Liu and co-workers report on a preliminary study with formaldehyde-fixed arterial allografts. In this way they provide a novel alternative for solving the problem of failing to achieve vascular access in hemodialysis patients. Formaldehyde fixation offers an effective way of reducing the antigenicity of heterologous arterial allograft. Preliminary clinical experience shows that technical survival of such preserved arterial allograft appears quite promising. Further studies will help to define the place of this allograft material in vascular access management of ESRD patients

Canaud, B.

Elsevier - Publisher Connector 

Formaldehyde-fixed arterial allograft as a novel vascular access alternative in end-stage renal disease patients 

Kidney International (2007) 72       1179
commentar yhttp://www.kidney-international.org
© 2007 International Society of Nephrology
Formaldehyde-fixed arterial 
allograft as a novel vascular access 
alternative in end-stage renal 
disease patients
B Canaud1
Liu and co-workers report on a preliminary study with formaldehyde-
fixed arterial allografts. In this way they provide a novel alternative 
for solving the problem of failing to achieve vascular access in 
hemodialysis patients. Formaldehyde fixation offers an effective 
way of reducing the antigenicity of heterologous arterial allograft. 
Preliminary clinical experience shows that technical survival of such 
preserved arterial allograft appears quite promising. Further studies 
will help to define the place of this allograft material in vascular access 
management of ESRD patients. 
Kidney International (2007) 72, 1179–1181. doi:10.1038/sj.ki.5002558
After three decades of maintenance renal 
replacement therapy, suboptimal vascu-
lar access is a major cause of morbidity 
in patients with end-stage renal disease 
(ESRD).1 It is the ﬁrst cause of hospitali-
zation due to dysfunction, thrombosis, or 
infection. Vascular access management rep-
resents a signiﬁcant economic burden to the 
health-care system, consuming 15%–20% 
of the budget allocated to ESRD treatment 
in the US (Medicare).2 Despite signiﬁcant 
progress, including presurgery vascular 
mapping,3–5 microvascular surgery, and 
early interventional radiology for correct-
ing dysfunction,6 many ESRD patients 
experience failure of primary autogenous 
arteriovenous fistula.7 Moreover, crea-
tion of new ﬁstulae exhausts native veins, 
and this has led to innovative approaches 
in using natural and synthetic material in 
creating vascular access (Figure 1).8–10
Liu and co-workers11 (this issue) intro-
duce a new vascular access option based 
on the use of formaldehyde-ﬁxed arterial 
allografts. Faced both with multiple native 
arteriovenous ﬁstula failure and with the 
excessive cost of polytetraﬂuoroethylene 
material in China, they hypothesized that 
arterial allografts collected from young 
brain-death subjects would provide an 
interesting vascular graft alternative. On 
the basis of this hypothesis, the authors 
launched a study in two parts. The ﬁrst 
phase of the study consisted of collecting 
femoral arteries (about 20 cm in length) in 
young brain-dead subjects. Brieﬂy, femo-
ral arteries were subsequently ﬁxed and 
denatured in formaldehyde solution, then 
washed and stored in preservative solution. 
Immunogenicity of this ﬁxed material was 
tested ex vivo by means of speciﬁc anti-
bodies produced after rabbit immuniza-
tion, exposed to unﬁxed donor material. 
In this preclinical phase, it was consistently 
shown that formaldehyde-fixed mate-
rial was non-immunogenic. The second 
phase of the study was a clinical trial in 
which 68 ﬁxed and preserved arterial allo-
grafts were implanted in 43 hemodialysis 
patients. Viral safety was monitored in the 
donors. Implantation was performed by 
trained vascular surgeons, mostly on the 
forearm and rarely on the groin. Blood ﬂow 
achieved in the artery allografts was 696 ± 
282 ml/min. The median primary patency 
was 28 months, and the median secondary 
patency was 141 months. Use of preserved 
artery allografts was simple and identical 
to use of native arteriovenous ﬁstulae. No 
acute or subacute allograft rejection was 
noted. Stenosis and thrombosis occurred 
in 37.3% (25/68) of patients. Pseudoan-
eurysm was rarely observed in the clinical 
phase (2.9%; 2/68). Interestingly, intimal 
hyperplasia with preserved structure of the 
media layer and smooth muscle cell archi-
tecture and no sign of rejection were noted 
on removed material after thrombosis.
Technical survival of formaldehyde-ﬁxed 
arterial allografts is not inferior to that of 
synthetic polytetraﬂuoroethylene grafts. 
Primary patency survival was 28 months, 
a value close to that for polytetraﬂuoroeth-
ylene, and secondary patency survival was 
141 months, a value close to that for native 
arteriovenous ﬁstulae. Accordingly, arterial 
allograft survival may be considered as a 
long-term vascular access oﬀering median 
survival expectancy close to that seen with-
polytetraﬂuoroethylene grafts and native 
ﬁstulae. These data require further pro-
spective studies to be conﬁrmed.
What do we learn from this study?
The femoral artery provides an excellent 
graft for vascular access in hemodialysis 
patients, conﬁrming previous study.12 It 
is a straight, well-calibrated, and relatively 
resistant vessel that could be easily handled 
and sutured by a vascular surgeon. Inter-
estingly, arteries, contrary to veins, have 
no valves or collateral branches, mean-
ing that they require speciﬁc preparation 
before being implanted. Constant diam-
eter and relatively low compliance of the 
artery structure as opposed to vein grafts 
are quite interesting physical characteristics 
that guarantee relatively high and constant 
ﬂow (more than 600 ml/min) over time.
Formaldehyde-ﬁxed arterial allografts 
provide a simple, safe, and eﬀective way of 
reducing the antigenicity of heterogenous 
graft material. In that sense, formalde-
hyde ﬁxation seems to be safer than cryo-
preservation technique, which does not 
1Nephrology, Dialysis and Intensive Care, 
Association pour Installation à domicile de 
I’Epuration Rénale and Institute de Recherche 
et Formation en Dialyse, Lapeyronie University 
Hospital, Montpellier, France
Correspondence: B Canaud, Nephrology, 
Dialysis and Intensive Care, Lapeyronie University 
Hospital, 371 Avenue du Doyen G. Giraud, 34295 
Montpellier, France.  
E-mail: b-canaud@chu-montpellier.fr
see original article on page 1249
1180   Kidney International (2007) 72
commentar y
preclude immunization. The ﬁxed arterial 
allograft did not bind antibodies against 
unfixed donor arteries. No immuniza-
tion was observed over time in patients 
receiving the arterial allograft. In other 
words, the use of such allograft material 
in ESRD patients does not increase the risk 
of alloimmunization, which has implica-
tions for future transplantability.
The physiology of formaldehyde-ﬁxed 
arterial allografts appears to be superior to 
that of venous material, because it keeps 
the structure and functionality of the 
artery. Rigidity and resistance are ensured 
by the smooth muscle architecture and 
ﬁbrous capsule of the artery wall structure. 
Because of the persistence of the endothe-
lium layer on the arterial graft, thrombotic 
risk seems to be improved. These biologi-
cal properties need to be explored and 
documented more carefully.
Preserved arterial allografts clearly oﬀer 
a relatively cheap vascular access for hemo-
dialysis patients exposed to multiple fail-
ures of native arteriovenous ﬁstulae.
What potential problems can be antici-
pated from implantation of preserved 
arterial allografts?
Implantation of allograft material of human 
origin carries a risk of transmitting a dis-
ease from the donor.13 Therefore, it seems 
mandatory to screen for infectious dis-
ease, including bacteria (mycobacteria), 
viruses (hepatitis B and C viruses, HIV, 
and slow viruses), fungi, and parasites.14 
Another concern is that of transmitting 
prion protein to the recipient.15 Donors 
must be screened for Creutzfeldt–Jakob 
disease. Long-term safety is of paramount 
importance, and longer studies with larger 
numbers of patients need to be done. 
Alloimunization against fixed arterial 
allografts should be detected over time.16 
This specific follow-up is of particular 
importance in ESRD patients registered 
on renal-transplant waiting lists.17 Search-
ing for anti-HLA antibodies should be 
performed regularly after arterial allograft 
implantation for patients awaiting kidney 
transplantation.
Formaldehyde sensitization is another 
concern in ESRD patients.18 Many hemo-
dialysis patients exposed to formaldehyde 
in the past (hemodialyzer reuse, dialysis 
machine disinfection) were sensitized and 
immunized against formaldehyde. It has 
been reported that speciﬁc formaldehyde 
antibodies may react with erythrocytes, 
inducing chronic hemolysis.19 Accordingly, 
washing and very sensible formaldehyde 
testing should be performed on arterial 
allografts in order to prevent such risk.
What are the implications of this prelimi-
nary study?
Liu and co-workers11 report on a pre-
liminary study with preserved ﬁxed arte-
rial allografts. In this way they provide a 
novel alternative for solving the problem 
of failing to achieve vascular access in 
hemodialysis patients. Preliminary results 
show that technical survival of preserved 
arterial allografts appears quite promising. 
However, it is necessary to compare these 
ﬁndings with those achieved with native 
arteriovenous ﬁstulae and already-used 
grafts in prospective, randomized trials. 
Further studies will help to deﬁne the place 
of preserved arterial allografts in vascular 
access management of ESRD patients.
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1Department of Pathology and Immunology, 
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St. Louis, Missouri, USA; and 2Department of 
Paediatric Nephrology, The Evelina Children’s 
Hospital, Guy’s and St Thomas’ Hospital NHS Trust, 
London, United Kingdom
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E-mail: ashaw@wustl.edu
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Formaldehyde-fixed arterial allograft as a novel vascular access alternative in end-stage renal disease patients

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