Auricular lung [CO14]), #3 (Geshu [BL17]) ≥ (Quchi [LI11]), #7 (Auricular lung [CO14]) ≥ (Sanyinjiao [SP6]), #8 (Auricular heart [Extra14]) ≥ (Sanyinjiao [SP6]), and #10 (Geshu [BL17]) ≥ (Auricular shenmen [TF4]), as shown in Table 2.

Figure 3.

Figure 3

Open in a new tab

A grouping matrix displaying the association rules derived from the meta-analysis of 40 randomized controlled trials on acupuncture treatments for uremic pruritus

Figure 4 displays a combination matrix diagram that visually depicts the connections of the association rules derived from the data presented as shown in Figure 3. The locations of the core acupoints are marked in Figure 5.

Figure 4.

Figure 4

Open in a new tab

Matrix of combinations illustrating the association rules derived from the meta-analysis of 40 randomized controlled trials investigating acupuncture treatments for uremic pruritus

Figure 5.

Figure 5

Open in a new tab

The site of the core acupoints is determined from the association rules obtained in the meta-analysis of 40 randomized controlled trials on acupuncture treatments for uremic pruritus

DISCUSSION

Acupoint stimulation has been shown to play a significant role in improving UP, according to the meta-analysis from which this study was derived[11]. In addition, this study revealed the three core combinations of acupoint stimulations commonly used to treat UP: (Auricular shenmen [TF4], Quchi [LI11] and Geshu [BL17]), (Auricular heart [Extra14], Sanyinjiao [SP6] and Auricular lung [CO14]), and (Auricular heart [Extra14], Xuehai [SP10], and Auricular lung [CO14]). This study appears to be the first to study the potential core acupoint combinations used in acupuncture and related techniques to treat UP.

Previous studies have documented the mechanisms of acupuncture and related techniques, including acupressure, TEAS, and auricular acupressure for treating pruritus[21]. Tang et al. found that acupuncture could alleviate acute itchiness through the downregulation of 5-HT, blocking its receptor expression, and electroacupuncture may relieve chronic itching by regulating cytokine and opioid peptide receptor activities[22]. Auricular acupressure has been reported to alleviate UP by reducing histamine levels[12], activating the nociceptor and central analgesic systems[23], and regulating the proportion of T lymphocyte subsets[24]. An RCT conducted by Kılıç Akça and Taşcı reported that acupressure and TEAS had anti-pruritus effects on dialysis patients according to the reduction in the level of antihistaminic agents[13].

In accordance with the theory of Chinese medicine that “lungs control the skin” the physiology includes regulating the mucosa immune system and activating skin-associated lymphoid tissues, such as immune cells in the epidermis and dermis[25]. According to the theory, “all pains and pruritus belong to the heart” it is believed that the heart controls blood vessels and blood syndromes[26]. The moisture from blood can help alleviate pruritus by nourishing the skin[26]. In addition, the theory “Blood confluence to Geshu (BL17)” indicates the significance of regulating blood circulation by acupoint Geshu stimulation[27]. These theories and mechanisms might explain how the core acupoint combinations with Auricular lung (CO14), Auricular heart (Extra14), Xuehai (SP10), and Geshu (BL17) have shown promising results in effectively alleviating the itching sensation experienced by dialysis patients. Compared to non-UP patients, UP patients exhibit higher levels of P, iPTH, and inflammatory indices[28]. Augmentation of peripheral nerve stimulation can result from elevated levels of calcium and phosphate[29]. PTH is linked to the activation of mast cells, inducing the release of histamine and provoking itching[30]. Our study demonstrated TF4, CO14, LI11, BL17, Extra14, SP6, and SP10 as the core acupoint combination for treating UP.

Three acupoints (SP10, SP6, and LI11) identified in our study were shown to improve UP symptoms and decrease the levels of phosphorus, PTH, and β2-MG of the UP patients by Chu et al.[31]. The other four acupoints (CO10, CO14, Extra14, and TF4) mentioned in our study were reported to improve UP symptoms and decrease the levels of phosphorus and PTH of the UP patients by Ding et al.[32]. Besides the aforementioned clinical trials, the acupoint (LI11), identified in our study, alleviated pruritus, restlessness, and sleep onset difficulties in a case series of 40 patients with UP underwent dialysis therapy[33]. In another case series treating 8 individuals, Shapiro et al. employed acupoints LI11, ST36, SP6, and SP10, demonstrating effective outcomes for UP[34] and three of the acupoints (LI11, SP6, and SP10) coincided with the acupoint combination we have identified.

The results had similar findings to previous studies on acupoints, which demonstrated that the combination of Geshu (BL17), auricular point Ear shenmen (TF4), and Auricular lung (CO14) effectively reduced immunoglobulin E and interleukin-4 serum levels and enhanced the quality of life of patients with urticaria[35]. In addition, acupuncture of the Auricular lung (CO14) combined with the Auricular heart (Extra14) affected urticaria and alleviated pruritus[36]. Karjalian et al. reported that the application of acupressure on Sanyinjiao (SP6), Xuehai (SP10), and Quchi (LI11) resulted in the alleviation of UP in dialysis patients by reducing serum phosphorus and parathyroid hormone levels[37], as shown in Table 3.

Table 3.

The potential effectiveness of acupuncture’s core acupoints in treating uremic pruritus

Point Chinese name English name Primary meridians Effectiveness
TF4 [76] Er shenmen Auricular shenmen Nil Increasing vagal tone, regulating systematic functioning, and reducing inflammation
LI11 [53] Quchi Crooked Pond Large Intestine Stimulating opiate-like substances release which blocks the slower C fiber impulses
BL17 [77] Geshu Diaphragm’s Hollow Bladder Nourishing blood and stopping itching sensation
Extra14 [78] Xinzang Auricular Heart Nil Nourishing blood to alleviate itching sensation, all pains, and pruritus belong to the heart
SP6 [77] Sanyinjiao Three Yin Meeting Spleen Promoting blood circulation and intensifying the blood activation sensation
CO14 [79] Fei Auricular Lung Nil Dispel wind-heat toxin to alleviate the itching sensation and lung control for the skin and hair
SP10 [77] Xuehai Sea of Blood Spleen Nourishing blood and stopping the itching sensation
Open in a new tab

Previous studies have disclosed that multi-point acupuncture was more effective than single-point acupuncture in treating primary insomnia[38] and dysmenorrhea[39]. Zhang et al. observed more brain activity regions after multi-point acupuncture compared with single-point acupuncture. This outcome could be attributed to the synergistic effect of multiple acupoints[40]. Nonetheless, there is limited supporting evidence of acupoint stimulation without the standard treatment for UP[8]. Therefore, it is crucial to employ data-mining techniques to identify the essential combinations of acupoints for the treatment of UP.

Despite identifying potential core acupoints for acupuncture and related techniques for treating UP, limitations exist within this study. First, the RCTs exhibit a high RoB might be related to the non-blinding outcome measurements and randomization processes. To address this, future studies should provide more detailed descriptions of their randomization procedures. Second, there is still limited information available regarding the mechanism of individual acupoints and their interactions. Finally, the analysis was limited by the small, regionally focused population and restricted by the prescription of acupoint combinations. Therefore, it is recommended that future studies should include a more diverse population and acupoint combinations.

CONCLUSION

The identified acupoint combinations for treating UP by acupuncture and related techniques were #1 Auricular shenmen (TF4), Quchi (LI11), and Geshu (BL17); #2 Auricular heart (Extra14), Sanyinjiao (SP6), and Auricular lung (CO14); and #3 Auricular heart (Extra14), Xuehai (SP10), and Auricular lung (CO14). An Apriori association rule and the observed effectiveness were used to identify core treatment approaches for UP. However, further studies are needed to investigate the interactions between acupoints and the underlying mechanisms of efficacy.

Data availability statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Financial support and sponsorship

This work was supported by grants from the Buddhist Tzu Chi Medical Foundation, Taiwan (TCMF-CM1-111-03).

Conflicts of interest

There are no conflicts of interest.

Supplementary material available online

Supplementary Figure 1

Risk of bias in the selected studies

TCMJ-36-195_Suppl1.tif (1.1MB, tif)

Acknowledgments

We would like to thank all our colleagues at Mackay Memorial Hospital and Taipei Tzu Chi Hospital for helping with this study. We greatly appreciate the technical support from the Core Laboratory of the Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation.

REFERENCES

  • 1.Satti MZ, Arshad D, Javed H, Shahroz A, Tahir Z, Ahmed MM, et al. Uremic pruritus: Prevalence and impact on quality of life and depressive symptoms in hemodialysis patients. Cureus. 2019;11:e5178. doi: 10.7759/cureus.5178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Combs SA, Teixeira JP, Germain MJ. Pruritus in kidney disease. Semin Nephrol. 2015;35:383–91. doi: 10.1016/j.semnephrol.2015.06.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Ko MJ, Peng YS, Wu HY. Uremic pruritus: Pathophysiology, clinical presentation, and treatments. Kidney Res Clin Pract. 2023;42:39–52. doi: 10.23876/j.krcp.21.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Osakwe N, Hashmi MF. StatPearls [Internet] Treasure Island (FL): StatPearls Publishing; 2024. Jan, Uremic pruritus evaluation and treatment. Available from: https://www.ncbi.nlm.nih.gov/books/NBK587340/PublishingLLC ; 2023. [PubMed] [Google Scholar]
  • 5.Li L, Liu R, Peng C, Chen X, Li J. Pharmacogenomics for the efficacy and side effects of antihistamines. Exp Dermatol. 2022;31:993–1004. doi: 10.1111/exd.14602. [DOI] [PubMed] [Google Scholar]
  • 6.Jhaj R, Asati DP, Chaudhary D, Sadasivam B. Topical steroid containing combinations: Burden of adverse effects and why the recent regulatory action may not be enough. Indian J Pharmacol. 2021;53:371–6. doi: 10.4103/ijp.IJP_728_19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Wiffen PJ, Derry S, Bell RF, Rice AS, Tölle TR, Phillips T, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6:CD007938. doi: 10.1002/14651858.CD007938.pub4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Lu PH, Tai YC, Yu MC, Lin IH, Kuo KL. Western and complementary alternative medicine treatment of uremic pruritus: A literature review. Tzu Chi Med J. 2021;33:350–8. doi: 10.4103/tcmj.tcmj_151_20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Zhang L, Li Y, Xiao X, Shi Y, Xu D, Li N, et al. Acupuncture for uremic pruritus: A systematic review and meta-analysis. J Pain Symptom Manage. 2023;65:e51–62.. doi: 10.1016/j.jpainsymman.2022.08.017. [DOI] [PubMed] [Google Scholar]
  • 10.Badiee Aval S, Ravanshad Y, Azarfar A, Mehrad-Majd H, Torabi S, Ravanshad S. A systematic review and meta-analysis of using acupuncture and acupressure for uremic pruritus. Iran J Kidney Dis. 2018;12:78–83. [PubMed] [Google Scholar]
  • 11.Lu PH, Chung CH, Chuo HE, Lin IH, Lu PH. Efficacy of acupoint stimulation as a treatment for uremic pruritus: A systematic review and meta-analysis. Front Med (Lausanne) 2022;9:1036072. doi: 10.3389/fmed.2022.1036072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Yan CN, Yao WG, Bao YJ, Shi XJ, Yu H, Yin PH, et al. Effect of auricular acupressure on uremic pruritus in patients receiving hemodialysis treatment: A randomized controlled trial. Evid Based Complement Alternat Med. 2015;2015:593196. doi: 10.1155/2015/593196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Kılıç Akça N, Taşcı S. Acupressure and transcutaneous electrical acupoint stimulation for improving uremic pruritus: A randomized, controlled trial. Altern Ther Health Med. 2016;22:18–24. [PubMed] [Google Scholar]
  • 14.Wu WT, Li YJ, Feng AZ, Li L, Huang T, Xu AD, et al. Data mining in clinical big data: The frequently used databases, steps, and methodological models. Mil Med Res. 2021;8:44. doi: 10.1186/s40779-021-00338-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Shang PP, Chen CT, Cheng M, Shi YL, Yang YQ, Wang Y, et al. Analysis of acupoint selection and combinations in acupuncture treatment of asthma based on data mining. Complement Med Res. 2022;29:136–46. doi: 10.1159/000521346. [DOI] [PubMed] [Google Scholar]
  • 16.Li ZX, Lan DC, Zhang HH, Sun J, Chen XZ, Huang RZ, et al. Acupoints selection exploring for acupuncture treatment of insulin resistance based on data mining. Zhen Ci Yan Jiu. 2016;41:545–9. [PubMed] [Google Scholar]
  • 17.Xu J, Lu Z, Zhang H, Shen Y, Zhao H. Analysis on acupoint selection and combination for amyotrophic lateral sclerosis treated with acupuncture based on data mining. Evid Based Complement Alternat Med. 2022;2022:6541600. doi: 10.1155/2022/6541600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Bayardo RJ, Agrawal R. Proceedings of the fifth ACM SIGKDD international conference on knowledge discovery and data mining. San Diego, California, USA: Association for Computing Machinery; 1999. Mining the most interesting rules; pp. 145–54. [Google Scholar]
  • 19.Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. doi: 10.1136/bmj.l4898. [DOI] [PubMed] [Google Scholar]
  • 20.Verzani J. Sebastopol, CA, USA: O’Reilly Media, Inc; 2011. Getting started with r studio. [Google Scholar]
  • 21.Xiong W, He FF, You RY, Xiong J, Wang YM, Zhang C, et al. Acupuncture application in chronic kidney disease and its potential mechanisms. Am J Chin Med. 2018;46:1169–85. doi: 10.1142/S0192415X18500611. [DOI] [PubMed] [Google Scholar]
  • 22.Tang Y, Cheng S, Wang J, Jin Y, Yang H, Lin Q, et al. Acupuncture for the treatment of itch: Peripheral and central mechanisms. Front Neurosci. 2021;15:786892. doi: 10.3389/fnins.2021.786892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev. 2020;100:945–82. doi: 10.1152/physrev.00017.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Yang T, Wang S, Zhang X, Liu L, Liu Y, Zhang C. Efficacy of auricular acupressure in maintenance haemodialysis patients: A systematic review and meta-analysis. J Clin Nurs. 2022;31:508–19. doi: 10.1111/jocn.15966. [DOI] [PubMed] [Google Scholar]
  • 25.Hu ZW, Zhuo YP. The basic concept and discussion of immunology of “lung governing skin and hair. ” Liaoning J Tradit Chin Med. 2004;31:200. [Google Scholar]
  • 26.Liqiao S, Fengzhi L, Yin W, Tong L, Ning K. Treatment of radiation dermatitis based on “all pains and itchy sores belong to the heart. ” Liaoning J Tradit Chin Med. 2023;50:71–3. [Google Scholar]
  • 27.Li-Jun G, Ji-Hong W, Yi-Cheng G. Exploration of the theory of blood confluence to Geshu. J Basic Chin Med. 2021;27:1925–8. [Google Scholar]
  • 28.Zhao JH, Zhu QS, Li YW, Wang LL. Determinants of the intensity of uremic pruritus in patients receiving maintenance hemodialysis: A cross-sectional study. PLoS One. 2021;16:e0245370. doi: 10.1371/journal.pone.0245370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Keshari S, Sipayung AD, Hsieh CC, Su LJ, Chiang YR, Chang HC, et al. IL-6/p-BTK/p-ERK signaling mediates calcium phosphate-induced pruritus. FASEB J. 2019;33:12036–46. doi: 10.1096/fj.201900016RR. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Bai YF, Wang CL, Xu MZ, Pan MJ, Sun QY, Chen RM. The clinical effectiveness and safety of traditional Chinese medicine uremic clearance granule combined with high-flux hemodialysis in the treatment of uremic pruritus: A protocol for systematic review and meta analysis. Medicine (Baltimore) 2021;100:e26423. doi: 10.1097/MD.0000000000026423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Chu LC, Hsu WC, Li CJ, Huang HH, Chen HL. Clinical effect for pruritus of replenishing and reducing acupuncture in maintenance hemodialysis and the influence of serum iPTH and β2–MG. Chronic Pathematol J. 2018;19:1763–6. [Google Scholar]
  • 32.Ding JF, Yau SM, Peng W, Wang H, Wang YM, Ju BB, et al. Observation and mechanism of auricular acupressure on uremic pruritus in peritoneal dialysis. Chin J Integrat Tradit West Nephrol. 2019;19:626–7. [Google Scholar]
  • 33.Chou J, Chen QK, Luo LM. Acupuncture treatment of uremic pruritus: A case series of 40 patients. Chin Acupunct. 2002;8:518. [Google Scholar]
  • 34.Shapiro RS, Stockard HE, Schank A. Successful treatment of uremic pruritus with acupuncture. Am J Acupunct. 1986;14:235–42. [Google Scholar]
  • 35.Wang YJ, Shi Y, Li HK, Sun B, Xue WH, Liu HQ. Chronic spontaneous urticaria treated with bloodletting therapy and auricular point sticking on the base of xuanfu theory: A randomized controlled trial. Zhongguo Zhen Jiu. 2022;42:157–61. doi: 10.13703/j.0255-2930.20210719-0005. [DOI] [PubMed] [Google Scholar]
  • 36.Hu Z, Tsai H. Recent evidence of auricular acupoint treatments of skin disease. Jiangsu J Tradit Chin Med. 2003;24:59–61. [Google Scholar]
  • 37.Karjalian F, Momennasab M, Yoosefinejad AK, Jahromi SE. The effect of acupressure on the severity of pruritus and laboratory parameters in patients undergoing hemodialysis: A randomized clinical trial. J Acupunct Meridian Stud. 2020;13:117–23. doi: 10.1016/j.jams.2020.05.002. [DOI] [PubMed] [Google Scholar]
  • 38.Feng WW, Yuan B, Shen FY, Fan WY, Mei DS, Bao BY, et al. Efficacy of uremic pruritus treatment in patients undergoing hemodialysis, a network meta-analysis for randomized clinical trials. Nephrol Ther. 2021;17:30–4. doi: 10.1016/j.nephro.2020.09.006. [DOI] [PubMed] [Google Scholar]
  • 39.Chen SZ, Cong Q, Zhang BF. Preliminary comparison on the time-effect rule of pain-relieving in the treatment of moderate dysmenorrhea between acupuncture on single-point and acupuncture on multi-point. Zhongguo Zhen Jiu. 2011;31:305–8. [PubMed] [Google Scholar]
  • 40.Zhang J, Zheng Y, Wang Y, Qu S, Zhang S, Wu C, et al. Evidence of a synergistic effect of acupoint combination: A resting-state functional magnetic resonance imaging study. J Altern Complement Med. 2016;22:800–9. doi: 10.1089/acm.2016.0016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Ardinata D, Zain-Hamid R, Roesyanto-Mahadi ID, Mihardja H. Interleukin-31 serum and pruritus dimension after acupuncture treatment in hemodialysis patients: A randomized clinical trial. Open Access Maced J Med Sci. 2021;9:196–201. [Google Scholar]
  • 42.Juan F. Observation on the application of integrated traditional Chinese and Western medicine nursing on complications after hemodialysis. GuangMing J Chin Med. 2021;36:3167–9. [Google Scholar]
  • 43.Jiang JJ, Ye XS, Jiang LY, Yang J, Yan WY, Chen Y, et al. Effect of hemoperfusion combined with acupuncture on pruritus in the elderly patients with uremia. Pract Geriat. 2021;35:1281–3. [Google Scholar]
  • 44.Zhang S. Clinical observation on the acupuncture in the treatment of skin itching due to blood deficiency and wind-dying in maintenance hemodialysis. Grad Thesis of Guangzhou Univ Chin Med. 2020 [Google Scholar]
  • 45.Liu CF. Clinical observation on acupuncture of quchi and xuehai in maintenance hemodialysis. Res Integrat Tradit Chin West Med. 2018;10:256–7. [Google Scholar]
  • 46.Nahidi Y, Badiee S, Torabi S, Abbasi SZ, Nazemian F, Saki A. Acupuncture effect on pruritus in hemodialysis patients: A randomized clinical trial. Iran Red Crescent Med J. 2018;20:1–7. [Google Scholar]
  • 47.Phan FA, Srilestari A, Mihardja H, Marbun MB. Effects of acupuncture on uremic pruritus in patients undergoing hemodialysis. J Phys Conf Ser. 2018;1073:062049. [Google Scholar]
  • 48.Pu LC. Effectiveness of the acupuncture combined hemodialysis plus hemoperfusion for uremic pruritus. Heath. 2017;8:109–10. [Google Scholar]
  • 49.Chang KS, Lei TS, Ju SR, Lan S, Shiu HJ, Fei TH, et al. Improvement of uremic pruritus in hmodialysis with citric acid: 17 cases. J Jiangxi Univ Tradit Chin Med. 2017;6:40–2. [Google Scholar]
  • 50.Ono S, Mukaino Y. Efficacy and cost effectiveness of the acupuncture treatment using a new skin stimulus tool called m-test which is a measure based on symptoms accompanied with body movements: A pragmatic RCT targeting hemodialysis patients. Evid Based Complement Alternat Med. 2015;2015:802846. doi: 10.1155/2015/802846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Ma LL, Chang PJ, Ren K. Treatment of uremic pruritus with acupuncture combined hemodialysis plus hemoperfusion. J Beijing Univ Tradit Chin Med. 2014;21:28–30. [Google Scholar]
  • 52.Chang F, Chiu CL, Huang HS, Fang SS, Shen Y. The effectiveness of treatment of uremic puritus with acupuncture combined hemodialysis plus hemoperfusion. J Pract Med. 2011;27:1687–9. [Google Scholar]
  • 53.Chou CY, Cheng YW, Kao MT, Huang CC. Acupuncture in haemodialysis patients at the Quchi (LI11) acupoint for refractory uraemic pruritus. Nephrol Dial Transplant. 2005;20:1912–5. doi: 10.1093/ndt/gfh955. [DOI] [PubMed] [Google Scholar]
  • 54.Ruei HR, Lin WM, Sha JP. Observation on therapeutic effect of 80 cases of uremic cutaneous pruritus treated with acupuncture. Chin Acupunct Moxibustion. 2002;22:235–6. [Google Scholar]
  • 55.Kao HM, Chang WH, Wang Y. Acupuncture for uremic cutaneous pruritus: 34 cases. J Tradit Chin Med. 2002;5:312. [PubMed] [Google Scholar]
  • 56.Mai DY. Auricular acupressure combined hemodialysis plus hmoperfusion for uremic cutaneous pruritus. World Latest Med Inf. 2021;21:188–92. [Google Scholar]
  • 57.Yan C, Li J, Liu G. The effection of the serum level of IL-6 on patients rceiving hemodialysis treatment for uremic pruritus by auricular acupressure. J Integrat Tradit West Nephrol. 2021;22:499–502. [Google Scholar]
  • 58.Yu R, Yang WD, Chen RJ, Huang NN, Lu XM. Auricular copper scarping therapy for uremic cutaneous pruritus: 50 cases. Fujian J Tradit Chin Med. 2021;52:52–4. [Google Scholar]
  • 59.Zhai J. Observation on the effect of auricular point on skin pruritus in hemodialysis patients with uremia. Contemp Med Symp. 2021;18:169–70. [Google Scholar]
  • 60.Chen D, Ou Yang TP, Wen F. Clinical observation of patients with chronic kidney disease-mineral and bone abnormalities by auricular point pressing combined with Ncturnal Ddialysis. Yunnan J Tradit Chin Med Mater Med. 2020;41:54–7. [Google Scholar]
  • 61.Yan C, Yau WG, Liu G, Wang H, Li J, Shia M. Observation of auricular acupressure on the pruritus of the patients in maintenance hemodialysis. Chin J Integrat Tradit West Nephrol. 2020;21:512–4. [Google Scholar]
  • 62.He CC, Guo JJ, Shia A, Wu LC, Jau DS, Wu SC, et al. Therapeutic effect of auricuIar acupressure on the treatment of pruritus in maintenance hemodiaIysis patients. Tradit West Nephrol. 2018;19:919–21. [Google Scholar]
  • 63.Lin L. The influence of Chinese medication fumigation combined auricular acupressure on cutaenous pruritus of chronic kidney disease. Chin J Integrat Tradit West Nephrol. 2018;19:626–7. [Google Scholar]
  • 64.Li L, Ma J. Effects of auricular points taping and pressing with nursing intervention on ESRD pruritus in maintenance hemodialysis patients. J Hubei Univ Chin Med. 2017;19:92–4. [Google Scholar]
  • 65.Tao C. Analysis of auricular acupressure on uremic cutaneous pruritus in hemodialysis. J Sci Nat. 2016;28:464–5. [Google Scholar]
  • 66.Shr CJ, Shiu C, Shiu TY, Tzou SL, Hu PP, Wang M. Clinical observation on treating MHD complications by hemoperfusion joint auricular acupressure. Clin J Chin Med. 2012;4:7–9. [Google Scholar]
  • 67.Hsu MC, Chen HW, Hwu YJ, Chanc CM, Liu CF. Effects of thermal therapy on uremic pruritus and biochemical parameters in patients having haemodialysis. J Adv Nurs. 2009;65:2397–408. doi: 10.1111/j.1365-2648.2009.05100.x. [DOI] [PubMed] [Google Scholar]
  • 68.Wang J, Liu P, Tsai BL. Acupoint injection for uremic cutaneous pruritus in hemodialysis maintenance: 55 cases. Jiangsu J Tradit Chin Med. 2021;53:51–4. [Google Scholar]
  • 69.Deng HY. Observation of acupoint injection combined acupuncture in uremic cutaneous pruritus: 23 cases. World Latest Med Inf. 2017;15:233–4. [Google Scholar]
  • 70.Wang M, Shr CJ, Hsiao HH. Observation of acupoint injection combined acupuncture in uremic ctaneous Ppruritus: 56 cases. Pract Clin J Integrat Tradit Chin West Med. 2004;4:17–8. [Google Scholar]
  • 71.Chen GM, Du JT, Kuang H, He YC, Li J. Clinical observation on treating skin itching in maintenance hemodialysis patients by self blood acupoint injection plus point massage. Clin J Chin Med. 2017;9:100–2. [Google Scholar]
  • 72.Yi JC, Zheng MX. Therapeutic effect of infrared aupoint Iirradiation combined with local irradiation on uremic pruritus caused by maintenance hemodiaIysis. J Yichun Univ. 2018;40:70–2. [Google Scholar]
  • 73.Chen Y. The efficacy of high-flux hemodialysis combined with acupoint press for uremic pruritus in hemodialysis patients. World Latest Med Inf. 2021;21:132–3. [Google Scholar]
  • 74.Jedras M, Bataa O, Gellert R, Ostrowski G, Wojtaszek E, Lange J, et al. Acupressure in the treatment of uremic pruritus. Dial Transplant. 2003;32:8–10. [Google Scholar]
  • 75.Jiu SG, Li YS, Li WY, Jin F, Miau HD. Umbilical acupoint sticking therapy combined different blood purification methods on cutaneous pruritus in hemodialysis patients. Gansu Zhongyi Xueyuan Xuebao. 2015;32:44–7. [Google Scholar]
  • 76.Chen CC, Chen SP, Lyu SY, Hsu CH. Application of auriculotherapy for post-burn scar syndrome in young adults with major burns. J Acupunct Meridian Stud. 2021;14:127–36. doi: 10.51507/j.jams.2021.14.4.127. [DOI] [PubMed] [Google Scholar]
  • 77.QI Y. Unexpected massive cutaneous pruritus treated by acupuncture. World J Acupunct-Moxibustion. 2012;22:65–6. [Google Scholar]
  • 78.Guan SF. The treatment of auricular acupressure in skin pruritus. Chin Acuponct Moxibustion. 2002;22:827. [Google Scholar]
  • 79.Bo XZ. Clinical experience of the treatment of chronic skin diseases by auricular point-pressing therapy combined with Chinese herbal medicine. J Chin Med. 2011:21–3. [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Figure 1

Risk of bias in the selected studies

TCMJ-36-195_Suppl1.tif (1.1MB, tif)

Data Availability Statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Articles from Tzu-Chi Medical Journal are provided here courtesy of Wolters Kluwer -- Medknow Publications

RESOURCES