CJASN ePress. Published on April 11, 2019 as doi: 10.2215/CJN.

00490119

Vascular Access for Hemodialysis Patients

New Data Should Guide Decision Making

Michael Allon

Abstract
This commentary critically examines key assumptions and recommendations in the 2006 Kidney Disease Outcomes
Quality Initiative vascular access guidelines, and argues that several are not relevant to the contemporary United Division of
States hemodialysis population. First, the guidelines prefer arteriovenous fistulas (AVFs) over arteriovenous grafts Nephrology,
University of Alabama
(AVGs), on the basis of their superior secondary survival and lower frequency of interventions and infections.
at Birmingham,
However, intent-to-treat analyses that incorporate the higher primary failure of AVFs, demonstrate equivalent Birmingham, Alabama
secondary survival of both access types. Moreover, the lower rate of AVF versus AVG infections is counterbalanced
by the higher rate of catheter-related bloodstream infections before AVF maturation. In addition, AVFs with assisted Correspondence:
maturation (interventions before successful AVF use), which account for about 50% of new AVFs, are associated Dr. Michael Allon,
with inferior secondary patency compared with AVGs without intervention before successful use. Second, the Division of
Nephrology,
guidelines posit lower access management costs for AVFs than AVGs. However, in patients who undergo AVF or
University of Alabama
AVG placement after starting dialysis with a central venous catheter (CVC), the overall cost of access management at Birmingham, Paula
is actually higher in patients receiving an AVF. Third, the guidelines prefer forearm over upper arm AVFs. However, Building 226, 1720
published data demonstrate superior maturation of upper arm versus forearm AVFs, likely explaining the 2nd Avenue South,
progressive increase in upper arm AVFs in the United States. Fourth, AVFs are thought to fail primarily because of Birmingham, AL
35294-0007. Email:
aggressive juxta-anastomotic stenosis. However, recent evidence suggests that many AVFs mature despite mallon@uabmc.edu
neointimal hyperplasia, and that suboptimal arterial vasodilation may be an equally important contributor to AVF
nonmaturation. Finally, CVC use is believed to result in excess mortality in patients on hemodialysis. However,
recent data suggest that CVC use is simply a surrogate marker of sicker patients who are more likely to die, rather
than being a mediator of mortality.
CJASN 14: ccc–ccc, 2019. doi: https://doi.org/10.2215/CJN.00490119

The three types of vascular access available for hemodi-
alysis are arteriovenous fistulas (AVFs), arteriovenous
grafts (AVGs), and central venous catheters (CVCs), and
each access type has advantages and disadvantages (1).
The 2006 Kidney Disease Outcomes Quality Initiative
(KDOQI) vascular access guidelines consider the out-
comes and complications of each vascular access to
make recommendations for the optimal selection of
access type and location (2). These recommendations
are on the basis of vascular access outcomes that may
have been true in the past, when there was more
stringent patient selection for AVF creation, but no
longer apply now that the great majority of patients
receive an AVF. To the extent that these recommen-
dations are no longer relevant to the current hemodi-
alysis population, they may lead to practices that are
not in the best interest of the patients. This commentary
examines several widely accepted assumptions about
vascular access that are inconsistent with recently
published research, and suggests the need to reex-
amine some existing guidelines (Table 1).
AVFs Are Better Than AVGs
The 2006 KDOQI vascular access guidelines state that
“options for fistula placement should be considered
first, followed by prosthetic grafts if fistula placement
is not possible” (2). The accompanying discussion
acknowledges that AVFs have a higher primary failure
rate (access never usable for dialysis) than AVGs. It
argues, however, that AVFs are still preferred to AVGs
because once they are successfully used for dialysis,
AVFs have superior secondary patency, require less
frequent interventions to maintain their patency, and
incur fewer infections. Although each of these state-
ments is correct, they do not adequately consider the
effect of AVF nonmaturation and CVC dependence on
these individual outcomes. Older publications, on which
the original KDOQI guidelines were based, observed
AVF nonmaturation in only 10% of patients (3–5).
More recent publications, reflecting widespread AVF
creation in the great majority of patients on dialysis,
have reported substantially higher (30%–60%) AVF
nonmaturation rates (6–8). Contemporary head-to-
head comparisons of AVF and AVG outcomes at two
large academic centers documented an absolute
primary failure rate of AVFs that was about 20%
higher than that of AVGs (9,10). Specifically, a study
in Birmingham, Alabama, of 322 new AVFs and 289
new AVGs observed primary failure rates of 38% and
15%, respectively (9). Similarly, a study in Toronto,

www.cjasn.org Vol 14 July, 2019 Copyright © 2019 by the American Society of Nephrology 1
2 CJASN

Table 1. Summary of myths versus facts about vascular access

Myths Facts

AVFs have better survival than AVGs
AVFs are cheaper than AVGs
Forearm AVFs are better than upper arm AVFs
AVFs fail to mature primarily because of aggressive
neointimal hyperplasia (inward remodeling)
CVCs are a major cause of death
When you include AVFs that fail to mature, secondary survival is equivalent
for AVFs and AVGs. Moreover, assisted AVF maturation is associated
with shorter secondary survival and more frequent interventions after
maturation
If you analyze by intent to treat, AVFs are more expensive
Most patients are getting upper arm AVFs because they have superior
maturation rates
AVF maturation reflects a balance between inward and
outward remodeling
CVC use is a surrogate marker of sicker patients. Very few deaths in patients
with CVC are directly due to CVC complications

AVF, arteriovenous fistula; AVG, arteriovenous graft; CVC, central venous catheter.

Canada, of 1012 new AVFs and 128 new AVGs documented
primary failure rates of 40% and 19%, respectively (10). Both
studies confirmed that secondary AVF survival was indeed
superior to that of AVGs (5 versus 2 years), when the analysis
was restricted to accesses successfully used for dialysis.
However, in an intent-to-treat analysis that included all
vascular accesses (including those with a primary failure),
secondary access survival was equivalent for AVFs and
AVGs (Figure 1). In fact, AVG survival was superior to that
of AVFs during the first 2 years after access placement.
Several smaller observational studies have arrived at similar
conclusions (11–13). Thus, among elderly patients with a high
comorbidity, whose median life expectancy is about 2 years,
AVGs may actually be the preferred choice. In contrast,
AVF placement is preferred in patients with a life expec-
tancy .5 years. Finally, the optimal access type in patients
with an expected survival of 2–5 years requires careful
consideration of the relative merits and disadvantages of
an AVF and AVG in that patient (14).
Whereas it is true that AVFs require less frequent
interventions (angioplasty, thrombectomy, or surgical revi-
sion) to maintain their patency after successful use (15), they
also require more frequent interventions before their
successful use (assisted survival). A substantial propor-
tion (27%–58%) of new AVFs require assisted maturation
(Table 2). A small, single-center study of 110 patients
undergoing placement of a new vascular access documented
assisted maturation (the need for an intervention before
successful use for dialysis) in 42% of patients receiving an
AVF versus 16% of those with an AVG (11). Subsequently, a
larger observational study of 289 AVFs and 310 AVGs from
the same center observed assisted survival in 50% of AVFs,
but only 18% of AVGs (16). Finally, a recent analysis of a
national cohort of 9458 elderly United States patients on
hemodialysis initiating dialysis with a CVC reported that
assisted maturation was required in 42% of AVFs versus
23% of AVGs (17). Two recent studies associated assisted
AVF maturation with a shorter secondary survival and
more frequent interventions to maintain patency (16,18). In
one study of 173 patients with a new AVF creation, AVF
survival after maturation was 20%–30% lower among
patients requiring two or more AVF interventions before
maturation, compared with those with unassisted AVF
maturation (18). Moreover, the frequency of AVF interventions
after maturation was 1.8- and 4.6-fold higher if the AVF
required one or two or more interventions to assist matu-
ration. An accompanying editorial (19) commented that,
“Although usability for dialysis is often considered an
indicator of successful maturation, how the fistula got
there (i.e., how it became usable) seems to be important.” A
second study of 289 patients with a new AVF observed a
two-fold higher likelihood of abandonment among AVFs
with assisted maturation versus unassisted maturation (16).
Remarkably, AVFs with assisted maturation had a second-
ary patency after maturation that was inferior to that of
AVGs with unassisted maturation (16) (Figure 2). It is
unclear whether the association of assisted maturation with
inferior long-term AVF outcomes is a consequence of the
intervention itself or simply a reflection of the use of poor-
quality vessels that lead to impaired maturation and the
need for adjuvant interventions.
The time from access placement to its first successful use
for dialysis is substantially longer for AVFs compared with
AVGs. The Dialysis Outcomes and Practice Patterns Study
reported that only 2% of AVFs, but 78% of AVGs, were
used for dialysis in the United States within 1 month of
their placement (20). A subsequent publication found that
the median time to first successful access cannulation in the
United States was 82 days for AVFs and 29 days for AVGs
(21). A recent US Renal Data System (USRDS) analysis of
patients undergoing access surgery after dialysis initiation
observed that 70% of those receiving an AVF remained
CVC-dependent after 3 months, compared with 40% of
those with an AVG (22). The time to successful cannulation
is further prolonged if the AVF requires assisted matura-
tion. For example, a large, single-center study observed a
median interval from AVF creation to successful cannula-
tion of 99 days for AVFs with unassisted maturation,
compared with 159 days for those with assisted matura-
tion (16). Analysis of a national cohort of elderly patients on
hemodialysis reported that the median time from access
placement to its successful use was 1 month for AVGs
without prior intervention, 2 months for AVGs with a prior
intervention, 3 months for AVFs with unassisted matura-
tion, and 4 months for AVFs with assisted maturation (17).
Among patients with vascular access placement after
initiation of dialysis, such delays in successful AVF use
translate into prolonged CVC dependence, with its
CJASN 14: ccc–ccc, July, 2019 New Perspectives on Vascular Access, Allon 3

A 1.0
Fistula
Graft
0.8

Proportion Surviving
0.6

0.4

0.2

0.0

Years 0 1 2 3 4 5 6 7 8 9 10
Fistula 1012 408 294 196 135 98 65 36 24 15 4
Graft 128 49 33 22 18 8 5 5 2 1 1
Number at risk

B 1.0
Fistula
Graft
0.8
Proportion Surviving

0.6

0.4

0.2

0.0

Years 0 1 2 3 4 5 6 7 8 9 10
Fistula 610 399 292 195 134 98 65 36 24 15 4
Graft 104 59 33 22 18 8 5 5 2 1 1
Number at risk

Figure 1. | Secondary survival of AVFs is superior to that of AVGs when primary failures are excluded, but similar when they are included.
Reprinted from reference 10, with permission.

associated risk of CVC-related bloodstream infections. In
one observational study, the duration of CVC dependence
until successful access use was 4 months for AVFs versus 1
month for AVGs. The proportion of patients experiencing a
catheter-related bloodstream infection before access use was
44% and 24%, respectively (9). After successful access use,
the annual rate of access infection was 9.7% for AVGs and
0.7% for AVFs. In other words, placement of an AVF rather
than AVG entailed a trade-off between early CVC infec-
tions and late AVG infections. CVCs are also associated
with a 7% risk of central vein stenosis (23), and ipsilateral
CVCs have been associated with decreased secondary AVF
survival (24).
AVFs Are Cheaper Than AVGs
The 2006 KDOQI vascular access guidelines state that the
“costs of implantation and access maintenance are lowest
for AVFs” (2). This is certainly true when the analysis is
restricted to endovascular and surgical procedures required
to maintain access patency after successful use (angioplasty,
thrombectomy, or surgical revision). In this regard, numer-
ous publications have reported that AVGs require a three- to
seven-fold greater frequency of such interventions than AVFs
(15), which would predictably translate into a higher cost for
AVG maintenance. A Canadian study compared the overall
cost of access management in new patients on dialysis,
including 157 who received an AVF and 33 who underwent
4 CJASN

Table 2. Frequency of interventions before successful AVF use

(assisted maturation) in published studies

Percent of Patients
Reference Patient Source with Assisted
AVF Maturation

Falk (48) Access ambulatory 58%

center
Lee et al. (18) Two academic centers 44%
Harms et al. (16) One academic center 50%
Allon et al. (8) Seven academic 27%
centers (HFM
Study)
Lee et al. (17) US Renal Data 42%
System

AVF, arteriovenous fistula; HFM, Hemodialysis Fistula

Maturation.

Figure 2. | Secondary access survival after successful use is inferior if

AVG surgery between 1999 and 2001 (25). The access was
placed pre-ESKD in 32% of the patients. The overall median
cost of access management in the first year after dialysis
initiation was lower in patients receiving an AVF versus an
AVG (CAN$4641 versus $8152). Remarkably, patients who
dialyzed exclusively with a CVC had the lowest annual cost
at CAN$3812, likely reflecting the low frequency of catheter-
related bloodstream infections. When the costs were calcu-
lated per patient-year at risk, they were highest with AVGs,
intermediate with CVCs, and lowest with AVFs. The costs
reported in this Canadian study may not reflect contempo-
rary costs in the United States because of differences in
vascular access practice patterns over time and among
countries, selection criteria for access type, the inclusion of
patients with pre-ESKD access surgery, and the short patient
follow-up time. It is also possible that interventions to
promote AVF maturation are more likely if dialysis has
already been started, because there is more pressure to
accelerate AVF use.
The cost calculation of vascular access management
differs when one focuses exclusively on patients who
initiate dialysis with a CVC, and subsequently undergo
placement of an AVF or AVG, i.e., an intent-to-treat anal-
ysis. In that case, the cost includes not just procedures
utilized to maintain access patency after its successful use,
but also procedures required before successful access use,
CVC exchanges due to dysfunction or infection, surgery to
place a second access if the first one fails to mature, and
hospitalizations for treatment of catheter-related blood-
stream infection. An analysis from one center reported that
the median annual cost of access management was twice
as high in patients with an AVF that failed to mature,
compared with patients in whom the AVF was successfully
used for dialysis ($16,652 versus $8146) (26). Similarly, in a
national cohort of elderly (age $66 years) patients who
underwent AVF creation after starting dialysis with a CVC,
the cost of access management was two- to three-fold higher
if the AVF required an intervention before successful use,
and four-fold higher if the AVF failed to mature (27). Given
that at least one third of new AVFs fail to mature (21), this
substantially increases the overall cost of patients receiving
an AVF. In fact, the median annual access management
an intervention was required prior to successful use. Access patency
was shorter for AVFs with prior intervention than for AVFs without
interventions (P,0.001). Access patency was shorter for AVGs with
prior interventions than AVGs without intervention (P,0.001). Access
patency was similar for AVFs and AVGs without prior interventions
(P50.16). Access patency was worse for AVFs with prior interventions
than for AVGs without prior interventions (P50.01). Modified from
reference 16.
cost at one center was almost $4000 greater in 295 patients
receiving an AVF compared with 113 patients receiving an
AVG in 2004–2012 ($10,642 versus $6810) (26). The higher
cost of access management in the patients who initially
received an AVF held true for multiple patient subsets
(Figure 3). It was largely driven by the greater frequency of
procedures to assist AVF maturation and/or to place
another access if the initial AVF failed. Unlike the study
by Manns et al. (25), the median overall cost of access
management in patients dialyzing exclusively with CVCs
was far higher, at $28,709 annually, largely driven by
hospitalizations for treatment of catheter-related blood-
stream infections.
Forearm AVFs Are Better Than Upper Arm AVFs
The 2006 KDOQI vascular access guidelines recom-
mend that “the surgeon should focus on sites distally on
the extremity, reserving proximal sites for potential future
access insertions should the initial access site fail” (2). This
recommendation fails to consider the inferior maturation
of forearm AVFs relative to upper arm AVFs, particularly
among women and older patients, observed when fore-
arm AVFs were commonly placed (28). This disparity
persisted even after adoption of routine preoperative
vascular mapping to ensure selection of appropriately
sized vessels (29). Of note, the age and sex disparities in
AVF maturation was prominent in patients receiving a
forearm AVF, but markedly attenuated in those with an
upper arm AVF (28,29). In the multicenter Dialysis Access
Consortium study, AVF thrombosis within 6 weeks of
its creation in the control arm was observed in 25% of
forearm AVFs versus 13% of upper arm AVFs, and AVF
nonmaturation within 6 months in 64 versus 53%,
CJASN 14: ccc–ccc, July, 2019
12,000
10,000
Median annual access cost ($)
8,000
**
6,000
4,000
2,000
0
Male
Figure 3. | The median annual cost of vascular access management is greater for AVF versus AVG in patients initiating hemodialysis with a CVC
and subsequently undergoing access placement. The comparisons are shown for several patient subsets, divided by sex, age, diabetes mellitus (DM)
status, and congestive heart failure (CHF) status. * P,0.05; ** P,0.01. Reprinted from reference 26, with permission.
respectively (7). Recognition of the higher maturation of
upper arm AVFs has led to a progressive shift from
forearm to upper arm AVFs in the United States. Re-
markably, over the past 20 years, the proportion of new
AVFs placed in the upper arm has increased from 30% to
68% (21). It appears that nephrologists and surgeons in the
United States have recognized the inferior outcomes of
forearm AVFs in certain patient subsets and modified
their practice patterns accordingly, in an attempt to
minimize AVF nonmaturation. These efforts have been
successful, such that AVF nonmaturation has decreased
from approximately 60% observed in the Dialysis Access
Consortium trial (2003–2007) (7) down to about 30%–35%
obtained more recently in the Hemodialysis Fistula Mat-
uration Study (2010–2013) (8) and the Dialysis Outcomes
and Practice Patterns Study 4–5 (2009–2015) (21). Despite
the marked decrease in the proportion of AVFs created in
the forearm, indicating a high selection bias, AVF non-
maturation remains higher for forearm than upper arm
AVFs (44% versus 33%) (21).
AVFs Fail to Mature Because of Aggressive Neointimal
Hyperplasia
An understanding of the pathophysiology of AVF
nonmaturation is critical to improving AVF maturation.
Nonmaturing AVFs are frequently found to have an un-
derlying juxta-anastomotic stenosis during imaging studies,
such as a postoperative ultrasound or angiogram (30,31). In
experimental models, AVFs routinely develop flow-limiting
juxta-anastomotic stenosis, and the histology reveals severe
neointimal hyperplasia (32,33). This observation has led
to the hypothesis that aggressive neointimal hyperpla-
sia results in focal stenosis, which in turn impairs AVF
maturation. In support of this hypothesis, severe focal intimal
hyperplasia was reported in four patients who underwent
surgical revision of a nonmaturing AVF (34). A subsequent
study described six patients in whom the native vein had
New Perspectives on Vascular Access, Allon 5
AVF AVG
*
** * **
**
Female Age>65 Age<65 DM Non-DM CHF non-CHF
minimal intimal hyperplasia, but the draining vein of the
nonmaturing AVF (obtained at the time of surgical revision)
exhibited severe neointimal hyperplasia (35). Taken together,
these two small reports suggested a central role of neointimal
hyperplasia in the pathogenesis of AVF stenosis and
nonmaturation. Subsequently, a much larger study obtained
draining vein samples during the second-stage transposi-
tion from 79 patients with planned two-stage AVFs (36).
After excluding nonmaturing AVFs, it found no correlation
between the magnitude of neointimal hyperplasia and early
AVF failure, suggesting that neointimal hyperplasia was
necessary, but not sufficient, for AVF nonmaturation. It is
unknown, however, whether the timing of neointimal
hyperplasia affects AVF maturation, i.e., whether early
inward remodeling is more deleterious than later remodeling.
Analysis of a large prospective cohort of patients
receiving a new AVF in the Hemodialysis Fistula Maturation
Study found that preexisting arterial reactivity, assessed
by brachial artery nitroglycerin-mediated dilation or flow-
mediated dilation, was positively correlated with the 6-week
AVF diameter and blood flow (37). This observation sug-
gested that the ability of the artery to dilate after AVF
creation was an important determinant of AVF matura-
tion. Collectively, these observations suggests that AVF
maturation depends on the relative balance between neointimal
hyperplasia (inward remodeling) and sustained vasodila-
tion (outward remodeling) (38). AVF nonmaturation would
occur primarily in the subset of patients with both
aggressive neointimal hyperplasia and impaired vaso-
dilation (Figure 4).
CVCs Are a Major Cause of Death in Patients on
Hemodialysis
Numerous observational studies have reported worse
survival in patients dialyzing with a CVC compared with
those with an AVF or AVG (39–42). Moreover, patients
switching from a CVC to an AVF/AVG have better
6 CJASN
Figure 4. | AVF maturation reflects the balance between inward remodeling (intimal hyperplasia) and outward remodeling (vasodilation).
Intimal hyperplasia without concurrent outward remodeling results in AVF nonmaturation. In contrast, concurrent inward and outward re-
modeling results in a mature AVF. Modified from reference 38.
survival than those who continue to dialyze with a CVC
(39,40). Unfortunately, all of these studies had a huge
selection bias that could not be overcome even with so-
phisticated statistical adjustment for comorbidities or pro-
pensity score adjustment. Patients dialyzing with a CVC are
inherently sicker than those dialyzing with an AVF or AVG.
Similarly, patients who continue to dialyze with a CVC are
inherently sicker than those who convert to an AVF (43,44).
The challenge in comparing patient survival between
patients who do or do not undergo AVF creation, is that
there are important differences not easily captured in
administrative databases. If a patient with advanced CKD
is perceived by the nephrologist or surgeon to have a
reasonable life span, it is likely that an AVF will be placed
promptly. In contrast, if the patient has a poor functional
status or limited life expectancy, the physician is more likely
to postpone AVF creation until after the patient starts
hemodialysis. Older patients are less likely to receive an
AVF before initiation of dialysis. Older patients also have a
higher likelihood of dying after initiating dialysis. Thus, the
association between starting hemodialysis with a CVC and
dying is confounded by their age. Similarly, a high comor-
bidity or poor functional status confound the association
between CVC use and patient mortality.
Brown et al. (45) addressed this vexing statistical di-
lemma by designing an innovative approach. They used
the USRDS database to compare the survival of three
groups of elderly patients on hemodialysis: those who
started hemodialysis with an AVF, those who started
hemodialysis with a CVC without pre-ESKD AVF surgery,
and those who started hemodialysis with a CVC after
undergoing pre-ESKD AVF surgery (even if the AVF failed
to mature). As expected, patients starting hemodialysis
with a CVC without pre-ESKD AVF surgery had worse
survival than those starting hemodialysis with an AVF.
However, the group initiating hemodialysis with a CVC after
an unsuccessful attempt at AVF creation had a patient
survival that was more similar to those who initiated dialysis
with an AVF (Figure 5). In other words, simply being selected
for pre-ESKD AVF surgery was a surrogate marker for a
healthier patient with a superior life expectancy.
Quinn et al. (46) evaluated cause-specific mortality in two
cohorts of Canadian patients on hemodialysis dialyzing
with a CVC, those with and without pre-ESKD AVF
creation. In agreement with the study by Brown et al.,
they observed a greater mortality in the group which
underwent attempted AVF placement before dialysis ini-
tiation. However, only 2.3% of deaths were adjudicated to
be CVC-related. A subsequent mediational analysis by the
same investigators found that patients dialyzing with a
CVC were more likely to develop an access complication
and to die, compared with those dialyzing with an AVF or
CJASN 14: ccc–ccc, July, 2019
Kaplan-Meier Survival Curves
1.0
0.8
Survival Probability
I
0.6
II
0.4 III
0.2
0.0
0 10 20
Time in Months After HD Initiation
Figure 5. | Patient survival after initiation of hemodialysis with a CVC is higher in those with versus without attempted pre-ESKD AVF
creation. Group 1, patients who initiated dialysis with an AVF; group 2, patients who initiated dialysis with a CVC after undergoing pre-ESKDAVF
surgery (even if the AVF failed to mature); group 3, patients who initiated dialysis with a CVC without pre-ESKD AVF creation. Patient survival in
group 2 was much more similar to that of group 1 than group 3. Reprinted from reference 45, with permission.
AVG (47). However, the excess deaths in the CVC cohort
could not be attributed to the excess in CVC complications.
In conclusion, since publication of the 2016 KDOQI
vascular access guidelines, substantial new data has been
published. This new information should be incorporated to
reinform current decision making about vascular access.
Acknowledgments
Dr. Allon is supported by grant 1R21DK104248-01A1 from the
National Institute of Diabetes, Digestive and Kidney Diseases.
Parts of this manuscript were presented at the American Society
of Nephrology Kidney Week meeting in San Diego, CA on October
24–28, 2018.
Disclosures
Dr. Allon reports personal fees from CorMedix.
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