International Journal of Clinical Medicine, 2011, 2, 196-200
doi:10.4236/ijcm.2011.23032 Published Online July 2011 (http://www.SciRP.org/journal/ijcm)
Drug-Eluting Stent for the Treatment of Early
Fistula Failure
Luigi di Serafino, Laura Scudiero, Mario de Laurentis, Federica Ilardi, Fabio Magliulo, Giuseppe
Carotenuto, Cinzia Perrino, Giovanni Esposito
Division of Cardiology, Federico II University, Naples, Italy.
Received November 26th, 2010; revised February 1st, 2011; accepted February 10th, 2011.
ABSTRACT
Introduction: Morbidity and mortality in chronic haemodialysis patients is related to dialysis efficiency. Several com-
plications may occur with vascular access usually associated with a stenosis. This is known to occur frequently in the
venous outflow. Stenosis of the arterial side is not as frequently discussed, but it is also likely to compromise fistula
function. Traditionally, surgical and percutaneous interventions have been used to treat failing fistulas, but the em-
ployment of drug-eluting stents for the treatmen t of failing fistulas due to the arterial sten osis ha s been described rarely.
Methods: A 65-year-old male patient referred to our ambulatory because of hand ischemia during haemodialysis
treatments only few days after radial-cep halic fistula creation. After physical and echo-color-doppler examination, an-
giography was performed and percutaneous intervention was proposed. After the positioning of a guiding catheter, the
lesion was crossed with a 0.014” guide wire followed by direct drug-eluting stent implantation. Results: Final an-
giogram sho wed a good result and a preserved flow through the fistula. Six months later the patien t was asymptomatic
and the fistula was still working. Conclusions: Although further prospective studies are necessary, percutaneous trans-
luminal angioplasty (PTA) with drug-eluting stents implantatio n could be considered a safe and effective technique for
the treatment of arteriovenous fistulas stenosis.
Keywords: Arteriovenous Fistula, Percutaneous Transluminal Angioplasty, Haemodialysis, Drug-Eluting Stents
1. Introduction
Autogenous fistula is a very common strategy for pa-
tients with end-stage renal disease who receive haemo-
dialysis. Primary placement of autogenous haemodialy-
sis fistulas is preferred to other types of haemodialysis
access due to benefits including longer patency, fewer
infection, lower mortality and higher quality of life [1].
However, autogenous haemodialysis fistulas are also
susceptible to dysfunction and failure [2]. Fistula failure
can be classified as early and late. Early fistula failure
refers to those cases in which the arteriovenous fistula
(AVF) never develops, or it fails within the first 3
months of usage. Late failure refers to those cases that
fail after 3 months of successful usage [3]. The clinical
manifestations of early fistula failure are: 1) inadequate
development to permit repetitive cannulation for dialysis;
2) inadequate flow limiting dialysis and 3) thrombosis.
However, generally, those clinical manifestations are
related to some anatomical problems [3,4], and a lesion
is usually found to be the cause of the dysfunction. Al-
though it has been common practice to abandon these
early spoilt fistulas, aggressive evaluation and treatment
of early fistula failures has been shown to result in the
salvage of a large percentage of patients [4].
Several studies reported that non-maturing AVFs
might be salvaged by various surgical and interventional
approaches. Surgical ligation of tributaries, superficiali-
zation procedures, or revision of anastomoses may sal-
vage a significant number of fistulas that fail to mature
adequately. Although autogenous AVFs fail to mature
for several reasons, a commonly encountered angio-
graphic finding is the presence of an anastomotic steno-
sis [5]. Thrombosis is the most frequent AVF complica-
tion resulting in the loss of access for haemodialysis.
Most events of thrombosis (more than 85% of cases)
coincide with the development of vascular stenosis,
generally located in the venous segment proximal to the
arteriovenous anastomosis. Stenosis in the arterial seg-
ment has been less studied, but also compromises the
patency of the vascular access, and also results in limb

Drug-Eluting Stent for the Treatment of Early Fistula Failure197
ischemia. Thus, it should be identified in the dialytic
population, generally composed of elderly patients with
comorbidities, many of whom with generalized arterial
disease.
Percutaneous transluminal angioplasty (PTA), per-
formed only using the plain old balloon angioplasty
(POBA) technique, has proved to be efficacious in the
treatment of stenoses located across the AVF [6]. Only
few reports are currently available regarding the use of
stents, which have been used predominantly in the case
of failed or complicated angioplasty (venous rupture,
elastic recoil, rapidly recurrent stenosis after PTA or
residual stenosis >30%) or as adjunctive therapy [7]. To
our knowledge, this is the first clinical case reporting
percutaneous correction of arterial stenosis responsible
for early fistula dysfunction using a drug-eluting stent.
2. Case Report
A 65-year-old male patient with history of hypertension,
smoking habit and suffering from autosomal dominant
polycystic kidney disease (ADPKD) referred to our am-
bulatory because of hand ischemia during hemodialysis
treatments.
In the 1998, he had undergone nephrectomy and, two
years later, kidney transplantation had been suggested
and performed. Ten years later (April 2010), the patient
needed haemodialysis, due to the failure of the trans-
planted kidney. Central venous catheters (CVCs) had
been used for one month until a left radial-cephalic fis-
tula (RCF) had been created. Unfortunately, few days
later, the patient reported a decrease in AVF thrill and he
suffered from hand ischemia during haemodialysis
treatments. These symptoms typically occurred within 1
hour after dialysis initiation and they were temporally
related to the gradual drop in blood pressure during the
treatment, limiting the patient ability to attain optimal
post-dialysis weight. Moreover, nephrologists referred a
decreased hemodialysis flow rate (<500 ml/min).
After physical examination, power- and color-doppler
were used to explore the left arm vessels, and a critical
stenosis (PSV > 3.5 m/s) of the left radial artery was eas-
ily evidenced, above the fistula (Figure 1). No other
critical stenosis was found through the venous segment
and across the fistula. Due to symptoms intensification,
the patient was admitted to our Cath-Lab and a left arm
angiography was performed using the right arterial fem-
oral access with a 6 Fr. Sheath introducer. The angio-
graphy showed a critical stenosis of the left radial artery
(Figure 2), and it showed also a competitive flow be-
yond the RCF because of the higher perfusion pressure
coming from the ulnar artery. In order to evaluate if the
lesion was due to the artery tortuosity or to a spam, the
operator injected nitrates (NTG), through the diagnostic
Figure 1. Pw- and color-doppler showed a critical stenosis
(PSV > 3.5 m/s) of the left radial artery, above the AVF.
catheter, and he asked the patient to perform prono-su-
pination movements of the left arm. Since the stenosis
did not change after NTG infusion and after forearm
prono-supination movements, the interventional proce-
dure was performed using the same right arterial femoral
access used for the angiography. Heparin (5000 UI) was
administered and a 6 Fr. Multiporpouse guiding catheter
(Medtronic Launcher® Coronary Guide Catheter) was
advanced into the left brachial artery using a 0,035” stiff
guide wire (Terumo, Radifocus® Guide Wire M stiff
type) as support. The catheter was stopped after the ori-
gin of the brachial artery before the bifurcation. The le-
sion was then crossed with a 0.014” guide wire (BHW,
190 cm, from Guidant Corp.) and direct stenting (En-
deavor® Resolute Drug-Eluting Stent, 4 × 15 mm Med-
tronic) was performed inflating the balloon up to 14 atm
(Figure 3). No post-dilation was considered necessary.
The last angiogram showed a good final result without
any residual stenosis (Figure 4) and a preserved flow
through the AV fistula and through the hand also fur-
nished from the ulnar artery. At the end of the procedure,
doppler examination demonstrated a normal flow through
Figure 2. (a) Angiography showed a critical stenosis of the
left radial artery. Stenosis did not change after NTG infu-
sion and after forearm prono-supination. (b) Widen wiew of
the lesion.

Drug-Eluting Stent for the Treatment of Early Fistula Failure
198
Figure 3. (a) The lesion was crossed with a 0.014” guide
wire (BHW, 190cm, from Guidant Corp). (b) Direct stent-
ing (Endeavor® Resolute Drug-Eluting Stent, 4 × 15 mm
Medtronic) was performed inflating the balloon up to
14atm. (c) The final angiogram, without contrast, showed
good stent strut apposition.
Figure 4. The final angiogram showed a good result without
any residual stenosis.
the radial artery and the optimal apposition of the stent
struts. After 6 months, color-doppler showed a normal
flow through the radial and ulnar arteries, and also a
normal stent patency with normal doppler velocities
(Figure 5). Presered function of the AV fistula has been
also clinically demonstrated through increased thrill, in-
creased haemodialysis flow rate (>500 ml/min) and no
upper left limb ischemia during haemodialysis. Follow
Figure 5. At 6 months echo-color-doppler showed patent
stent with normal flow through the vessel.
up is still on-going.
3. Discussion
Several international professional societies [8] recom-
mend an autogenous fistula as the access of choice for
haemodialysis. Insertion of vascular access has become
one of the most common operations performed by vas-
cular surgeons [9], but only 42% - 80% of AVFs mature
adequately for haemodialysis [10-13].
Reduction in haemodialysis access blood flow rates
can compromise the delivery of adequate dialysis and
may cause acute ischemia and thrombosis. Chronic is-
chemia related to the presence of a dialysis access is a
relatively infrequent, but potentially catastrophic com-
plication. It can be due to three main mechanisms: 1)
venous hypertension (diagnosis that can be easily made
by clinical observation of a significant limb swelling and
sometimes visible collateral venous circulation), 2) steal
syndrome (flow reversal in the portion of the artery distal
to the fistula due to a lower pressure system on the out-
flow side of the anastomosis) and 3) arterial lesions.
In the past, fistula ligation was the preferred treatment
strategy for patients with hand ischemia after access sur-
gery. However, this approach required the abandonment
of potentially valuable vascular access sites. Several oth-
er surgical approaches have been proposed to treat steal
syndrome and to preserve the access, most of them re-
ducing fistula flow [14-16], thus increasing the risk of
thrombosis. In contrast, the treatment of ischemia by
arterial PTA increases flow to the access.
Few reports have been published regarding diagnosis
and treatment of lesions of the radial artery. The largest
series reported 11 cases of dilation of the radial artery
because of low fistula flow, hand ischemia or access
thrombosis [17]. The results were combined with those
achieved after dilation of brachial and ulnar arteries,
yielding a primary patenc y rate of 50% at 1 year. Propor-
tions of 6% - 7% of stenosis located in the radial artery

Drug-Eluting Stent for the Treatment of Early Fistula Failure199
were reported by Turmel and Manninen [5,18]. Stent-
graft placement has been also proposed as solution to the
complication of restenosis caused by neo-intimal hyper-
plasia only along the venous outflow.
Although arterial restenosis appears to be significantly
less common compared to the situation that currently
occurs in the venous system, larger studies showed a
40% primary patency rate at 12 months after arterial PTA
(performed with POBA) [17]. This means that about 60%
of patients could have been submitted to a new interven-
tion at 12 months. Moreover, flow-limiting restenosis
could be considered the primum movens to the AVF
thrombosis followed by its failure. For these reasons,
restenosis should be avoided, in particular for older pa-
tients to who could be difficult to find a new access and
who do not tolerate the onset of a new su b-optimal dialy-
sis session. The use of drug-eluting stents could be pro-
posed to ensure a better primary patency rate. Indeed,
although arterial restenosis appears to be different in
each arterial district, the experience coming from the
percutaneous treatments of the coronary artery disease
can be useful also for the treatment of the arterial vessels
disease in the upper limbs. This suggests that the use of
drug-eluting stents might reduce neointimal proliferation
also in this district, ensuring a better primary AVF patency
for these patients.
Endeavor® Resolute drug-eluting stent, which we used
in our case, has a proprietary new biocompatible polymer
called BioLinx. The BioLinx polymer is designed to
confer the same biocompatibility as the Endeavor stent’s
phosphorylcholine (PC) polymer while extending the
duration of drug exposure (Zotarolimus) in the vessel.
Developed by Medtronic scientists, BioLinx is the first
polymer specifically created for use on a drug-eluting
stent. The BioLinx polymer features a unique blend of
hydrophilic and hydrophobic elements for optimal per-
formance. Extensive preclinical studies have established
the biocompatibility and drug delivery capabilities of the
BioLinx polymer. Patients treated with the Endeavor
Resolute stent in the RESOLUTE clinical trial required
no repeat procedures through 9 months and had experi-
enced no protocol-defined stent thrombosis through 12
months of follow-up. Instent late lumen loss at 9 months,
the study’s primary endpoint, was met at 0.22  0.27 mm,
providing assurance of vessel healing in the targeted
range while preventing repeat procedures. Among the
trial’s 130 patients, only one required clinically-driven
Target Lesion Revascularition (TLR) or Target Vessel
Revascularization (TVR) through 12 months. The inci-
dence of major adverse cardiac events was 8.5 through
12 months [19].
We report the case of a patient who was suffering from
left hand ischemia during sub-optimal haemodialysis
treatments. The interventional procedure was performed
without any complication and after direct stent implanta-
tion no further dilatation was necessary. Peri-procedural
Color-doppler examination showed a good final result
with complete stent struts apposition to the arterial wall.
The patient, after successful angioplasty of the pre-an-
astomotic inflow stenosis, had a significant increase in
fistula pressure. Adaptive remodelling and enhanced
blood flow in the fistula permitted hemodialysis to be
successfully performed. 6 months later, the patient was
asymptomatic and the AV access was still working.
Moreover, echo-color-doppler examination showed the
patent stent without any image of in-stent restenosis ref-
erable to the neointimal pro liferation. To our knowledge,
this is the first case report of PTA using a drug-eluting
stent in a case of radial artery stenosis responsible for
early fistula failure.
4. Conclusions
Traditionally, surgical and percutaneous interventions
have been employed to treat failing fistulas and included
surgical revision, PTA with or without stent placement.
PTA could be considered as the treatment of choice in
cases of malfunctioning AVFs and it should always be
attempted before making a new surgical access in order
to preserve the vascular tree. The employment of drug-
eluting stents for the treatment of failing fistulas due to
the arterial stenosis has not been already described. Fur-
ther prospective studies are necessary to confirm that
PTA with drug-eluting stents implantation is a safe and
effective technique to correct such lesions.
REFERENCES
[1] K. R. Polkinghorne, S. P. McDonald, R. C. Atkins and P.
G. Kerr, “Vascular Access and All-Cause Mortality: A
Propensity Score Analysis,” Journal of American Society
of Nephrology, Vol. 15, No. 2, 2004, pp. 477-486.
doi:10.1097/01.ASN.0000109668.05157.05
[2] C. L. Bent, D. K. Rajan, K. Tan, et al., “Effectiveness of
Stent-Graft Placement for Salvage of Dysfunctional Arte-
riovenous Hemodialysis Fistulas,” Journal of Vascular
Interventional Radiology, Vol. 21, No. 4, 2010, pp. 496-
502. doi:10.1016/j.jvir.2009.12.395
[3] G. A. Beathard, “Angioplasty for Arteriovenous Grafts
and Fistulae,” Seminars Nephrology, Vol. 22, No. 3, 2002,
pp. 202-210. doi:10.1053/snep.2002.31739
[4] G. A. Beathard, S. M. Settle and M. W. Shields, “Salvage
of the Nonfunctioning Arteriovenous Fistula,” American
Journal of Kidney Diseases, Vol. 33, No. 5, 1999, pp.
910-916. doi:10.1016/S0272-6386(99)70425-7
[5] L. Turmel-Rodrigues, A. Mouton, B. Birmele, et al.,
“Salvage of Immature Forearm Fistulas for Haemodialy-
sis by Interventional Radiology,” Nephrology Dialysis
Transplantation, Vol. 16, No. 12, 2001, pp. 2365-2371.

Drug-Eluting Stent for the Treatment of Early Fistula Failure
200
doi:10.1093/ndt/16.12.2365
[6] D. G. Miquelin, L. F. Reis, A. A. da Silva and J. M. de
Godoy, “Percutaneous Transluminal Angioplasty in the
Treatment of Stenosis of Arteriovenous Fistulae for He-
modialysis,” International Archives Medicine, Vol. 1, No.
1, 2008, p. 16. doi:10.1186/1755-7682-1-16
[7] M. R. Chan, S. Bedi, R. J. Sanchez, et al., “Stent Place-
ment versus Angioplasty Improves Patency of Arterio-
venous Grafts and Blood Flow of Arteriovenous Fistu-
lae,” Clinical Journal of the American Society Nephrol-
ogy, Vol. 3, No. 3, 2008, pp. 699-705.
doi:10.2215/CJN.04831107
[8] S. Ohira, H. Naito, I. Amano, et al., “2005 Japanese So-
ciety for Dialysis Therapy Guidelines for Vascular Ac-
cess Construction and Repair for Chronic Hemodialysis,”
Therapeutic Apheresis Dialysis, Vol. 10, No. 5, 2006, pp.
449-462. doi:10.1111/j.1744-9987.2006.00410.x
[9] J. M. Weiswasser, D. Kellicu t, S. Arora and A. N. Sidawy,
“Strategies of Arteriovenous Dialysis Access,” Seminars
Vascular Surgery, Vol. 17, No. 1, 2004, pp. 10-18.
doi:10.1053/j.semvascsurg.2003.11.008
[10] A. Asif, P. Roy-Chaudhury and G. A. Beathard, “Early
Arteriovenous Fistula Failure: A Logical Proposal for
When and How to Intervene,” Clinical Journal of Ameri-
can Society Nephrology, Vol. 1, No. 2, 2006, pp. 332-339.
doi:10.2215/CJN.00850805
[11] S. T. Patel, J. Hughes and J. L. Mills Sr, “Failure of Arte-
riovenous Fistula Maturation: An Unintended Conse-
quence of Exceeding Dialysis Outcome Quality Initiative
Guidelines for Hemodialysis Access,” Journal of Vascu-
lar Surgery, Vol. 38, No. 3, 2003, pp. 439-445.
doi:10.1016/S0741-5214(03)00732-8
[12] S. S. Berman and A. T. Gentile, “Impact of Secondary
Procedures in Autogenous Arteriovenous Fistula Matura-
tion and Maintenance,” Journal of Vascular Surgery, Vol.
34, No. 5, 2001, pp. 866-871.
[13] L. M. Dember, G. J. Beck, M. Allon, et al., “Effect of
Clopidogrel on Early Failure of Arteriovenous Fistulas
for Hemodialysis: A Randomized Controlled Trial,” The
Journal of American Medical Association, Vol. 299, No.
18, 2008, pp. 2164-2171.
[14] M. Haimov, H. Schanzer and M. Skladani, “Pathogenesis
and Management of Upper-Extremity Ischemia Following
Angioaccess Surgery,” Blood Purification, Vol. 14, No. 5,
1996, pp. 350-354. doi:10.1159/000170286
[15] J. C. West, D. J. Bertsch, S. L. Peterson, et al., “Arterial
Insufficiency in Hemodialysis Access Procedures: Cor-
rection by ‘Banding’ Technique,” Transplantation Pro-
ceedings, Vol. 23, No. 2, 1991, pp. 1838-1840.
[16] A. B. Redfern and N. B. Zimmerman, “Neurologic and
Ischemic Complications of Upper Extremity Vascular
Access for Dialysis,” The Journal of Hand Surgery, Vol.
20, No. 2, 1995, pp. 199-204.
doi:10.1016/S0363-5023(05)80007-3
[17] A. Guerra, A. Raynaud, B. Beyssen, J. Y. Pagny, M.
Sapoval and C. Angel, “Arterial Percutaneous Angio-
plasty in Upper Limbs with Vascular Access Devices for
Haemodialysis,” Nephrology Dialysis Transplantation,
Vol. 17, No. 5, 2002, pp. 843-851.
doi:10.1093/ndt/17.5.843
[18] H. I. Manninen, E. Kaukanen, K. Makinen and P. Karha-
paa, “Endovascular Salvage of Nonmaturing Autogenous
Hemodialysis Fistulas: Comparison with Endovascular
Therapy of Failing Mature Fistulas,” Journal of Vascular
Interventional Radiology, Vol. 19, No. 6, 2008, pp. 870-
876. doi:10.1016/j.jvir.2008.02.024
[19] I. T. Meredith, S. Worthley, R. Whitbourn, et al., “Clini-
cal and Angiographic Results with the Next-Generation
Resolute Stent System: A Prospective, Multicenter, First-
in-human Trial,” JACC: Cardiovasc Interventions, Vol. 2,
No. 10, 2009, pp. 977-985.
doi:10.1016/j.jcin.2009.07.007