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The handle http://hdl.handle.net/1887/31463 holds various files of this Leiden University
dissertation.
Author: Ocak, Gürbey
Title: Vascular complications in kidney disease
Issue Date: 2015-01-14
Chapter 8
Hemodialysis catheters increase mortality
as compared to arteriovenous accesses
especially in elderly patients
Gürbey Ocak
Nynke Halbesma
Saskia le Cessie
Ellen K. Hoogeveen
Sandra van Dijk
Jeroen Kooman
Friedo W. Dekker
Raymond T. Krediet
Elisabeth W. Boeschoten
Marion Verduijn Nephrol Dial Transplant. 2011; 26(8): 2611-2617
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Chapter 8
ABSTRACT
Background: Catheter use has been associated with an increased mortality risk in
hemodialysis patients. However, differences in the all-cause and cause-specific mortality
risk between catheter use and arteriovenous access use in young and elderly hemodialysis
patients has not yet been investigated.
Methods: In this prospective cohort study of 1109 incident hemodialysis patients from 38
centers in the Netherlands, hazard ratios (HRs) with 95% confidence intervals (95% CIs) were
calculated for 2-year all-cause, infection-related, and cardiovascular mortality in patients with
a catheter as compared to patients with an arteriovenous access stratified for age (< 65 years
and ≥ 65 years).
Results: Of the 1109 patients, 919 had an arteriovenous access and 190 had a catheter. The
mortality rate was 76 per 1000 person-years in young patients with an arteriovenous access,
129 per 1000 person-years in young patients with a catheter, 222 per 1000 person-years
in elderly patients with an arteriovenous access, and 427 per 1000 person-years in elderly
patients with a catheter. The adjusted HR was 3.15 (95% CI 2.09-4.75) for elderly patients
with a catheter as compared to young patients with an arteriovenous access. The adjusted
HRs in elderly patients with a catheter as compared to elderly patients with an arteriovenous
access were 1.54 (95% CI 1.13-2.12) for all-cause mortality, 1.60 (95% CI 0.62-4.19) for
infection-related mortality, and 1.67 (95% CI 1.04-2.68) for cardiovascular mortality.
Conclusion: Especially elderly hemodialysis patients with a catheter have an increased allcause, infection-related and cardiovascular mortality risk as compared to patients with an
arteriovenous access.
124
Hemodialysis catheters increase mortality as compared to arteriovenous accesses
INTRODUCTION
Dialysis patients require a vascular access for hemodialysis therapy. However, vascular
access problems are responsible for 25% to 50% of hospitalizations in hemodialysis patients
and are also associated with high costs.1-6 While evidence from randomized-controlled trials
is lacking, there is a broad consensus that arteriovenous accesses (fistula or graft) are
superior to central venous catheters. Catheter use for hemodialysis has been associated
with an increased risk for thrombosis,7,8 short access survival,8,9 and an increased risk for
infections.10-13 Therefore, the National Kidney Foundation Kidney Disease Outcome Quality
Initiative (NKF K/DOQI) guidelines14 and the European Best Practice Guidelines15 recommend
the use of arteriovenous accesses instead of catheters for vascular access in hemodialysis
patients.
Despite this preference and recommendation for arteriovenous access use instead of
catheters, limited studies have investigated the association between catheter use and
mortality in elderly hemodialysis patients. Three studies from the United States have reported
an increased mortality risk in elderly hemodialysis patients (elderly defined as age ≥ 65 years
in two studies and aged ≥ 67 years in one study) ranging from a 1.3 to 2.1-fold increased
risk for mortality in patients with a catheter as compared to patients with an arteriovenous
access.16-18 Moreover, information about differences in the association between catheter use
and all-cause and cause-specific mortality in incident hemodialysis patients is limited and
needs further exploration. This information is important, since the cause-specific and all-cause
mortality risk could be different in elderly patients as compared to young patients, leading to
age-specific treatment strategies.
8
Therefore, we investigated the association between catheter use versus arteriovenous
access use and effect on all-cause and cause-specific (infection-related and cardiovascular)
mortality risk in elderly hemodialysis patients as compared to young hemodialysis patients
from a Dutch cohort of incident dialysis patients.
METHODS
Patients
The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) is a prospective
multicenter cohort study in which incident adult end-stage renal disease patients from 38
dialysis centers in the Netherlands were included.19 All patients gave informed consent and
the study was approved by all local medical ethics committees. We followed patients at three
months and six months after start of dialysis and thereafter every six months until death
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Chapter 8
or censoring, i.e. transfer to a nonparticipating dialysis center, withdrawal from the study,
transplantation, or end of the follow-up period (April 2006).
Eligibility included age older than 18 years, no previous renal replacement therapy, and
survival of the initial three months of dialysis. For the current analyses, we used data from
hemodialysis patients included between January 1997 and April 2004. The baseline was
defined at three months after the start of dialysis. This time point of three months was chosen
because patients’ switch to another therapy or deaths within this period were most probably
due to their health status before the start of dialysis, rather than to the dialysis modality.
Demographic and clinical data
Data on age, sex, primary kidney disease, comorbidity, predialysis care, diabetes, and
cardiovascular disease (angina pectoris, myocardial infarction, heart failure, ischemic stroke,
or claudication) were collected at the start of dialysis treatment. Primary kidney disease was
classified according to the codes of the European Renal Association-European Dialysis and
Transplant Association (ERA-EDTA).20 We grouped patients into four classes of primary kidney
disease: glomerulonephritis, diabetes mellitus, renal vascular disease, and other kidney
diseases. Other kidney diseases consisted of patients with interstitial nephritis, polycystic
kidney diseases, other multisystem diseases, and unknown diseases. The comorbidity was
scored on the basis of the number comorbid conditions according to the comorbidity index
described by Davies et al.21. The patients were classified as having no, intermediate, or
severe comorbidity. Since comorbidity is an important confounder for the association between
arteriovenous access use versus catheter use and mortality, the Davies score is used to adjust
for comorbidity. The Davies score is based on the presence or absence of seven comorbid
conditions, producing three risk groups. The Davies score assigns 1 point for each of the
following conditions: ischemic heart disease (defined as prior myocardial infarction, angina
pectoris, or ischemic changes on electrocardiogram), left ventricular dysfunction (defined as
clinical evidence of pulmonary edema not due to errors in fluid balance), peripheral vascular
disease (includes distal aortic, lower extremity, and cerebrovascular disease), malignancy,
diabetes, collagen vascular disease, and other significant disorder (e.g. chronic obstructive
pulmonary disease). Predialysis care was defined as a referral to a nephrologist for at least
three months before initiation of dialysis to provide patients with adequate medical preparation.
Data on vascular access, Kt/Vurea delivered by hemodialysis, and body mass index (BMI)
were collected at 3 months after the start of dialysis. Catheters included both tunneled and
non-tunneled catheters (jugular and femoral) and arteriovenous accesses included native
fistulas and grafts; data on native fistula and graft were not available, though. BMI was
calculated as weight in kilograms divided by height in meters squared. The Kt/Vurea delivered
126
Hemodialysis catheters increase mortality as compared to arteriovenous accesses
by hemodialysis was estimated according to the second-generation Daugirdas formula on
the basis of one plasma urea measurement before and one immediately after the dialysis
session, the ultrafiltration, and the duration of the session as described previously.22,23 Blood
and 24-hour urine samples were obtained at 3 months after the start of dialysis. Albumin,
creatinine, urea, cholesterol, and C-reactive protein (CRP) were determined from the blood
samples. Urea and creatinine levels were also measured in the urine samples. Renal function,
expressed as glomerular filtration rate (GFR), was calculated as the mean of creatinine and
urea clearance corrected for body surface area (ml/min per 1.73 m2). GFR was missing
in 250 patients and serum albumin in 35 patients. The missing values for GFR and serum
albumin were imputed with multiple imputation, a recommended technique where missing
data for a subject are imputed by a value that is predicted by using the subject’s other, known
characteristics,24,25 i.e. using demographic characteristics, mortality, catheter use and serum
albumin, creatinine, and GFR at different time points. We used standard imputation methods
in SPSS statistical software (version 17.0; SPSS, Chicago, Illinois).
Outcome definition
The endpoint of this study was 2-year mortality. We classified causes of death according to the
codes of the ERA-EDTA and grouped death causes into cardiovascular, infection-related, and
other mortality. The following codes were designated as cardiovascular mortality: myocardial
ischemia and infarction; cardiac failure/fluid overload/pulmonary edema; cardiac arrest,
cause unknown; cerebrovascular accident; hemorrhage from ruptured vascular aneurysm;
mesenteric infarction; hyperkalemia; hypokalemia; cause of death uncertain/unknown. The
following codes were designated as infection-related mortality: pulmonary infection; infections
elsewhere except viral hepatitis; septicaemia; tuberculosis; generalized viral infection;
peritonitis. All other deaths were designated as other.
Statistical analysis
Continuous variables are presented as mean ± standard deviation (SD) or as median and
interquartile rage (IQR) depending on the normality of the data. Categorical variables are
presented as number with valid percentages. For continuous data, differences for arteriovenous
access use versus catheter use were tested with t test or Mann–Whitney–Wilcoxon test,
depending on the distribution of the data. Chi-square test was used for categorical variables.
A P value less than 0.05 was considered significant.
Survival curves were determined with the Kaplan-Meier method and mortality rates per 1000
person-years were calculated for four categories of hemodialysis patients defined by age
group and vascular access (elderly arteriovenous access users aged ≥ 65 years, young
arteriovenous access users aged < 65 years, elderly catheter users aged ≥ 65 years, and
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Chapter 8
young catheter users aged < 65 years). We calculated crude and adjusted hazard ratios (HRs)
with 95% confidence intervals (95% CIs) for all-cause, infection-related, and cardiovascular
mortality within 2-year of follow-up in young and elderly hemodialysis patients using Cox
proportional hazard analysis. Furthermore, we calculated HRs for elderly catheter users aged
≥ 65 years, elderly arteriovenous access users aged ≥ 65 years, and young catheter users
aged < 65 years as compared to young arteriovenous access users aged < 65 years. In an
additional analysis, HRs for mortality were calculated for very old patients with a catheter aged
≥ 75 years as compared to very old patients with an arteriovenous access and as compared
to young patients with an arteriovenous access aged < 65 years. HRs were adjusted for
age, sex, primary kidney disease, Davies comorbidity score, predialysis care, GFR, CRP,
cholesterol, BMI, serum albumin levels, and Kt/Vurea delivered by hemodialysis. The
association between catheter use and mortality was studied with an intention-to-treat design
since we were interested in the effect of initial vascular access on mortality. All analysis have
been done in SPSS statistical software version 17.0; SPSS, Chicago, Illinois.
RESULTS
A total of 1109 patients were included between January 1997 and April 2004 and were
treated with hemodialysis therapy at 3 months after start of dialysis in the NECOSAD. Of
these patients, 190 (17.1%) had a catheter and 919 (82.9%) had an arteriovenous access
for hemodialysis as vascular access. Table 1 shows the baseline characteristics of these
patients. There were no differences between patients with a catheter or arteriovenous access
according to age, sex, angina pectoris, myocardial infarction, ischemic stroke, claudication,
diabetes, Davies comorbidity score, distribution of primary kidney disease, and Kt/Vurea
delivered by hemodialysis. The patients with a catheter had a lower BMI, received less often
predialysis care, had more often heart failure, had lower serum albumin levels, had lower
cholesterol levels, had higher CRP levels, and had a lower GFR as compared to patients with
an arteriovenous access (p<0.05 for all).
128
Hemodialysis catheters increase mortality as compared to arteriovenous accesses
Table 1. Baseline characteristics
Age (years) (%)
< 65 years
≥ 65 to 75 years
≥ 75 years
Sex, male (%)
BMI (kg/m2)
Primary kidney disease (%)
Diabetes mellitus
Glomerulonephritis
Renal vascular disease
Others
Cardiovascular disease (%)
Angina pectoris
Myocardial infarction
Heart failure
Ischemic stroke
Claudication
Diabetes mellitus (%)
Davies comorbidity score (%)
No
Intermediate
Severe
Predialysis care (%)
< 65 years
≥ 65 to 75 years
≥ 75 years
Serum albumin (g/L)
Cholesterol (mmol/L)
CRP (mg/L)
GFR (ml/min per 1.73 m2)
Hemodialysis Kt/Vurea (week)
Arteriovenous access
N=919
Catheter
N=190
63.7 ± 13.6
51.6 ± 10.6 (44.8)
70.0 ± 2.9 (33.1)
79.0 ± 3.1 (22.1)
58.7
24.7 ± 4.3
63.2 ± 14.5
50.1 ± 11.4 (44.2)
70.1 ± 2.8 (33.2)
78.8 ± 3.1 (22.6)
55.8
24.5± 4.5
15.6
11.1
21.0
52.3
16.8
5.8
27.4
50.0
11.9
13.5
12.1
9.7
16.2
23.1
11.6
15.3
20.5
8.4
17.9
24.2
38.7
50.6
10.7
76.1
79.9
73.0
72.9
37.0 (33.3-40.0)
4.8 ± 1.2
6.0 (3.0-12.5)
3.1 (1.5-4.9)
2.8 ± 0.8
35.8
48.9
15.3
55.3
46.4
61.9
62.8
35.0 (32.0-38.0)
4.5 ± 1.2
7.6 (3.0-13.0)
2.9 (1.1-4.5)
2.8 ± 0.9
8
All-cause mortality
Of the 190 patients with a catheter, 72 patients died within two years. Of the 919 patients with
an arteriovenous access, 217 died within two years. Figure 1 shows the Kaplan-Meier curves
for all-cause mortality in young and elderly patients with an arteriovenous access or catheter for
the first two years of follow-up. Table 2 shows the HRs for 2-year mortality for both age groups:
young patients with a catheter as compared to young patients with an arteriovenous access
and elderly patients with a catheter as compared to elderly patients with an arteriovenous
access. The mortality rate was lowest for young arteriovenous access users and was highest
for elderly catheter users. The HR for 2-year mortality was 1.54 (95% CI 0.87-2.74) in young
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patients with a catheter as compared to young patients with an arteriovenous access after
adjustment for age, sex, primary kidney disease, Davies comorbidity score, angina pectoris,
myocardial infarction, heart failure, ischemic stroke, claudication, predialysis care, GFR,
CRP, cholesterol, BMI, serum albumin levels, and Kt/Vurea delivered by hemodialysis.
The adjusted HR for 2-year mortality was 1.54 (95% CI 1.13-2.12) in elderly patients with
a catheter as compared to elderly patients with an arteriovenous access. However, on an
absolute scale catheter use in elderly patients as compared to arteriovenous access use
in elderly is associated with more deaths than catheter use in young patients as compared
to arteriovenous access use in young patients (absolute risk difference of 205 per 1000
person-years versus 53 per 1000 person-years). As compared to young patients with an
arteriovenous access, both young patients with a catheter and elderly patients with a catheter
or arteriovenous access had an increased risk (Table 3); elderly patients with a catheter had
Figure 1. Kaplan-Meier survival curve for arteriovenous access versus catheter in young and elderly
an almost 6-fold crude and 3-fold adjusted increased mortality risk as compared to young
hemodialysis patients
patients with an arteriovenous access.
100
Shunt < 65 years
Cumulative survival (%)
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Chapter 8
Catheter < 65 years
75
Shunt ≥ 65 years
50
Catheter ≥ 65 years
25
0
0.0
Number at risk:
Shunt < 65 years
412
Catheter < 65 years 84
Shunt ≥ 65 years
507
Catheter ≥ 65 years 106
0.5
371
70
424
80
1.0
1.5
2.0
320
62
376
61
273
54
325
53
235
42
282
41
Years of follow-up
Figure 1. Kaplan-Meier survival curve for arteriovenous access versus catheter in young and
elderly hemodialysis patients
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Hemodialysis catheters increase mortality as compared to arteriovenous accesses
Table 2. All-cause mortality for catheter as compared to arteriovenous access in young and elderly
hemodialysis patients
Young
< 65 years
Elderly
≥ 65 years
Mortality rate per 1000 py
Crude HR (95% CI)
Adjusted* HR (95% CI)
Adjusted† HR (95% CI)
Mortality rate per 1000 py
Crude HR (95% CI)
Adjusted* HR (95% CI)
Adjusted† HR (95% CI)
Arteriovenous access
(graft or fistula)
Catheter
76
1 (reference)
1 (reference)
1 (reference)
222
1 (reference)
1 (reference)
1 (reference)
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1.70 (0.97-2.99)
1.74 (0.99-3.08)
1.54 (0.87-2.74)
427
1.93 (95% CI 1.42-2.61)
1.70 (95% CI 1.25-2.31)
1.54 (95% CI 1.13-2.12)
py, person-years; HR, hazard ratio; CI, confidence interval. *Adjusted for age, sex, Davies comorbidity
score, angina pectoris, myocardial infarction, heart failure, ischemic stroke, claudication, and primary
kidney disease. †Additional adjusted for predialysis care, GFR, CRP, cholesterol, BMI, serum albumin
levels, and hemodialysis Kt/Vurea.
Table 3. All-cause mortality for young and elderly patients with a catheter or arteriovenous access
Arteriovenous access < 65 years
Catheter < 65 years
Arteriovenous access ≥ 65 years
Catheter ≥ 65 years
Mortality rate Crude HR
per 1000
(95% CI)
person-years
Adjusted* HR
(95% CI)
Adjusted† HR
(95% CI)
76
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222
427
1 (reference)
1.71 (0.97-3.02)
2.12 (1.53-2.94)
3.55 (2.39-5.28)
1 (reference)
1.49 (0.84-2.66)
2.06 (1.48-2.86)
3.15 (2.09-4.75)
1 (reference)
1.70 (0.97-2.99)
2.93 (2.13-4.02)
5.64 (3.84-8.27)
HR, hazard ratio; CI, confidence interval. *Adjusted for sex, Davies comorbidity score, angina pectoris,
myocardial infarction, heart failure, ischemic stroke, claudication, and primary kidney disease. †Additional
adjusted for predialysis care, GFR, CRP, cholesterol, BMI, serum albumin levels, and hemodialysis Kt/
Vurea.
Cause-specific mortality
Of the 72 patients with a catheter who died within the first two years of follow-up, 7 died
because of infections (1 young and 6 elderly patients), 34 because of cardiovascular causes
(9 young and 25 elderly patients), and 31 died because of other reasons (6 young and 25
elderly patients). Of the 217 patients with an arteriovenous access who died within 2 years
of follow-up, 27 died because of infections (7 young and 20 elderly patients), 103 because of
cardiovascular causes (25 young and 78 elderly patients), and 87 died because of other reasons
(17 young and 70 elderly patients). Figure 2 shows the adjusted HRs for cause-specific 2-year
mortality in young and elderly patients. The adjusted HRs in elderly patients with a catheter
were 1.60 (95% CI 0.62-4.19) for infection-related mortality and 1.67 (95% CI 1.04-2.68) for
cardiovascular mortality as compared to elderly patients with an arteriovenous access. HRs in
elderly patients with a catheter as compared to young patients with an arteriovenous access
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were 2.92 (95% CI 0.91-9.37) for infection-related mortality and 3.09 (95% CI 1.70-5.60) for
cardiovascular mortality after adjustment for sex, primary kidney disease, Davies comorbidity
score, angina pectoris, myocardial infarction, heart failure, ischemic stroke, claudication,
predialysis care, GFR, CRP, cholesterol, BMI, serum albumin levels, and Kt/Vurea delivered
adjusted
HRs in very old patients were 1.83 (95% CI 1.14-2.93) for all-cause mortality,
by hemodialysis.
2.32 (95% CI 0.57-9.40) for infection-related mortality, and 1.96 (95% CI 0.96-4.02) for
Very old patients
cardiovascular
compared
to verypatients
old patients
an arteriovenous
access.
There were 43mortality
very oldas(aged≥
75 years)
with with
a catheter,
26 patients
of whom died
within two years (11 cardiovascular causes, 3 infection-related causes, and 12 other causes).
Furthermore, 72 patients of the 203 very old patients with an arteriovenous access died within
two years
(32 cardiovascular
infection-related
causes,
and 32
other
causes). The
Figure
2. Adjusted
hazard ratios causes,
with 95%8confidence
intervals
for all-cause
and
cause-
mortality rate per 1000 person-years was 244 for very old arteriovenous access users and
specific mortality for catheter as compared to arteriovenous access in young and elderly
505 for very old catheter users. The adjusted HRs in very old patients were 1.83 (95% CI
hemodialysis
patients
1.14-2.93) for
all-cause mortality, 2.32 (95% CI 0.57-9.40) for infection-related mortality, and
1.96 (95% CI 0.96-4.02) for cardiovascular mortality as compared to very old patients with an
arteriovenous access.
5
4
4
0
0
Other
1
CV
1
Young (< 65 years)
Other
2
CV
2
3
Infection
HR
All-cause
3
Infection
HR
5
All-cause
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Elderly (≥ 65 years)
Figure 2. Adjusted hazard ratios with 95% confidence intervals for all-cause and cause-specific
mortality for catheter as compared to arteriovenous access in young and elderly hemodialysis
patients
Hazard
ratios
are adjusted
for age, for
sex,age,
Davies
comorbidity
angina pectoris,
infarction, heart
failure, infarction,
Hazard
ratios
are adjusted
sex,
Daviesscore,
comorbidity
score,myocardial
angina pectoris,
myocardial
heart failure,
ischemicprimary
stroke,
claudication,
primary
kidney
disease,
care, GFR, CRP,
ischemic
stroke, claudication,
kidney
disease, predialysis
care, GFR,
CRP,
cholesterol,predialysis
BMI, serum albumin
cholesterol, BMI, serum albumin levels, and hemodialysis Kt/Vurea.
levels, and hemodialysis Kt/Vurea.
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Hemodialysis catheters increase mortality as compared to arteriovenous accesses
DISCUSSION
In this prospective cohort study of incident dialysis patients, we showed that catheter use was
associated with an increased 2-year all-cause mortality risk as compared to arteriovenous
access use. Elderly patients (aged ≥ 65 years) with a catheter had a 54% increased risk for
mortality within 2 years as compared to elderly patients with an arteriovenous access and
had a 3-fold increased risk for mortality within 2 years as compared to young patients (aged
< 65 years) with an arteriovenous access. Very old patients with a catheter (aged ≥ 75 years)
had an 83% increased mortality risk as compared to very old patients with an arteriovenous
access. Among elderly patients, catheter use increased especially infection-related and
cardiovascular mortality as compared to arteriovenous access use. The occurrence of
septicemia or bacteremia has been shown to be associated with subsequent cardiovascular
morbidity and mortality.26 Our findings provide support to the guidelines which indicate that
the use of catheters for hemodialysis should be discouraged. We showed that, especially
in elderly hemodialysis patients, catheter use should be discouraged, since older age and
catheter use are associated with an even higher increased mortality risk.
The 1.54-fold increased risk for mortality within two years of follow-up in elderly hemodialysis
patients in our Dutch cohort is comparable to the increased risk found in cohorts from the United
States. Three studies have reported a 1.3- to 2.1-fold increased risk for mortality in elderly
patients with a catheter as compared to elderly patients with an arteriovenous access.16-18 The
first study used data from the United States Medicare dialysis population from 1995 to 1997.16
They showed that catheter use was associated with a 1.7-fold increased one-year mortality
as compared to native fistula use in elderly dialysis patients aged ≥ 67 years. The second
study used data from the United States Renal Data System.17 They showed in a subgroup
analysis that catheter use was associated with a 2.1-fold increased mortality as compared
to native fistula use in elderly dialysis patients aged ≥ 65 years over a mean follow-up of one
year. Finally, the Choices for Healthy Outcomes in Caring for End-stage renal disease study
showed in a subgroup analysis that catheter use was associated with a 1.3-fold increased
mortality as compared to native fistula use in elderly dialysis patients aged ≥ 65 years over a
follow-up of three years.18
Previous studies have reported that catheter use is associated with sepsis and bacteremia,10-13
with decreased delivered dose of dialysis due to decreased blood flow rates,27 and higher
levels of inflammatory factors.28 In addition, several studies have shown an increased infectionrelated and cardiovascular mortality risk in patients with a catheter as vascular access,
especially in the first three months of dialysis.29,30 However, to our knowledge, there are no
studies that investigated infection-related or cardiovascular mortality associated with catheter
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Chapter 8
use in elderly patients. We showed that elderly patients with a catheter had a 60% increased
risk for infection-related mortality and a 67% increased risk for cardiovascular mortality as
compared to elderly patients with an arteriovenous access. Including the first three months of
dialysis would probably have led to an even higher infection-related mortality. Furthermore,
we showed that very old patients with a catheter had a 2.3-fold increased risk for infectionrelated mortality and a 2.0-fold increased risk for cardiovascular mortality as compared to
very old patients with an arteriovenous access. The confidence intervals for the HR for the
infection-related 2-year mortality were wide due to a low number of patients with infectionrelated mortality.
Missing values for GFR and serum albumin were imputed. Patients with missing GFR or
serum albumin used more often catheters and had relatively higher mortality rates. Analyses
excluding patients who had a missing GFR or serum albumin values would have led to biased
results, since relative more patients with a catheter with higher mortality rates would have
been excluded.24 This would have resulted in a decreased mortality risk for catheter use as
compared to arteriovenous access use. Therefore, imputation of GFR and serum albumin
using demographic characteristics, mortality, catheter use, and creatinine, serum albumin and
GFR at different time points leads to more reliable results.
The comparison between catheter use and arteriovenous access use in an observational
design makes confounding-by-indication the most important obstacle. It is important to realize
that these observational studies have limitations to prove causality, since the observed
increased mortality risk in patients with a catheter may partly reflect the effect of differences
between arteriovenous access and catheter users. Catheter use has been associated with less
predialysis care, lower GFR, lower serum albumin levels, and more co-morbidity as compared
to arteriovenous access users.31-33 In our analyses, we took this into account by correcting
for these confounders, but this cannot exclude possible residual confounding. Therefore, our
study shows that catheter use is associated with an increased mortality risk, but this does
not necessarily prove that catheter use increases mortality risk. However, even additional
adjustment for diabetes, angina pectoris, myocardial infarction, heart failure, ischemic stroke,
and claudication did not change the results. Furthermore, we compared catheter use with
arteriovenous access use and not with native fistula use since this information was lacking
in our study. Therefore, as according to the literature mortality is higher in patients with a
graft compared to patients with a native fistula,18,30 patients with catheters in our study would
have had even higher relative mortality risks. Moreover, we had no information about the
type of catheters (tunneled or non-tunneled), the insertion place of the catheters, and the
use of antimicrobial locks for catheters to investigate differences in mortality risk in patients
with a catheter. An intention-to-treat analysis was chosen for the analyses, because we
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Hemodialysis catheters increase mortality as compared to arteriovenous accesses
were interested in the association between mortality and initial vascular access treatment
in elderly dialysis patients. This is important, since guidelines especially discourage catheter
use as initial vascular access treatment.14,15 In addition, an intention-to-treat analysis also
avoids bias caused by transferring patients with an arteriovenous access with complications
to the catheter group. An as-treated design would therefore overestimate the mortality-risk for
patients with a catheter.
In conclusion, our study shows that catheter compared to arteriovenous access use is
associated with an increased mortality, especially among elderly patients. Our findings are
consistent with the guidelines which indicate that the use of catheters for hemodialysis should
be discouraged. We showed that this is especially true for the elderly hemodialysis population.
ACKNOWLEDGEMENTS
We thank the investigators and study nurses of the participating dialysis centers an the data
managers of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)
for collection and management of data. The members of the Netherlands Cooperative Study
on the Adequacy of Dialysis (NECOSAD) Study Group include A.J. Apperloo, J.A. Bijlsma, M.
Boekhout, W.H. Boer, P.J.M. van der Boog, H.R. Büller, M. van Buren, F.Th. de Charro, C.J.
Doorenbos, M.A. van den Dorpel, A. van Es, W.J. Fagel, G.W. Feith, C.W.H. de Fijter, L.A.M.
Frenken, W. Grave, J.A.C.A. van Geelen, P.G.G. Gerlag, J.P.M.C. Gorgels, R.M. Huisman,
K.J. Jager, K. Jie, W.A.H. Koning-Mulder, M.I. Koolen, T.K. Kremer Hovinga, A.T.J. Lavrijssen,
A.J. Luik, J. van der Meulen, K.J. Parlevliet, M.H.M. Raasveld, F.M. van der Sande, M.J.M.
Schonck, M.M.J. Schuurmans, C.E.H. Siegert, C.A. Stegeman, P. Stevens, J.G.P. Thijssen,
R.M. Valentijn, G.H. Vastenburg, C.A. Verburgh, H.H. Vincent, and P.F. Vos. We thank the
nursing staff of the participating dialysis centers and the staff of the NECOSAD trial office for
their invaluable assistance in the collection and management of data for this study. This work
was supported in part by an unrestricted grant from the Dutch Kidney Foundation. The funding
source was involved in neither the collection, interpretation, and analysis of the data nor the
decision for the writing and submission of this report for publication.
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