n 1997, the National Kidney Foundations original Dialysis Outcomes Quality Initiative
(DOQI) vascular access practice guidelines sought
to increase the placement of autologous arteriovenous fistulas in US hemodialysis (HD) patients.1
The DOQI set goals of at least 50% fistula rates for
new (incident) patients and 40% for prevalent patients. In the United States in 2003, the Centers for
Medicare & Medicaid Services, the End-Stage Renal Disease (ESRD) Networks, and key provider
representatives jointly recommended adoption of a
National Vascular Access Improvement Initiative
to achieve the DOQI goals. In 2005, this effort
From the 1Arbor Research Collaborative for Health, Ann
Arbor, MI; 2Department of Nephrology, Dialysis and Transplantation, Alessandro Manzoni Hospital, Lecco, Italy; and
3
Division of Nephrology, Department of Internal Medicine
and Kidney Epidemiology and Cost Center, University of
Michigan, Ann Arbor, MI.
Received January 22, 2010. Accepted in revised form
August 2, 2010. Originally published online as doi:10.1053/
j.ajkd.2010.08.010 on October 21, 2010.
Address correspondence to David A. Goodkin, MD, 3807
134th Ave NE, Bellevue, WA 98005. E-mail: davidagoodkin@
comcast.net
2010 by the National Kidney Foundation, Inc.
0272-6386/10/5606-0005$36.00/0
doi:10.1053/j.ajkd.2010.08.010
1032
1033
comorbid conditions, and laboratory values. Despite extensive adjustment, it is possible that unmeasured confounding factors influenced these mortality differences, with sicker patients a priori both
unable to undergo creation of a fistula and more
likely to die. Although patients in this study dialyzing with a catheter or an AVG were older and had
higher prevalences of numerous comorbid conditions compared with patients dialyzing with a fistula, examining case-mixadjusted facility vascular
access percentages using instrumental variable analysis showed similar results. These findings are
corroborated by studies from the US Renal Data
System (USRDS),7 Australian and New Zealand
Dialysis and Transplant Association Registry,8 and
ESRD Network 6 in the United States.9
Differences in mortality have long been recognized in HD patients in Japan, Europe, and the
United States,10 and differences in patient demographics and burdens of comorbid disease have
explained only a portion of the varying risks of
death,11 suggesting that differing practice patterns also may account for variability in mortality. In Fig 1, mortality risk is compared between
Europe and the United States, first unadjusted,
then adjusted for case mix and select laboratory
values, and last, also adjusted for access type.6
As indicated in Fig 1, there would be no significant difference in mortality risk between Euro-
Figure 1. Case-mixadjusted mortality hazard ratio (HR) for hemodialysis (HD) patients in the United States versus Europe
(EUR), with and without adjustment for differences in facility vascular access use. The HR of mortality for HD patients in the United
States versus EUR (n 24,398) stratified by study phase is shown after different levels of adjustment: unadjusted; adjusted for
patient age, sex, black race, number of years with end-stage renal disease, body weight, 14 summary comorbid conditions,
whether treated in a hospital-based unit, facility median treatment time, facility percentage of patients with serum phosphorus level
5.5 mg/dL, and facility percentage of patients with serum calcium level 10 mg/dL; and further adjusted for percentage of facility
vascular access use plus the previous 23 adjustments. All models accounted for facility clustering effects. EUR refers to France,
Germany, Italy, Spain, and the United Kingdom. Data source: Pisoni et al.6
1034
pean and US patients matched for clinical characteristics if the pattern of vascular access use for
US patients was similar to the pattern in Europe
(ie, if fistula use was increased and catheter and
AVG use was decreased in the United States).
Vascular access practice differences also accounted for almost 30% of the greater US mortality compared with Japan. In a recent study from
Fresenius units in the United States, researchers
showed that catheters are associated with the
greatest mortality risk; fistulas, with the lowest
mortality; and importantly, changing from a catheter to a fistula or AVG, with significantly improved survival.12 A recent analysis from the
DOPPS similarly showed a survival benefit associated with conversion from a catheter to a permanent access in incident HD patients.13 Clearly,
these analyses reinforce the impetus to maximize
the use of fistulas, decrease the use of catheters,
and provide support for the efforts of the FFBI
and other renal advocacy groups.
Mortality is not the only adverse consequence
associated with using AVGs or catheters rather
than fistulas. Fistula use also is associated with
lower morbidity. Risks of all-cause hospitalization, hospitalization for any infection, or hospitalization for vascular accessrelated infection (accounting for 18.6% of all infection-related
hospitalizations) were substantially greater with
increased facility catheter or AVG use compared
with fistula use.6 The risk of vascular access
related infection was 5- to 7-fold higher for
catheters than for fistulas.14 Vascular access survival also is superior with fistulas compared with
AVGs.15-18 The aggregate costs of access repair
and replacement are extremely high. According
to the USRDS, in 2007, dialysis access event
costs per patient per year were $3,194 for patients with fistulas, $5,960 for patients with catheters, and $7,451 for patients with AVGs.18 The
burden on HD patients related to access complications, including pain, anxiety, hospitalization,
and sepsis, are considerable. Again, the mandate
to maximize the use of fistulas and minimize the
use of catheters is compelling.
Goodkin et al
1035
Figure 2. Distribution of percentages of facility patients using a fistula by region in Dialysis Outcomes and Practice
Patterns Study II (DOPPS II). Percentages of facility fistula use were determined from access use in a prevalent
cross-section of hemodialysis (HD) patients within each facility at entry. Analyses were restricted to 312 facilities reporting
vascular access use at study entry for a minimum of 13 patients (median, 27 patients, with 20-40 patients in 90% of
facilities). Values in inset are median (25th, 75th percentile). Abbreviations: AVF, arteriovenous fistula; North Am, Canada
and United States; EUR/ANZ, Belgium, France, Germany, Italy, Spain, Sweden, United Kingdom, Australia, and New
Zealand. Adapted from Pisoni et al6 with permission of the National Kidney Foundation.
in the DOPPS with historically excellent vascular access results, such as Italy, Germany, and
Spain, have shown decreasing prevalences of
fistula use and increasing catheter use during the
same time frame (Italian data are shown in Fig
3). Even in Japan, the prevalence of fistula use
decreased from 93% to 90% and use of AVGs
increased from 3% to 7%, although catheter use
remained the lowest of any country at 2%. These
findings of variability in access type across facilities/nations and increased fistula placement during recent years in the United States suggest that
1036
Goodkin et al
placement for each 2-fold-higher number of fistulas created during training (P 0.0001). In
DOPPS data, surgeons in the United States receive the least vascular access training, with the
average trainee placing only 50 HD accesses, of
which only 16 are fistulas (Fig 5A). Therefore, it
is not surprising that the prevalence of fistulas in
the United States is the lowest and the prevalence
of catheters is the highest of any of the 12 nations
in the DOPPS. Other studies also have examined
the relation between the surgeons who create
fistulas and outcomes. A study of the patency of
108 fistulas created by 1 of 7 surgeons found in
multivariate regression analysis adjusted for patient demographics and diabetes that only the
specific surgeon was a continuous significant
determinant of fistula patency.27 A subsequent
report also concluded that surgeon selection had
a significant impact on fistula placement and
survival, although this study compared only 2
vascular access surgeons and considered only 75
patients.28
Concerns exist regarding successful access
placement by surgical trainees. Early in the
DOPPS experience, 1 study showed that fistula
use was substantially lower than AVG use when
1037
600
56
Catheter
79
AVG
# VA Created
500
AVF
400
300
35
426
200
24
10
100
0
82
69
34
4
39
BE
# surgeons = 17
92
IT
13
1
19
14
123
132
3
21
81
JPN UK
57
10
11
31
19
19
16
23
50
111
171
115
14
20
16
FR
SP
GE ANZ CA SW
US
10
13
14
36
18
16
18
B
extreme,
very much
% of surgeons
moderate
some
none
# surgeons = 17
13
55
10
10
13
14
18
16
18
35
Figure 5. (A) Mean number of accesses placed by vascular access surgeons during training, by country. (B) Degree
of emphasis on vascular access creation during surgical training by country. Results are based on responses by
surgical operators responsible for creating new vascular accesses for hemodialysis patients in 222 facilities participating in Dialysis Outcomes and Practice Patterns Study II (DOPPS II; 2002-2004). Restricted to surgeons who created at
least 1 arteriovenous fistula (AVF) or graft (AVG) in the previous year. Abbreviations: ANZ, Australia and New Zealand;
BE, Belgium; CA, Canada; FR, France; GE, Germany; IT, Italy; JPN, Japan; SP, Spain; SW, Sweden; UK, United
Kingdom; US, United States; VA, vascular access. Adapted from Saran et al26 with permission of Wolters Kluwer
Health.
1038
Goodkin et al
Box 1. Eleven FFBI Change Concepts for
Increasing Fistulas
1. Routine CQI review of vascular access
2. Timely referral to nephrologist
3. Early referral to surgeon for AVF only evaluation
and timely placement
4. Surgeon selection based on best outcomes, willingness, and ability to provide access services
5. Full range of surgical approaches to AV fistula
evaluation and placement
6. Secondary AV fistula placement in patients with AV
grafts
7. AV fistula placement in patients with catheters when
indicated
8. AV fistula cannulation training
9. Monitoring and maintenance to ensure adequate
access function
10. Education for caregivers and patients
11. Outcomes feedback to guide practice
Abbreviations: AV, arteriovenous; AVF, arteriovenous
fistula; CQI, continuous quality improvement; FFBI, Fistula
First Breakthrough Initiative.
Source: Fistula First website.2
1039
1040
CONCLUSIONS
Worldwide clinical data establish a compelling case for maximizing the use of fistulas and
minimizing the use of catheters. Multiple statistically rigorous cohort studies have shown a robust
association of fistula use with longer patency and
fewer access complications versus AVGs, as well
as with the lowest risks of infection, hospitalization, and death versus AVGs and catheters. It is
particularly remarkable to note that the difference
in mortality between US and European HD patients, which is statistically significant after adjusting for a battery of demographic and comorbid
factors, is no longer significant when differences
in vascular access prevalence rates are taken into
account. Thus, the greater use of catheters/AVGs
and markedly lower use of fistulas in the United
States may be killing patients.
It is reasonable to acknowledge that not every
HD patient is suitable for creation of a fistula and
a small number of patients with permanent arteriovenous vascular access develop high-output
congestive heart failure.45 However, fistula use
has been associated with lower cardiovascular
mortality overall compared with catheter use.46
Furthermore, the greatly superior overall clinical
outcomes associated with fistula use, when examining differences within or between regions, justify making every effort to maintain fistulas in
most HD patients. It is highly unlikely that a
randomized controlled trial of fistula versus AVG
or catheter use will ever be conducted based on
the strength and uniformity of observational studies in the field. The consistently high rates of
fistula use in nations such as Japan, Italy, and
Germany show that the goal of widespread fistula use is attainable, and the progressive improvement in fistula prevalence in the United
States during the past 14 years shows that efforts
Goodkin et al
ACKNOWLEDGEMENTS
The authors thank Dr Sabina Libardi for sharing her
knowledge of training practices for Italian nephrologists in
the field of vascular access.
Support: The DOPPS is administered by Arbor Research
Collaborative for Health and is supported by scientific
research grants from Amgen (since 1996), Kyowa Hakko
Kirin (since 1999, in Japan), Genzyme (since 2009), and
Abbott (since 2009), without restrictions on publications.
Financial Disclosure: Dr Goodkin has consulted for Affymax, AMAG Pharmaceuticals, Amgen, FibroGen, Keryx
Biopharmaceuticals, Registrat-MAPI, and Xenon Pharmaceuticals. Dr Pisoni has received speaker fees from Amgen,
Kyowa Hakko Kirin, and Vifor; has served as a consultant
for Pursuit Vascular; and has served on an advisory panel for
Merck. Dr Locatelli has served on advisory boards for
Affymax, Amgen-Dompe, Janssen-Cilag, Merck, and Roche
and serves on a safety committee for Sandoz. Drs Port and
Saran have served on a nephrology advisory board for
Amgen.
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