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DOI: 10.1542/peds.

2006-0557
; originally published online August 7, 2006; 2006;118;e786 Pediatrics
McNeil
Prayong Vachvanichsanong, Pornsak Dissaneewate, Apiradee Lim and Edward
Southern Thailand
Childhood Acute Renal Failure: 22-Year Experience in a University Hospital in

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ARTICLE
Childhood Acute Renal Failure: 22-Year Experience
in a University Hospital in Southern Thailand
Prayong Vachvanichsanong, MD
a
, Pornsak Dissaneewate, MD
a
, Apiradee Lim, MSc
b
, Edward McNeil, MS
b
a
Department of Pediatrics and
b
Epidemiology Unit, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
The authors have indicated they have no nancial relationships relevant to this article to disclose.
ABSTRACT
OBJECTIVES. The objectives of this study were to review the prevalence, cause, and
morbidity and mortality rates of acute renal failure in a large tertiary care insti-
tution in southern Thailand, to examine any differences in acute renal failure cases
diagnosed during a 22-year period, and to determine the risk factors indicating
death.
METHODS. The case records for children 1 month to 17 years of age who were
diagnosed as having acute renal failure between February 1982 and December
2004, in the Department of Pediatrics, Songklanagarind Hospital, in southern
Thailand, were reviewed.
RESULTS. A total of 311 children with 318 episodes of acute renal failure were
included, that is, 177 boys (55.7%) and 141 girls (44.3%), 1 month to 16.7 years
of age (mean age: 7.6 5.1 years; median age: 7.8 years). The causes of acute renal
failure in each age group were signicantly different. Overall, sepsis was the major
cause of acute renal failure, accounting for 68 episodes (21.4%), followed by
hypovolemia, poststreptococcal glomerulonephritis, systemic lupus erythemato-
sus, and infectious diseases. Renal replacement therapy was performed in 55 cases
(17.3%). The overall mortality rate was 41.5%. Logistic regression analysis
showed that disease groups and creatinine levels were signicant independent
predictors of outcomes.
CONCLUSIONS. The incidence of acute renal failure in Songklanagarind Hospital was
0.5 to 9.9 cases per 1000 pediatric patients, with a mortality rate of 41.5%. Sepsis
was a major cause of acute renal failure and death. Causes of acute renal failure
and serum creatinine levels were signicant independent predictors of death.
www.pediatrics.org/cgi/doi/10.1542/
peds.2006-0557
doi:10.1542/peds.2006-0557
Key Words
acute renal failure, renal replacement
therapy, peritoneal dialysis
Abbreviations
ARFacute renal failure
PSAGNpoststreptococcal
glomerulonephritis
SLEsystemic lupus erythematosus
RRTrenal replacement therapy
CGNchronic glomerulonephritis
Accepted for publication Apr 10, 2006
Address correspondence to Prayong
Vachvanichsanong, MD, Department of
Pediatrics, Faculty of Medicine, Prince of
Songkla University, Hat Yai 90110, Thailand.
E-mail: vprayong@msn.com
PEDIATRICS (ISSNNumbers: Print, 0031-4005;
Online, 1098-4275). Copyright 2006 by the
American Academy of Pediatrics
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A
CUTE RENAL FAILURE (ARF), the sudden deteriora-
tion of renal function, is not common in general
clinical practice but is not uncommon at tertiary referral
centers.
1
There are a variety of causes and treatment
options, and outcomes vary from country to country and
from hospital to hospital. ARF is a life-threatening con-
dition, especially in children, with signicantly increased
morbidity and mortality rates. Early detection and ap-
propriate treatment can provide complete recovery, a
major goal of ARF therapy. ARF, particularly the non-
oliguric form, is often missed when only clinical symp-
toms are considered or is found by chance through ab-
normal biochemical test results. The objectives of this
study were to review the prevalence, causes, and mor-
bidity and mortality rates of ARF in a major tertiary care
center in southern Thailand, to examine any differences
in ARF cases diagnosed in different periods during the
preceding 22 years, and to determine the mortality risk
factors.
METHODS
The case records of children, 1 month to 17 years of age,
who were diagnosed as having ARF between February
1982 and December 2004 in the Department of Pediat-
rics, Songklanagarind Hospital, in southern Thailand
were reviewed. To have comparable numbers of cases,
we divided the patients into 3 eras, namely, 1982 to
1994, 1995 to 1999, and 2000 to 2004. ARF was dened
on the basis of a sudden increase in serum creatinine
concentration of 177 mol/L (2.00 mg/dL), a serum
creatinine concentration that was 2 times previous or
subsequent values and that was also higher than the
upper limit of normal values for the patients age,
2
or, for
patients with preexisting chronic renal impairment, an
increase in serum creatinine concentration of 2.00 mg/
dL, with the serum creatinine concentration later re-
turning to the initial level. Patients with acute deterio-
ration of chronic renal failure were excluded. The cause
of ARF was considered to be the major problem leading
to ARF.
The cases were classied according to different com-
mon renal problems known to be found in the following
5 age groups: infants (1 month to 1 year), toddlers (1
year to 5 years), younger children (5 years to 10
years), older children (10 years to 13 years), and teen-
agers (13 years). Fishers exact tests and
2
tests were
used to compare differences among categorical variables.
Logistic regression analysis was used to evaluate multi-
ple risk factors. P values of .05 were considered signif-
icant. R software, version 2.2.0, was used for all statisti-
cal analyses.
3
RESULTS
A total of 311 children with 318 episodes of ARF satised
the inclusion criteria and had admission forms available
for review (1 patient had 3 episodes of ARF and 5
patients had 2 episodes). There were 177 boys (55.7%)
and 141 girls (44.3%) (age range: 1 month to 16.7 years;
mean age: 7.6 5.1 years; median age: 7.8 years).
The incidence of ARF through the years is shown in
Fig 1, which shows a dramatic increase in 1995, com-
pared with previous years. Although there was a signif-
icant hospital expansion at that time, including pediatric
case admissions, the ARF/total pediatric case ratio in-
creased from 0.5 to 3.3 cases per 1000 cases before 1995
to 4.6 to 9.9 cases per 1000 cases after 1995.
Causes of ARF according to age group, renal replace-
ment therapy (RRT), and mortality rates are shown in
Table 1. The causes of ARF were classied into 11 groups
(8 children had unknown causes). The causes of ARF in
each age group were signicantly different (P .001).
Overall, sepsis was the major cause of ARF, accounting
for 68 episodes (21.4%), followed by hypovolemia, post-
streptococcal glomerulonephritis (PSAGN), systemic lu-
pus erythematosus (SLE), and infectious diseases. Of the
30 infectious disease cases, 11 involved leptospirosis and
19 dengue hemorrhagic shock syndrome.
RRT was performed for 55 patients (17.3% overall;
intermittent peritoneal dialysis, continuous peritoneal
dialysis, and continuous arteriovenous hemoltration in
12, 40, and 3 cases, respectively). Of those, 35 patients
(63.6%) died.
Continuous arteriovenous hemoltration was per-
formed for 2 patients with dengue hemorrhagic shock
syndrome who had unstable hemodynamic features and
1 patient who had multiple injuries, without evidence of
hypovolemia, for whom the denitive cause of ARF was
not determined. These 3 patients died as a result of
multiorgan failure.
Examination of the association between dialysis and
disease showed that patients with SLE, chronic glomer-
ulonephritis (CGN), infectious diseases, and miscella-
neous and unknown causes of renal failure tended to
require dialysis more than patients with other diseases.
FIGURE 1
Comparisonof the incidences of general pediatric admissions andARF cases accordingto
year.
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Figure 2 shows that these patients had very high creat-
inine levels. In our institution, it is standard procedure to
perform RRT for children who develop symptoms of
volume overload and/or metabolic disturbances as well
as increasing creatinine levels. Therefore, children with
creatinine levels of 5 mg/dL normally receive RRT.
A total of 174 children recovered completely, 116
died, 6 refused treatment, and 22 developed chronic
renal failure, of whom 16 died, 4 are alive currently, and
2 were lost to follow-up monitoring. The overall mor-
tality rate was 41.5%, with an immediate mortality rate
of 36.5%. Male and female patients had similar mortal-
ity rates (39.5% and 40.0%, respectively). The mortality
rates for infants, toddlers, young children, older chil-
dren, and teenagers were 53.8%, 30.8%, 38.2%, 46.3%,
and 41.4%, respectively (P .12), but rates were signif-
icantly different between diseases (P .0001).
In a comparison of the 3 eras (19821994, 1995
1999, and 20002004), no statistically signicant differ-
ences were demonstrated regarding gender and age
group (P .8 and P .5, respectively); however, the
causes of ARF were signicantly different (P .006).
RRT rates were not signicantly different (P .3). The
mortality rates declined from 47% to 43% to 35% in the
3 periods, respectively, but these rates were not signi-
cantly different (P .18) (Table 2).
Logistic regression analysis showed that disease
groups and creatinine levels were signicant indepen-
dent predictors of outcome (death) (Table 3). We chose
hypovolemia as the reference disease group because
PSAGN and kidney, ureter, and bladder anomalies did
not cause any deaths and hypovolemic ARF had the
lowest mortality rate. Children with sepsis, malignancy,
or CGN were 10 times more likely to die as a result of
ARF, children with malignancy or unknown or miscel-
laneous diseases were 6 to 9 times more likely to die, and
children with toxins or infectious diseases were 3 to 4
TABLE 1 Distributions of Age Groups and Causes of ARF, Showing Maximal Creatinine Levels of >2 mg/dL, RRT, and Mortality Rates
Cause No. (%)
Total 1 mo to 1 y 15 y 510 y 1013 y 13 y Creatinine Levels of 2 mg/dL RRT Death
Sepsis 68 (21.4) 19 (27.9) 13 (19.1) 7 (10.3) 16 (23.5) 13 (19.1) 36 (52.9) 6 (8.8) 45 (66.2)
Hypovolemia 39 (12.3) 10 (25.6) 11 (28.2) 9 (23.1) 7 (18.0) 2 (5.1) 18 (46.2) 1 (2.6) 4 (10.3)
PSAGN 38 (12.0) 0 (0) 6 (15.8) 21 (55.3) 6 (15.8) 5 (13.2) 16 (42.1) 1 (2.6) 0 (0.0)
SLE 32 (10.1) 0 (0) 2 (6.3) 6 (18.8) 10 (31.3) 14 (43.8) 27 (84.4) 18 (56.3) 20 (62.5)
Infectious diseases 30 (9.4) 1 (3.3) 3 (10.0) 9 (30.0) 7 (23.3) 10 (33.3) 23 (76.6) 9 (30.0) 10 (33.3)
Malignancies 29 (9.1) 2 (6.9) 10 (34.5) 6 (20.7) 8 (27.6) 3 (10.3) 15 (51.7) 4 (13.8) 15 (51.7)
Heart failure 26 (8.2) 12 (46.2) 3 (11.5) 5 (19.2) 4 (15.4) 2 (7.7) 12 (46.2) 1 (3.8) 14 (53.9)
CGN 11 (3.5) 1 (9.1) 0 (0) 2 (18.2) 4 (36.4) 4 (36.4) 8 (72.7) 4 (36.4) 7 (63.6)
Toxins 7 (2.2) 1 (14.3) 2 (28.6) 1 (14.3) 0 (0.0) 3 (42.9) 4 (57.1) 0 (0.0) 2 (28.6)
KUB anomalies 6 (1.9) 1 (16.7) 5 (83.3) 0 (0) 0 (0.0) 0 (0.0) 3 (50.0) 0 (0.0) 0 (0.0)
Miscellaneous 24 (7.6) 4 (16.7) 9 (37.5) 8 (33.3) 3 (12.5) 0 (0.0) 16 (66.7) 8 (33.3) 11 (45.8)
Unknown 8 (2.5) 1 (12.5) 1 (12.5) 2 (25.0) 2 (25.0) 2 (25.0) 5 (62.5) 3 (37.5) 4 (50.0)
Total 318 (100.0) 52 65 76 67 58 183 (57.6) 55 (17.3) 132 (41.5)
KUB indicates kidney, ureter, and bladder.
FIGURE 2
Comparison of serumcreatinine levels according to disease cause. KUB indicates kidney,
ureter, and bladder.
TABLE 2 Distributions of Causes, RRT, and Mortality Rates of ARF
According to Year of Admission
No. (%)
1995 19951999 20002004
Cause
Sepsis 23 (24.7) 25 (21.6) 20 (18.4)
Hypovolemia 15 (16.1) 15 (12.9) 9 (8.3)
PSAGN 11 (11.8) 7 (6.0) 20 (18.4)
SLE 7 (7.5) 18 (15.5) 7 (6.4)
Infectious diseases 6 (6.5) 15 (12.9) 9 (8.3)
Malignancies 12 (12.9) 12 (10.3) 5 (4.6)
Heart failure 4 (4.3) 5 (4.3) 17 (15.6)
CGN 3 (3.2) 6 (5.2) 2 (1.8)
Toxins 2 (2.2) 2 (1.7) 3 (2.8)
KUB anomalies 0 (0.0) 0 (0.0) 6 (5.5)
Miscellaneous 9 (9.7) 7 (6.0) 8 (7.3)
Unknown 1 (1.1) 4 (3.5) 3 (2.8)
RRT 14 (15) 25 (22) 16 (15)
Death 44 (47) 50 (43) 38 (35)
Total 93 116 109
KUB indicates kidney, ureter, and bladder.
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times more likely to die than were children with hypo-
volemia. Children who presented with serum creatinine
concentrations of 2 mg/dL were twice as likely to die as
a result of ARF than were children who presented with
serum creatinine concentrations of 2 mg/dL (P
.009), although there was no additional correlation be-
tween creatinine levels of 2 mg/dL and increased risk
of death.
DISCUSSION
Because our institution is the major tertiary care center
for 14 provinces in southern Thailand, all severe or
complicated cases from the region are referred to us.
There was a sudden increase in the number of ARF cases
beginning in 1995 (Fig 1). We presume that this was
attributable to the arrival of a pediatric nephrologist in
the hospital in 1993, with a subsequent increase in re-
ferrals that took 2 years to eventuate. For the ARF
cases, we found sepsis to be a major cause, although
there are many other causes. For example, hemolytic
uremic syndrome was reported as a major cause of ARF
in some studies,
1,48
whereas hemolytic uremic syn-
drome was found in only 7 cases in our study (2% of all
cases, classied as miscellaneous in our study).
Other studies indicated that sepsis is a major cause of
death in ARF.
911
In centers where cardiac surgery is
available, surgery for treatment of congenital heart dis-
ease has been a major cause of death, because of hypoxia
and poor perfusion leading to multiorgan failure.
8
One
tertiary care center in the United Kingdom reported that
cardiac surgery was a major cause of ARF in a group of
neonates.
8
Our study did not include neonates. In our
institution, however, cardiac surgery has been per-
formed only since 2000 and, during the study period,
was still limited in the neonatal group, although, as
shown in Table 2, the proportion of congestive heart
failure-attributable ARF increased from 4% in the rst 2
eras to 16% in the most recent era (since 2000).
Hypovolemia was the second most common cause of
ARF in our study. The causes of hypovolemia included
gastroenteritis and inadequate uid therapy for patients
who presented with other problems, such as trauma and
injury. Fortunately, early detection and proper manage-
ment in our institution produced favorable outcomes in
such cases. Of the 39 hypovolemic ARF cases, only one
8-month-old child, who had diarrhea with an elevated
serum creatinine level of 9.6 mg/dL, required intermit-
tent peritoneal dialysis for 2 days and then recovered
completely.
The prevalence of PSAGN-attributable ARF seems
quite high in this study, because simple PSAGN is not
commonly found in our institution. However, because of
our role as a referral destination, cases of PSAGN with
renal failure need to be referred to us for conrmation of
diagnosis and treatment.
SLE is one of the most common causes of severe
glomerulonephritis in children and young adults. Ag-
gressive chemotherapy is required to rescue renal func-
tion, and sometimes RRT is essential before renal func-
tion can recover. Of the 32 patients with SLE, 12
recovered completely, 13 died in the hospital, and 7
developed chronic renal failure and died. SLE cases were
classied differently from other CGN cases, because such
cases have more-severe glomerulonephritis and disease
progression is rapid. In this study, however, we found
that SLE cases had similar outcomes, compared with
other causes of CGN (classied here as CGN).
Malignancies, such as leukemia, lymphoma involving
the kidneys, neuroblastoma, and Wilms tumors, and
nephrotoxic chemotherapy were less common than sep-
sis. However, children with malignancies tend to de-
velop sepsis, particularly during chemotherapy. If such
malignancies that cause mass effects resulting in kidney,
ureter, and bladder obstruction are corrected in a timely
way, such as through surgical intervention or percuta-
neous nephrostomy, then favorable outcomes can be
TABLE 3 Logistic Regression Analyses Showing Disease Groups and SerumCreatinine Levels of >2 mg/
dL Predicting Mortality Rates
Univariate Analysis Multivariate Analysis
Odds Ratio 95% CI P Odds Ratio 95% CI P
Cause (reference: hypovolemia)
Sepsis 17.1 5.454.1 .0000 12.2 4.930.7 .0000
Malignancy 9.4 2.633.2 .0005 10.6 3.434.2 .0001
CGN 15.3 3.176.3 .0009 10.6 2.349.2 .0026
Heart failure 10.2 2.837.1 .0004 8.7 3.025.3 .0001
SLE 14.6 4.151.3 .0000 7.6 2.523.0 .0003
Miscellaneous 7.4 2.027.4 .0027 4.8 1.515.0 .0070
Unknown 8.7 1.649.3 .0140 4.6 1.020.5 .0456
Infectious diseases 4.4 1.215.8 .0242 3.3 1.110.1 .0403
Toxin 3.5 0.5024.3 .2054 1.3 0.27.2 .7640
Creatinine level of 2 mg/dL
(reference: 2 mg/dL)
2.1 1.33.4 .0013 1.9 1.13.1 .0140
CI indicates condence interval.
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expected. In this study, there were 2 episodes of tumor
lysis syndrome and 3 cases of obstructive uropathy, of
which all had favorable outcomes (the obstructive ne-
phropathy cases were classied in the miscellaneous
group).
Nephrotoxic ARF commonly is associated with ami-
noglycoside.
12
In our study, aminoglycoside-related ARF
was not found. However, because methods to differen-
tiate between aminoglycoside-related ARF and sepsis are
not available in general practice, sepsis is normally given
as the cause of ARF; therefore, this failure to note any
such cases is to be expected and cannot be interpreted to
mean that the condition was not present. In fact, ARF
may result from a combination of factors with additive
effects that lead to renal injury, such as sepsis with
aminoglycoside, congestive heart failure with enalapril,
or SLE with sepsis.
RRT was administered to patients with severe ARF
who were unable to maintain uid and electrolyte bal-
ance. We did not compare mortality rates between pa-
tients with and without RRT, because there was concern
about selection bias. Normally, dialysis is the last modal-
ity of treatment for ARF with volume load or metabolic
disturbances. Therefore, patients who received dialysis
were likely to have severe ARF, and the mortality rate
would be expected to be higher in this group. This means
not that RRT is a poor procedure but that RRT is a rescue
procedure when renal failure occurs; RRT is the most
important procedure for bridging the time needed for
recovery. In this study, peritoneal dialysis saved more
than one third of the patients who required it (20 of 52
patients, 38%).
We again emphasize that our institution is a tertiary
referral center, where most patients who are referred
have severe medical or surgical conditions. The overall
mortality rate in our series was 41.5%, which is compa-
rable to results from studies in both developing and
developed countries.
1321
Williams et al
4
reported that a
large number of nonsurviving ARF cases were found in
the postcardiac surgery groups in the 2 decades they
surveyed (19791988 and 19891998). They found that
younger patients had poorer prognoses but sepsis-attrib-
utable ARF was signicantly less prevalent in the second
decade (3%, compared with 23%; P .001). The data
from our study are not directly comparable to the data
from the study by Williams et al,
4
because we are not a
well-established cardiac center. Sepsis was a major cause
of ARF in each era, with the sepsis mortality rates not
improving, although antibiotics certainly advanced dur-
ing this time. However, mortality rates for ARF do not
always directly reect the quality of treatment, because
disease cause seems to be the most important risk factor.
The cause of ARF changed during the 22-year period
of our study (Table 2) and the mortality rate generally
improved, although not signicantly. In our hospital, the
RRT rate has not increased, which suggests that RRT
does not have any effect on the mortality rate. RRT is not
a treatment of choice, because it is known that RRT is
not essential in all ARF cases. Supportive treatment usu-
ally plays the most important role.
In Thailand, the past decade has seen much improve-
ment in transportation; however, there are various fac-
tors to consider and we could not determine whether
this improvement would have a positive or negative
effect on our ndings. Better transportation would in-
crease the number of cardiac cases referred to institu-
tions where the patients would have a better chance of
survival, but the ability of patients, particularly severely
debilitated children, to travel long distances also might
affect mortality rates in our institution. Mortality rates
could increase because of the increasing number of car-
diac surgical procedures performed or could decrease
because of improved treatment.
At least 2 studies reported that patients 1 year of age
had higher mortality rates,
22,23
but this was not seen in
our study. The reasons for this difference likely involved
the different causes of ARF and probably also the sever-
ity of the condition; one half of the patients in our group
had serum creatinine concentrations of 1 to 2 mg/dL,
which indicates that overall our patients ARF was less
severe.
Usually ARF is a secondary problem following the
failure of other organs, rather than resulting from orig-
inal renal disease. Usually, when the primary problem is
treatable, the ARF also has an excellent outcome with
appropriate care, with or without RRT.
8
For patients
with multiorgan failure, mortality rates are very high,
even with RRT,
1,4,10,24,25
being 50% for patients with
failure of 3 organs in at least 1 study.
25
ARF itself is not a fatal condition, because RRT is
advanced in this era,
26
but timing is a major consider-
ation. The best way to avoid the condition is prevention,
followed by early detection, then conservative treat-
ment, and nally referral to an institution where RRT is
available. However, problems with other vital organs (ie,
brain, heart, lung, or liver) also inuence the outcome if
these problems are not correctable.
18
It is anticipated that
RRT and ICU care will continue to advance, which
should improve the outcomes of ARF cases, but we must
consider the fact that congenital heart disease surgery
and oncologic treatments are also advancing, which will
increase the number of cases and complications. ARF
related to other systemic diseases occurs more frequently
than ARF attributable to primary renal disease; there-
fore, advances in treating the condition, with reductions
in mortality rates, may well be offset by an increased
number of cases resulting from secondary causes. In this
study, the cause of ARF was signicantly associated with
age and with the resultant mortality rate
5,21,25
but the
mortality rate itself was not related directly to age,
4,11,16
that is, there was a strong association between cause and
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age group and also mortality rates; however, age was not
an independent predictor of mortality rates.
CONCLUSIONS
The incidence of ARF in Songklanagarind Hospital was
found to be 0.5 to 9.9 cases per 1000 pediatric patients,
with a mortality rate of 41.5%. Sepsis was a major cause
of ARF and death. Causes of ARF and serum creatinine
levels were signicant independent predictors of mortal-
ity rates. The rate of ARF has increased over the years,
although the mortality rate has not improved signi-
cantly; this is a problem we should be addressing.
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DOI: 10.1542/peds.2006-0557
; originally published online August 7, 2006; 2006;118;e786 Pediatrics
McNeil
Prayong Vachvanichsanong, Pornsak Dissaneewate, Apiradee Lim and Edward
Southern Thailand
Childhood Acute Renal Failure: 22-Year Experience in a University Hospital in

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