Acupuncture Application in Chronic Kidney Disease and Its Potential Mechanisms

The American Journal of Chinese Medicine, Vol. 46, No.
6, 1169–1185
© 2018 World Scientific Publishing Company
Institute for Advanced Research in Asian Science and Medicine
DOI: 10.1142/S0192415X18500611
by KAOHSIUNG MEDICAL UNIVERSITY on 10/05/18. Re-use and distribution is strictly not permitted, except for Open Access articles.
Acupuncture Application in Chronic Kidney

Disease and its Potential Mechanisms
Wei Xiong,*,a Fang-Fang He,*,a Ren-Yu You,† Jing Xiong,* Yu-Mei Wang,*
Am. J. Chin. Med. 2018.46:1169-1185. Downloaded from www.worldscientific.com
Chun Zhang,* Xian-Fang Meng‡ and Hua Su*

*Department of Nephrology, Union Hospital
†
Department of Radiology, Union Hospital
Tongji Medical College
Huazhong University of Science and Technology
Wuhan 430022, P. R. China
‡
Department of Neurobiology, School of Basic Medical Sciences
Tongji Medical College
Huazhong University of Science and Technology
Wuhan 430030, P. R. China
Published 21 September 2018
Abstract: Chronic kidney disease (CKD) is an increasing major public health problem
worldwide. The number of CKD patients on hemodialysis is growing rapidly as well.
Acupuncture technique is one of the traditional Chinese medicine methods and has been used
in a variety of diseases. Nowadays, the clinical application of acupuncture technique for
CKD patients has become the focus for its effectiveness and security. In this paper, we will
review the therapeutic effects and mechanisms of different acupuncture techniques for CKD
patients. In patients with CKD, acupuncture improves renal function, reduces proteinuria,
controls hypertension, corrects anemia, relieves pain, and controls many hemodialysis-
related complications such as uremic pruritus, insomnia and fatigue. The mechanisms are
related to the regulation of sympathetic nerve and the activation of bioactive chemicals. In
conclusion, acupuncture is proved to be beneficial for CKD patients. More research,
however, is needed to verify the potential mechanisms.
Keywords: Acupuncture; Traditional Chinese Medicine; Chronic Kidney Disease; Hemodi-

alysis; Review.
Correspondence to: Dr. Xian-Fang Meng and Dr. Hua Su, Department of Neurobiology, School of Basic Medical
Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China,
E-mail: xfmeng@mails.tjmu.edu.cn (X.-F. Meng); Department of Nephrology, Union Hospital, Tongji Medical
College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, P. R.
China. Tel: (þ86) 27-8572-6712, Fax: (þ86) 27-8361-7730, E-mail: dr suhua@hust.edu.cn (H. Su).
a
These authors contributed equally to this work.
1169
1170 W. XIONG et al.
Introduction
Chronic kidney disease (CKD) is defined as kidney damage or glomerular filtration rate
(GFR) of below 60 ml/min per 1.73 m2 for at least 3 months, irrespective of the causes. It is
acknowledged as a major health issue worldwide with increasing prevalence and high
health-care expenditures (Imai and Matsuo, 2008). The causes of CKD include diabetes,
hypertension, primary glomerulonephritis, renovascular diseases, inherited kidney diseases
and so on. Identification of the causes is important for effective treatment options. With the
progression of CKD, proteinuria, renal hypertension, anemia, and nerve damages are also
developed. In patients undergoing hemodialysis, uremia pruritus, insomnia and fatigue are
the main complications which conventional treatments cannot aid. Therefore, novel
approaches are needed to enhance the efficacy of conventional treatments.
Traditional Chinese medicine (TCM) has been used in China for over 3000 years (Chen
et al., 2016; Yu et al., 2017b). It has been proved to be effective in the treatment of many
diseases with few side effects (Zhang et al., 2013; Auyeung et al., 2016; Li et al., 2017a).
Traditional acupuncture, one of the primary treatments in TCM, is conducted by inserting
fine needles into certain anatomical locations (acupoints) on the body (Liu et al., 2016;
Fang et al., 2017). Nowadays, the theory and practice of acupuncture have been developed
and many new techniques are involved, such as electroacupuncture (EA), moxibustion
(MO), acupressure, laser irradiation and electromagnetic waves (Liu et al., 2017; Seo et al.,
2017b; Wei et al., 2017). EA is to stimulate acupoints by needles applying short current
pulse at different frequencies. MO is to heat acupoints by burning the compressed, pow-
erhead, combustible mass from the young leaves of Eurasian Artemisia. Acupressure is a
non-invasive treatment which is to stimulate acupoints by hands and fingers. Lasers are
also applied to acupuncture by stimulating acupoints with low-intensity, non-thermal laser
irradiation. Recently, acupuncture has been suggested as a promising intervention for
patients with CKD or end-stage renal disease (ESRD) (Che-Yi et al., 2005; Garcia et al.,
2005). The benefits and harms of acupuncture for CKD patients have also been evaluated
(Kim et al., 2016). However, most of these studies just drew a simple conclusion about the
advantages or disadvantages of acupuncture and few of them summarized the potential
mechanisms. Evidence based medicine about acupuncture techniques for CKD is still
lacking. In this article, we will review the effects of different acupuncture techniques for
CKD patients and their potential mechanisms as well.
Application of Acupuncture in Chronic Kidney Disease
Improvement of Renal Function
As CKD progresses, the renal function is declined gradually. Clinically, the renal function
is assessed by serum creatinine, urea nitrogen, and estimated glomerular filtration rate
(eGFR). Histopathologically, the deterioration of renal function predicates the progression
of glomerulosclerosis and tubulointerstitial fibrosis. Acupuncture has been shown to reduce
serum creatinine levels and increase eGFR levels in patients with CKD. Yu et al. led a
ACUPUNCTURE APPLICATION IN CHRONIC KIDNEY DISEASE 1171
clinical trial among 53 CKD patients and found that acupuncture at bilateral Hegu (LI4),
Zusanli (ST36), and Taixi (KI3) for twelve weeks reduced serum creatinine levels and
increased eGFR levels with no serious adverse effects (Yu et al., 2017a). However, this
study has two major limitations: the sample size was small and the follow-up time only
lasted for twelve weeks. Larger sample size and longer follow-up time are required in a
future study.
Acupuncture activates vasomotion and improves the renal local microcirculation by
hemodynamic or non-hemodynamic effects. A recent study revealed that MO had the
similar effect of losartan on improving renal function in experimental focal segmental
glomerulosclerosis (FSGS) models. They demonstrated that MO at Shenshu (BL-23) and
Geshu (BL-17) acupoints attenuated podocyte injury by preserving its marker proteins
nephrin and podocin and inhibited tubuloinsterstitial fibrosis by reducing pro-fibrotic
cytokine TGF-β1, myofibroblast marker α-SMA and extracellular matrix component
fibronectin (Li et al., 2017b). Experimental studies on 5/6 nephrectomy models showed
that EA and MO also attenuated glomerulosclerosis and tubulointerstitial fibrosis and
retarded the deterioration of the renal function (Paterno et al., 2008). These studies imply
that acupuncture plays a protective role on renal function by improving renal local
microcirculation and alleviating glomerulosclerosis and tubulointerstitial fibrosis.
However, in a randomized clinical trial (RCT) involving 60 diabetic nephropathy
patients, the differences of serum creatinine and urea nitrogen levels between
acupoint thread embedding at Pishu (BL-20), ST-36, BL-23 combined with medicine
group and Western medicine routine therapy group were not statistically significant
after three months treatment (Chen et al., 2012). The conflicting results might be
related to the complexity of acupuncture because the efficacy was influenced by many
factors such as different acupuncture techniques, the choice of acupoints and the
follow-up time.
Reduction of Proteinuria
Proteinuria is one of the most common clinical manifestations in CKD. Zhu et al. com-
pared the clinical efficacy in the treatment of albuminuria between acupuncture at Xia-
sanhuang and benazepril hydrochloride among 106 chronic nephritis patients. The total
effective rate in the acupuncture group was higher than the western medicine group (Zhu
and Luo, 2015). However, it still needs to be investigated that whether acupuncture
technique combined with western medicine has a better effect than acupuncture alone as
acupuncture is often applied as an adjunctive therapy.
Proteinuria is usually caused by the destruction of glomerular filtration barrier (GFB).
Podocytes and slit diaphragm are important for maintaining the integrity of GFB. A recent
study demonstrated that MO reduced the increased urinary protein in FSGS models, which
was mediated by preserving podocyte marker proteins nephrin and podocin (Li et al.,
2017b).
In CKD patients, renal sympathetic overactivity also contributes to proteinuria. The
overactivity of renal sympathetic nerve enhances calcium influx, induces podocyte
wrinkling, and then results in the destruction of GFB. Previous studies indicated that
acupuncture inhibited the activity of renal sympathetic nerves (Tjen et al., 2016; Wang
et al., 2016), which might be another potential mechanism of reducing proteinuria.
Control of Hypertension
Approximately 80% to 90% of CKD patients develop renal hypertension which would in
turn accelerate the deterioration of renal function. Therefore, the control of blood pressure
plays a critical role in preventing the progression of CKD. Renal hypertension is usually
intractable and the combination of antihypertensive drugs is often required, which results in
noncompliance (Nahas, 2005; Namgung et al., 2017). Since the last decade, acupuncture
has been widely used for preventing and treating hypertension. In a randomized, single-
blind trial, the mean 24-hour ambulatory systolic and diastolic blood pressures in the
acupuncture group both decreased significantly than the sham acupuncture group after
treated for six weeks. No serious side effects were observed during the treatment course
(Flachskampf et al., 2008). As the effects did not outlast the period of treatment, longer
trials are needed to test the continuous effect of acupuncture.
The pathological mechanisms of renal hypertension are complicated, including the
activation of sympathetic nervous system (SNS) and intrarenal renin-angiotensin-aldoste-
rone system (RAAS), the increase of oxidative stress, endothelin-1 (ET-1), inflammation
and so on. The kidney contains abundant sensory afferent fibers, which sensitize ion
concentration, hydrostatic pressure, ischemia and metabolites. Under injurious stimuli,
these factors activate the afferent nerve, then lead to SNS activation. SNS regulates the
blood pressure mainly through epinephrine (E) and norepinephrine (NE) binding to
β-adrenergic receptors (β-ARs). Yang et al. reported that acupuncture at Taichong (LR3)
decreased the mean blood pressure by downregulating E and NE, decreasing β1-adrenergic
receptor (β1-AR) expression and increasing β2-adrenergic receptor (β2-AR) expression
(Yang et al., 2017). These results suggest that acupuncture controls the blood pressure by
regulating the factors related to SNS activity.
The overactivation of RAAS is another pathogenic mechanism of renal hypertension.
When renal parenchymal damage occurs, insufficient blood flow excites the stretch
receptors of afferent glomerular arterioles and stimulates the excretion of renin in juxta-
glomerular cells. The excessive excretion of renin leads angiotensinogen convert to an-
giotensin (Ang) I, which is then converted to Ang II by angiotensin-converting enzyme
(ACE). Ang II is the main effector of RAAS, which causes intense vasoconstriction of the
renal blood vessels via binding to angiotensin II type 1 receptors (AT1R) (Zhang et al.,
2016). The blockade of Ang II with ACE inhibitors (ACEIs) or angiotensin-receptor
blockers (ARBs) is the critical measure for controlling hypertension in CKD patients
(Lewis et al., 2001). Lee et al. and Yang et al. identified that acupuncture lowered the
blood pressure in spontaneously hypertensive rats by decreasing the levels of renin and
aldosterone (Lee et al., 2013; Yang et al., 2017). Another study reported that EA lowered
the blood pressure in spontaneously hypertensive rats by downregulating the levels of ACE
and AT1R (Xin et al., 2017). These studies suggest that acupuncture controls the blood
pressure by influencing RAAS.
Oxidative stress in the kidney is widely recognized as a contributor to the development
of hypertension in CKD patients (Mathis et al., 2012). Oxidative stress usually results from
the overproductions of oxidative-free radicals and reactive oxygen species (ROS) (Jiang
et al., 2016; Newsholme et al., 2016). ROS increases the sensitivity of afferent arteriole to
Ang II and promotes the expression of the sodium potassium two chloride transporter,
which leads to increased reabsorption of sodium and water (Carlstrom et al., 2010). Pre-
vious studies demonstrated that acupuncture at ST36 and KI3 attenuated oxidative stress
and reduced the blood pressure (Xu, 1993; Chen and Ma, 2003). Oh et al. found that EA
rescued the decreased expression of oxidative stress resistance protein HO-1/2 in renal
failure-induced hypertension in rat models (Oh et al., 2012). Nitric oxide (NO), an en-
dothelium-derived relaxing factor, could alleviate oxidative stress (Kaushik et al., 2016).
Kim et al. indicated that EA at ST36 reduced the blood pressure through increasing NO
production activated by endothelial NO synthase (NOS) and neuronal NOS (Kim et al.,
2006). Collectively, we suggest that acupuncture improves renal hypertension by inhibiting
oxidative stress.
Moreover, ET-1 is also a key molecule in regulating renal hypertension (Moorhouse
et al., 2013). It can cause intense vasoconstriction of the renal blood vessels and is posi-
tively correlated with Ang II (Lin et al., 2014). The binding of Ang II to AT1R induces the
release of ET-1. ET-1 leads to strong renal vasoconstriction via binding to endothelin-1
type A receptor (ETAR). Previous studies identified that Ang II and ET-1 receptor blockers
reduced systemic blood pressure both in animal models and patients (Leask, 2010). In
different types of hypertension, acupuncture was demonstrated to reduce the blood pressure
through downregulating ET-1 (Jiang, 2003; Pan et al., 2010). Importantly, long-term EA
significantly blocked the AT1R-ET-1-ETAR pathway by inhibiting the expressions of
AT1R and ETAR (Huo et al., 2014). Therefore, we suggest that ET-1 might be a target
molecule for acupuncture mediating the reduction of renal hypertension.
Correction of Anemia
Anemia is one of the most common complications in CKD patients, which affects their life
quality and survival time. Renal anemia is often caused by insufficient erythropoietin
(EPO) production due to the destruction of nephron. EPO is a proteohormone synthesized
by proximal tubule cells, and has a crucial regulatory effect on the development of red
blood cells. Conventional therapies including recombinant human EPO (rHuEpo) and oral
iron sometimes have unsatisfactory effects on renal anemia. Therefore, new measures for
improving renal anemia are urgently needed.
Because of the ubiquitous micro-inflammatory state in CKD patients, rHuEpo by tra-
ditional injection usually has poor effects on anemia and many patients exist EPO resistance
(Bamgbola, 2011). As some researchers found that acupoints injection decreased the level of
C-reactive protein (CRP) and improved micro-inflammatory state, it might have a better
effect than traditional injection (Cao et al., 2010). Moreover, these studies implied that
acupoints injection helped to reduce the dosage of EPO, which decreased the cost and met
the health economic requirement (Cao et al., 2010). However, further studies are required as
the sample size is not large enough to get affirmative conclusions. Other mechanisms of
anemia correction and the improvement of micro-inflammatory state remain unclear.

In addition, acupuncture also enhances the therapeutic efficacy of oral iron therapy
through improving intestinal iron absorption. The potential mechanism is probably mediated
by downregulating the systemic leptin-hepcidin levels (Xie et al., 2017). Therefore, when
combined with traditional therapy, acupuncture has a beneficial effect on renal anemia.
Relieve of Pain
Pain is one of the most distressing symptoms among CKD patients. In CKD, most pain is
musculoskeletal in origin, but neuropathic pain is also involved. There are several types of
pain that occurr in CKD patients, including peripheral neuropathic pain, joint pain, carpal
tunnel syndrome and autosomal dominant polycystic kidney disease (ADPKD)-associated
pain. Chronic back pain often occurs in ADPKD patients due to enlarging cysts, and it is
usually uncontrolled by oral analgesics (Badani et al., 2004). Seo et al. led a double-blind,
randomized study among 54 patients with chronic low back pain and found that irritation,
pain intensity, and functional status in the bee venom acupuncture (BVA) group had a
significant improvement than the sham group after three weeks treatment (Seo et al.,
2017a). The credible analysis showed that participants in both groups expected a longer
treatment and believed that the treatments were effective. The maximum tolerable injection
dose of BVA needs to be confirmed in future experiments. Moreover, the etiology and
pathogenesis of pain in CKD patients are still lacking, which restricts the development of
therapeutic interventions.
Acupuncture has been widely applied in the management of pain in many diseases in
both tissue damage-induced inflammatory nociception and nerve damage-induced neu-
ropathy (Zhang et al., 2014). Many bioactive chemicals, such as opioids, serotonin, nor-
epinephrine, glutamate receptors and transporters and cytokines are involved in relieving
the pain by acupuncture (Zhang et al., 2014). Opioids are one of the most important
chemicals, which can desensitize peripheral nociceptors, decrease inflammatory cytokines
and activate descending inhibitory system. A previous study showed that both high and
low frequencies of EA relieved thermal, mechanical and spontaneous pain by regulating μ
and δ opioid receptors (Kim et al., 2009). Further investigations are still needed to confirm
the effects of acupuncture and its mechanisms on pain management in CKD patients.
Control of Hemodialysis Related Complications
CKD and ESRD have drawn major public attention, and the number of ESRD patients
undergoing hemodialysis is sharply increasing worldwide (El Nahas and Bello, 2005). The
hemodialysis patients always suffer from many distressing symptoms, including uremic
pruritus, insomnia, fatigue, muscle atrophy and hypotension (Tong et al., 2009). These
complications weaken their life quality and result in increased mortality and more frequent
hospitalization (Lopes et al., 2002). In this part, we will discuss the application of acu-
puncture techniques in hemodialysis patients.
Uremic Pruritus
Uremic pruritus (UP) is one of the most afflictive and bothersome symptoms which affects
hemodialysis patients. A recent study revealed that 42% of hemodialysis patients suffered
from UP (Narita et al., 2008). Traditional methods for controlling UP include the use of
biocompatible dialyzers, skin emollients, gabapentin, opioid receptor modulators, and even
ultraviolet B phototherapy (Manenti et al., 2009). However, the efficacy of these methods
is still unsatisfactory.
Acupuncture has been widely used in several types of pruritus, including histamine-
induced itch in healthy volunteers, atopic dermatitis and asteatotic eczema (Pfab et al.,
2005, 2012; Napadow et al., 2014). There are also several studies focusing on UP. Gao
et al. led a RCT among 68 cases of UP. The effective rate was higher in acupuncture group
(97%) than in western medicine group (70.6%) (Gao, 2002). However, the degree of
confidence in the estimate with the effects is very low as it is a non-blinded study. Another
randomized, double-blind, controlled trial among 41 uremic patients demonstrated that
both thermal therapy group with far-infrared rays at the Sanyinjiao acupoint and control
group with non-thermal therapy improved UP (Hsu et al., 2009). However, this trial did not
include a control group without treatment, which restricted the objective estimation of the
placebo effect. Concomitantly, the small sample size and many dropouts limited the power
to detect the statistically significant differences between the two groups.
There are several hypotheses proposed for the mechanisms of acupuncture treatment.
One of the most common hypotheses is the influence on the endogenous opioid system.
Selective intervention of the endogenous opioid system plays an important role in the
management of UP. Narita et al. demonstrated that κ-opioid agonist (nalfurafine) had
beneficial effects on UP, whereas μ-opioid antagonist (naltrexone) failed to relieve UP
(Narita et al., 2008). Acupuncture promoted the selective release of opioids in the spinal
cord to block the impulses of pruritus transmitted from the periphery by slowly conductive
C fibers (Melzack and Wall, 1965). Therefore, we suggest that acupuncture relieves UP by
regulating the release of opioids to inhibit the afferent fibers.
Another hypothesis is associated with histamine and mast cells. Histamine, as a con-
ductive chemical, affects many cellular responses including allergy, inflammation, and
gastric acid secretion. When the body is subjected to physical and chemical irritations or
allergic reactions, the degranulation of mast cells occurs, which results in the release of
histamine and subsequent biological effects. In addition, intradermal application of hista-
mine by iontophoresis or injection caused itching after a characteristic latency of up to one
minute (Kremer et al., 2014). As a previous study showed that the skin of ESRD patients
with UP represented higher histamine levels as well as more mast cells than healthy
volunteers (Dugas-Breit et al., 2005), we speculate that acupuncture relieves UP by
inhibiting increased histamine and mast cells.
Insomnia
Insomnia is observed in more than 85% hemodialysis patients, which is related to high
health-care utilization, poor quality of life and high mortality in maintenance hemodialysis
patients (Anand et al., 2013). Therefore, the management of insomnia is very important.
Current methods often cause a lot of adverse effects, such as memory problems, drug
resistance, drug dependency and addiction, especially for hemodialysis patients acquiring
higher dose of medications.
Acupressure is a non-invasive treatment which is usually used in patients with different
cancers, which may be also beneficial to ESRD patients with insomnia. Several studies
identified that acupressure improved the mean Pittsburgh Sleep Quality Index (PSQI)
score, awake time and the quality of sleep in hemodialysis patients with insomnia (Shiow-
Luan Tsay et al., 2003; Shariati et al., 2012). Shenmen (HT7) acupoint on the wrist has
been proved to be a vital acupoint. Recently, in a randomized controlled trial among 108
hemodialysis patients, acupressure at the bilateral HT7 significantly decreased the total
PSQI score compared with placebo acupressure and non-treatment group, which was
consistent with previous studies (Arab et al., 2016). However, whether the applied pressure
is identical between the intervention group and control group is uncertain despite of
normative training.
The mechanisms of acupressure for improving sleep disorder in hemodialysis patients
have not been well studied yet, for the causes of insomnia in ESRD patients are compli-
cated with many pathophysiologic abnormalities, psychological problems, lifestyle and
treatment-related factors. Neurotransmitters involved in sleep-wake regulation and auto-
nomic nervous system may have a close relationship with acupuncture therapy. NE,
serotonin (5HT), histamine, dopamine (DA), and acetylcholine (ACh) are major wake-
promoting neurotransmitters, while gamma-aminobutyric acid (GABA) and ACh are major
neurotransmitters which are involved in non-rapid eye movement and rapid eye movement.
Zhou et al. showed that acupuncture effectively improved insomnia by regulating hypo-
thalamic GABA and GABA receptors, and lengthening pole-climbing time in rats (Zhou
et al., 2012). In addition, insomnia is also associated with sympathetic hyperactivity. Since
acupuncture has an effect on inhibiting sympathetic activity and activating parasympathetic
nerves (Torres-Rosas et al., 2014; Yang et al., 2017), this may be another mechanism for
improving insomnia.
Fatigue
Fatigue is another common symptom in hemodialysis patients. The prevalence of fatigue

has been reported from 60% to 97% recently (Bonner et al., 2008). Previously, fatigue was
rarely treated by medicine, for it was viewed as a subjective perception. Recently, the
treatment of fatigue is becoming more and more concerned by clinicians. Traditional
pharmacological treatments for fatigue usually have unsatisfactory results along with ad-
verse side effects (Sugawara et al., 2002). A recent study revealed that application of the
transcutaneous electrical acupoint stimulation (TEAS) on LI4, ST36 and Sanyinjiao (SP6)
produced a better recovery rate of fatigue than the sham group after 10 sessions of inter-
vention (Hadadian, 2016). Another study also reported that TEAS significantly reduced the
degree of fatigue in hemodialysis patients (Tsay, 2004). The limitation of these studies was
the short follow-up period after treatment. More studies should be conducted to include a
larger sample size with longer follow-up period.
Fatigue is a multidimensional and multifactorial problem, which is associated with
sociodemographic (age, gender, race, social support), biological (hemoglobin, CRP, IL-6,
malnutrition), and psychological (depression/anxiety, cognitions, behaviors, sleep dis-
orders) factors in ESRD patients. Since acupuncture has beneficial effects on some of these
factors, such as downregulating CRP (Cao et al., 2010) and IL-6 (Guo et al., 2013),
improving depression (Liao et al., 2017) and sleep disorders (Arab et al., 2016), these
factors might be the potential mechanisms for improving fatigue by acupuncture.
Others
Muscle atrophy is also an important complication of CKD. Although the mechanisms of

muscle atrophy associated with CKD have been identified, definitive treatments are still
lacking. Hu et al. reported that low-frequency electrical stimulation (LFES) on Yang Ling
Quan (GB34) improved protein metabolism and promoted myogenesis, which resulted in
the improvement of muscle atrophy in 5/6 nephrectomy mice (Hu et al., 2015). The
potential mechanism could be associated with the upregulation of the insulin-like growth
factor 1 (IGF-1) signaling pathway, as it increases protein synthesis and suppresses protein
degradation.
Hypotension often occurs during hemodialysis (Locatelli et al., 2010). A previous study
showed that bilateral stimulation of P5-6 acupoints antagonized phenylbiguanide-induced
depressor and bradycardia reflexes by activating sensory fibers in the median nerve and
neural pathways (Tjen et al., 2014). Therefore, acupuncture might also be used for re-
ducing the severity of hypotension in hemodialysis patients (Tsai et al., 2016).
There are also several case reports suggesting acupuncture application on CKD patients
with erectile dysfunction (Kim et al., 2011) and hot flashes (Kim et al., 2010), but further
clinical trials and studies are needed.
Conclusion
In this paper, we systematically introduced the applications (Table 1) and mechanisms

(Fig. 1) of acupuncture techniques in the treatment of CKD. Acupuncture is a non-
pharmacological treatment and unlikely to be involved in altering pharmacokinetics or
causing drug interactions in patients with CKD. As previously described, acupuncture has
been applied in a variety of comorbidities in CKD patients and the efficacy is gradually
recognized and accepted worldwide (Thomas et al., 2001). However, the standards of
operation and treatment for acupuncture are still inconsistent. More evidence-based
medical evidence is needed to standardize the application of acupuncture. Additionally,
Table 1. The Application of Acupuncture Techniques in CKD Patients

1178
Symptoms or Complications Treatments
(References) Intervention Control Effects
Renal function (Yu et al., 2017; Chen Acupuncture technique: EA Subcutaneous layer at 1.5 cm lateral Reduce serum creatinine levels and
et al., 2012) Acupoints: bilateral Hegu, Zusanli, to the aforementioned acupoints, increase eGFR levels
and Taixi without electrical discharge
Time: 12 weeks
Acupuncture technique: acupoints Western medicine BUN and creatinine have no notable
thread embedding combined with variation
western medicine routine therapy
Acupoints: bilateral Pishu, Zusanli,
Shenshu and Yishu
Time: 3 months
Proteinuria (Zhu and Luo, 2015) Acupunctum technique: manual acu- Benazepril hydrochloride Reduce proteinuria
puncture
Acupoints: Xiasanhuang
Time: 2 months
Hypertension (Flachskampf et al., Acupuncture technique: manual acu- Needling points without relevance for Lower ambulatory systolic and
W. XIONG et al.
2008) puncture lowering blood pressure accord- diastolic blood pressures

Acupoints: 16 acupoints according to ing to traditional Chinese medi-
typical prescriptions cine concepts
Time: 6 weeks
Anemia (Cao et al., 2010) Acupuncture technique: acupoint in- Normal subcutaneous injection Increase Hb, Hct and SF
jection
Acupoints: unilateral Shenshu and
Zusanli
Time: 2 months
Pain (Seo et al., 2017) Acupuncture technique: BVA The same amount of normal saline Improve pain intensity and functional
Acupoints: Shenshu, Qihaishu, status
Dachangshu, Huantiao, Yaoyang-
guan, Mingmen, Xuanshu
Time: 3 weeks
Table 1. (Continued)
Symptoms or Complications Treatments

(References) Intervention Control Effects
Uremic pruritus (Gao, H. 2002; Hsu Acupuncture technique: manual Western medicine Alleviate UP
et al., 2009) acupuncture
Acupoints: Quchi and Zusanli
Time: 4 weeks
Acupuncture technique: thermal A plain adhesive patch placed on the Improve UP and VAS. but have no
therapy with far-infrared rays same acupoint differences
Acupoints: Sanyinjiao
Time: 2 months
Insomnia (Arab et al., 2016) Acupuncture technique: acupressure Sham acupressure: points at 0.5 cm Decrease PSQI score
Acupoints: bilateral Shenmen from the true points and not on
Time: 4 weeks the traditional meridian pathways
Non-treatment
Fatigue (Hadadian, 2016) Acupuncture technique: TEAS Without electro-stimulation Lower scores of fatigue
Acupoints: Hegu, Zusanli and
Sanyinjiao
Time: 5 weeks
Notes: EA, electropuncture; eGFR, estimated glomerular filtration rate; BUN, blood urea nitrogen; MO, moxibustion; Hb, hemoglobin; Hct, hematocrit; SF, serum
ferritin; BVA, bee venom acupuncture; UP, uremic pruritus; VAS, visual analogue scale; PSQI, Pittsburgh Sleep Quality Index; TEAS, transcutaneous electrical
ACUPUNCTURE APPLICATION IN CHRONIC KIDNEY DISEASE
acupoint stimulation.
1179
* Improve renal local microcirculation

Renal function
* Alleviate glomerulosclerosis and tubulointerstitial fibrosis
* Decrease podocin, nephrin

Proteinuria
* Depress sympathetic nerve
* Depress SNS
* Inhibit RAAS
Hypertension
* Inhibit oxidative stress, promote NO production
Acupuncture techniques
* Downregulate ET-1
Anemia * Improve rHuEpo and oral iron efficacy
Pain * Regulate bioactive chemicals
* Uremic pruritus: activate endogenous opioid system, decrease

histamine and mast cells
Hemodialysis related * Insomnia: regulate neurotransmitters in sleep-wake regulation
complications and depress sympathetic activity
* Fatigue: influence multifactors
* Muscle atrophy: upregulate IGF-1 signaling pathway

Others
* Others are not well studied
Figure 1. The potential mechanisms of acupuncture techniques in CKD patients. Acupuncture improves many
clinical symptoms or complications of CKD, including improving renal function, reducing proteinuria, controlling
hypertension, correcting of anemia, relieving of pain, controlling of hemodialysis-related complications, through
different mechanisms. SNS, sympathetic nervous system; RAAS, renin-angiotensin-aldosterone system; NO, nitric
oxide; ET-1, endothelin-1; rHuEpo, recombinant human erythropoietin; IGF-1, insulin-like growth factor 1.
high-quality clinical trials including large samples with longitudinal design are also
demanded to prove the safety and efficacy of acupuncture.
Acknowledgments
This work was supported by Grants from the National Natural Science Foundation of China
(Nos. 81471490, 81671066, 81570671, 81400720, 81570657, 81770736, 81770711,
81522010, and 81470964) and the Program for HUST Academic Frontier Youth Team of
Huazhong University of Science and Technology to Dr. Chun Zhang (2016).
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Acupuncture Application in Chronic Kidney Disease and Its Potential Mechanisms

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The American Journal of Chinese Medicine, Vol. 46, No.

Acupuncture Application in Chronic Kidney

Chun Zhang,* Xian-Fang Meng‡ and Hua Su*

Published 21 September 2018

Keywords: Acupuncture; Traditional Chinese Medicine; Chronic Kidney Disease; Hemodi-

Application of Acupuncture in Chronic Kidney Disease

Improvement of Renal Function

anemia correction and the improvement of micro-inﬂammatory state remain unclear.

Control of Hemodialysis Related Complications

Fatigue is another common symptom in hemodialysis patients. The prevalence of fatigue

Muscle atrophy is also an important complication of CKD. Although the mechanisms of

In this paper, we systematically introduced the applications (Table 1) and mechanisms

Table 1. The Application of Acupuncture Techniques in CKD Patients

2008) puncture lowering blood pressure accord- diastolic blood pressures

Symptoms or Complications Treatments

* Improve renal local microcirculation

* Decrease podocin, nephrin

Anemia * Improve rHuEpo and oral iron efficacy

Pain * Regulate bioactive chemicals

* Uremic pruritus: activate endogenous opioid system, decrease

* Muscle atrophy: upregulate IGF-1 signaling pathway

enhances endothelin-1-induced vasoconstriction through upregulating endothelin type A

hemodialysis patients. Complement. Ther. Med. 20: 417–423, 2012.

Xu, N. Effect of electroacupuncture at “taixi” point on plasma thromboxane A2 and prostacyclin in

hypertensive rats. Neural Plast. 2017: 1–9, 2017.

to essence of acupuncture. Complement. Ther. Med. 21: 253–259, 2013.

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