Original Investigation

Daily Variation in Death in Patients Treated by Long-term

Dialysis: Comparison of In-Center Hemodialysis to
Peritoneal and Home Hemodialysis
Rathika Krishnasamy, MD,1,2 Sunil V. Badve, MD,1,2 Carmel M. Hawley, M Med Sci,1,2
Stephen P. McDonald, PhD,1,3 Neil Boudville, M Med Sci,1,4 Fiona G. Brown, PhD,1,5
Kevan R. Polkinghorne, PhD,1,5 Kym M. Bannister, MD,1,3 Kathryn J. Wiggins, PhD,1,6
Philip Clayton, MM Clin Epi,1,7,8 and David W. Johnson, PhD1,2
Background: There has been little study to date of daily variation in cardiac death in dialysis patients and
whether such variation differs according to dialysis modality and session frequency.
Study Design: Observational cohort study using ANZDATA (Australia and New Zealand Dialysis and
Transplant) Registry data.
Setting & Participants: All adult patients with end-stage kidney failure treated by dialysis in Australia
and New Zealand who died between 1999 and 2008.
Predictors: Timing of death (day of week), dialysis modality, hemodialysis (HD) session frequency, and
demographic, clinical, and facility variables.
Outcomes & Measurements: Cardiac and noncardiac mortality.
Results: 14,636 adult dialysis patients died during the study period (HD, n 10,338; peritoneal dialysis
[PD], n 4,298). Cardiac death accounted for 40% of deaths and was significantly more likely to occur on
Mondays in in-center HD patients receiving 3 or fewer dialysis sessions per week (n 9,503; adjusted OR,
1.26; 95% CI, 1.14-1.40; P 0.001 compared with the mean odds of cardiac death for all days of the week).
This daily variation in cardiac death was not seen in PD patients, in-center HD patients receiving more than 3
sessions per week (n 251), or home HD patients (n 573). Subgroup analyses showed that deaths related
to hyperkalemia and myocardial infarction also were associated with daily variation in risk in HD patients. This
pattern was not seen for vascular, infective, malignant, dialysis therapy withdrawal, or other deaths.
Limitations: Limited covariate adjustment. Residual confounding and coding bias could not be excluded.
Possible type 2 statistical error due to limited sample size of home HD and enhanced-frequency HD cohorts.
Conclusions: Daily variation in the pattern of cardiac deaths was observed in HD patients receiving 3 or fewer
dialysis sessions per week, but not in PD, home HD, and HD patients receiving more than 3 sessions per week.
Am J Kidney Dis. 61(1):96-103. Crown Copyright 2012 Published by Elsevier Inc. on behalf of the National Kidney
Foundation, Inc. All rights reserved.
INDEX WORDS: Cardiac failure; cardiovascular disease; cerebrovascular accident; hemodialysis; hyperkalemia; peritoneal dialysis; septadian rhythm; myocardial infarction; incidence; prevalence; stroke; sudden
cardiac death; treatment modality.

ardiovascular disease is the primary cause of

death in dialysis patients, responsible for up to
40% of deaths in Australia, New Zealand, and the
United States.1,2 The increased incidence of cardiovascular disease in individuals treated by dialysis can be
explained only in part by an elevated prevalence of
traditional risk factors, such as diabetes mellitus,
hypertension, dyslipidemia, obesity, smoking, and lack
of physical activity.3,4 Risk also may be conferred by

nontraditional factors commonly found in advanced

chronic kidney disease, such as abnormal calcium/
phosphate metabolism, anemia, malnutrition, inflammation, oxidative stress, hyperhomocysteinemia, and
elevated lipoprotein(a) level.3,5-8 Moreover, there have
been recent data to suggest an important role for salt
and water overload in addition to the uremic toxin,
electrolyte, and volume flux that occur during hemodialysis (HD).9-11

From the 1Australia and New Zealand Dialysis and Transplant

(ANZDATA) Registry, Adelaide; 2Department of Renal Medicine,
University of Queensland at Princess Alexandra Hospital, Brisbane; 3University of Adelaide at Central Northern Adelaide Renal
& Transplant Services, Adelaide; 4School of Medicine and Pharmacology, University of Western Australia, Perth; 5Department of
Nephrology & Medicine, Monash Medical Center and Monash
University, Clayton, Victoria; 6Department of Renal Medicine,
Royal Melbourne Hospital, Melbourne; 7Department of Renal
Medicine, Royal Prince Alfred Hospital; and 8School of Public
Health, University of Sydney, Sydney, Australia.

Received February 6, 2012. Accepted in revised form July 11,

2012. Originally published online August 20, 2012.
Address correspondence to David W. Johnson, PhD, Department of Nephrology, Level 2, ARTS Bldg, Princess Alexandra
Hospital, Ipswich Rd, Woolloongabba, Brisbane Qld 4102, Australia. E-mail: david_johnson@health.qld.gov.au
Crown Copyright 2012 Published by Elsevier Inc. on behalf of the
National Kidney Foundation, Inc. All rights reserved.
0272-6386/$36.00
http://dx.doi.org/10.1053/j.ajkd.2012.07.008

96

Am J Kidney Dis. 2013;61(1):96-103

Dialysis Modality and Cardiac Death

Some evidence suggests that dialysis modality also

may factor into cardiovascular disease risk. Bleyer
et al12 found an increased risk of cardiac death in HD
patients immediately after weekends, an observation
that may be due to the increased frequency of hyperkalemia and fluid overload in this period. A subsequent
study by the same group13 involving 80 sudden cardiac deaths in HD patients showed a bimodal distribution of death, with a 1.7-fold increased risk of death in
the 12-hour period beginning with the HD procedure
and 3-fold increased mortality risk in the 12 hours
before HD at the close of the weekend interval. They
speculated that alternate daily HD may help prevent
sudden cardiac death. These data were supported by a
recent study by Foley et al14 that also reported that
HD patients had a heightened risk of cardiovascular
events after a long interdialytic interval. More recently, analysis of DOPPS (Dialysis Outcomes and
Practice Patterns Study) data also showed a daily
variation in mortality, particularly for cardiovascular
deaths, with substantial differences between US, European, and Japanese patients.15 In contrast, the continuous nature of peritoneal dialysis (PD) may minimize
cardiovascular risk arising from fluctuations in body
fluid, uremic toxins, and electrolyte compositions.
To date, few studies have investigated daily variation in cardiac death in dialysis patients and whether
such variation differs between HD and PD and between conventional HD and enhanced-frequency HD
or enhanced-hours HD. HD in Australia and New
Zealand is performed for longer hours and generally
with lower blood flow rates compared with the United
States and thus may show different results. In addition,
Australia and New Zealand have a high proportion of
PD and home-based HD patients, many of whom perform longer hours dialysis, with a substantial proportion
performing at least alternate daily dialysis, which is
different from the reported US cohort data.
The aim of the present study was to evaluate
the effects of dialysis modality and HD frequency on the
daily rhythm of cardiac and noncardiac mortality in
the Australian and New Zealand end-stage kidney failure populations, using data from the ANZDATA (Australia and New Zealand Dialysis and Transplant) Registry.

METHODS
The study included all adult patients with end-stage kidney
failure receiving maintenance dialysis in Australia and New Zealand who died between January 1, 1999, and December 31, 2008.
Complete details of the structure and methods of the ANZDATA
Registry have been reported elsewhere.16
The primary outcome measure was cardiac death after starting
dialysis therapy, examined according to its timing (day of the
week). Cause of cardiac death was reported to the registry by the
patients attending nephrologist according to the following categories: myocardial ischemia (presumed), myocardial ischemia/
infarction, pulmonary edema, hyperkalemia, hemorrhagic pericarAm J Kidney Dis. 2013;61(1):96-103

ditis, hypertensive cardiac failure, other cause of cardiac failure,

and cardiac arrest (cause uncertain; whether in or out of hospital).
Deaths were reported as myocardial ischemia or infarction if there
was direct evidence, such as dynamic electrocardiogram and
cardiac enzyme level changes or autopsy report. Deaths were
classified as presumed myocardial ischemia if there was a strong
clinical suspicion in the absence of such direct evidence. Thus, in
this cohort, cardiac arrest (cause uncertain) and myocardial ischemia (presumed) were the codes for sudden death. In line with the
USRDS (US Renal Data System) Cardiovascular Special Studies
Center methodology,17 death attributed to hyperkalemia was excluded from the definition of sudden cardiac death. However, in
contrast to the USRDS, the ANZDATA Registry treats death due to
hyperkalemia as a cardiac rather than noncardiac cause of death
because the mechanism of fatal hyperkalemia generally is cardiac
arrhythmia. No information was collected regarding laboratory
parameters, prescribed medications, percutaneous or surgical revascularizations, or other treatments used.
The timing of noncardiac deaths also was examined, including
death due to vascular causes (cerebrovascular accident, aortic aneurysm rupture, bowel infarction, pulmonary embolus, gastrointestinal
hemorrhage, dialysis access-site hemorrhage, and other hemorrhage),
infection, dialysis therapy withdrawal, accident, suicide, or miscellaneous causes. Patients experiencing cardiac death after dialysis therapy
withdrawal were classified as death due to dialysis withdrawal.
Results were expressed as frequencies and percentages for
categorical variables, mean standard deviation for continuous
normally distributed variables, and median [interquartile range]
for continuous non-normally distributed variables. Analyses were
carried out by dividing patients into 2 groups according to whether
they were receiving PD or HD at the time of death. Differences
between the 2 groups were analyzed by 2 test for categorical data
(including day of the week of death), t test for continuous normally
distributed data, and Mann-Whitney test for continuous nonnormally distributed data.
The independent predictors of cardiac versus noncardiac death
were determined by multivariable logistic regression using backward stepwise elimination based on the likelihood ratio. Covariates included in the model were the parameter of interest: day of
the week on which death occurred, in addition to dialysis modality
(PD vs HD) or dialysis submodality (automated PD, continuous
ambulatory PD, home HD, and in-center HD), age, sex, racial
origin, body mass index, late referral (referral to nephrologist
within 3 months of starting renal replacement therapy), smoking
status (never, former, or current), chronic lung disease, coronary
artery disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus, country of treatment (Australia or New
Zealand), and center size (based on quartiles of numbers of
patients). Interaction terms were examined for days of the week
and dialysis submodality. Comorbid conditions included in the
model represented those most recently reported in annual survey
forms to the ANZDATA Registry. For analysis of the association
between day of week of death and cardiac death in the home HD
cohort, deviation from means coding18 was used in all logistic
regression analyses presented. In this method, rather than compare
each day of the week with a reference day, the odds of cardiac
death for a given day of the week was compared with the odds of
cardiac death for all days of the week. This coding method is suited
to this analysis in which there was no obvious choice for which day
of the week should be the referent group. This was especially
important for the home HD cohort, who had more flexible dialysis
schedules than facility HD patients. Complete data were available
for all covariates. Data were analyzed using the software packages
SPSS for Windows, release 18.0 (www.ibm.com/software/analytics/
spss/) and Stata, version 11 (www.stata.com/). P 0.05 was
considered statistically significant.
97

Krishnasamy et al

RESULTS
Patient Characteristics
During the study period, 14,636 adult dialysis patients died in Australia and New Zealand (modality at
time of death: HD, n 10,338; PD, n 4,298). Of
the 10,338 HD patients who died, 573 (6%) performed home HD and 9,765 (94%) received in-center
HD. Of 4,298 PD patients who died, 1,343 (31%)
were treated with automated PD and 2,955 (69%)
were receiving continuous ambulatory PD. Compared
with patients who died while treated by PD, patients
who died while treated by HD were more likely to be
slightly older, male, and white; reside in Australia;
start dialysis therapy between 2004 and 2008; dialyze
in a smaller center; have end-stage kidney failure
secondary to chronic glomerulonephritis rather than
diabetic nephropathy; and have chronic lung disease,
peripheral vascular disease, and diabetes mellitus
(Table 1). Generally, the magnitudes of these differences were small. Hours per session and frequency of
dialysis sessions for in-center and home-based HD
patients are listed in Table 2.
Cardiac Death
A total of 5,856 (40%) patient deaths were due to
cardiac causes (myocardial infarction in 1,564 [27%],
sudden cardiac death in 3,778 [64%], pulmonary edema
in 107 [2%], cardiac failure in 314 [5%], hyperkalemia
in 80 [1%], and hemorrhagic pericarditis in 13 [0.2%]).
Of 3,778 sudden cardiac deaths, 2,168 (37%) were due
to cardiac arrest (cause uncertain) and 1,610 (27%) were
due to presumed myocardial infarction.
Day of the week was a significant predictor of
cardiac death on univariate analysis (Sunday odds
ratio [OR], 0.87 [95% confidence interval (CI), 0.800.95; P 0.002]; Monday OR, 1.18 [95% CI, 1.091.28; P 0.001]; Tuesday OR, 1.08 [95% CI, 0.991.17; P 0.06]; Wednesday OR, 0.97 [95% CI,
0.90-1.05; P 0.5]; Thursday OR, 1.01 [95%
CI, 0.93-1.09; P 0.9]; Friday OR, 0.99 [95% CI,
0.91-1.08; P 0.8]; and Saturday OR, 0.92 [95% CI,
0.85-1.00; P 0.06]; global P 0.001; Fig 1). Using
multivariable binary logistic regression analysis, the
day of the week was a significant independent predictor of cardiac death in all dialysis patients, with higher
odds of death on Mondays and lower odds of death on
Sundays. P values for lower odds of death on Saturday and higher odds of death on Tuesday were 0.08
and 0.06, respectively (Table 3). The other independent predictors of cardiac death were younger age,
male sex, indigenous racial origin (Aboriginal and
Torres Strait Islander or Maori and Pacific Islander),
prior coronary artery disease, reflux nephropathy, obesity, dialysis in Australia, and dialysis prior to 2004.
98

Table 1. Characteristics of the Study Populations

HD
PD
(n 10,338) (n 4,298)

Characteristics

Age (y)
Women
Race
White
Aboriginal and Torres Strait Islander
Maori and Pacific Islander
Asian
Other

67.413.1 67.112.6
4,256 (41) 1,946 (45)
8,025 (78)
878 (9)
916 (9)
328 (3)
191 (2)

3,012 (70)
255 (6)
683 (16)
226 (5)
122 (3)

1,224 (12)
3,387 (34)
3,065 (31)
2,315 (23)

455 (11)
1,489 (35)
1,355 (32)
925 (22)

Late referral
Smoking status
Current
Former
Never

2,677 (26)

1,080 (25)

1,446 (14)
4,411 (43)
4,481 (43)

551 (13)
1,833 (43)
1,914 (44)

Chronic lung disease

Coronary artery disease
Peripheral vascular disease
Cerebrovascular disease
Diabetes mellitus
ESKF Cause
Chronic glomerulonephritis
Diabetic nephropathy
Renovascular nephrosclerosis
Polycystic kidney disease
Reflux nephropathy
Miscellaneous
Unknown

3,142 (30)
7,606 (74)
5,314 (51)
3,650 (35)
4,435 (43)

1,120 (26)
3,208 (75)
2,343 (55)
1,585 (37)
2,163 (50)

2,274 (22)
3,073 (30)
1,663 (16)
425 (4)
262 (2)
1,881 (18)
760 (7)

788 (18)
1,685 (39)
725 (17)
116 (3)
78 (2)
601 (14)
305 (7)

Country of residence
New Zealand
Australia

1,461 (14)
8877 (86)

1,322 (31)
2976 (69)

Era
1999-2001
2002-2003
2004-2006
2007-2008

2,197 (21)
1,772 (17)
3,608 (35)
2,761 (27)

1,175 (28)
872 (20)
1,419 (33)
832 (19)

Center size
Small, 360 patients
Small-medium, 360-699 patients
Medium-large, 700-839 patients
Large, 840 patients

157 (2)
1,083 (10)
2,695 (26)
6,403 (62)

14 (0)
252 (6)
971 (23)
3,061 (71)

BMI
Underweight, 20 kg/m2
Normal, 20-24.9 kg/m2
Overweight, 25-29.9 kg/m2
Obese, 30 kg/m2

Note: Values for age given as mean standard deviation; all

other values given as number (percentage). Details of characteristics of HD patients (categorized by those dialyzing 3 times per
week, 3 times per week, or at home) are provided in Table S1
(available as online supplementary material).
Abbreviations: BMI, body mass index; ESKF, end stage kidney
disease; HD, hemodialysis; PD, peritoneal dialysis.

Am J Kidney Dis. 2013;61(1):96-103

Dialysis Modality and Cardiac Death

Table 2. Length and Frequency of Dialysis Sessions for
In-Center and Home-Based HD Patients
Dialysis
Characteristic

In-Center HD
(n 9,765)

Home HD
(n 573)

0.001

Session lengtha
4 h
4h
4 h

1,218 (12.5)
5,328 (54.6)
3,208 (32.9)

34 (6.0)
125 (21.8)
413 (72.2)

Session frequencya
3/wk
3/wk

251 (2.6)
9,503 (97.0)

108 (18.8)
464 (81.0)

cant, no statistically significant septadian variation

was demonstrated in the HD cohort in relation to
sudden cardiac death (Table 4).

0.001

Note: Values given as number (percentage).

Abbreviation: HD, hemodialysis.
a
There were 11 missing data for facility HD and 1 missing data
for home HD.

Cardiac Death According to Dialysis Modality

When HD and PD patients were analyzed separately, a septadian rhythm of increased cardiac deaths
was observed in HD patients only (Table 3; Fig 2).
The day on which PD patients died, including subgroups such as those receiving automated PD, did not
significantly vary throughout the week.
In HD patients, day of the week was a significant
predictor of cardiac death in in-center HD patients
receiving 3 or fewer dialysis sessions per week (n
9,503) and, importantly, was not evident in those
receiving in-center HD more than 3 times per week
(n 251; Table 3). In-center HD patients receiving 3
or fewer dialysis sessions per week experienced a
higher odds of death on Mondays (OR, 1.26; 95% CI,
1.14-1.40), but a lower odds of death on Saturdays
(OR, 0.85; 95% CI, 0.76-0.95) and Sundays (OR,
0.88; 95% CI, 0.78-0.96). This variability in cardiac
death for in-center patients was not seen in PD or
home HD patients (Table 3; Fig 3).

Noncardiac Death
No septadian pattern was identified with respect to
vascular, infective, malignant, dialysis therapy withdrawal, or other deaths (data not shown).

DISCUSSION
The novel finding of the present study was the demonstration that a septadian rhythm of cardiac death was
apparent for only in-center HD patients receiving 3 or
fewer dialysis sessions per week. To our knowledge, this
also is the first study to analyze the pattern of cardiac
death in a home HD cohort. We further show that PD
patients have less variability in the pattern of cardiac
death compared with HD patients. The overall occurrence of noncardiac death was distributed more evenly
between dialysis modalities. In addition, this study identified clinical variables that predicted cardiac versus
noncardiac deaths in dialysis patients who died, including older age, male sex, indigenous racial origin, prior
cardiac disease, obesity, and dialysis prior to 2004.
Few studies have assessed the pattern of cardiac
death in dialysis patients. An analysis of USRDS
registry data involving 375,482 patients by Bleyer et
al12 found increased cardiac and sudden cardiac death
rates on Mondays for M-W-F (Monday, Wednesday,
and Friday) HD patients and on Tuesdays for T-T-S
(Tuesday, Thursday, and Saturday) HD patients. A
recent analysis of the USRDS registry by Foley et al14
for thrice-weekly HD patients in 2004-2007 also
reported an escalation of adverse events, including
cardiovascular mortality and cardiovascular-related
hospitalization, after a 2-day interval without HD.
Although the present study was unable to determine

Cardiac Death in Home HD Patients

In this subgroup of patients, the daily variation in
the odds of cardiac death did not show a definite
septadian pattern when assessing each day of the
week compared to the average odds of cardiac death
(Table 3). Because the P value for the overall model
was not significant, there was no definite variation in
daily rates of death in this cohort (Table 3).
Types of Cardiac Death in HD Patients
An association was seen between day of the week
and deaths due to hyperkalemia and myocardial infarction: hyperkalemia (Monday OR, 1.89; 95% CI, 1.183.02) and myocardial infarction (Monday OR, 1.19;
95% CI, 1.03-1.38). However, because the global P
value for the model examining the association of days
of the week and sudden cardiac death was not signifiAm J Kidney Dis. 2013;61(1):96-103

Figure 1. Occurrence of cardiac (black bars) and noncardiac

(white bars) deaths in 14,636 Australian and New Zealand
dialysis patients in 1999-2008, according to the day of the week
of death.
99

Krishnasamy et al
Table 3. Multivariable Logistic Regression Analyses of the Day of the Week as a Predictor of Cardiac Death
Patient Group

Day of Week

Adjusted OR (95% CI)

All dialysis patients (n 14,636)

P
0.001a

Saturday

0.92 (0.85-1.00)

Sunday

0.87 (0.79-0.95)

0.003

Monday

1.22 (1.12-1.33)

0.001

Tuesday

1.08 (0.99-1.18)

0.06

Wednesday

0.96 (0.88-1.05)

0.4

Thursday

0.98 (0.90-1.07)

0.7

Friday

0.99 (0.91-1.09)

0.9

Saturday

1.04 (0.89-1.21)

0.6

Sunday

0.94 (0.80-1.11)

0.5

Monday

1.13 (0.96-1.31)

0.1

Tuesday

1.04 (0.89-1.21)

0.6

Wednesday

0.91 (0.78-1.07)

0.3

Thursday

0.91 (0.78-1.06)

0.2

Friday

1.05 (0.90-1.23)

All PD patients (n 4,298)

0.08

0.8a

All HD patients (n 10,338)

0.5
0.001a

Saturday

0.87 (0.78-0.97)

Sunday

0.84 (0.75-0.94)

0.002

Monday

1.27 (1.15-1.40)

0.001

Tuesday

1.10 (0.99-1.23)

0.07

Wednesday

0.98 (0.89-1.09)

0.8

Thursday

1.02 (0.92-1.13)

0.7

Friday

0.96 (0.87-1.07)

In-center HD 3/wk (n 9,503)

0.01

0.5
0.001a

Saturday

0.85 (0.76-0.95)

Sunday

0.88 (0.78-0.96)

0.03

Monday

1.26 (1.14-1.40)

0.001

Tuesday

1.08 (0.97-1.20)

0.1

Wednesday

0.99 (0.89-1.10)

0.9

Thursday

1.03 (0.92-1.15)

0.6

Friday

0.95 (0.85-1.06)

0.4

Saturday

1.27 (0.40-3.47)

0.1

Sunday

0.79 (0.25-2.51)

0.7

Monday

2.69 (0.84-8.61)

0.1

Tuesday

1.45 (0.49-4.23)

0.5

Wednesday

1.07 (0.33-3.50)

0.9

Thursday

1.16 (0.40-3.41)

0.8

Friday

1.12 (0.36-3.47)

0.8

Saturday

1.23 (0.74-2.03)

0.4

Sunday

0.54 (0.34-0.86)

0.01

Monday

1.19 (0.72-1.98)

0.5

Tuesday

1.04 (0.68-1.60)

0.9

Wednesday

1.13 (0.69-1.85)

0.6

Thursday

1.18 (0.72-1.94)

0.5

Friday

0.90 (0.54-1.51)

0.7

In-center HD 3/wk (n 251)

0.005

0.7a

Home HD patients (n 573)

0.07a

Note: Deviation from means coding was used, such that the odds of cardiac death for a given day of the week were compared with the odds of cardiac
death for all days of the week. Analysis adjusted for age, sex, racial origin, body mass index, late referral, smoking status, chronic lung disease, coronary
artery disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus, country of treatment (Australia or New Zealand), and center size.
Multivariable logistic regression analyses of the day of the week as a predictor of cardiac death in HD patients, by dialysis sessions per week in all versus
home patients, are provided in Table S2.
Abbreviations: CI, confidence interval; HD, hemodialysis; OR, odds ratio; PD, peritoneal dialysis.
a
Global.

100

Am J Kidney Dis. 2013;61(1):96-103

Dialysis Modality and Cardiac Death

Table 4. Association Between Day of the Week and Types of
Cardiac Death in HD Patients
Day of Week

Adjusted OR (95% CI)

Hyperkalemia

Figure 2. Occurrence of cardiac deaths in 10,338 hemodialysis (HD; black bars) and 4,298 peritoneal dialysis (PD; white
bars) patients in Australia and New Zealand in 1999-2008,
according to the day of the week of death.

whether patients on thrice-weekly dialysis were MW-F or T-T-S patients, we observed higher overall
odds of death on Mondays in all HD patients, with
P 0.07 for Tuesdays. Confining the analysis to
in-center patients, a higher odds of death was apparent
on only Mondays. Importantly, the present investigation also made the novel finding that receiving more
frequent HD than the usual 3 times per week or
receiving PD was not associated with a heightened
risk of death on Mondays and Tuesdays.
There are a number of possible mechanisms contributing to the observed excess of cardiac deaths as
dialysis becomes more intermittent. The intermittent
nature of HD could be proarrhythmogenic as a result
of fluctuations in fluid and potassium status. Karnik
et al9 found that a potassium bath of 0 or 1 mEq/L was
associated with increased risk of cardiac arrest. In a
different study, Bleyer et al13 found a trend toward
lower serum potassium levels several months prior to

Figure 3. Percentage of cardiac death by day of the week for

home hemodialysis (HD; striped bars), in-center HD (grey bars),
and peritoneal dialysis (white bars). Errors bars represent 95%
confidence intervals.
Am J Kidney Dis. 2013;61(1):96-103

Sudden cardiac
death

Myocardial
infarction

Saturday
Sunday
Monday
Tuesday
Wednesday
Thursday
Friday

0.87 (0.46-1.67)
0.59 (0.27-1.31)
1.89 (1.18-3.02)
1.53 (0.92-2.55)
1.02 (0.55-1.89)
0.92 (0.50-1.71)
0.71 (0.34-1.47)

Saturday
Sunday
Monday
Tuesday
Wednesday
Thursday
Friday

0.95 (0.85-1.07)
0.93 (0.83-1.06)
1.17 (1.05-1.30)
1.03 (0.92-1.15)
0.97 (0.86-1.09)
0.97 (0.86-1.09)
0.98 (0.87-1.11)

Saturday
Sunday
Monday
Tuesday
Wednesday
Thursday
Friday

0.86 (0.73-1.02)
0.76 (0.63-0.92)
1.19 (1.03-1.38)
1.13 (0.97-1.32)
1.02 (0.86-1.20)
1.05 (0.90-1.24)
1.06 (0.90-1.24)

0.045a
0.7
0.2
0.008
0.1
0.9
0.8
0.4
0.1a
0.4
0.3
0.004
0.6
0.6
0.6
0.8
0.008a
0.09
0.004
0.02
0.1
0.9
0.5
0.5

Note: Adjusted for dialysis submodality, age, sex, racial origin,

body mass index, late referral, smoking status, chronic lung
disease, coronary artery disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus, country of treatment
(Australia or New Zealand), and center size.
Abbreviations: CI, confidence interval; HD, hemodialysis; OR,
odds ratio.
a
Global.

experiencing sudden cardiac deaths in the first 12

hours of HD. Similarly, our study found that cardiac
deaths due to hyperkalemia were increased significantly on Mondays for HD patients, possibly related
to the long weekend break outweighing the impact of
dietary potassium restrictions. Moreover, both hyperand hypokalemia can contribute to large electrolyte
shifts, leading to QT dispersion during HD.19
Other fluctuating factors, including volume status
and metabolic derangement, also may have contributed to the septadian pattern of cardiac death observed
in HD patients dialyzing 3 or fewer sessions per week.
Flythe et al10 reported that higher ultrafiltration rate was
associated with increased all-cause and cardiovascular
mortality. They suggested that limiting patients fluid
intakes and extending dialysis hours might minimize
large volume shifts. Our finding of evenly distributed
deaths throughout the week in PD, home HD, and
101

Krishnasamy et al

in-center HD patients receiving more than 3 dialysis

sessions per week would support this recommendation.
The DOPPS data analysis showed interesting differences between the United States, Europe, and Japan in
relation to rates of death and days of the week.15
Contributing factors to these complex patterns are
incompletely understood, but likely to include dialysis practices. It also is important to note that even in
the general population, there is a body of literature to
support that Mondays are associated with a higher risk
of sudden cardiac death. It has been postulated that
rhythmic fluctuations in human physiology and socially determined rhythms in human behaviour20 are
determining factors. It is tempting to speculate that in
intermittent HD patients, there are further exacerbations
of these rhythms related to dialysis timing.
Another novel finding of this study was the lower
odds of cardiac death on Saturdays and Sundays in HD
patients. It is conceivable that HD staff alter their management (eg, by more assiduously achieving dry weight)
or patients alter their behavior (eg, by more rigidly
adhering to dietary or fluid restrictions) toward the end
of the week in an attempt to decrease risk over the long
weekend break. Alternatively, the observation of lower
odds of cardiac death on the weekend may represent
either a chance finding (type 1 error) or discovery bias
(ie, patients dying on the weekend may be less likely to
be discovered until Monday or Tuesday, when their next
dialysis is scheduled, and this delay may increase the
likelihood that the death is reported as being due to a
cardiac cause).
In home HD patients, there was no definite septadian pattern of cardiac death. Importantly, the pattern
of higher odds of death on Mondays and Tuesdays
was not seen in this group. The problem of uncertainty
about which days of the week patients were doing
dialysis in the home group and thus which day should
represent the true reference for comparison was addressed with deviation coding.
The strengths of our study are the very large size
and comprehensiveness of the sample. We analyzed
data relating to all dialysis patients in Australia or
New Zealand who died during the study period; thus,
various types of centers were included, and these can
be expected to have different approaches to the use of
dialysis modalities. This substantially enhanced the
external validity of our results. The eras covered by
the cohort are contemporaneous; this is important
because selection criteria and practices may have
evolved over time in both HD and PD. A key difference of our registry cohort from that of others, such as
the USRDS, was the high prevalence of PD (41%)
and the higher risk profile of the PD group.
Nevertheless, the study had several limitations. In
particular, the relatively small sample sizes of the
102

home HD and enhanced-frequency HD groups may

have resulted in clinically important differences in
mortality risks by day of the week being missed due to
type 2 statistical errors. ANZDATA also does not
include detailed information for PD or HD prescription, days of HD sessions, medication use (including
vitamin D), patient adherence to treatment, HD catheter use, hospitalizations, individual unit management
protocols, laboratory values, residual urine output, or
severity of comorbid conditions, so that unidentified
associations could not be fully excluded. Although we
adjusted for many patient characteristics, residual
confounding may have persisted. Results also may
have been affected by selection bias because the
dialysis modality would have been chosen in a nonrandom fashion. As with other registries, ANZDATA is
voluntary and does not have an external audit of data
accuracy (thus cause of death coding would not have
been validated). Consequently, the possibility of coding/classification bias cannot be excluded.21 Our findings also may have been affected by discovery bias.
Social supports may have differed between patients
undergoing home-based dialysis therapy and facility
HD, resulting in differential likelihoods of delayed
discovery of death on weekends. Although our study
included all those who initiated dialysis as their first
modality of renal replacement therapy, in Australia,
the incidence rates of renal replacement therapy currently are about 100 per million per year, much lower
than in the United States and somewhat lower than in
many European nations (but largely similar to rates in
other countries, such as Sweden, the Netherlands, and
Poland).2 Differences in patient characteristics may
be responsible for the differences in findings. Also, it
is possible that there are systematic differences in
treatment outcomes between countries. Although we
were not able to find published data that permit
comparisons of PD mortality rates, HD mortality rates
vary substantially in a way that cannot be accounted
for by measured comorbid conditions.22
In conclusion, the present study showed that the
usual septadian pattern of cardiac mortality observed
in HD patients receiving conventional thrice-weekly
dialysis was not seen in PD patients, HD patients
receiving more than 3 dialysis sessions per week, or
those receiving home HD. Studies of larger populations of home HD and enhanced-frequency HD patients are required to be confident that a clinically
important septadian pattern of cardiac mortality does
not occur in these groups.

ACKNOWLEDGEMENTS
The authors gratefully acknowledge the substantial contributions of the entire Australian and New Zealand nephrology community (physicians, surgeons, database managers, nurses, renal operaAm J Kidney Dis. 2013;61(1):96-103

Dialysis Modality and Cardiac Death

tors, and patients) in providing information for and maintaining the
ANZDATA Registry database.
Support: None.
Financial Disclosure: Dr Johnson is a consultant for Baxter
Healthcare Pty Ltd and previously has received research funds
from this company. He has also received speakers honoraria and
research grants from Fresenius Medical Care and is a current
recipient of a Queensland Government Health Research Fellowship. Dr Bannister is a consultant for Baxter Healthcare Pty Ltd. Dr
Brown is a consultant for Baxter and Fresenius and has received
travel grants from Amgen and Roche. Dr Polkinghorne has received speaking honoraria and travel grants from Amgen Australia.
Assoc Prof Hawley has received research funding from Baxter
Healthcare Pty Ltd and Fresenius Medical Care. She also has
received travel grants from Amgen Australia. Dr McDonald is a
consultant for Amgen Australia and Shire Australia. Assoc Prof
Boudville previously has received research funds from Roche;
travel grants from Roche, Amgen, and Jansen Cilag; and speaking
honoraria from Roche. The remaining authors declare that they
have no relevant financial interests.

SUPPLEMENTARY MATERIAL
Table S1: Characteristics of HD patients, by dialysis sessions
per week, and by home modality.
Table S2: Multivariable logistic regression analyses of the day
of the week as a predictor of cardiac death in HD patients, by
dialysis sessions per week in all vs home patients.
Note: The supplementary material accompanying this article (http://
dx.doi.org/10.1053/j.ajkd.2012.07.008) is available at www.ajkd.org

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