VOL_116_002_SUPS_A_547636 155..159


Upsala Journal of Medical Sciences. 2011; 116: 155–159

ORIGINAL ARTICLE

Acute renal failure in severe pancreatitis: A population-based study

HUNG-YUAN LIN3, JIUN-I LAI1,2, YI-CHUN LAI1,2, PO-CHOU LIN1,2,
SHIH-CHIEH CHANG1,2 & GAU-JUN TANG1,2

1National Yang-Ming University School of Medicine, Taiwan, Republic of China, 2Department of Medicine, National
Yang-Ming University Hospital, Taiwan, Republic of China, and 3Shih-Hsin University, Department of Information
Management, Taiwan, Republic of China

Abstract
Introduction. Acute pancreatitis (AP) is a common illness with varied mortality and morbidity. Patients with AP complicated
with acute renal failure (ARF) have higher mortality than patients with AP alone. Although ARF has been proposed as a leading
mortality cause for AP patients admitted to the ICU, few studies have directly analyzed the relationship between AP and ARF.
Methods. We performed a retrospective study using the population-based database from the Taiwan National Health Insurance
Research Database (NHIRD). In the period from 1 January 2005 to 31 December 2005, every patient with AP admitted to the
ICU was included and assessed for the presence of ARF and mortality risk.
Results. In year 2005, there were a total of 221,101 admissions to the ICU. There were 1,734 patients with AP, of which
261 (15.05%) patients also had a diagnosis of ARF. Compared to sepsis and other critical illness, patients with AP had a higher
risk of having a diagnosis of ARF, and patients with both diagnoses had a higher mortality rate in the same ICU hospitalization.
Conclusion. AP is associated with a higher risk of ARF, and, when both conditions exist, a higher risk of mortality is present.

Key words: Acute renal failure, intensive care, severe acute pancreatitis

Introduction

Acute pancreatitis (AP) is a relatively common med-
ical illness with a wide range of morbidity and mor-
tality, with an estimated incidence of 35–80 cases per
100,000 each year (1). Severe acute pancreatitis
(SAP), as proposed by Bradley, known as the Atlanta
classification, is established by either an APACHE II
score >8, Ranson score >3 (2), the presence of more
than one organ failure, or local complications (3).
SAP has been associated with an increased mortality,
estimated from 7% to 47% (4,5). Acute renal failure
(ARF) in the setting of AP has been shown to have a
10-fold increase in mortality (74.7% versus 7%) in a
study of 563 patients (6). A similar result was reported
in another study, showing 71.2% mortality versus
6.8% in SAP patients with or without ARF (7).
In agreement with the above studies, a recent

cross-sectional study reported a 5-fold increase
(66.6% with ARF versus 14.5% without ARF) in
mortality in SAP patients, providing an updated
assessment of the clinical standpoint (8). To our
knowledge, few studies directly pin-pointed the rela-
tionship between SAP and ARF in ICU patients (8),
although both conditions are common etiologies
in the ICU and pose diagnostic and therapeutic
challenges.
In Taiwan, the National Health Insurance (NHI)

program was started in 1995 and covers nearly all
inhabitants. Because all claims data of in-patients are
available to researchers in electronic form, it is pos-
sible to conduct a large-series retrospective study to
investigate the prevalence of AP and ARF and related
mortality data in ICU patients in Taiwan (9). In light
of the above background, we conducted a study using
the population-based database of the NHI program in

Correspondence: Shih-Chieh Chang, MD, Department of Medicine, National Yang-Ming University Hospital,No. 152, Xin-Min Road, Yilan, Taiwan, 26042.
Fax: +886-3-935-1838. E-mail: dtsurga9@yahoo.com.tw

(Received 29 November 2010; accepted 6 December 2010)

ISSN 0300-9734 print/ISSN 2000-1967 online � 2011 Informa Healthcare
DOI: 10.3109/03009734.2010.547636



Taiwan, aiming to: 1)assess the prevalence and char-
acteristics of AP patients admitted to the ICU, and 2)
identify the prevalence of ARF coexisting with AP,
and determine if a relationship exists that can serve as
future treatment guide. We then further analyze the
statistical significance of the data distribution and
identify risk factors leading to increased mortality.
This population-based study method is a novel
approach in assessment of patients with pancreatitis
admitted to ICU, and we anticipate the results to
provide clinical significance in treatment planning for
intensivists and internists.

Methods

Database

Pooled data obtained from the Taiwan National
Health Insurance Research Database (NHIRD) in
the period from 1 January 2005 to 31 December
2005 were used for analysis in this study. The
NHIRD is a nation-wide database including all
in-patient medical benefit claims for the Taiwanese
population, with an inclusion rate of over 96% of the
population. The database includes registries of
contracted medical facilities and board-certified phy-
sicians, monthly records of in-patient claims summa-
ries, and other in-patient hospitalization details. Each
individual operation’s procedure codes and diagnosis
codes are included with compliance to classifica-
tion using the International Classification of Disease,
9th revision, Clinical Modification (ICD-9-CM).
This study was approved by the ethics committee of

the authors’ institution on the basis that no disclosure
of any patient’s privacy or individual data could be
made public due to the encoding nature of the
database.

Study sample

We included every ICU hospitalization episode from
1 January 2005 to 31 December 2005. The database
included a total of 221,101 patients. We then selected
patients with a diagnosis ICD-9 code compatible
with acute pancreatitis (ICD-9 code 577.0) and acute
renal failure (584.x; x = 0–9). Age, gender, ICD-9
classification codes, and mortality data were recorded
(Figure 1).
Each admission episode was recorded for the main

diagnosis ICD code using the International Classifi-
cation of Disease, 9th revision, Clinical Modification
(ICD-9-CM). The nature of the claims database was
that laboratory information was not included, there-
fore only the admission date, discharge date, patient
profile, and ICD-9 diagnosis codes were available;
there was no way of knowing if the coding was correct
for each patient. However, according to the National
Health Insurance policy, a protocol existed of peer
review from another independent physician for the
claims. If the diagnosis or claim was found at fault, the
claim would be revoked; therefore, an internal vali-
dation system exists for the accuracy of each claim
reviewed. We rely on this internal control to assume
accuracy of our database and the study results.

Statistical analysis

In this study, MySQL 4.1 (1995–2008 MySQL AB,
2008–2009 Sun Microsystems, Inc.), was used as
database software for data linkage and processing.
Descriptive data were presented, including number
of patients and percentages. Multivariate logistic
regression was used to assess hazard ratios and risk
(SPSS software, version 14.0, SPSS Corp., Chicago,
IL, USA). Results are displayed as coefficients, odds

221,101 patients admitted to
ICU from 1 Jan 2005 to 30 Dec
2005  

1,734 patients admitted to ICU
due to acute pancreatitis

261 patients with both
pancreatitis and acute renal
failure  

1. Test for a higher prevalence in AP
    patients compared with

a. All non-AP patients

b. Non-AP patients with another specific
    diagnosis   

2. Test for higher mortality in AP patients
     having ARF, compared with AP patients
     without ARF  

Figure 1. Study design.

156 H.-Y. Lin et al.



ratios, and 95% confidence intervals. A P value
£ 0.05 (two-tailed) was considered as statistically
significant.

Results

Statistics of ICU admissions in year 2005

During the period of 1 January 2005 to 31 December
2005, there were a total of 221,101 valid ICU
admissions. The gender ratio was male/female:
60.5%/39.5%. The age distribution is summarized
in Table I.
During the period of 1 January 2005 to 31 Decem-

ber 2005, there were a total of 1,734 ICU admissions
which included the diagnosis of acute pancreatitis
(ICD-9 code:577.0). The gender ratio was male/
female: 66.9%/33.1%. The age distribution and
mortality rate for each age-group are summarized
in Table II.

Acute pancreatitis is associated with an increased
incidence of acute renal failure

We included every ICU admission to assess patients
with diagnosis of acute renal failure (defined as cases
with ICD-9 coding of 584.x; x = 0–9), diagnosis of
acute pancreatitis (ICD-9 code:577.0), and patients
with both diagnoses. Our results showed 261 patients
having both diagnosis of AP and ARF (male/female
ratio: 74.33%/35.67%). We then compared the
probability of ARF occurring in patients with and
without AP. Using logistic regression, the incidence
of ARF coexisting with AP was 15.05% (261/1734),
with an odds ratio of 4.82 when compared to non-
AP patients (coefficient value 1.582; odds ratio 4.862;
P < 0.01).

To avoid confounding factors and to further vali-
date this finding, we separately tested patients with AP
against non-AP patients admitted due to another
diagnosis for the incidence of ARF. We selected
the five leading diagnoses for ICU admission: ische-
mic heart disease (ICD-9 code: 410–414), lung-
related disorders (including respiratory failure)
(ICD-9 code: 518), pneumonia (ICD-9 code: 486),
cerebrovascular disease (including hemorrhage and
infarction of cerebral arteries) (ICD-9 code: 431–
434),and sepsis (ICD-9 code: 038). We included
non-AP patients who had either one of the above
diagnoses, and classified them into five groups
according to each diagnosis. We then tested the AP
group against each group separately. Using multi-
variate logistic regression, the AP group showed a
significant increase in risk of having a diagnosis
of ARF when compared against the other groups
(Table III).
Our results show that patients with AP had a higher

risk of having a diagnosis of ARF in the same ICU
hospitalization, when compared with either all
non-AP patients or non-AP patients with an individ-
ual diagnosis.

The presence of acute renal failure is associated with
increased mortality in ICU patients admitted due to acute
pancreatitis

We assessed whether AP coexisting with ARF was
associated with increased mortality. Patients with
both diagnosis of AP and ARF had a mortality rate
of 23.76% in the same hospitalization when compared
to patients with AP alone without ARF, who had a
mortality rate of 8.08% (odds ratio 3.752 (2.640–
5.331); P < 0.05) (Table IV). Mortality was defined

Table I. Age distribution of ICU admissions in 2005.

Age Number
Percentage

(%)

18 and under 16,571 7.5

19–28 8,685 3.9

29–38 11,831 5.3

39–48 16,599 7.5

49–58 26,140 11.8

59–68 29,984 13.6

69–78 48,533 22.0

Above 78 62,758 28.4

Total 221,101 100

Table II. Age distribution of ICU admissions of acute pancreatitis
in 2005.

Age Number
Prevalence

(%)
Mortality
rate (%)

18 and under 26 1.5 3.8

19–28 43 2.5 2.3

29–38 179 10.3 7.3

39–48 347 20.0 10.4

49–58 263 15.2 6.1

59–68 211 12.2 8.1

69–78 302 17.4 9.9

Above 78 363 20.9 18.5

Acute renal failure in severe pancreatitis 157



as death from any cause in the same course of ICU
hospitalization.

Discussion

Severe acute pancreatitis (SAP) in the intensive care
unit poses a therapeutic challenge with significant
mortality (10). The pathophysiology began as severe
systemic inflammatory response in the early stages
and necrosis of the pancreas later on (10). It is in the
systemic inflammatory process that hypovolemia
ensues, either from wide-spread vasodilation or fluid
sequestration, with tissue hypoperfusion and ulti-
mately causing organ damage and failure (11). Several
studies have described organ failure accompanying
pancreatitis, with renal failure always one of the cul-
prit organs (5,10,11). Acute renal failure has been
shown to increase mortality in SAP patients (4,5,10),
and the progression of acute renal failure should alert
the physician of progressive disease.
In our study, a total of 1,734 patients were admitted

to the ICU due to acute pancreatitis (0.78%). The
prevalentage-groups were age 39–48 (20.01%) and
age over 78 (20.93%),which correlated with the risk
factors such as increased alcohol consumption in the
mid-40s age-group (12). The prevalent age-groups
(age 39–48 and age >70) also presented with the
highest mortality (10.4% and 18.5%, respectively).
The prevalence of acute renal failure coexisting with
acute pancreatitis was 15.05%, significantly higher
than non-pancreatitis patients. In non-pancreatitis

patients, patients with sepsis had the highest incidence
of acute renal failure (13.2%). Compared to pneu-
monia, cerebrovascular disease, myocardial infarc-
tion, and respiratory failure, sepsis involves more
wide-spread inflammation and organ damage and
probably has a more similar pathophysiology with
pancreatitis patients with coexisting acute renal
failure.
Commonly used prognostic scoring systems for

pancreatitis include the Ranson Criteria, APACHE
II score, and the Atlanta classification which is usually
used for standardizing clinical trials using the above
classifications (13). In the Ranson criteria an increase
in blood urea nitrogen was indexed as a scoring point,
while in the APACHE II system serum creatinine was
included as one factor (14). Our study validates this
concept that acute renal failure is associated with
extremely high mortality in SAP patients, and also
shows that severe acute pancreatitis itself is asso-
ciated with higher incidence of acute renal failure.
The exact mechanism for pancreatitis-related renal
failure is not yet well settled, but studies have shown
that systemic inflammation, cytokine production,
free radicals, and other factors influencing micro-
circulation play a role (15).
In a recent study (8), the investigators assessed

multivariate risk factors that would predict outcome.
Age, history of kidney disease, and abdominal com-
partment syndrome were found to be independent
prognostic factors (8). The study, using a different
approach from that of ours, concluded an increased
mortality and duration of ICU stay. The results cor-
roborate our study with its lack of information about
patient outcome being there with deprived of defin-
itive predictive power. Combination of that study and
ours would provide strong evidence of increased
mortality effect of ARF on SAP patients.
Our study provides a novel approach to investigate

ICU patients by using a large-scale population-based
study. Because of the near universal inclusion of the
Taiwanese population in the National Health Insur-
ance, the NHIRD reflects a ‘real world’ database

Table III. Risk of acute renal failure in non-pancreatitis patients with separate diagnoses compared to pancreatitis patients.

Disease group Coefficient Odds ratio
Percentage with
acute renal failure P value

1 Ischemic heart disease �2.213 0.109 (0.089–0.134) 2.5% <0.05
2 Lung-related disorders (including respiratory failure) �0.979 0.376 (0.308–0.457) 8.3% <0.05
3 Pneumonia �1.081 0.339 (0.278–0.414) 7.3% <0.05
4 Cerebrovascular disease (including hemorrhage and

infarction of cerebral arteries)
�2.493 0.083 (0.066–0.103) 1.9% <0.05

5 Sepsis �0.432 0.649 (0.534–0.789) 13.2% <0.05

Table IV. Mortality risk in pancreatitis patients with and without
acute renal failure.

Number
Mortality
number

Mortality
rate (%)

Patients with pancreatitis
and acute renal failure

261 62 23.8

Patients with pancreatitis
without acute renal failure

1,473 119 8.1

158 H.-Y. Lin et al.



representing statistical significance and near minimal
sampling error or selection bias. Our weakness lies in
misclassification errors, which is under control owing
to the peer review validation of all claims as previously
mentioned. Another limitation is that the NHIRD
database only includes claims data and relevant treat-
ment data, while laboratory data are not included.
This poses a significant limitation to our study that the
exact APACHE II score or other scoring system of
each patient could not be obtained. We could only
rely on the assumption that for a patient to be admit-
ted to the ICU, an APACHE II score of more than
8 should be common; indeed, according to our peer
validation, the claim of a patient admitted to the ICU
with an APACHE II score less than 8 would very
likely be revoked. Therefore, by definition of the
Atlanta criteria, patients admitted to the ICU with
the diagnosis of acute pancreatitis should classify as
severe acute pancreatitis (SAP). Also, the nature of
the database precluded the assumption of a causal
relationship. However, this study still brings impor-
tant messages with strong statistical significance
owing to its large number of cases and its near total
sampling with little room for selection and sampling
bias. We can judiciously conclude that acute pancre-
atitis patients admitted to the ICU (very possibly
mostly SAP patients) have a higher risk of having
an acute renal failure, and having both diagnoses
may lead to higher mortality.
In conclusion, our study of 1,734 patients with acute

pancreatitis admitted to the ICU revealed that acute
renal failure was more frequently encountered in this
critical illness associated with higher mortality. Our
results imply that deterioration of renal function in
SAP patients should be closely monitored and the
possibility of renal damage should be prevented. Our
study provides a novel approach to studying ICU
patients using a population-based database. Although
large case numbers and real-world descriptions are the
strengths of our study, further controlled studies with
complete clinical characteristics are needed for dem-
onstration of a definite causal relationship.

Declaration of interest: This study had no specific
funding source. All authors declare no conflicts of

interest for this work. Hung-Yuan Lin and Jiun-I Lai
contributed equally to this work.

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Acute renal failure in severe pancreatitis 159