Dialysis

Associations of Dialysis Modality and Infectious Mortality in Incident

Dialysis Patients in Australia and New Zealand
David W. Johnson, PhD,
1,2
Hannah Dent, BSc(Hons),
1,3
Carmel M. Hawley, MMedSci,
1,2
Stephen P. McDonald, PhD,
1,4
Johan B. Rosman, MD,
1,5
Fiona G. Brown, PhD,
1,6
Kym M. Bannister, MD,
1,7
and Kathryn J. Wiggins, MD
1,8
Background: The aim of the present investigation is to compare rates, types, causes, and timing of
infectious death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients in Australia and New
Zealand.
Study Design: Observational cohort study using the Australian and New Zealand Dialysis and
Transplant Registry data.
Setting & Participants: The study included all patients starting dialysis therapy between April 1,
1995, and December 31, 2005.
Predictor: Dialysis modality.
Outcomes &Measurements: Rates of and time to infectious death were compared by using Poisson
regression, Kaplan-Meier, and competing risks multivariate Cox proportional hazards model analyses.
Results: 21,935 patients started dialysis therapy (rst treatment PD, n 6,020; HD, n 15,915)
during the study period, and 1,163 patients (5.1%) died of infectious causes (PD, 529 patients; 7.6%
versus HD, 634 patients; 4.2%). Incidence rates of infectious mortality in PD and HD patients were 2.8
and 1.7/100 patient-years, respectively (incidence rate ratio PD versus HD, 1.66; 95% condence
interval [CI], 1.47 to 1.86). After performing competing risks multivariate Cox analyses allowing for an
interaction between time on study and modality because of identied nonproportionality of hazards, PD
consistently was associated with increased hazard of death from infection compared with HD after 6
months of treatment (6 months hazard ratio [HR], 1.08; 95% CI, 0.76 to 1.54; 6 months to 2 years HR,
1.31; 95%CI, 1.09 to 1.59; 2 to 6 years HR, 1.51; 95%CI, 1.26 to 1.80; 6 years HR, 2.76; 95%CI, 1.76
to 4.33). This increased risk of infectious death in PDpatients was largely accounted for by an increased
risk of death caused by bacterial or fungal peritonitis.
Limitations: Patients were not randomly assigned to their initial dialysis modality. Residual confound-
ing and coding bias could not be excluded.
Conclusions: Dialysis modality selection signicantly inuences risks, types, causes, and timing of
fatal infections experienced by patients with end-stage kidney disease in Australia and New Zealand.
Am J Kidney Dis 53:290-297. 2009 by the National Kidney Foundation, Inc.
INDEX WORDS: Bacteremia; continuous ambulatory peritoneal dialysis; hemodialysis; peritoneal
dialysis; peritonitis; pneumonia; septicemia; bacterial infection; fungal infection; incidence; prevalence;
treatment modality; viral infection.
I
nfection is a major cause of morbidity and the
second leading cause of death in dialysis
populations.
1,2
The most common types of fatal
infections recorded in dialysis registries are sep-
ticemia, peritonitis, pneumonia, wound infec-
tions, and urosepsis.
1,3
Some studies have ob-
served greater rates of septicemia,
4
endocarditis,
5
and pneumonia
1
in patients treated with hemodi-
alysis (HD) compared with peritoneal dialysis
(PD). However, other studies have not ob-
Fromthe
1
Australia and NewZealand Dialysis and Trans-
plant Registry, Adelaide;
2
Department of Renal Medicine,
University of Queensland at Princess Alexandra Hospital,
Brisbane;
3
Discipline of Public Health, University of Ad-
elaide;
4
Department of Nephrology and Transplantation
Services, University of Adelaide at the Queen Elizabeth
Hospital, Adelaide, Australia;
5
Renal Department, Middle-
more Hospital, Otahuhu, Auckland, New Zealand;
6
Depart-
ment of Nephrology, Monash Medical Center, Clayton, Victo-
ria;
7
Department of Nephrology, Royal Adelaide Hospital,
Adelaide; and
8
University of Melbourne Department of Ne-
phrology, St Vincents Hospital, Fitzroy, Victoria, Australia.
Received February 25, 2008. Accepted in revised form
July 7, 2008. Originally published online as doi:
10.1053/j.ajkd.2008.06.032 on September 22, 2008.
Address correspondence to David W. Johnson, PhD,
Department of Nephrology, Level 2, ARTS Bldg, Princess
Alexandra Hospital, Ipswich Rd, Woolloongabba, Bris-
bane Qld 4102, Australia. E-mail: david_johnson@health.
qld.gov.au
2009 by the National Kidney Foundation, Inc.
0272-6386/09/5302-0013$36.00/0
doi:10.1053/j.ajkd.2008.06.032
American Journal of Kidney Diseases, Vol 53, No 2 (February), 2009: pp 290-297 290
served an appreciable impact of dialysis modal-
ity on infection type,
6
and the US Renal Data
System (USRDS) Registry has reported no
signicant difference in septicemia rates be-
tween PD and HD patients.
6
A recent North
American single-center study reported that di-
alysis modality was not an independent predic-
tor of overall infection rate in a cohort of
incident dialysis patients, but was a strong
predictor of type of infection that they experi-
enced.
7
Specically, HD was associated with a
greater risk of bacteremia, whereas PD was
associated with a greater risk of peritonitis.
Some of the apparent disparity in ndings
between these different studies may be caused
by their signicant limitations, including single-
center design, data coding ambiguity, use of
outdated data, dialysis modality selection bias,
lack of adjustment for demographic and clini-
cal variables, and residual confounding.
The aim of the present study is to evaluate the
effects of dialysis modality on frequency, types,
and causes of fatal infections in a large incident
end-stage renal disease (ESRD) population.
METHODS
Study Population
The study included all patients with ESRD in Australia
and New Zealand who were older than 18 years and started
dialysis therapy between April 1, 1995, and December 31,
2005. Follow-up continued until December 31, 2005.
Complete details of the structure and methods of the
Australia and New Zealand Dialysis and Transplant
(ANZDATA) Registry have been reported elsewhere.
8
Avail-
able data for this study consisted of information about the
underlying cause of ESRD, demographic details, a limited
range of comorbidities (presence of coronary artery disease,
peripheral vascular disease, cerebrovascular disease, chronic
lung disease, diabetes mellitus, and smoking), body mass
index, and whether the patient had started dialysis therapy
within 3 months of referral to a nephrologist. The primary
outcome measure was infectious death after starting dialysis
therapy. Cause of infectious death was reported to the
registry by the patients attending nephrologist according to
the site of fatal infection (lung, peritoneum, septicemia,
wound, stula, urinary tract, liver, central nervous system, or
other) and its microbiological cause (viral, bacterial, fungal,
protozoal, or not specied/identied). Septicemia denoted
bloodstream infection with an organism (ie, bacteremia or
fungemia) in which the primary site of infection was not
known. No information was collected regarding labora-
tory parameters, antibiotic sensitivities, or antibiotics or
other treatments used.
Statistical Analysis
Results are expressed as frequencies and percentages for
categorical variables, mean SD for continuous normally
distributed variables, and median and interquartile range for
continuousnonnormallydistributedvariables. Baselineanaly-
ses were carried out by dividing patients into 2 groups
according to whether they were receiving PD or HD at rst
treatment (day 0). Differences between the 2 groups were
analyzed by using
2
test for categorical data, unpaired t-test
for continuous parametric data, and Mann-Whitney test for
continuous nonparametric data. Comparison of rates of
infectious mortality between PD and HD patients was per-
formed by using Poisson regression and presented as inci-
dence rate ratio (IRR) with 95% condence interval (CI).
Time to infectious death was evaluated by using multivariate
Cox proportional hazards survival analyses using a compet-
ing risks approach. This involved tting the Cox model on
an augmented data set, as described by Lunn and McNeil.
9
A
shared frailty was included to allow for possible center
effect. Dialysis modality was included in the model as a
time-varying covariate. Adelay of 60 days was allowed after
a change in dialysis modality so that deaths occurring within
60 days of a change were attributed to the previous modality.
Covariates included in the model were age, sex, racial
origin, body mass index, late referral (referral to nephrolo-
gist within 3 months of starting renal replacement therapy),
smoking status (never/former or current), chronic lung dis-
ease, coronary artery disease, cerebrovascular disease, periph-
eral vascular disease, diabetes mellitus, country of treatment
(Australia or New Zealand), center size (based on quartiles
of numbers of patients), and dialysis vintage. Data were
censored for kidney transplantation, recovery of kidney
function, loss to follow-up, and end of study (December 31,
2005). Proportional hazards assumptions were checked by
using Schoenfeld residuals and scaled Schoenfeld residuals,
examined by means of formal hypothesis test and graphi-
cally. First-order interaction terms between signicant covari-
ates were examined for all models. There was no evidence of
an interaction between modality and dialysis vintage. Cumu-
lative incidence was used to estimate probabilities of spe-
cic types of infectious death because this approach takes
into account the presence of competing risks with deaths
from other types of infection. Nonoverlapping 95% con-
dence bands indicate a signicant difference (at the 5%
level) in cumulative incidence between the 2 treatment
groups. Data were analyzed using the software packages
SPSS for Windows, release 12.0 (SPSS Inc, North Sydney,
Australia) and Stata/SE 9.2 (Stata Corp, College Station,
TX). P less than 0.05 is considered statistically signicant.
RESULTS
Baseline Characteristics
During the study period, 21,935 patients started
dialysis therapy in Australia and New Zealand
(rst treatment PD, n 6,020; HD, n 15,915).
Total study follow-up was 57,065 person-years
(PD, 19,100 person-years; HD, 37,965 person-
years). Compared with patients starting dialysis
Dialysis Modality and Infection 291
on HD therapy, patients starting on PD therapy
were more likely to be older, women, diabetic,
nonobese, treated in New Zealand, and referred
to a nephrologist more than 3 months before
starting renal replacement therapy (Table 1). Pro-
portions of patients who had changed modality
for PD versus HD were 8.5% versus 21.1% at 6
months, 27.9% versus 24.7% at 2 years, and
63.6% versus 26.9% at 6 years. Although PD
patients were more likely to change modality at
least once, patients starting HD therapy were
more likely to change modality within the rst 6
months of treatment. Statistically signicant dif-
ferences were observed in comorbid illness bur-
den between the 2 groups, although the magni-
tudes of these differences were small. The
prevalence of automated PD use in PD patients
during the study period was 15.7%.
Infectious Mortality
A total of 1,163 patients (5.1%) died of infec-
tious causes during the study period (PD, 529
patients; 7.6% versus HD, 634 patients; 4.2%).
Incidence rates of infectious mortality in PD and
HD patients were 2.8 and 1.7/100 patient-years,
respectively (unadjusted IRR for PD versus HD,
1.66; 95% CI, 1.47 to 1.86). When cumulative
incidence functions were calculated for infec-
Figure 1. Cumulative incidence with 95% condence
bands of deaths in peritoneal dialysis (PD) and hemodialy-
sis (HD) patients from infection.
Table 1. Baseline Characteristics of the Study Populations
Characteristic
Peritoneal Dialysis
(n 6,020)
Hemodialysis
(n 15,915) P
Age (y) 62.7 (51.0-71.3) 60.4 (47.8-70.8) 0.001
Women 2,828 (47%) 6,240 (39%) 0.001
White 4,400 (73%) 11,912 (75%) 0.008
Body mass index 0.001
Underweight 220 (4%) 709 (5%)
Normal 2,492 (42%) 6,415 (41%)
Overweight 2,080 (35%) 4,937 (31%)
Obese 1,212 (20%) 3,771 (24%)
Late referral 986 (17%) 4,447 (28%) 0.001
Current smoker 724 (12%) 2,246 (14%) 0.001
Chronic lung disease 829 (14%) 2,621 (16%) 0.001
Coronary artery disease 2,448 (41%) 6,323 (40%) 0.2
Peripheral vascular disease 1,709 (28%) 4,171 (26%) 0.001
Cerebrovascular disease 973 (16%) 2,347 (14%) 0.009
Diabetes mellitus 2,430 (40%) 5,856 (37%) 0.001
New Zealand residence 1,572 (26%) 2,443 (15%) 0.001
Vintage 0.001
1995-1997 1,393 (23%) 3,183 (20%)
1998-2000 1,649 (27%) 4,374 (27%)
2001-2003 1,886 (31%) 4,959 (31%)
2004-2005 1,092 (18%) 3,399 (21%)
Never change modality 4,069 (68%) 12,142 (76%) 0.001
Center size (no. of patients) 0.001
Small (340) 1,196 (20%) 4,376 (28%)
Small-medium (340-610) 1,337 (22%) 4,012 (25%)
Medium-large (611-740) 1,755 (29%) 3,143 (20%)
Large (740) 1,732 (29%) 4,384 (28%)
Johnson et al 292
tious deaths, 95% condence bands did not over-
lap after 2 years, conrming that PD therapy was
associated with an increased risk of death from
infection after 2 years of treatment (Fig 1). On
competing risks multivariate Cox proportional
hazards model analysis, cause-specic hazard
ratios (HRs) of both fatal infection and death
from other causes between PD and HD patients
were found to be nonconstant over time (ie,
nonproportional hazards). The proportional haz-
ards assumption was also violated for body mass
index, late referral to a nephrologist, and current
smoking status. To deal with nonproportional
hazards, the follow-up period was divided into
survival during the rst 6 months of treatment,
between 6 months and 2 years of treatment,
between 2 and 6 years of treatment, and after 6
years of treatment. In each of these periods, the
proportional hazards assumption was veried
and interaction terms between time on study and
each of the covariates showing nonproportional
hazards were included in the model to obtain
HRs for each period. Using this model, the
hazard of death from infection in PD patients
was not signicantly different from that in HD
patients in the rst 6 months of treatment (6
months HR, 1.08; 95% CI, 0.76 to 1.54), but was
consistently and signicantly increased in PD
patients compared with HD patients after 6
months of treatment (6 months to 2 years HR;
1.31; 95% CI, 1.09 to 1.59; 2 to 6 years HR, 1.51;
95% CI, 1.26 to 1.80; 6 years HR; 2.76, 95%
CI, 1.76 to 4.33). In addition to dialysis modality,
the other consistent predictors of increased risk
of infectious death were Aboriginal and Torres
Strait Islander origin, current smoking, chronic
lung disease, treated in Australia, and center size.
Causes of Infectious Mortality
Causes of infectious death are listed in Table 2.
Peritonitis was signicantly more common as a
cause of death in PD patients compared with HD
patients (IRR, 56.9; 95% CI, 23.3 to 139). There
were no signicant differences between PD and
HD patients in relative incidences of septicemia,
pneumonia, wound infections, or other infec-
tions. In the Cox analysis (using competing risk
cumulative incidence functions), the excess infec-
tious mortality associated with PD compared
with HD therapy was explained by an augmented
risk of peritonitis (Fig 2). Cumulative incidences
of deaths from peritonitis in PD and HD patients
were 0.012 and 0.001 at 2 years and 0.047 and
0.002 at 6 years, respectively. There were no
signicant differences between PD and HD pa-
tients in cumulative incidences of septicemia,
pneumonia, wound infections, or other infec-
tions (data not shown).
Of 1,163 infectious deaths registered, patho-
genic microorganisms were identied and reported
Figure 2. Cumulative incidence with 95% condence
bands of deaths from peritonitis in peritoneal dialysis (PD)
and hemodialysis (HD) patients.
Table 2. Outcomes of Hemodialysis and Peritoneal
Dialysis (modality at death or censoring) Patients in
Australia and New Zealand, 1995 to 2005
Parameter
Peritoneal Dialysis
(n 6,943)
Hemodialysis
(n 14,992)
Follow-up (y) 19,100 37,965
Total deaths 3,431 (17.96) 5,571 (14.67)
Infectious deaths
Septicemia 117 (0.61) 239 (0.63)
Peritonitis 220 (1.1) 21 (0.06)
Pneumonia 84 (0.44) 163 (0.43)
Wound infection 38 (0.20) 67 (0.18)
Fistula infection 1 (0.01) 17 (0.04)
Urosepsis 4 (0.02) 5 (0.01)
Central nervous
system 5 (0.03) 9 (0.02)
Liver 2 (0.01) 3 (0.01)
Other 58 (0.30) 113 (0.29)
Total 529 (2.76) 634 (1.67)
Modality change 1,931 (32%) 3,748 (24%)
Kidney
transplantation 1,111 (10%) 2,810 (14%)
Lost to follow-up 5 (0.1%) 19 (0.1%)
Recovery of kidney
function 4 (0.04%) 111 (0.29%)
Note: Death outcomes expressed as number (incidence
rate/100 patient-years).
Dialysis Modality and Infection 293
in 368 PD patients and 480 HD patients. Recorded
causes of fatal fungal and bacterial infections are
listed in Tables 3 and 4, respectively.
Rates of fatal fungal infection were signi-
cantly increased in PD patients compared with
HD patients (IRR, 5.19; 95% CI, 3.02 to 8.94).
This increased risk was largely accounted for by
an increased risk of fatal fungal peritonitis in PD
patients (IRR, 25.85; 95% CI, 8.22 to 130.74).
The cumulative incidence of death from fungal
infections (Fig 3) was signicantly greater for
PD patients after 2.5 years of treatment. At 2
years, cumulative incidences were 0.003 and
0.001 for PD and HD patients and 0.009 and
0.001 at 6 years, respectively.
Rates of fatal bacterial infections were also
increased in patients on PD therapy at the time of
death (IRR, 1.52; 95% CI, 1.33 to 1.74). Again,
this increased risk was largely accounted for by
an increased risk of fatal bacterial peritonitis in
PDpatients (IRR, 20.38; 95%CI, 12.21 to 36.50).
The cumulative incidence of death from bacterial
infections (Fig 4) was signicantly greater in PD
patients after 3 years of treatment. Cumulative
incidences for PD and HD patients were 0.023
and 0.019 at 2 years and 0.081 and 0.052 at 6
years, respectively.
There were no signicant differences ob-
served in cumulative incidences of deaths from
Figure 4. Cumulative incidence with 95% condence
bands of deaths from bacterial infections in peritoneal
dialysis (PD) and hemodialysis (HD) patients.
Table 3. Fatal Fungal Infections in Hemodialysis and
Peritoneal Dialysis Patients in Australia and New
Zealand, 1995 to 2005
Site of Fatal
Fungal Infection
Peritoneal Dialysis
(19,100 patient-
years)
Hemodialysis
(37,965 patient-
years)
Fungemia 4 (0.02) 1 (0.003)
Peritonitis 39 (0.20) 3 (0.01)
Pneumonia 2 (0.01) 9 (0.02)
Wound infection 1 (0.01) 1 (0.003)
Fistula infection 0 (0) 0 (0)
Urosepsis 0 (0) 1 (0.003)
Central
nervous system 1 (0.01) 2 (0.01)
Liver 0 (0) 0 (0)
Other 0 (0) 1 (0.003)
Total 47 (0.25) 18 (0.05)
Note: Deaths expressed as number (incidence rate/100
patient-years).
Table 4. Fatal Bacterial Infections in Hemodialysis
and Peritoneal Dialysis (modality at death) Patients in
Australia and New Zealand, 1995 to 2005
Site of Fatal
Bacterial Infection
Peritoneal Dialysis
(19,100 patient-
years)
Hemodialysis
(37,965 patient-
years)
Septicemia 72 (0.38) 180 (0.47)
Peritonitis 165 (0.86) 16 (0.04)
Pneumonia 44 (0.23) 100 (0.26)
Wound infection 31 (0.16) 64 (0.17)
Fistula infection 1 (0.01) 15 (0.04)
Urosepsis 4 (0.02) 4 (0.01)
Central
nervous system 2 (0.01) 3 (0.01)
Liver 1 (0.01) 2 (0.01)
Other 48 (0.25) 96 (0.25)
Total 368 (1.92) 480 (1.26)
Note: Deaths expressed as number (incidence rate/100
patient-years).
Figure 3. Cumulative incidence with 95% condence
bands of deaths from fungal infections in peritoneal dialy-
sis (PD) and hemodialysis (HD) patients.
Johnson et al 294
viral infections or deaths caused by an organism
that was not identied or specied (data not
shown).
DISCUSSION
The present study shows that PD treatment
was associated with an increased risk of death
from infection compared with HD. This excess
risk was accounted for by an increased occur-
rence of fatal peritonitis. No signicant differ-
ences were observed between PD and HD pa-
tients with respect to cumulative incidences of
fatal pneumonia, septicemia, or other infections.
These results differ from those of a recent
single-center North American study of 119 HD
and 62 PD patients in which dialysis modality
was signicantly associated with type of infec-
tion, but was not predictive of overall infection
rates.
7
Specically, peritonitis occurred exclu-
sively in PD patients and bacteremia occurred
exclusively in HD patients. There was a trend
toward increased overall infection risk with PD
(relative risk, 1.30; 95% CI, 0.93 to 1.8; P
0.1), such that the negative ndings compared
with those of our much larger study may simply
reect a lack of statistical power in the former.
Our studys ndings were within the broad CIs
from this study.
In keeping with the ndings of Aslam et al,
7
the risk of fatal peritonitis in our study was
greatly increased in PD patients compared with
HD patients. A novel nding was that the risk
was not proportional over time, but increased
with increasing duration of dialysis therapy. The
explanation for this nding was not able to be
determined from our study, but may be related to
decreasing residual kidney function in PD pa-
tients, cumulative peritoneal exposure to bioin-
compatible uids resulting in impaired host de-
fense against infection, establishment of biolms
in PD catheters acting as a nidus for infection,
and a progressive decrease in use of HD cath-
eters with increasing time on HD therapy be-
cause of the creation of permanent vascular ac-
cess. Moreover, the excess risk of infectious
death in PD patients was explained primarily by
the occurrence of bacterial and fungal peritonitis.
Although there is limited evidence supporting
oral nystatin coadministration with antibiotic
courses in PD patients to prevent fungal peritoni-
tis
10,11
and topical antimicrobial prophylaxis (eg,
mupirocin and gentamicin)
11
to prevent bacterial
peritonitis, the extent to which Australasian units
had adopted this practice is not known. A recent
Australasian survey suggested that nearly 70%
of units do not routinely use recommended infec-
tion control measures in PD patients (D.W.J.,
unpublished data). Moreover, treatment proto-
cols for patients with peritonitis in Australian
and New Zealand renal units are unknown, al-
though delayed catheter removal has been identi-
ed as a key contributing factor to peritonitis-
related deaths.
12
The overall peritonitis rates
observed in Australia (1 episode/20.3 patient-
months)
3
and New Zealand (1 episode/17.0 pa-
tient-months)
3
were more frequent than those
reported in Canada (1 episode/27.6 patient-
months),
13
the United States (1 episode/32.7
patient-months),
13
and many Asian countries.
14
However, the reported death rate from peritonitis
in Australia and New Zealand (5%; K.M.B.,
unpublished data) was similar to that noted in
other countries (3% to 6%).
13
Results of our
study therefore are likely to still be generalizable
to other countries.
The inuence of dialysis modality on septice-
mia in patients with ESRD is more contentious
than for peritonitis, with some studies reporting a
clearly increased risk in HDpatients,
5,7,15
whereas
others describe similar rates of bacteremia be-
tween the 2 dialysis modalities.
6
Abbott and
Agodoa
5,15
identied HD (versus PD) as a strong
independent risk factor for both septicemia and
endocarditis in 327,993 incident dialysis pa-
tients. Conversely, Powe et al
6
conducted a longi-
tudinal cohort study of 4,918 incident patients
with ESRD and found that although the rate of
septicemia was greater for HD patients (11.7%)
than PD patients (9.4%) during the 7 years of
follow-up, the difference was not statistically
signicant for any period. Some of the apparent
disparity may be explained by data-coding ambi-
guity, given that sepsis and septicemia may be
confused with peritonitis by coding physi-
cians.
7,16
Such ambiguity was avoided in the
present study by the use of more specic terms
(bacteremia and peritonitis) in the ANZDATA
Registry. It also is likely that the differential
effect of dialysis modality on bacteremia rates is
inuenced by the prevalence of dialysis catheter
use in HD populations.
17
Arecent analysis of the
Dialysis Morbidity and Mortality Wave 2 Study
Dialysis Modality and Infection 295
(DMMS Wave 2)
18
identied initial dialysis ac-
cess as the main antecedent of bacteremia or
septicemia. The HR for PD catheters was not
signicantly different from those for arterio-
venous grafts or native arteriovenous stulae,
but was substantially less than those for perma-
nent or temporary HD catheters. Other studies
have observed that the risk of bacteremia progres-
sively increases from native stulae to grafts to
dialysis catheters.
19-21
HD access type was not
specically able to be examined in the present
study, although the overall prevalence of HD
catheter use in Australia (4%)
22
and New Zea-
land (24%)
23
is similar to or less than that re-
ported in other countries (18% to 33%).
24,25
In contrast to the USRDS data,
1
our study did
not observe a lower risk of fatal pneumonia in
PD compared with HD patients on univariate
analysis. Reasons for this nding are uncertain,
but may reect patient selection because PD
patients in Australia and New Zealand were
signicantly less likely to have preexisting
chronic lung disease, although the absolute differ-
ence in frequencies was small (14% versus 16%;
P 0.001).
The strengths of this study include its very
large sample size and inclusiveness and robust-
ness of ndings across different statistical meth-
ods. We included all patients who began dialysis
therapy in Australia or New Zealand during the
period; thus, a variety of centers were included
with varying approaches to the use of dialysis
modalities and varying rates of transplantation.
This greatly enhanced the external validity of our
ndings. Moreover, our cohort consisted solely
of incident patients, thereby avoiding the poten-
tially confounding factor of survivor bias associ-
ated with prevalent population studies. The time
span of the cohort was contemporaneous, which
was of particular relevance because selection
criteria and practices may have changed over
time in both HD and PD therapy. Appropriate
analyses were performed to cater for nonpropor-
tional hazards, and competing risks analyses
were undertaken. Dialysis modality was handled
as a time-varying covariate. A key difference of
our registry cohort from that of others, such as
the USRDS, is the high penetration of PDtherapy
(41%) and the higher risk prole of the PD
group, which helped minimize error bias related
to nonrandom dialysis modality selection.
Nevertheless, the study has a number of limita-
tions. The strength of registry analyses with
respect to their extent of coverage must be bal-
anced against their main weakness, which is
limited depth of coverage. ANZDATA does not
collect detailed information for PD or HD pre-
scription, patient compliance, nonfatal infection
data, HD catheter use, hospitalizations, indi-
vidual unit management protocols, laboratory
values, residual urine output, or severity of comor-
bidities; therefore, unidentied associations could
not be entirely excluded. Although we adjusted
for a large number of patient characteristics, the
possibility of residual confounding also cannot
be excluded. In common with other registries,
ANZDATAis a voluntary registry and there is no
external audit of data accuracy (including coding
of cause of death). Consequently, the possibility
of coding/classication bias cannot be excluded.
26
Although we included all patients who started
dialysis therapy as their rst renal replacement
therapy modality, overall treated ESRD inci-
dence rates in Australia currently are around
100/million/year, substantially less than in the
United States and slightly less than in many
European countries, although broadly similar to
rates in other countries, such as Sweden, The
Netherlands, and Poland.
1
Differences in patient
characteristics might explain the differing re-
sults; alternatively, it might be that there are
systematic differences in treatment outcomes be-
tween countries. Although there are no published
data that allow comparisons of PD mortality
rates, there is substantial variation in HD mortal-
ity rates that is not explained by measured comor-
bidities.
27
In conclusion, the present study shows that
dialysis modality is an independent predictor of
rates, types, causes, and times of occurrence of
infectious death in incident patients with ESRD.
This excess risk is caused primarily by a height-
ened risk of peritonitis, which increases with
increasing time on dialysis therapy. Although the
increased risk of infection-related mortality in
PD patients in our study should not be inter-
preted as an endorsement of HDover PDtherapy,
these study ndings should form part of the basis
for informing shared decision making about di-
alysis modality selection in conjunction with
patient preference, individual circumstances, lo-
cal infection rate data, unit practice patterns
Johnson et al 296
(including HD catheter use rates), and the other
well-characterized pros and cons of selecting PD
versus HD therapy. Further attention to infection
control management in PD patients, especially
antimicrobial prophylaxis measures, would also
appear warranted.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge the substantial contri-
butions of the entire Australian and New Zealand nephrol-
ogy community (physicians, surgeons, database managers,
nurses, renal operators, and patients) in providing informa-
tion for and maintaining the ANZDATARegistry databas.
Support: None.
Financial Disclosure: Professor Johnson is a consultant
for Baxter Healthcare Pty Ltd and has previously received
research funds from this company. He has also received
speakers honoraria and research grants from Fresenius
Medical Care. Dr Bannister is a consultant for Baxter
Healthcare Pty Ltd. Dr McDonald has received speaking
honoraria from AMGEN Australia, Fresenius Australia, and
Solvay Pharmaceuticals and travel grants from AMGEN
Australia, Genzyme Australia, and Jansen-Cilag.
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