Carpal tunnel syndrome in patients with arteriovenous fistula for haemodialysis: A narrative review of the current literature

Abstract

The ideal choice of vascular access in patients requiring haemodialysis is an arteriovenous fistula. However, an important often under-reported complication encountered at follow-up is symptoms of tingling or numbness in the hand. This may represent carpal tunnel syndrome, impairment of the median nerve as it traverses through the carpal tunnel at the wrist by focal compression of this nerve. Contributory factors in the presence of an arteriovenous fistula may include venous hypertension and varying steal syndrome phenomena provoking micro-ischaemia. Studies that investigated the evolution of carpal tunnel syndrome in haemodialysis patients with an arteriovenous fistula revealed that the frequency of carpal tunnel syndrome associated with an arteriovenous fistula on haemodialysis ranged from 10.4% to 42.6%. An association between duration of haemodialysis with arteriovenous fistula and carpal tunnel syndrome development was also observed. Surgical release of carpal tunnel provided complete relief of paraesthesia in all treated patients in the examined, demonstrating an alleviation of symptoms and improved function of hand and quality of life in patients with an arteriovenous fistula. However, the aetiology and risk factors for development of carpal tunnel syndrome remain unclear and further studies should attempt to elucidate the pathophysiology of this occurrence in the presence of arteriovenous fistulas.

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https://doi.org/10.1177/1129729820948690
The Journal of Vascular Access
2021, Vol. 22(5) 795 –800
© The Author(s) 2020
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DOI: 10.1177/1129729820948690
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Vascular Access
Introduction
The ideal choice of vascular access in patients requiring
haemodialysis (HD) is an arteriovenous fistula (AVF). The
benefits of this include reduced infection rates with hospital
re-admissions and prolonged survival compared with arte-
riovenous grafts and central venous catheters.1 However,
there are longer term complications which include throm-
bosis, aneurysm formation and vascular steal phenome-
non.2 An important short- to medium-term finding often
encountered at follow up is symptoms of tingling or numb-
ness in the hand. The symptoms are often suggestive of car-
pal tunnel syndrome (CTS),3 although, this may not always
be the case. The purpose of this narrative review is to high-
light clinical, neurophysiological and histopathological
Carpal tunnel syndrome in patients
with arteriovenous fistula for
haemodialysis: A narrative review
of the current literature
Yasmin Grant1, Simon Freilich2, Maxim D Horwitz3,
David Shemesh4 and Jeremy Crane1
Abstract
The ideal choice of vascular access in patients requiring haemodialysis is an arteriovenous fistula. However, an important
often under-reported complication encountered at follow-up is symptoms of tingling or numbness in the hand. This
may represent carpal tunnel syndrome, impairment of the median nerve as it traverses through the carpal tunnel at the
wrist by focal compression of this nerve. Contributory factors in the presence of an arteriovenous fistula may include
venous hypertension and varying steal syndrome phenomena provoking micro-ischaemia. Studies that investigated the
evolution of carpal tunnel syndrome in haemodialysis patients with an arteriovenous fistula revealed that the frequency
of carpal tunnel syndrome associated with an arteriovenous fistula on haemodialysis ranged from 10.4% to 42.6%. An
association between duration of haemodialysis with arteriovenous fistula and carpal tunnel syndrome development was
also observed. Surgical release of carpal tunnel provided complete relief of paraesthesia in all treated patients in the
examined, demonstrating an alleviation of symptoms and improved function of hand and quality of life in patients with an
arteriovenous fistula. However, the aetiology and risk factors for development of carpal tunnel syndrome remain unclear
and further studies should attempt to elucidate the pathophysiology of this occurrence in the presence of arteriovenous
fistulas.
Keywords
Arteriovenous fistula, carpal tunnel, carpal tunnel syndrome, vascular access, haemodialysis
Date received: 8 April 2019; accepted: 9 July 2020
1 Department of Transplant Surgery, Imperial College Renal and
Transplant Centre, Hammersmith Hospital, London, UK
2 Department of Clinical Neurophysiology, Luton and Dunstable
University Hospital, NHS Foundation Trust, Luton, UK
3 Department of Hand Surgery, Chelsea and Westminster Hospital
NHS Trust, London, UK
4 Department of Surgery and Haemodialysis Access Unit, Shaare Zedek
Medical Centre, Jerusalem, Israel
Corresponding author:
Yasmin Grant, Department of Transplant Surgery, Imperial College
Renal and Transplant Centre, Hammersmith Hospital, 4th Floor, Ham
House, Du Cane Road, White City, London W12 0HS, UK.
Email: yasmin.grant14@imperial.ac.uk
948690JVA0010.1177/1129729820948690The Journal of Vascular AccessGrant et al.
review-article2020
Review

796 The Journal of Vascular Access 22(5)
insights into the appropriate diagnosis and management of
the tingling hand post-AVF formation.
CTS is the most common entrapment neuropathy affect-
ing around 10% of the UK population with a prevalence of
around 3%.4–6 It is caused by impairment of the median
nerve as it traverses through the carpal tunnel at the wrist by
focal compression of this nerve,7,8 as well as local ischae-
mia.9 While CTS can present acutely such as following a
wrist fracture, it is most often due to a chronic build-up of
multiple elements which lead to increased pressure within
the carpal tunnel. Histopathological findings show thicken-
ing of the flexor tendons, oedema,10 collagen proliferation,
fibrosis, amyloid deposition and thickening of blood vessel
walls11 which all contribute to the above process.12 Those
depositions are often precipitated by the well-known aetio-
logical risk factors of chronic friction of the flexor tendons,
or patients with tenosynovitis of the wrist flexor tendons.12
However, not all CTS is attributable to chronic tendon
friction, as common risk factors include genetic predispo-
sitions (positive family history without occupational repet-
itive hand use), obesity, hypothyroidism, inflammatory
arthropathy such as rheumatoid arthritis and diabetes.13–15
Patients with diabetes are at increased risk of macro- and
micro-vascular complications which, of course, include
end stage renal failure (ESRF) and requirement for HD.
Therefore, the HD patient cohort (many of whom are dia-
betic) is at increased risk of having pre-existing CTS even
before AVF formation.16
To complicate matters further, it has been shown exper-
imentally that ischaemic provocation of patients with CTS
via a tourniquet will worsen CTS symptoms as well as
increase neurophysiological conduction abnormalities.17
Thus, the presence of an AVF (often associated with vary-
ing steal syndrome phenomena) could precipitate symp-
toms of a pre-existent asymptomatic carpal tunnel lesion
via additional micro-ischaemia, as well as independently
increasing inflammatory depositions within the carpal tun-
nel.18 A further theory regarding development of CTS in
AVF formation includes venous hypertension leading to
compression of the median nerve.4,11,12 Amyloidosis, spe-
cifically β2-microglobulin amyloidosis, is also a serious
complication of long-term HD and hence, link duration of
HD with CTS,6,19 independent of AVF formation.
It is clear that the pathophysiology of CTS in patients
dialysing with AVFs is currently unknown and there is con-
troversy as to whether AVF increases the risk of CTS devel-
oping. Correct and timely interventions are required for
these different conditions and hence, the need to review the
known literature to identify an evidence-based approach.
A narrative review of the literature revealed the follow-
ing summarised in Table 1.
Incidence of carpal tunnel syndrome
The frequency of CTS with AVF on HD ranged from
10.4% to 42.6% in the analysed studies.24,26–28 However, a
study by Kwon et al.26 did not find a difference between
the incidence of CTS in patients with AVFs (n = 57) com-
pared with central venous catheters (n = 7, p = 0.816). More
broadly, the frequency of CTS was not different in the HD
group (n = 64) versus peritoneal dialysis (PD; n = 48,
p = 0.823), with a mean duration on HD and PD of
45.9 ± 41.9 and 59.4 ± 44.7 months, respectively. The
investigators felt that these differences could be explained
by the fact that prior studies used clinical findings without
nerve conduction study confirmation and recommended
accurate diagnosis of CTS to be undertaken early by elec-
trophysiological studies.26
Natural history/duration of HD
Kopec found a significant correlation between duration of
HD and CTS development, with all patients on ⩾20 years
of HD developing CTS and requiring surgical release.24 In
this study of 386 patients, 40 of whom who had CTS were
on HD for an average of 16.05 years as opposed to the non-
CTS group who were on HD for an average of 4.51 years.
CTS developed in all patients dialysed from 20 to 30 years
(n = 10), in 67% of patients dialysed for 15–19 years (n = 10)
and in 42% of patients dialysed from 10 to14 years (n = 16).
Duration of dialysis therapy was the only statistically sig-
nificant risk factor for CTS.24 Kwon et al.26 also found a
tendency for patients on HD to develop CTS later, although
this was not statistically significant. However, only a small
proportion of Kwon’s patients on HD developed CTS
(n = 8) and so the study may have been underpowered, mak-
ing it difficult to reach statistical significance.
Aetiology
The development of CTS in patients on HD with AVFs may
differ from idiopathic CTS in several ways. One study by
Warren and Otieno27 showed patients with an AVF on the
wrist have a significantly increased risk of developing CTS
on the same side. Of 36 patients, hand volumes were inves-
tigated in symptomatic patients to find that non-dominant
hands with AVFs (18%, p < 0.001 and 21%, p < 0.01 in
males and females, respectively) had an increased volume
compared to age-matched controls (5.1%, p > 0.1 and 5.7%,
p > 0.1 in males and females, respectively). This is of
importance as patients tend to have their fistulas on the non-
dominant hand, while CTS tends to occur on the dominant
hand in the general population.28 Lindstedt first reported
persistent swelling of the forearm and hand in patients with
iatrogenic AVFs. The authors suggested that oedema may be
due to valve destruction of superficial veins distal to the
AVF. This process is furthered when the arm is compressed
to halt bleeding after HD and the superficial venous pres-
sure may reach the level of systemic arterial pressure. Thus,
it is postulated that this process encroaches on the crowded
carpal tunnel which can compress the median nerve.29 This
is echoed in oedema after trauma or associated fluid

Grant et al. 797
Table 1. Study descriptions and demographics.
Author Year Study type Number of patients with
CTS/total number of
patients (%)
Site of AVF Mean age in
years (range)
M:F ratio Diagnosis of
CTS
Use of steroid
therapy (n)
Mean length of HD
Harding and Fanu20 1997 Case series 2/2 Two ipsilateral 69 (42–54) 1:1 Clinical
examination
Yes (1) 18 months
Khan21 2008 Observational 19/19 Undisclosed 59 (41–48) 12:7 NCS No 12.6 years
Kimura etal.22 1986 Case series 16 (22 extremities) Undisclosed Undisclosed Undisclosed NCS Yes (20) Undisclosed
Kocyigit etal.23 2013 Observational 12/12 Undisclosed 63 ± 7 7/5 NCS No Undisclosed
Kopec etal.24 2010 Observational 40/386 (10.4%) 14 ipsilateral, 23
bilateral, 3 contralateral
54.5 (36–83) 2:1 NCS No 16.05 months (18–100)
Kumar etal.25 1975 Case report 2/2 Two ipsilateral 45 (43–48) 1:1 NCS No 19 months–36 months
Kwon etal.26 2011 Observational 8/64 (12.5%) versus 4/48
on PD (8.3%)
Undisclosed Undisclosed Undisclosed NCS No 45.6 months ± 41.9 months
Warren and
Otieno27
1975 Case report 23/36 (64%) Undisclosed 40.8 ± 6.3 17:6 Clinical
examination
No 1.8 ± 1.3 years
AVF: arteriovenous fistula; CTS: carpal tunnel syndrome; HD: haemodialysis; NCS: nerve conduction study; PD: peritoneal dialysis.

798 The Journal of Vascular Access 22(5)
retention in pregnancy.25 Warren also found that venous
pressures were significantly raised before HD,27 while
Kocyigit found that venous pressure was significantly
reduced following CTS decompression.23 Moreover in the
latter study, amyloid deposition as stained by Congo red was
absent in all of their patients biopsy specimens.23 Both of
these studies point towards venous hypertension as a possi-
ble aetiological factor in CTS pathogenesis, however, do not
elucidate on underlying mechanism for reduction in venous
pressure post treatment.
β2-microglobulin amyloid deposits are another pro-
posed aetiological factor in CTS with AVF and was found
in all biopsied samples after surgical decompression in 1
study of 21 patients.24 β2-microglobulin deposition causes
inflammation which leads to adhesions and oedema that in
turn mechanically compress the median nerve, in dialysis
independent of vascular access type. However, no com-
ment was provided on the overall mean duration of dialy-
sis in the biopsied patients. It may be that the majority of
these patients with amyloid deposits had been on HD for a
prolonged period of time leading to accumulation of β2-
microglobulin in the tendons and synovium,24 and thus,
symptoms of CTS may have developed regardless of pres-
ence of AVF. Importantly, Kocyigit did not find any amy-
loid deposits on histology of surgical specimens as
discussed earlier, indicating that CTS development could
not be explained by amyloid accumulation. However, the
mean duration of HD for Kocyigit’s patient cohort was
3.5 years, which is considerably shorter than the mean
duration of CTS patients with amyloid deposits. This may
indicate that more time is required for amyloid accumula-
tion within the carpal tunnel.24 It is clear that the aetiology
is multi-factorial and treatment must take patient specific
factors into account.
Type/site of AV fistula
In a small case report of two patients in 1977, it was sug-
gested that CTS was provoked by a vascular steal mecha-
nism related to Cimino-Brescia fistula at the forearm.20
However, our review identified three further studies which
did not find a correlation between incidence of CTS and
site of AVF.22,24,26 Furthermore, no statistical differences
were noted between the requirement of surgical procedure
for CTS and location of AVF (p = NS).24 However, it is
acknowledged that the site of fistula is not the sole aetio-
logical factor in dialysis-related CTS as Kopec found that
CTS occurred bilaterally in HD patients with AVFs, indi-
cating that a systemic aetiology perhaps related to dialysis
CTS may be involved.24
Concomitant steal syndrome
In a study of 170 patients with CTS in AVF, three patients
were found to have concurrently diagnosed steal syndrome.
The diagnosis of vascular steal phenomenon was made by
characteristic examination findings and demonstration of
reduced, absent and/or retrograde digital blood flow in the
distal part of the radial artery with the aid of a Doppler
ultrasonographic probe.26
Clinical/electrophysiological diagnosis
The symptomatology of CTS may also present a dilemma,
as peripheral neuropathy, vascular steal syndrome and CTS
can cause pain and/or numbness of the hands. Hence, the
differentiation of the three entities is important and this
involves understanding that the methods used by authors of
these studies to diagnose CTS. Several studies have observed
that not all methods are equal in reliably diagnosing CTS.
Nevertheless, six of the eight analysed studies utilised nerve
conduction studies (NCS) to aid diagnosis.22–26 It is impor-
tant to note that uraemic peripheral neuropathy may also
present in a similar fashion to CTS. Interestingly, general-
ised sensory and motor neuropathy was diagnosed in 12
patients (19%) as detected by neurophysiology.26
There is poor agreement between Hand Surgeons on the
role of pre-operative neurophysiology in the management
of CTS. A variety of validated neurophysiological grading
systems of severity have been well-described in the litera-
ture and the Canterbury and Padua grading scales feature
prominently in current UK practice in the general popula-
tion.18,29 These have been shown to correlate well with dis-
ease severity and surgical outcomes, however, were not
utilised in the studies identified. Thus, in addition to the
diagnostic benefit of NCS in identifying median neuropa-
thies across the carpal tunnel, severity and prognosis can
be reliably determined.
Steroid therapy
In a case report by Harding, only one patient had tempo-
rary relief from prednisolone injection.23 In a further case
report, a single patient was treated conservatively with
splinting with partial relief.25 In the authors’ practice, min-
imal symptoms with minor neurophysiological changes
are treated with non-operative measures such as splinting,
activity modification and steroid injection. In the presence
of muscle wasting and sensory blunting as well as intru-
sive symptoms, there is little role for splinting and steroid
therapy.
Surgical management
Established CTS treated by surgical release demonstrated
alleviation of symptoms and improved function of hand
and quality of life in the majority of patients in the exam-
ined studies. In a cohort of 19 patients with CTS on HD
(17 with AVFs), early and regular screening using NCS
was suggested for early detection of CTS leading to early

Grant et al. 799
treatment, which can include a splint or surgical decom-
pression.21 In the study, 85% (n = 16) reported improve-
ment in symptoms, with only scar pain remaining in 21%
(n = 4) at an average follow-up of 18.6 months. In a further
study, two patients in a study of 36 patients with CTS
underwent surgical decompression and both reported good
relief and no recurrence at average follow-up of 18
months.27 In addition, a case series of two patients, partial
relief of CTS was obtained by ligation of the AVF, whereas
complete relief was obtained by surgical decompression of
the median nerve at the wrist in both patients.25 A further
study of 40 patients by Kopec found rapid relief of paraes-
thesia and pain symptoms. In the treatment of recurrences,
resection of the thickened tendinous sheaths of the finger
flexor was recommended.24 In a case report by Kumar, one
patient was treated with surgical release with relief of par-
aesthesia but persistence of oedema.25 Surgical release for
patients was required in 100% (n = 5) who dialysed for
25–30 years in a study by Kwon et al.26
All patients treated with surgical release in this review
were reported to experience partial to complete relief sug-
gesting that carpal tunnel decompression is a worthwhile
intervention for these troubling symptoms. In this particu-
lar cohort of patients, presentation may be later on with
more advanced symptoms and there is no scope here for
non-operative measures. The authors’ recommendation is
that carpal tunnel release should be therefore performed by
an experienced hand surgeon.
Limitations
Limitations of this study are the heterogeneity and lack of
methodological detail in a relatively small sample of stud-
ies of the diagnosis and management of CTS in AVF. There
are compelling reasons to identify the aetiology and best
management of CTS in HD with AVF in order to assess
and negate the risk of occurrence of the condition.
Conclusion
It is clear that the tingling hand post AVF formation pre-
sents a common diagnostic conundrum for the vascular
access surgeon in the setting of other differentials such as
peripheral neuropathy and vascular steal syndrome. It is
apparent that the aetiology remains multi-factorial and fre-
quency of CTS with AVF varies widely according to the
criteria and methods used for the diagnosis. There appears
to be two distinct categories of dialysis-related CTS;
venous hypertension24 and dialysis-related amyloidosis,25
although the latter findings were not reproducible.26 There
is currently very little new evidence and a great deal of
heterogeneity within the current literature. Further large
scale, high-quality prospective studies are required to
investigate the pathophysiology of AVF-related CTS to
help improve the quality of care for HD patients. Clinicians
should be aware of the diagnosis and try and make it early
as possible to prevent permanent nerve damage. It is rec-
ommended that in the presence of carpal tunnel like symp-
toms, early neurophysiology is performed with expedited
release of the carpal tunnel if symptoms and nerve tests
confirm median nerve compression.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship and/or publication of this article.
ORCID iD
Yasmin Grant https://orcid.org/0000-0001-5921-823X
References
1. Vassalotti JA, Jennings WC, Beathard GA, et al. Fistula
first breakthrough initiative: targeting catheter last in fistula
first. Semin Dial 2012; 25(3): 303–310.
2. Salahi H, Fazelzadeh A, Mehdizadeh A, et al. Complications
of arteriovenous fistula in dialysis patients. Transplant Proc
2006; 38(5): 1261–1264.
3. Perfetto F, Moggi-Pignone A, Livi R, et al. Systemic
amyloidosis: a challenge for the rheumatologist. Nat Rev
Rheumatol 2010; 6(7): 417–429.
4. Atroshi I, Gummesson C, Johnsson R, et al. Prevalence
of carpal tunnel syndrome in a general population. JAMA
1999; 282: 153–158.
5. Ferry S, Pritchard T, Keenan J, et al. Estimating the preva-
lence of delayed median nerve conduction in the general
population. Brit J Rheumatol 1998; 37: 630–635.
6. de Krom MC, Knipschild PG, Kester AD, et al. Carpal tun-
nel syndrome: prevalence in the general population. J Clin
Epidemiol 1992; 45: 373–376.
7. Ochoa J, Fowler TJ and Gilliat RW. Anatomical changes in
peripheral nerve lesions compressed by a pneumatic tourni-
quet. J Anat 1972; 113: 43–455.
8. Rudge P, Ochoa J and Gilliatt RW. Acute peripheral nerve com-
pression in the baboon. J Neurol Sci 1974; 23(3): 403–420.
9. Gelberman RH, Rydevik BL, Pess GM, et al. Carpal tunnel
syndrome. Orthop Clin North Am 1988; 19: 115–124.
10. Faithfull DK, Moir DH and Ireland J. The micropathology
of the typical carpal tunnel syndrome. J Hand Surg Br 1986;
11(1): 131–132.
11. Neal NC, McManners J and Stirling GA. Pathology of the
flexor tendon sheath in the spontaneous carpal tunnel syn-
drome. J Hand Surg Br 1987; 12(2): 229–232.
12. Werner RA, Franzblau A and Gell N. Randomized con-
trolled trial of nocturnal splinting for active workers with
symptoms of carpal tunnel syndrome. Arch Phys Med
Rehabil 2005; 86(1): 1–7.
13. Hakim AJ, Cherkas L, El Zayat S, et al. The genetic contri-
bution to carpal tunnel syndrome in women: a twin study.
Arthritis Rheum 2002; 47(3): 275–279.

800 The Journal of Vascular Access 22(5)
14. Bland JDP. The relationship of obesity, age, and carpal tun-
nel syndrome: more complex than was thought? Muscle
Nerve 2005; 32(4): 527–532.
15. Wiberg A, Ng M, Schmid AB, et al. A genome-wide associ-
ation analysis identifies 16 novel susceptibility loci for car-
pal tunnel syndrome. Nat Commun 2019; 10: 1030, https://
doi.org/10.1038/s41467-019-08993-6
16. Lok CE, Oliver MJ, Rothwell DM, et al. The growing vol-
ume of diabetes-related dialysis: a population based study.
Nephrol Dial Transplant 2004; 19(12): 3098–3103.
17. Lundborg G, Gelberman RH, Minteer-Convery M, et al.
Median nerve compression in the carpal tunnel-functional
response to experimentally induced controlled pressure. J
Hand Surg Am 1982; 7(3): 252–259.
18. Bland JD. A neurophysiological grading scale for carpal
tunnel syndrome. Muscle Nerve 2000; 23(8): 1280–1283.
19. van Rijn RM, Huisstede BM, Koes BW, et al. Associations
between work-related factors and the carpal tunnel syn-
drome – a systematic review. Scand J Work Environ Health
2009; 35(1): 19–36.
20. Harding AE and Fanu JL. Carpal tunnel syndrome related
to antebrachial Cimino-Brescia fistula. J Neurol Neurosurg
Psychiatry 1977; 40(5): 511–513.
21. Khan UD. An assessment of symptomatic relief after carpal
tunnel release in patients on haemodialysis. Nephron Clin
Pract 2008; 110(4): c264–c267.
22. Kimura I, Sekino H, Ayyar DR, et al. Carpal tunnel syn-
drome in patients on long-term hemodialysis. Tohoku J Exp
Med 1986; 148(3): 257–266.
23. Kocyigit I, Unal A, Guney A, et al. Carpal tunnel release
surgery and venous hypertension in early haemodialysis
patients without amyloid deposits. Scientific World Journal
2013; 2013: 481348.
24. Kopec J, Gadek A, Drozdz M, et al. Carpal tunnel syndrome
in hemodialysis patients as a dialysis-related amyloidosis
manifestation – incidence, risk factors and results of surgi-
cal treatment. Med Sci Monit 2011; 17(9): CR505–CR509.
25. Kumar S, Trivedi HL and Smith EKM. Carpal tunnel
syndrome: a complication of arteriovenous fistula in hae-
modialysis patients. Can Med Assoc J 1975; 113(11–2):
1070–1072.
26. Kwon HK, Pyun SB, Cho WY, et al. Carpal tunnel syn-
drome and peripheral polyneuropathy in patients with end
stage kidney disease. J Korean Med Sci 2011; 26(9): 1227–
1230.
27. Warren DJ and Otieno LS. Carpal tunnel syndrome in
patients on intermittent haemodialysis. Postgrad Med J
1975; 51(597): 450–452.
28. Middleton SD and Anakwe RE. Carpal tunnel syndrome.
BMJ 2014; 349: g6437.
29. Lindstedt E. Venous pressure in arteriovenous fistula. Scand
J Urol Nephrol 1972; 14: 1–52.