Acupuncture on Renal Function in Patients with Chronic Kidney Disease: A Single-Blinded,Randomized,Preliminary Controlled Study

Abstract

Objective:

To evaluate the feasibility effect of acupuncture on renal function in patients with chronic kidney disease (CKD).

Methods:

In total, 59 patients with CKD were randomized into acupuncture (AG; n = 30) and sham acupuncture (CG; n = 29) treatment groups. In the AG, acupuncture was applied to bilateral Hegu (LI4), Zusanli (ST36), and Taixi (KI3) to obtain qi, and electroacupuncture (2 Hz) was applied to two acupoint pairs (right Zusanli and Taixi and left Zusanli and Taixi) once per week for 12 weeks. In the CG, the acupuncture methods were identical to in the AG, and the acupuncture needle was applied to the subcutaneous layer at 1.5 cm lateral to the aforementioned acupoints, without electrical discharge. The levels of serum creatinine and estimated glomerular filtration rate (eGFR) were measured at 3 months (observation period; O), immediately before the acupuncture treatment (baseline; B), at 12 weeks (after treatment completion; T12), and at the 3-month follow-up (postacupuncture treatment; P).

Results:

In total, 53 patients (AG, n = 28; CG, n = 25) with CKD completed the trial. The serum creatinine levels at baseline (B) were 1.45 mg/dL in the AG and 1.67 mg/dL in the CG (p = 0.1298). Furthermore, the change in serum creatinine levels after the acupuncture treatment (T12) was 1.41 mg/dL in the AG and 1.65 mg/dL in the CG (p = 0.0489). The eGFR at baseline was 51.85 mL/min/1.73 m² in the AG and 42.50 mL/min/1.73 m² in the CG (p = 0.0855). The change in the eGFR after the acupuncture treatment was 54.50 mL/min/1.73 m² in the AG and 43.60 mL/min/1.73 m² in the CG (p = 0.0470).

Conclusion:

Acupuncture at bilateral Hegu, Zusanli, and Taixi for 12 weeks reduced creatinine levels and increased eGFR levels. The study only provided a feasibility method for the treatment of patients with CKD. However, the results of this preliminary study warrant further investigation.

Introduction

Chronic kidney disease (CKD) is a global health problem. In 2010, end-stage renal disease (ESRD) was considered the ninth leading cause of death in the United States,¹ accounting for a total medical expense of U.S. $2.83 billion. Since 2000, Taiwan has had the highest incidence and prevalence of ESRD worldwide, affecting 400 patients with CKD per million persons, according to the U.S. Renal Data System (2007).² Statistics from the Bureau of National Health Insurance indicates that ESRD affected 0.23% of the entire population; however, dialysis accounted for 7.2% of the healthcare budget.³ Hence, ESRD cannot be neglected. The high prevalence of ESRD in Taiwan may be due to the high rate of CKD in this country.

The course of CKD can be divided into five stages, and disease progression is characterized by a decline in renal function and the glomerular filtration rate (GFR).⁴ The prevalence of CKD is gradually increasing and it currently has few therapeutic options, which result in an increased psychologic and economic burden on the patients. Patients typically experience frustration and helplessness after being diagnosed with CKD, and this depression is known to affect the mortality rate in patients with ESRD.⁵ Furthermore, the incidence of CKD increased with the prevalence of chronic diseases, such as diabetes mellitus (DM), high blood pressure, and cardiovascular diseases, in young populations⁶ and in the aging population (>65 years).⁷ In addition to high blood pressure, DM, and obesity,⁸ hypercholesterolemia; high uric acid levels; cigarette smoking; and consumption of alcohol, traditional medicine, and nonprescription medications (over-the-counter medications) are key factors that affect the kidney.⁹ Symptoms that develop during CKD progression are proteinuria, peripheral edema, high blood pressure, anemia, and fatigue.¹⁰

Acupuncture as the complementary and alternative therapeutic method has been used for treating various diseases. To the best of our knowledge, reports about the clinical trial for acupuncture treating CKD are few; an animal study showed that the stimulation of Zusanli (ST36) by electroacupuncture (EA) could help to prevent the decrease in endothelial nitric oxide synthase in the blood, which reduces pressure in the renal artery and has a protective effect against a decline in renal function.¹¹ Moreover, EA reduced serum levels of tumor necrosis factor-alpha (TNF-α) and exerted anti-inflammatory effects.¹² Periorbital acupuncture, a modified type of acupuncture, alleviates chemically induced renal injury in animals.¹³ Moreover, acupoint massage is a noninvasive technique that involves massaging an acupuncture point to elevate energy that promotes health and comfort. For instance, massaging Ear Shenmen (MA-TF1), Hand Shenmen (HT7), and Yung Chuan (K11) helps treat sleep disturbances¹⁴; massaging Sanyinjiao (SP6), Zusanli, and Yanglingchuan (GB34) can improve fatigue.¹⁵ Besides, acupressure or acupuncture on Hegu (LI4) exerts pain-relieving and anti-inflammatory effects.¹⁶ Moreover, acupuncture on Taixi (KI3) treats impotence, renal disease, and cognitive disorders.¹⁷

CKD can slowly progress into renal failure, over a few months or years, under the influence of risk factors. In case of severe renal failure, the symptoms are those of uremic syndrome, such as dizziness, nausea, vomiting, confusion, weakness, and loss of appetite, cramping, or shock.¹⁸ At this stage, no medication is helpful, and patients require kidney transplantation or dialysis to sustain life. Therefore, the authors assume that acupuncture can prevent or slow down renal function decline, even improve in patients with CKD. The authors designed a single-blinded, randomized, preliminary controlled study to investigate the feasibility effect of acupuncture on renal function, including serum creatinine and the estimated GFR (eGFR), in patients with CKD.

Materials and Methods

Patients

In total, 81 patients with CKD were enrolled from March 2014 to March 2015 at the Chi Mei Medical Center (Tainan, Taiwan). Twenty patients were excluded because they did not meet the inclusion criteria, and two patients refused to participate in the trial. Thus, 59 patients with CKD were randomized into the trial (Fig. 1). The research protocol was reviewed and approved by the Institutional Review Board of Chi Mei Medical Center (IRB no. 10302-006). Written informed consent was obtained from all patients before the trial. Each patient was first evaluated, and CKD diagnosis was confirmed by nephrologists. Serum biochemistry and routine urine analyses were performed, and blood pressure was measured for all patients before the study. Specific inclusion and exclusion criteria^19,20 are listed as follows.

FIG. 1.

Flowchart of screening and enrollment.

The inclusion criteria included (1) age, 20–80 years; (2) eGFR, 15–89 mL/min/1.73 m² and stage 2–4 CKD according to the Kidney Disease Outcomes Quality Initiative (KDOQI) classification; and (3) CKD defined as either kidney damage or eGFR <60 mL/min/1.73 m² for 3 months and kidney damage defined as pathologic abnormalities or damage markers, including abnormalities in blood or urine tests or imaging studies, according to the KDOQI CKD guidelines.

The exclusion criteria were (1) intake of nonsteroidal anti-inflammatory or immunosuppressive drugs or a diagnosis of diseases, such as acute myocardial infarction and cerebrovascular accident, within the past 6 months; (2) blood pressure exceeding 200/120 mmHg; (3) obstructive uropathy; and (4) comorbidity of insulin-dependent DM, collagen disease, or cancer.

The authors recorded the demographic and basic clinical characteristics, namely sex; age; body–mass index (BMI); stage of CKD; history of DM and hypertension; levels of blood urea nitrogen (BUN), serum creatinine, eGFR, and high-sensitivity C-reactive protein (hs-CRP); and systolic and diastolic blood pressure, before the acupuncture treatment.

Study design, randomization, and grouping

This preliminary study is a part of a 2-arm, parallel, patient-blinded, sham-controlled randomized clinical trial conducted at the Chi Mei Medical Center (Tainan, Taiwan), in accordance with the Declaration of Helsinki and Guidelines for Good Clinical Practice. The eligible patients were randomized into the acupuncture (AG; n = 30) and sham acupuncture (CG; n = 29) treatment groups (Fig. 1) in a 1:1 allocation ratio, blinded to group allocation, and received treatment for 12 weeks (Fig. 1). The outcome assessment and statistical analysis were performed by an investigator who was blinded to the patient randomization.

Sample size

This trial was a preliminary study, and therefore, the statistical power or sample size was calculated only according to the previous study.²¹

Intervention

Acupuncture was performed by a Chinese physician with acupuncture experience exceeding 10 years. In the AG, stainless steel disposable acupuncture needles (length, 2 cun; gauge, #30; Yu Kuang, Taiwan) were inserted into bilateral Hegu, Zusanli, and Taixi. The acupuncture needles were then manually twisted 3–5 times to obtain qi; at this point, the acupuncturist has a tugging sensation similar to that experienced when a fish takes the bait, whereas the patients experience a strong feeling of tightness. Two acupoint pairs (i.e., right Zusanli and Taixi and left Zusanli and Taixi) were stimulated through EA (2 Hz) and were connected to an EA apparatus (HC-0501; Hung-Tai Co., Kaohsiung, Taiwan). Furthermore, the intensity of electrical stimulation was adjusted to ∼2 mA to obtain a visible twitching of the muscles. Electrical stimulation was applied for 20 min and performed once every week for 12 consecutive weeks (i.e., 12 sessions). The patients did not feel pain or discomfort. The acupuncture methods were identical in both CG and AG, except that the acupuncture needles were inserted into the subcutaneous layer to a depth of 5 mm, and their location was 1.5 cm lateral to the aforementioned acupoints. No manual twisting or electrical stimulation was conducted.

The acupoints were selected according to the traditional meridian theory of Traditional Chinese Medicine. Hegu is located on the dorsum of the hand, between the first and second metacarpal bones, in the middle of the second metacarpal bone on the radial side; it belongs to the large intestine meridian. Acupuncture at Hegu exerts pain-relieving and anti-inflammatory effects. Moreover, the Zusanli acupoint is located 3 cun below the knee and belongs to the stomach meridian. Acupuncture at Zusanli may reduce renovascular hypertension and produce an anti-inflammatory effect that plays a renoprotective role.^11,12 The Taixi acupoint is located on the medial border of the foot, posterior to the medial malleolus, and it belongs to the kidney meridian.²² Acupuncture at Taixi may treat deafness, tinnitus, insomnia, nocturnal emission, impotence, renal disease, headache, toothache, and cognitive disorders.¹⁷

The Consolidated Standards of Reporting Trials checklist was used.²³ The intervention was recorded in accordance with the Standards for Reporting Intervention in Clinical Trials of Acupuncture (Table 1).²⁴

Table 1.

Standards for Reporting Intervention in Clinical Trials of Acupuncture (2010)

Acupuncture rationale	1. Traditional Chinese Medicine
	2. The theory of the traditional meridian system
	3. Recent studies: Zhang et al.,¹⁶ Kim et al.,¹¹ Huang et al.,¹² Chen et al.¹⁷
Detail needling	1. Six needles
	2. Bilateral Hegu (LI4), Zusanli (ST36), Taixi (K13)
	3. The depth was adjusted accordingly to obtain qi
	4. Hegu was stimulated to obtain qi, and Zusanli and Taixi were stimulated to obtain muscle twitch
	5. Hegu was manually stimulated; Zusanli and Taixi were electrically stimulated
	6. Two cun in length; gauge, #30
Treatment regimen	1. Twelve sessions
	2. Once per week for 20 min
Other treatment components	1. No moxibustion, cupping, herbs, or exercise
	2. No setting and context treatment
Practitioner background	1. A Chinese physician with acupuncture experience exceeding 10 years
Control or comparator interventions	1. Sham acupuncture
	2. Acupuncture needles inserted to 1.5 cm lateral to Hegu, Zusanli, and Taixi
	3. Subcutaneous layer
	4. No obtaining qi or muscle twitch
	5. Zusanli and Taixi, no electrical stimulation

Outcome measures

The primary outcome measures were changes in (1) serum creatinine levels, (2) eGFR, and (3) serum hs-CRP levels. The secondary outcome measures were (1) blood biochemistry, including levels of BUN, sodium (Na⁺), potassium (K⁺), calcium (Ca⁺⁺), phosphate (P), albumin, uric acid, triglyceride, and total cholesterol; (2) counts of blood cells, including red blood cell, hemoglobin (Hb), hematocrit (Hct), and white blood cell (WBC); and (3) urine protein and the albumin–creatinine ratio (ACR).

The serum creatinine levels and eGFR were measured at 3 months (observation period; O), immediately before the acupuncture treatment (baseline; B), at 12 weeks (after treatment completion; T12), and at the 3-month follow-up (postacupuncture treatment; P). Moreover, the serum hs-CRP levels, blood biochemistry, blood cell counts, urine protein, and ACR were measured at baseline and T12.

Statistical analysis

All analyses in this study were performed using SPSS for Windows (version 17.0) (SPSS, Inc., Chicago, IL). The results are presented as frequency with percentages for categorical variables and as the mean ± standard deviation or median with the interquartile range for continuous variables. Moreover, the differences in categorical variables between the AG and CG were analyzed by performing Pearson's chi-squared or Fisher's exact test. The Student's t test or Wilcoxon rank-sum test was performed to estimate the differences in continuous variables between the AG and CG. In addition, for estimating the differences in creatinine, the eGFR, and hs-CRP at different periods in the AG and CG, the authors performed the Wilcoxon signed-rank test. A p value <0.05 was considered statistically significant.

Results

In total, 59 patients (AG, n = 30; CG, n = 29) with CKD were enrolled in the trial, and finally, 53 (AG, n = 28; CG, n = 25) patients completed the trial. Two patients in the AG withdrew due to failure to return; and in the CG, two patients withdrew refusing continuous acupuncture treatment and two patients withdrew due to failure to return. All the patients withdrew not due to adverse event induced by acupuncture.

Basic characteristics

The demographic and baseline clinical characteristics, namely sex; age; BMI; stage of CKD; history of DM and hypertension; levels of serum BUN, serum creatinine, eGFR, and serum hs-CRP; and systolic and diastolic blood pressure, were not significantly different between the AG and CG (all, p > 0.05, Table 2).

Table 2.

Demographic and Basic Clinical Characteristics

	AG (n = 28)	CG (n = 25)	p
Gender			0.6090^a
Male	25 (89.29)	22 (88.00)
Female	3 (10.71)	3 (12.00)
Age (years)	58.50 (51.00–69.00)	61.00 (56.00–67.00)	0.3355^b
BMI (kg/m²)	24.92 (23.88–26.36)	25.78 (23.03–29.07)	0.4927^b
CKD			0.1740^c
Stage 2	9 (32.14)	4 (16.00)
Stage 3	16 (57.14)	14 (56.00)
Stage 4	3 (10.71)	7 (28.00)
History
Diabetes	8 (28.57)	8 (32.00)	0.7861^c
Hypertension	4 (14.29)	7 (28.00)	0.3126^a
Laboratory tests
BUN (mg/dL)	22.00 (17.00–27.50)	21.00 (14.00–42.00)	0.9924^b
Creatinine (mg/dL)	1.45 (1.27–1.99)	1.67 (1.37–2.53)	0.1298^b
eGFR (mL/min/1.73 m²)	51.85 (34.95–60.95)	42.50 (28.20–53.80)	0.0855^b
hs-CRP (mg/dL)	1.10 (0.50–2.69)	0.79 (0.50–2.02)	0.4361^b
Blood pressure
SBP (mmHg)	125.00 (114.50–135.00)	131.00 (120.00–138.00)	0.1227^b
DBP (mmHg)	74.50 (66.00–85.00)	80.00 (75.00–88.00)	0.1749^b

Data are represented as median (Q1−Q3) with the interquartile range for continuous variables.

Fisher^'s exact test.

Mann–Whitney U test.

Chi-squared test.

AG, acupuncture treatment group; BMI, body mass index; BUN, blood urea nitrogen; CG, sham acupuncture treatment group; CKD, chronic kidney disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; hs-CRP, high-sensitivity C-reactive protein; SBP, systolic blood pressure.

Acupuncture on serum creatinine, eGFR, and serum hs-CRP in patients with CKD

The serum creatinine levels at the observation period and baseline were not significantly different between the AG and CG (both, p > 0.05, Table 3), whereas the differences in serum creatinine at baseline and T12 and at baseline and P were lesser in the AG than in the CG (p = 0.0017 and 0.0182, respectively, Table 3).

Table 3.

Acupuncture on Serum Creatinine, Estimated Glomerular Filtration Rate, and Serum High-Sensitivity C-Reactive Protein in Patients with Chronic Kidney Disease

	AG (n = 28)	CG (n = 25)	p
Creatinine (mg/dL)
O	1.49 (1.25 to 1.86)	1.66 (1.36 to 2.46)	0.4017
B	1.45 (1.27 to 1.99)	1.67 (1.37 to 2.53)	0.1298
T12	1.41 (1.19 to 1.87)	1.65 (1.30 to 3.04)	0.0489^*
P	1.32 (1.14 to 1.79)	1.81 (1.40 to 3.09)	0.0467^*
B-T12	−0.08 (−0.20 to 0.02)	0.09 (−0.05 to 0.03)	0.0017^*
B-P	−0.19 (−0.32 to 0.08)	0.11 (−0.16 to 0.72)	0.0182^*
eGFR (mL/min/1.73 m²)
O	51.3 (38.1 to 65.0)	42.7 (29.20 to 55.90)	0.2585
B	51.85 (34.95 to 60.95)	42.50 (28.20 to 53.80)	0.0855
T12	54.50 (38.60 to 67.25)	43.60 (23.20 to 53.80)	0.0470^*
P	59.90 (41.40 to 67.70)	40.80 (22.30 to 58.20)	0.0191^*
B-T12	3.05 (−0.70 to 7.40)	−2.00 (−4.20 to 1.90)	0.0054^*
B-P	7.90 (1.80 to 15.00)	−0.25 (−5.80 to 7.30)	0.0305^*
hs-CRP (mg/dL)
B	1.10 (0.50 to 2.69)	0.79 (0.50 to 2.02)	0.4361
T12	0.80 (0.50 to 2.39)	0.90 (0.50 to 2.03)	0.8773
B-T12	−0.04 (−0.59 to 1.20)	−0.03 (−1.03 to 1.04)	0.9398

Data are represented as median (Q1−Q3) with the interquartile range for continuous variables. Mann−Whitney U test.

B (n = 53), baseline, just before the acupuncture treatment; B−P, the difference between B and P; B−T12, the difference between B and T12; O (n = 43), observation period, 3 months before the baseline; P (n = 30), 3-month follow-up; T12 (n = 53), immediately after the acupuncture treatment.

p < 0.05 for AG versus CG.

The eGFR at the observation period and baseline was not significantly different in the AG and CG (both p > 0.05, Table 3), whereas the differences in the eGFR at baseline and T12 and at baseline and P were higher in the AG than in the CG (p = 0.0054 and 0.0305, respectively; Table 3).

The serum hs-CRP levels at baseline and T12 were not significantly different between the AG and CG (both p > 0.05, Table 3). The difference in serum hs-CRP at baseline and T12 was nonsignificant between the AG and CG (p > 0.05, Table 3).

Acupuncture on blood biochemistry, blood cells, urine protein, and the ACR

The serum levels of BUN, sodium, potassium, calcium, phosphate, albumin, uric acid triglyceride, and total cholesterol; counts of RBC, Hb, Hct, and WBC; urine protein; and the ACR at baseline and T12 were not significantly different between the AG and CG (all p > 0.05, Table 4). The difference in all of these components at baseline and T12 was not significant between the AG and CG (all p > 0.05, Table 4).

Table 4.

Acupuncture on Blood Biochemistry and Urine Protein in Patients with Chronic Kidney Disease

	AG (n = 28)	CG (n = 25)	p
BUN (mg/dL)
B	22.00 (17.00–27.50)	21.00 (14.00–42.00)	0.9924
T12	22.50 (17.00–27.50)	27.50 (17.00–45.00)	0.4942
Na⁺ (mg/dL)
B	141.00 (139.80–142.10)	140.85 (138.65–141.90)	0.4798
T12	141.30 (139.90–141.85)	140.40 (138.20–142.95)	0.5516
K⁺ (mg/dL)
B	4.28 (3.96–4.61)	4.19 (3.97–4.81)	0.9096
T12	4.18 (3.98–4.42)	4.35 (4.15–4.85)	0.1496
Ca⁺⁺ (mg/dL)
B	9.20 (8.70–9.50)	8.90 (8.70–9.50)	0.5613
T12	9.20 (8.90–9.45)	9.05 (8.50–9.40)	0.5872
P (mg/dL)
B	3.70 (3.40–3.80)	3.20 (3.00–3.75)	0.0774
T12	3.60 (3.10–4.10)	3.45 (3.10–3.70)	0.4980
Albumin (g/dL)
B	4.20 (4.00–4.40)	4.15 (4.00–4.40)	0.8961
T12	4.10 (4.00–4.30)	4.05 (3.85–4.20)	0.3495
Uric acid (mg/dL)
B	7.05 (5.90–8.65)	7.00 (6.50–8.50)	0.7664
T12	7.50 (6.20–9.00)	7.00 (6.10–8.00)	0.4213
Triglyceride (mg/dL)
B	119.00 (78.00–180.00)	132.00 (112.00–177.00)	0.5540
T12	120.50 (80.00–166.00)	125.00 (79.00–215.00)	0.6206
Cholesterol total (mg/dL)
B	195.00 (157.00–213.00)	197.00 (177.00–213.00)	0.7136
T12	179.50 (148.00–218.00)	164.50 (148.00–187.00)	0.4852
RBC (10⁶/μL)
B	4.45 (3.92–5.03)	4.37 (3.85–4.82)	0.4411
T12	4.59 (3.99–4.82)	4.34 (3.99–4.82)	0.3264
Hb (g/dL)
B	13.50 (11.40–15.40)	11.90 (11.10–13.80)	0.0745
T12	14.10 (12.10–14.80)	12.50 (10.80–14.10)	0.0847
Hct (%)
B	40.80 (34.00–48.10)	36.30 (33.60–42.50)	0.0885
T12	42.05 (35.30–44.40)	37.00 (32.10–41.10)	0.0983
WBC (10³/μL)
B	7.45 (6.10–8.10)	7.30 (5.40–9.40)	0.4830
T12	6.40 (5.90–7.10)	7.10 (5.30–10.10)	0.3581
Urine protein (mg/dL)
B	20 (10–65)	20 (10–30)	0.9778
T12	20 (10–30)	20 (10–30)	0.9169
ACR
B	134.50 (9.0–333.00)	268.00 (52.00–1068.00)	0.2246
T12	103.35 (25.00–302.00)	332.00 (129.00–728.00)	0.2246

Data are represented as median (Q1−Q3) with the interquartile range for continuous variables. Mann−Whitney U test.

ACR, albumin–creatinine ratio; B, baseline, just before the acupuncture treatment; Hb, hemoglobin; Hct, hematocrit; RBC, red blood cells; T12, after the acupuncture treatment; WBC, white blood cells.

Adverse events

No serious adverse event occurred in the patients throughout the study; however, the treatment caused bleeding, pain, or bruising in a few patients. These symptoms typically disappeared spontaneously without any treatment, and no patient withdrew from the trial for these reasons.

Discussion

These findings revealed that after the acupuncture treatment for 12 weeks (once per week), the reduction in the serum creatinine levels was higher in the AG than in the CG. By contrast, the increase in eGFR was higher in the AG than in the CG. The serum creatinine levels and eGFR were similar at the observation period and baseline. Creatinine is a kind of waste product of the body, and the serum creatinine level exceeding the normal limit range may be an early sign of kidney damage or kidney disease progression. The eGFR represents an ability of the kidney to eliminate waste product and excess fluid from the blood.²⁵ Therefore, acupuncture treatment was suggested to be beneficial for renal function in patients with CKD.

These results also revealed that the acupuncture treatment could not change the hs-CRP levels because the difference in hs-CRP at baseline and T12 was similar in the AG and CG. CRP is a biomarker of inflammation, and the hs-CRP level rapidly increases in response to tissue damage or inflammation.²⁶ Elevated CRP levels may reflect increased inflammation and oxidative stress.²⁷ The hs-CRP levels were higher in African American patients with CKD than in those without CKD.²⁸ Dervisoglu et al. reported that CRP and hs-CRP are closely associated with CKD and heart diseases and may act as a predictor of deterioration in CKD and inflammation.²⁹ Furthermore, CRP can be induced by WBC, and the elevation in CRP levels may be associated with endothelial cell dysfunction and oxidative stress. The hs-CRP levels increase with the reduction in GFR.^30,31 Acupuncture treatment can reduce the WBC count within a short period in children with acute appendicitis.³² Long-term acupuncture treatment can reduce hs-CRP levels in obese patients.³³ Moreover, acupuncture at Zusanli and Taixi can result in anti-inflammatory effects to reduce the CRP levels in patients with Crohn's disease.³⁴ Overall, these results indicated that acupuncture for 12 weeks reduces serum creatinine levels and increases eGFR, whereas the hs-CRP levels remain unchanged. Therefore, the association between acupuncture and improved renal function and hs-CRP remains unclear, and future studies are warranted.

These findings also indicated that acupuncture treatment for 12 weeks could not change the serum levels of BUN, sodium, potassium, calcium, phosphate, albumin, uric acid, triglyceride, and total cholesterol; RBC, Hb, Hct, and WBC counts; urine protein; and the ACR. The levels at baseline and after the treatment and differences in the aforementioned factors at baseline and treatment completion were nonsignificant between the AG and CG. Therefore, acupuncture for 12 weeks does not affect blood biochemistry, blood cells, and urine protein. In addition, no serious adverse event was observed, but a few patients experienced spontaneous bleeding, pain, or bruising in the acupuncture location. Thus, acupuncture is safe.

This study has several limitations: (1) the sample was small because of the preliminary study design. (2) The patient cases were only followed for 3 months after the 12-week acupuncture treatment; however, CKD is a chronic and progressive disease requiring a long-term follow-up. (3) The most satisfactory selection of acupoints for treating CKD remains unclear. Therefore, more studies and supporting evidence are required in the future.

In conclusion, acupuncture at bilateral Hegu, Zusanli, and Taixi for 12 weeks reduced the serum creatinine levels and increased the eGFR. The study only provided a feasibility method for the treatment of patients with CKD. However, further studies are warranted for validating the findings of this preliminary study.

Footnotes

Acknowledgments

This study was supported by a grant from Chinese Medicine Research Center, China Medical University (Ministry of Education, The Aim for the Top University Plan) and also supported, in part, by the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW106-TDU-B-212-113004).

Authors' Contributions

J.-S.Y. designed the protocol, performed the trial, and wrote the manuscript; C.-H.H., H.-Y.W., and Y.-H.C. participated in the discussions and provided opinions; C.-L.H. was an advisor, participated in designing the protocol, and revised the manuscript.

Author Disclosure Statement

No competing financial interests exist.

References

Hsu

C-C

, Hwang

S-J

, Wen

C-P

, et al. High prevalence and low awareness of CKD in Taiwan: A study on the relationship between serum creatinine and awareness from a nationally representative survey. Am J Kidney Dis, 2006; 48:727–738.

Tsai

, Tseng

, Tan

, et al. End-stage renal disease in Taiwan: A case-control study. J Epidemiol, 2009; 19:169–176.

Chen

, Hsu

, Yamagata

, Langham

. Challenging chronic kidney disease: Experience from chronic kidney disease prevention programs in Shanghai, Japan, Taiwan and Australia. Nephrology, 2010; 15 Suppl 2:31–36.

Lin

, Li

, Pai

, et al. Chronic kidney-disease screening service quality: Questionnaire survey research evidence from Taichung City. BMC Health Serv Res, 2009; 9:239.

Amira

. Prevalence of symptoms of depression among patients with chronic kidney disease. Niger J Clin Pract, 2011; 14:460–463.

Djukanovic

, Lezaic

, Dimkovic

, et al. Early detection of chronic kidney disease: Collaboration of Belgrade nephrologists and primary care physicians. Nefrologia, 2012; 32:59–66.

Hwang

, Lin

, Chen

, et al. Increased risk of mortality in the elderly population with late-stage chronic kidney disease: A cohort study in Taiwan. Nephrology Dial Transplant, 2008; 23:3192–3198.

Schmieder

, Ruilope

, Barnett

. Renal protection with angiotensin receptor blockers: Where do we stand. J Nephrol, 2011; 24:569–580.

Chen

, Mohler

3rd , Xie

, et al. Risk factors for peripheral arterial disease among patients with chronic kidney disease. Am J Cardiol, 2012; 110:136–141.

10.

Martinez-Castelao

, Gorriz

, Portoles

, et al. Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in Spain: The MERENA observational cohort study. BMC Nephrol, 2011; 12:53.

11.

Kim

, Pica

, Duran

. Acupuncture reduces experimental renovascular hypertension through mechanisms involving nitric oxide synthases. Microcirculation, 2006; 13:577–585.

12.

Huang

, Tsai

, Wang

, et al. Acupuncture stimulation of ST36 (Zusanli) attenuates acute renal but not hepatic injury in lipopolysaccharide-stimulated rats. Anesth Analg, 2007; 104:646–654.

13.

Liu

, Song

, You

, et al. The effect of oculo-acupuncture on recovery from ethylene glycol-induced acute renal injury in dogs. Am J Chin Med, 2007; 35:241–250.

14.

Tsay

, Rong

, Lin

. Acupoints massage in improving the quality of sleep and quality of life in patients with end-stage renal disease. J Adv Nurs, 2003; 42:134–142.

15.

Tsay

. Acupressure and fatigue in patients with end-stage renal disease-a randomized controlled trial. Int J Nurs Stud, 2004; 41:99–106.

16.

Zhang

, Yip

, Li

. Acupuncture treatment for plantar fasciitis: A randomized controlled trial with six months follow-up. Evid Based Complement Alternat Med, 2011; 2011:154108.

17.

Chen

, Xu

, Li

, et al. Acupuncture at the Taixi (KI3) acupoint activates cerebral neurons in elderly patients with mild cognitive impairment. Neural Regen Res, 2014; 9:1163–1168.

18.

Lopez-Almaraz

, Correa-Rotter

. Dialysis disequilibrium syndrome and other treatment complications of extreme uremia: A rare occurrence yet not vanished. Hemodial Int, 2008; 12:301–306.

19.

Fried

, Duckworth

, Zhang

, et al. Design of combination angiotensin receptor blocker and angiotensin-converting enzyme inhibitor for treatment of diabetic nephropathy (VA NEPHRON-D). Clin J Am Soc Nephrol, 2009; 4:361–368.

20.

Group

. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet, 1997; 349:1857–1863.

21.

, Shen

, Chen

, et al. Effects of electroacupuncture on benign prostate hyperplasia patients with lower urinary tract symptoms: A single-blinded, randomized controlled trial. Evid Based Complement Alternat Med, 2011; 2011:303198.

22.

, Cheng

, Zhang

, et al. Effects of acupuncture at Taixi acupoint (KI3) on kidney proteome. Am J Chin Med, 2011; 39:687–692.

23.

Consort. 2010 Online document at: www.consort-statement.org/, 2016. (accessed February 5, 2016 ).

24.

STRICTA. 2010. Online document at: www.stricta.info/, 2016, 24. (accessed February 5, 2016 ).

25.

The National Kidney Foundation. Tests to measure kidney function, damage and detect abnormalities—The National Kidney Foundation. 2016. Online document at: www.kidney.org/atoz/content/kidneytests (accessed February 1, 2017 ).

26.

Mayo Medical Laboratories.. HSCRP—clinical: C-reactive protein, high sensitivity, serum. 2016. Mayo Medical Laboratories. Online document at: www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/82047 (accessed February 1, 2017 ).

27.

Horiuchi

, Mogi

. C-reactive protein beyond biomarker of inflammation in metabolic syndrome. Hypertension, 2011; 57:672–673.

28.

Fox

, Benjamin

, Sarpong

, et al. The relation of C-reactive protein to chronic kidney disease in African Americans: The Jackson Heart Study. BMC Nephrol, 2010; 11:1.

29.

Dervisoglu

, Kozdag

, Etiler

, Kalender

. Association of glomerular filtration rate and inflammation with left ventricular hypertrophy in chronic kidney disease patients. Hippokratia, 2012; 16:137–142.

30.

Jalal

, Chonchol

, Etgen

, Sander

. C-reactive protein as a predictor of cardiovascular events in elderly patients with chronic kidney disease. J Nephrol, 2012; 25:719–725.

31.

Nerpin

, Helmersson-Karlqvist

, Riserus

, et al. Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men: A cross-sectional study. BMC Res Notes, 2012; 5:537.

32.

Nager

, Kobylecka

, Pham

, et al. Effects of acupuncture on pain and inflammation in pediatric emergency department patients with acute appendicitis: A pilot study. J Alternat Complement Med, 2015; 21:269–272.

33.

Abdi

, Zhao

, Darbandi

, et al. The effects of body acupuncture on obesity: Anthropometric parameters, lipid profile, and inflammatory and immunologic markers. ScientificWorldJournal, 2012; 2012:603539.

34.

Bao

, Zhao

, Liu

, et al. Randomized controlled trial: Moxibustion and acupuncture for the treatment of Crohn's disease. World J Gastroenterol, 2014; 20:11000–11011.