J Gastrointest Surg (2012) 16:19401946

DOI 10.1007/s11605-012-1961-z

ORIGINAL ARTICLE

Acute Appendicitis in Patients with End-Stage Renal Disease

Pei-Wen Chao & Shuo-Ming Ou & Yung-Tai Chen &
Yi-Jung Lee & Feng-Ming Wang & Chia-Jen Liu &
Wu-Chang Yang & Tzeng-Ji Chen & Tzen-Wen Chen &
Szu-Yuan Li

Received: 22 May 2012 / Accepted: 28 June 2012 / Published online: 10 July 2012
# 2012 The Society for Surgery of the Alimentary Tract

Abstract
Background Acute appendicitis in patients with end-stage renal disease (ESRD) poses a diagnostic challenge.
Delayed surgery can contribute to higher morbidity and mortality rates. However, few studies have evaluated this
disease among ESRD patients. Our study focused on the lack of data on the incidence and risk factors of acute
Contributorship: Chao PW and Ou SM designed the study, ran the data,
performed the statistical analysis, analyzed the data, and helped write
the manuscript. Chen YT contributed to the study design and ran the
data. Wang FM, Lee YJ, and Liu CJ advised on data analysis. Chen TJ
and Yang WC contributed to the study design. Li SY designed the
study, helped write the manuscript, and is the guarantor.
P.-W. Chao
Department of Anesthesiology, Wan Fang Hospital,
Taipei Medical University,
Taipei, Taiwan
S.-M. Ou
Division of Nephrology, Department of Medicine,
Taipei Veterans General Hospital,
Taipei, Taiwan
Y.-T. Chen
Department of Medicine,
Taipei City Hospital Heping Fuyou Branch,
Taipei, Taiwan
Y.-T. Chen
Division of Nephrology, Department of Medicine,
Taipei Veterans General Hospital,
Taipei, Taiwan
Y.-J. Lee
Faculty of Medicine,
National Yang-Ming University School of Medicine,
Taipei, Taiwan
Y.-J. Lee
Department of Neurology, Neurological Institute,
Taipei Veterans General Hospital,
Taipei, Taiwan
F.-M. Wang : T.-W. Chen
Division of Nephrology, Department of Internal Medicine,
Taipei Medical University Hospital,
Taipei, Taiwan

C.-J. Liu
Faculty of Medicine,
National Yang-Ming University School of Medicine,
Taipei, Taiwan

C.-J. Liu
Division of Hematology and Oncology, Department of Medicine,
Taipei Veterans General Hospital,
Taipei, Taiwan

W.-C. Yang
Division of Nephrology, Department of Medicine,
Taipei Veterans General Hospital and School of Medicine,
National Yang-Ming University,
Taipei, Taiwan

T.-J. Chen
Department of Family Medicine,
Taipei Veterans General Hospital and School of Medicine,
National Yang-Ming University,
Taipei, Taiwan

S.-Y. Li (*)
Division of Nephrology, Department of Medicine,
Taipei Veterans General Hospital and Institute of Clinical
Medicine, National Yang-Ming University,
Taipei, Taiwan
e-mail: syli@vghtpe.gov.tw

J Gastrointest Surg (2012) 16:19401946

1941

appendicitis among ESRD patients and compared the outcomes in patients who underwent different dialysis
modalities.
Methods This national survey was conducted between 1997 and 2005 and included ESRD patients identified from the
Taiwan National Health Insurance database. The incidence rate of acute appendicitis in ESRD patients was compared with
that in randomly selected age-, sex-, and Charlson comorbidity score-matched non-dialysis controls. A Cox regression hazard
model was used to identify risk factors.
Results Among 59,781 incident ESRD patients, matched one-to-one with controls, there were 328 events of acute appendicitis. The incidence rate of 16.9 per 10,000 person-years in the ESRD cohort was higher than that in the control cohort (p0
0.003). The independent risk factors were atrial fibrillation (hazard ratio [HR], 2.08), severe liver disease (HR, 1.74), diabetes
mellitus (HR, 1.58), and hemodialysis (HR, 1.74). Compared with the control cohort, subsequent perforation and mortality
rates of acute appendicitis were also higher in the ESRD cohorts. There was no effect of dialysis modality on the patient
outcomes.
Conclusions ESRD patients had a higher risk for acute appendicitis and poorer outcomes than non-dialysis populations. A
careful examination of ESRD patients presenting with atypical abdominal pain to avoid misdiagnosis is extremely important
to prevent delayed surgery.
Keywords Acute appendicitis . End-stage renal disease .
Epidemiology . Renal replacement therapy . Mortality

Introduction
Acute appendicitis is a condition characterized by inflammation of the inner lining of the vermiform appendix that
spreads to its other parts.1 Fitz et al.2 presented the first
comprehensive description of appendicitis and advocated
early surgical removal of the appendix in 1886. Appendicitis
thus became one of the common diseases for emergency
abdominal surgery, with a lifetime occurrence of approximately 79% and perforation rates of 1935%.35 The annual incidence of appendicitis is about 25 cases per 10,000,
with a malefemale ratio of 1.4:1.3 The disease can present
with an extremely wide variety of clinical manifestations,
and the diagnosis may elude even the most experienced
clinicians. Delays in surgery can lead to perforation of the
appendix, sepsis, shock, and even death. The prognosis of
uncomplicated appendicitis is excellent, but misdiagnosis
worsens the situation appreciably, resulting in higher morbidity and mortality.6,7
Diagnosis of appendicitis is a challenge in patients with
end-stage renal disease (ESRD) treated with hemodialysis
(HD) or peritoneal dialysis (PD) due to minimal abdominal
signs, lack of febrile responses, and atypical laboratory
results.812 In addition, ESRD patients are usually burdened
with more comorbidities, motor and endocrine function disturbances of gastrointestinal tract, and increased inflammation
status and uremic toxins.13,14 However, data are still lacking
on the incidence, risk factors, perforation, and mortality rates
in ESRD patients presenting with acute appendicitis. In addition, no published studies have explored whether different
dialysis modalities have a different impact on patient survival.
Because the Taiwan National Health Insurance provides
comprehensive coverage, it offered us a good opportunity to

evaluate the rate of acute appendicitis among ESRD patients.

We designed a longitudinal nationwide population-based cohort study to evaluate the relative risks of acute appendicitis in
ESRD patients and compared the hazards for different dialysis
modalities. The aim of our study was to examine incidence
rate, perforation or complication rate, mortality rate, and risk
factors of acute appendicitis in ESRD patients. The results
also facilitated comparison between prior findings in general
populations and ESRD patients.

Patients and Methods

Data Source
This study used data from the National Health Insurance
Research Database (NHIRD) of Taiwan. The Taiwan National
Health Insurance (NHI) program, which the government initiated in 1995, covers 99% of the population of 23 million
people 15. In 1999, the Bureau of NHI began to release all
claims data in electronic form under the NHIRD project.
Various extracted datasets are available to researchers, and
hundreds of researchers have used the NHIRD as the basis
for their studies. Since the NHI dataset consists of de-identified
secondary data for research purposes, the study was exempted
from a full review by the Institutional Review Board of our
hospital. We excerpted data from a specially ordered dataset
that includes all claim information from patients under the
registry of catastrophic illness from January 1997 to December
2005. Because patients who have NHI-defined catastrophic
illness, including ESRD requiring chronic dialysis, can be
exempted from related medical expenses, the government has
implemented a strict verification program. Certification of
ESRD requiring chronic dialysis involves careful exclusion
of the causes of acute renal failure, supported medical records,
examination reports, and imaging studies with a comprehensive review by nephrology specialists.

J Gastrointest Surg (2012) 16:19401946

1941

appendicitis among ESRD patients and compared the outcomes in patients who underwent different dialysis
modalities.
Methods This national survey was conducted between 1997 and 2005 and included ESRD patients identified from the
Taiwan National Health Insurance database. The incidence rate of acute appendicitis in ESRD patients was compared with
that in randomly selected age-, sex-, and Charlson comorbidity score-matched non-dialysis controls. A Cox regression hazard
model was used to identify risk factors.
Results Among 59,781 incident ESRD patients, matched one-to-one with controls, there were 328 events of acute appendicitis. The incidence rate of 16.9 per 10,000 person-years in the ESRD cohort was higher than that in the control cohort (p0
0.003). The independent risk factors were atrial fibrillation (hazard ratio [HR], 2.08), severe liver disease (HR, 1.74), diabetes
mellitus (HR, 1.58), and hemodialysis (HR, 1.74). Compared with the control cohort, subsequent perforation and mortality
rates of acute appendicitis were also higher in the ESRD cohorts. There was no effect of dialysis modality on the patient
outcomes.
Conclusions ESRD patients had a higher risk for acute appendicitis and poorer outcomes than non-dialysis populations. A
careful examination of ESRD patients presenting with atypical abdominal pain to avoid misdiagnosis is extremely important
to prevent delayed surgery.
Keywords Acute appendicitis . End-stage renal disease .
Epidemiology . Renal replacement therapy . Mortality

Introduction
Acute appendicitis is a condition characterized by inflammation of the inner lining of the vermiform appendix that
spreads to its other parts.1 Fitz et al.2 presented the first
comprehensive description of appendicitis and advocated
early surgical removal of the appendix in 1886. Appendicitis
thus became one of the common diseases for emergency
abdominal surgery, with a lifetime occurrence of approximately 79% and perforation rates of 1935%.35 The annual incidence of appendicitis is about 25 cases per 10,000,
with a malefemale ratio of 1.4:1.3 The disease can present
with an extremely wide variety of clinical manifestations,
and the diagnosis may elude even the most experienced
clinicians. Delays in surgery can lead to perforation of the
appendix, sepsis, shock, and even death. The prognosis of
uncomplicated appendicitis is excellent, but misdiagnosis
worsens the situation appreciably, resulting in higher morbidity and mortality.6,7
Diagnosis of appendicitis is a challenge in patients with
end-stage renal disease (ESRD) treated with hemodialysis
(HD) or peritoneal dialysis (PD) due to minimal abdominal
signs, lack of febrile responses, and atypical laboratory
results.812 In addition, ESRD patients are usually burdened
with more comorbidities, motor and endocrine function disturbances of gastrointestinal tract, and increased inflammation
status and uremic toxins.13,14 However, data are still lacking
on the incidence, risk factors, perforation, and mortality rates
in ESRD patients presenting with acute appendicitis. In addition, no published studies have explored whether different
dialysis modalities have a different impact on patient survival.
Because the Taiwan National Health Insurance provides
comprehensive coverage, it offered us a good opportunity to

evaluate the rate of acute appendicitis among ESRD patients.

We designed a longitudinal nationwide population-based cohort study to evaluate the relative risks of acute appendicitis in
ESRD patients and compared the hazards for different dialysis
modalities. The aim of our study was to examine incidence
rate, perforation or complication rate, mortality rate, and risk
factors of acute appendicitis in ESRD patients. The results
also facilitated comparison between prior findings in general
populations and ESRD patients.

Patients and Methods

Data Source
This study used data from the National Health Insurance
Research Database (NHIRD) of Taiwan. The Taiwan National
Health Insurance (NHI) program, which the government initiated in 1995, covers 99% of the population of 23 million
people 15. In 1999, the Bureau of NHI began to release all
claims data in electronic form under the NHIRD project.
Various extracted datasets are available to researchers, and
hundreds of researchers have used the NHIRD as the basis
for their studies. Since the NHI dataset consists of de-identified
secondary data for research purposes, the study was exempted
from a full review by the Institutional Review Board of our
hospital. We excerpted data from a specially ordered dataset
that includes all claim information from patients under the
registry of catastrophic illness from January 1997 to December
2005. Because patients who have NHI-defined catastrophic
illness, including ESRD requiring chronic dialysis, can be
exempted from related medical expenses, the government has
implemented a strict verification program. Certification of
ESRD requiring chronic dialysis involves careful exclusion
of the causes of acute renal failure, supported medical records,
examination reports, and imaging studies with a comprehensive review by nephrology specialists.

1942

Study Design and Patient Selection

We conducted a retrospective cohort study from January 1,
1997 to December 31, 2005. Age, gender, modality of renal
replacement therapy (RRT), and comorbid diseases of
patients were retrieved from the database. Each patient
was followed from the initiation of RRT to the diagnosis
of acute appendicitis, death, withdrawal from the original
RRT, or until December 31, 2005.
To compare the incidence of appendicitis of our ESRD
patients and the general population, a longitudinal health insurance dataset of 1,000,000 beneficiaries (randomly sampled
from the original NHIRD) was used as a control group. NHIRD
published the Longitudinal Health Insurance Database (LHID)
dataset in 2000. The LHID-2000 contains the entire original
claim data of 1,000,000 beneficiaries who enrolled in 2000,
which were randomly sampled from the 2000 Registry for
Beneficiaries (ID) of the NHIRD. Registration data of all beneficiaries of the National Health Insurance program from January 1 to December 31 2000 were drawn for random sampling.
Definition of Renal Replacement Therapies, Appendicitis,
and Comorbidity
Stable HD patients are those with catastrophic illness registration cards for ESRD and insurance claims for HD treatment for more than 3 months. Stable PD patients are those
with catastrophic illness registration cards for ESRD and
insurance claims for PD for more than 3 months. Kidney
transplant recipients are those with catastrophic illness registration cards for kidney transplantation (V42.0) and insurance claims for immunosuppressant agents for more than
3 months. Acute appendicitis is defined by ICD-9 codes
540541. ICD-9 code 540.9 was classified as an uncomplicated case of appendicitis, and codes 540.0 and 540.1 were
classified as perforated appendicitis.16 Charlson score and
patient comorbidities including diabetes mellitus (DM), dyslipidemia, hypertension, connective tissue disease, heart
failure, severe liver disease, dementia, and atrial fibrillation
were also analyzed. Charlson score was calculated as defined previously.17

J Gastrointest Surg (2012) 16:19401946

Multivariate Cox proportional hazard regression was performed using backward elimination to analyze independent
risk factors for acute appendicitis. Risk factors with p values
less than 0.1 in univariate Cox analysis were entered into the
multivariate analysis. All probabilities were two-tailed. A p
value less than 0.05 was considered significant.

Results
Characteristics of the Study Population
Figure 1 shows a flowchart for patient selection. A total of
74,921 incident ESRD patients were identified in our 9-year
study cohort. After excluding patients who were under
20 years of age or older than 100 years of age (n0790), those
who were kidney transplant recipients (n03,367), those who
were on dialysis for less than 90 days (n010,642), and those
who had history of appendicitis before receiving RRT (n0
341), we enrolled 59,781 patients for analysis. Study subjects
were predominantly female (52.5%), and the mean age was
60.8 years (standard deviation013.7). Our ESRD cohort included 54,588 HD patients (91.3%) and 5,193 PD patients
(8.7%). Hypertension (87.9%), dyslipidemia (31.4%), and
DM (31.2%) were the most common comorbidities. After
matching based on age, sex, Charlson score, and all listed
comorbidities, 59,781 ESRD patients were successfully
matched one-to-one with 59,781 control subjects. Demographic characteristics and comorbidities of the ESRD and
matched cohorts are shown in Table 1.
Comparison of the Incidence Rates of Acute Appendicitis
Between the ESRD and Matched Cohort
A total of 328 cases acute appendicitis occurred in ESRD
patients (314 HD and 14 PD patients) during the follow-up

Statistical Analysis
Normally distributed continuous data are expressed as
means standard deviations. Numeric data with nonnormal distributions are expressed as medians and interquartile ranges. To compare parameters between different dialysis modalities, the 2 test was used for categorical variables;
ANOVA and the MannWhitney U test were used for parametric and nonparametric continuous variables, respectively. The incidence of acute appendicitis was calculated by the
KaplanMeier method and compared by the log-rank test.

Fig. 1 Patient selection flow chart

J Gastrointest Surg (2012) 16:19401946

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Table 1 Baseline patient characteristics

Demographic data
Age (years)SD
Male gender
Charlson score
Score 1
Score 2
Score 3
Score 4-6
Score7
Comorbid disease
Diabetes mellitus
Dyslipidemia
Hypertension
Connective tissue
disease
Heart failure
Severe liver
disease
Atrial fibrillation

ESRD group
N=59,781

Control group
N=59,781

P value

60.813.7
47.5% (28,409)

60.813.8
47.5% (28,409)

0.833
1.000

57.4% (34,311)
20.5% (12,278)
11.9% (7,102)
9.9% (5,891)
0.3% (199)

57.4% (34,311)
20.5% (12,278)
11.9% (7,102)
9.9% (5,891)
0.3% (199)

1.000
1.000
1.000
1.000
1.000

31.2% (18,656)
31.4% (18,772)
87.9% (52,545)

31.2% (18,656)
31.4% (18,772)
87.2% (52,112)

1.000
1.000
0.047

2.5% (1,465)

5.0% (2,969)

<0.001

14.3% (8,546)
3.4% (2,033)

7.9% (4,730)
1.1% (628)

<0.001
<0.001

1.7% (1,013)

2.2 (1,291)

<0.001

Data are % (no.) of patients, unless otherwise indicated

ESRD end-stage renal disease, SD standard deviation

period of 193,692 person-years. The incidence of acute

appendicitis in the ESRD cohort was higher than that in
the matched cohort (16.9 vs. 13.1 per 10,000 person-years,
p00.003, Table 2, Fig. 2). Among the male and female
patients, the incidences were 17.5 and 16.5 per 10,000
person-years, respectively. In terms of different dialysis
modalities, the incidence of acute appendicitis in HD
patients was significantly higher than that in PD patients
(17.7 vs. 8.6 per 10,000 person-years, p00.007, Fig. 3).
Independent Predictors of Acute Appendicitis in the ESRD
Cohort
The univariate Cox regression analysis identified the risk
factors for acute appendicitis were ESRD, Charlson
score, DM, severe liver disease, atrial fibrillation, and HD

Fig. 2 KaplanMeier plots of the cumulative incidence of acute appendicitis among ESRD and control cohort

(Table 3). The multivariate Cox proportional hazards analysis indicated that the following variables were statistically
significant: atrial fibrillation (HR 2.08, 95% confidence
interval [CI] 1.034.19; p00.042), HD (HR 1.74, 95% CI
1.052.87; p00.016), severe liver disease (HR 1.74, 95% CI
1.052.87; p00.032), and DM (HR 1.58, 95% CI 1.26
1.97; p<0.001).
Analysis of Perforation Rates and Outcome of Acute
Appendicitis in the ESRD Cohort
Our study showed that the ESRD cohort (106 of 328;
32.3%) suffered from higher rates of perforated appendicitis, as compared with 50 of 347 matched controls (14.4%)
(p<0.001). Among 328 ESRD patients, 13 (4.0%) died of
acute appendicitis. Of note, none of the matched cohort died
of acute appendicitis in our study. The rates of perforated
appendicitis (101/314 [32.2%] vs. 5/14 [35.7%], p00.781)
and mortality (13/314 [4.1%] vs. 0/14 [0%], p00.437) were
comparable between the HD and PD groups.

Table 2 Incidence and crude and adjusted HRs of acute appendicitis in the ESRD and matched cohort
No. of
patients
All patients
119,562
ESRD cohort
59,781
Control cohort 59,781

Crude HR (95% CI) P value Adjusteda HR

No. of
No. of patients Incidence rate
(95% CI)
person-years with AP
(per 10 4 person-years)
458,210
193,692
264,518

674
327
347

16.9
13.1

HR hazard ratio, ESRD end-stage renal disease, AP acute appendicitis

a

Adjusted for age, sex, Charlson score, and all comorbidities listed in Table 1

1.27 (1.091.48)
As reference

0.002

P value

1.26 (1.081.47) 0.003

As reference

1944

J Gastrointest Surg (2012) 16:19401946

Fig. 3 After adjusting for atrial fibrillation, diabetes mellitus, and

severe liver disease, the cumulative risk of acute appendicitis among
ESRD patients requiring different dialysis modalities

Discussion
This is the first study to confirm that ESRD patients have a
higher risk for the development of acute appendicitis and,
subsequently, higher perforation and mortality rates than
non-dialysis patients. Among them, HD patients have a
1.93-fold higher risk for the development of acute appendicitis than PD patients. There was no significant difference in
perforation and mortality rates of acute appendicitis between
the HD and PD patients.
Table 3 Multivariate Cox regression for acute appendicitis in
the ESRD cohort

ESRD end-stage renal disease,

HR hazard ratio, CI confidence
interval, HD hemodialysis, PD
peritoneal dialysis

Our population-based study demonstrated that the rate of

incidence of acute appendicitis in ESRD patients (16.9 per
10,000 person-years) was higher than in the matched cohort
(13.1 per 10,000 person-years). The incidence rate in the
matched cohort was slightly lower than the incidence found
by Addiss et al.3 This may be because patients who were
under 20 years of age were excluded from our analysis,
while previous epidemiologic studies have reported that
appendicitis is most common between the ages of 10 and
20 years. Furthermore, the incidence rate in male ESRD
patients (17.5 per 10,000 person-years) was higher than that
in female ESRD patients (16.5 per 10,000 person-years).
This result is in agreement with that by Addiss et al.3 who
reported male preponderance of acute appendicitis in the
general population.
Previous studies have shown that ESRD patients not only
have frequent gastrointestinal symptoms but also have
higher incidences of peptic ulcers, gastroparesis, acute pancreatitis, and mesenteric ischemia.1821 However, data on
acute appendicitis has been lacking. Appendiceal obstruction has been proposed as the primary cause of appendicitis.
Common causes of obstruction include fecaliths (hard fecal
masses), calculi, lymphoid hyperplasia, infectious processes, and benign or malignant tumors.2224 Chronic constipation is the common problem in ESRD patients, and fecalith
formation may increase with time.25 Several factors are
believed to cause constipation in these patients, including
poor nutritional status, underlying gastrointestinal motility
disorders, sedentary lifestyle, fluid restriction, limited dietary fiber intake to avoid hyperkalemia, and various medications, such as calcium and iron supplements, phosphate
binders, and resins.26 Yasuda et al.26 reported that HD
patients had 3.14 times higher relative risk of constipation
than PD patients. The higher incidence rate of acute

Univariate

Multivariate

HR

P value
Value

95%
Lower

CI
Upper

Male gender
Age (per 1 year)
Charlson score
Diabetes mellitus
Dyslipidemia
Hypertension
Connective tissue disease
Heart failure
Severe liver disease

1.06
1.00
1.13
1.64
1.10
1.03
1.39
1.33
1.86

0.599
0.493
0.014
<0.001
0.459
0.854
0.329
0.072
0.016

0.85
0.99
1.03
1.31
0.86
0.76
0.72
0.97
1.12

1.32
1.01
1.24
2.04
1.41
1.39
2.70
1.81
3.07

Dementia
Atrial fibrillation
HD (PD as reference)

0.80
2.23
2.07

0.558
0.026
0.008

0.38
1.10
1.21

1.69
4.49
3.53

HR

P value
Value

95%
Lower

CI
Upper

1.58

<0.001

1.26

1.97

1.74

0.032

1.05

2.87

2.08
1.74

0.042
0.016

1.03
1.05

4.19
2.87

J Gastrointest Surg (2012) 16:19401946

appendicitis in ESRD patients in our study, especially those

on HD, may be partially due to chronic constipation with
fecalith formation.
In our study, we identified DM and severe liver disease as
risk factors for acute appendicitis in ESRD patients. Diabetic nephropathy is the leading cause of ESRD worldwide,27
and Yang et al.28 reported that, since 2001, DM also became
the leading cause of ESRD (35.3%) in Taiwan. Diabetic
autonomic neuropathy is a stealthy complication of diabetes
that results in chronic dyspepsia, disturbed GI motility, or
chronic constipation.29 Chronic liver disease and cirrhosis is
the fifth leading cause of death in Taiwan, a hepatitis B and
C endemic area.30,31 Cirrhotic patients sometimes have disturbed GI motility which correlates well with the severity of
liver damage.3235 Disordered motility of the small bowel
and colon is usually associated with the development of
bezoars and bacterial overgrowth.36,37 Increasing bowel fluid secretion, impaired bowel motility, and bacteria overgrowth may increase intra-luminal pressure of the
appendix and induce acute appendicitis.
Obstruction by a fecalith is frequently implicated but not
always required for the development of appendicitis.38
Bowel ischemia-induced appendicitis has been found in an
experimental model by Nunes et al.39 Li et al.40 found that
the risk of mesenteric ischemia for ESRD patients was 44.1
times higher than that of the general population. Atrial
fibrillation, as an independent risk factor for mesenteric
ischemia in ESRD patients, is related to adverse consequences of reduction in cardiac output and atrial or atrial appendage thrombus formation.41,42
The global mortality rate of acute appendicitis is 0.38%,
and it is often due to complications of the disease itself
rather than surgical intervention. In patients older than
70 years, the rate rises mainly due to diagnostic and therapeutic delay. In addition to the elderly patients, we also
found that the rate of mortality due to appendicitis in our
ESRD cohort (4.0%) was much higher than that found in
previous studies in general populations.43 Furthermore, our
study also showed that ESRD patients had significantly
higher risk for perforated appendicitis than non-dialysis
populations. Perforated appendicitis is associated with increased morbidity and mortality compared with nonperforating appendicitis. The poorer outcomes of acute
appendicitis in ESRD patients may be explained by delay
in diagnosis, burden of comorbidities, and hemodynamic
instability. Previous studies have also suggested that fecalith
formations are associated with an increased risk of bowel
perforation in ESRD patients.44,45
Potential limitations of this study should be noted. First, as
an innate limitation to the NHIRD database, several individual
data, including smoking status, body mass index, and hemodynamic stability during HD sessions, were not available in the
dataset. Second, the cause of acute appendicitis, such as

1945

obstructive or non-obstructive etiology, was not taken into

consideration for the analyses. Third, because the results of
imaging studies such as ultrasonography or computed tomography were not available in the dataset, we could not assess
correlations between clinical manifestations and imaging
features.
In conclusion, this cohort study identified an incidence
rate of acute appendicitis of 16.9 per 10,000 person-years in
ESRD patients. ESRD itself was an independent risk factor
for acute appendicitis. ESRD patients had higher perforation
and mortality rates than that in non-dialysis patients. Therefore, more liberal use of additional diagnostic tools and
early surgical consultation should be recommended for
ESRD patients with suspected acute appendicitis.
Acknowledgments This study was based in part on data from the
National Health Insurance Research Database provided by the Bureau
of National Health Insurance, Department of Health, and managed by
the National Health Research Institutes. The conclusions presented in
this study are those of the authors and do not necessarily reflect the
views of the Bureau of National Health Insurance, the Department of
Health, or the National Health Research Institute.
Funding Research was funded by Taipei Veterans General Hospital
research grant (V100B-030).

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