Acta Clinica Belgica

International Journal of Clinical and Laboratory Medicine

ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20

Epidemiology and outcome of acute kidney injury

in children, a single center study

Werner Keenswijk, Jill Vanmassenhove, Ann Raes, Evelyn Dhont & Johan
VandeWalle

To cite this article: Werner Keenswijk, Jill Vanmassenhove, Ann Raes, Evelyn Dhont & Johan
VandeWalle (2017): Epidemiology and outcome of acute kidney injury in children, a single center
study, Acta Clinica Belgica, DOI: 10.1080/17843286.2017.1302625

To link to this article: http://dx.doi.org/10.1080/17843286.2017.1302625

Published online: 17 Mar 2017.

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Original Paper
Epidemiology and outcome of acute kidney
injury in children, a single center study
Werner Keenswijk¹  , Jill Vanmassenhove2, Ann Raes¹  , Evelyn Dhont3  ,
Johan VandeWalle¹ 
¹
Department of Pediatrics, Pediatric Nephrology, Ghent University Hospital, Ghent, Belgium, 2Department of
Internal Medicine, Division of Nephrology, Ghent University Hospital, Ghent, Belgium, 3Department of Pediatric
Intensive Care, Ghent University Hospital, Ghent, Belgium

Background: Information on the epidemiology of Acute Kidney Injury (AKI) in children is scarce. We performed
a single center retrospective cohort study to analyze the incidence of AKI, the male/female ratio, the underlying
etiology, and age at presentation. We also aimed to assess outcome measured by mortality, duration of PICU
stay, and development of Chronic Kidney Disease (CKD).
Methods: Records were searched for children presenting with or developing AKI between 1st January 2008 and
1st January 2015. AKI was classified according to the pediatric Rifle criteria while the cause of AKI was defined
as the major underlying disease.
Results: Of the 28,295 children admitted, 167 episodes of AKI were identified, equaling 5.9 cases per 1000
children. Patients classified as Failure at presentation according to pRifle criteria where significantly more likely
to need dialysis (27/50, 54%) compared to those presenting with Injury (12/57, 21.1%) or Risk (6/60, 10 %).
Diarrhea-associated Hemolytic Uremic Syndrome (D+HUS) was the most frequent cause (20.3 %) peaking during
the summer months, followed by cardiac surgery (13.7%), medication-related nephrotoxicity (13.2%), and acute
Glomerulonephritis (12%). The median age of children admitted with AKI was 6.1 years (range 0.1–17) and 50.8%
of cases were male. Twenty five (15%) children died while 27 (16.1%) developed CKD.
Conclusions: Pediatric AKI poses a significant problem and strategies aimed at prevention, early detection,
treatment, and adequate follow-up are needed. D+HUS is the most common underlying cause and effective
surveillance of Enterohemorrhagic E. coli infections in association with additional measures is highly recommended.
Keywords:  Acute kidney injury, Epidemiology, Etiology, Outcome

Introduction play a role in the development and etiological distribution

Acute kidney injury (AKI) is associated with increased
morbidity and mortality, both in children and adults.1
The International Society of Nephrology (ISN) has
launched the ‘0 by 25’ campaign [http://www.theisn.org/
news/item/2083-evidence-awareness-action] to reduce the
burden of AKI with a strong emphasis on developing coun-
tries. AKI is however also frequently encountered in high
income countries and there is a lack of data concerning the
epidemiology and the burden of this condition on pediatric
patients and the community as a whole.2 Epidemiologic
data concerning factors such as the incidence, age at
presentation, risk factors, underlying conditions, and
outcome could increase awareness among clinicians and
policy-makers which in turn enables strategies aimed
at prevention, early detection, adequate treatment, and
follow-up. So far no such studies have been performed in
Belgium providing the above-mentioned data in children.
Socio-economic, geographic, and environmental factors
Correspondence to: Werner Keenswijk, Department of Pediatrics,
Pediatric Nephrology, Ghent University Hospital De Pintelaan 185,
Belgium. Email: secretariaat.pediatrie@uzgent.be
of AKI.3 In pediatric studies done in developing countries,
the most important causes seem to be primary kidney dis-
ease, sepsis, and gastro enteritis4,5 while in Western coun-
tries this condition is more likely to be linked to Hemolytic
Uremic Syndrome (HUS), sepsis, and congenital cardiac
surgery.2,6
This study is aimed at:
(1) Analyzing the incidence, male/female ratio, etiology, age,
and stage of AKI at presentation.
(2) Assessing outcome of children with AKI measured by
mortality, duration of PICU (Pediatric Intensive care
Unit) stay, and development of Chronic Kidney Disease
(CKD).
(3) Creating awareness among clinicians and policy-mak-
ers enabling prevention, early detection, treatment, and
adequate follow-up.
Methods
Ethics
Ethical clearance for this study was obtained from the eth-
ical committee of Ghent University. No informed consent

© Acta Clinica Belgica 2017

DOI 10.1080/17843286.2017.1302625 Acta Clinica Belgica   2017 1
Keenswijk et al.  Epidemiology and outcome of acute kidney injury in children
was obtained because of the retrospective nature of this
study but researchers strictly adhered to procedures ensur-
ing patient confidentiality.
Study location
This study was undertaken at the Ghent University
Hospital, located in Belgium. The Ghent University
Hospital is a tertiary center that serves as a referral center
for several regional hospitals. In addition to the gen-
eral pediatric ward, a PICU is attached to this hospital.
Children presenting at regional hospitals with AKI are
generally referred to this tertiary center where annually
more than 4000 children are admitted.
All children who at admission presented with AKI or
developed AKI during hospitalization between the 1st of
January 2008 and the 1st January 2015 were included in
this study.
Data collection
This is a retrospective, descriptive, single center study
of all pediatric AKI cases (non-neonatal) presenting at
the Ghent University Hospital between the period of
1st January 2008 and 1st January 2015. We included
patients ≥ 1 month and ≤ 18 years of age.
AKI was classified according to pRifle criteria (see
Table 1).
The severity of AKI was evaluated using the pRifle
criteria with ‘R’ for risk, ‘I’ for injury, and ‘F’ for failure.
Patients with a background of CKD or hydronephrosis
were excluded from this study. Electronic patient files were
searched and relevant data concerning etiology, clinical
features such as hypertension and diuresis as well as lab-
oratory parameters were collected.
Outcomes were measured in regard to mortality and
the presence of CKD 6 months after the primary insult.
In addition, information concerning length of PICU stay
and need of dialysis was obtained.
Patients with AKI usually present either via the outpa-
tient clinic, the emergency room or referral from regional
hospitals. The renal unit also gets consulted by other
departments within the hospital in case of AKI in hospi-
talized patients. Standard management of patients with
AKI includes full patient history and clinical examination.
Laboratory investigations such as full blood count, serum
Table 1  Pediatric Modified Rifle Definition.
  Estimated CCl Urine output
Risk eCCl decrease by 25% <0.5 ml/kg/h for 8 h
Injury eCCl decrease by 50% <0.5 ml/kg/h for 16 h
Failure eCCl decrease by <0.3 ml/kg/h for 24 h
75% or eCCl<35 ml/ or anuric for 12 h
min/1.73 m2
Loss Persistent failure > 4  
weeks
End stage End-stage renal dis-  
ease (persistent failure
>3 months)
Note: eCCl, estimated creatinine clearance; pRIFLE, pediatric risk,
injury, failure, loss, and end-stage renal disease.
2 Acta Clinica Belgica   2017
creatinine, BUN, serum electrolytes, and urinalysis are
also performed. In addition, all patients receive ultrasound
imaging to identify characteristics of the underlying con-
ditions and to exclude obstructive renal disease. Patients
with electrolyte imbalances such as hyperkalemia, fluid
overload, hypertensive crises or that need dialysis are gen-
erally transferred to the PICU for intensive monitoring.
Definitions
HUS was defined by the acute triad of intravascular
hemolysis, low platelets, and signs of renal dysfunction
e.g. edema, hypertension, and rising serum creatinine.
Diarrhea-associated HUS was differentiated from atyp-
ical HUS by the absence of complement abnormalities
(low Complement factor C3 and/or C4) and the typical
prodrome of bloody diarrhea and/or positive fecal cul-
ture for Enterohemorrhagic E. coli bacteria (EHEC). All
detected fecal E. coli strains underwent genetic PCR typ-
ing to determine the specific serotype.
Cardiac surgery was defined as the cause of AKI after
either reduction of eCCl or oliguria within the first 48
hours postoperatively.
Nephrotoxicity as a cause of AKI was considered as the
underlying cause when a normal renal function preceded
the administration of the specific drug with deteriorating
kidney function within 48 hours without other factors
explaining the decline in function.
Sepsis was defined as a systemic inflammatory response
due to a proven bloodstream infection.
A diagnosis of acute Glomerulonephritis was suspected
based on the presence of hematuria with dysmorphic red
cell casts in urine with ultrasound abnormalities including
increased kidney size and echogenecity. Diagnosis was con-
firmed by renal biopsy in those cases where differentiation
based on laboratory parameters (e.g. presence of anti double
stranded DNA, anti Streptolysin O titer) was not possible.
Hypertension was defined as systolic and diastolic blood
pressure greater than the 95th percentile for age, gender, and
length using the normogram published in the fourth report of
the National High blood pressure Education Group.7 Blood
pressure was either measured with a digital blood pressure
device (Welch Allyn, ProBP 3400) or intra-arterially in cer-
tain children, admitted to the PICU. Outcome is presented
by dividing the children in groups of full recovery (survival
and renal recovery), mortality, and development of CKD.
Chronic Kidney Disease was defined according to the
KDIGO definition as: structural or functional abnormal-
ities of the kidney regardless of GFR for ≥ 3 months or
GFR < 60ml/min/1.73m² for ≥ 3 months. eGFR or esti-
mated creatinine clearance was measured using the mod-
ified Schwartz equation.
Data management and statistical analysis
The data were managed using SPSS version 23 (IBM,
SPSS). Continuous data were summarized as mean or
median, while categorical data are presented as percentages.
 Keenswijk et al.  Epidemiology and outcome of acute kidney injury in children

Univariate analyses for group comparisons were performed
using either independent samples t test or One-way Anova
with post-hoc Tukey. A p-value < 0.05 was considered as
statistically significant. The incidence of AKI in admitted
children was measured in relation to the total number of
children admitted to the Ghent University Hospital between
the 1st of January 2008 and the 1st of January 2015.
Results
Of the 28,295 children admitted to the Ghent University
Hospital between 1st January 2008 and 31st December
2014, 167 episodes of AKI were identified, equaling 5.9
cases per 1000 children.
The median age of children admitted with AKI was
6.1 years (range 0.1-17) and 50.8% of cases were male.
Twenty five (15%) children died while 27 (16%) devel-
oped CKD (Table 2).
Peritoneal dialysis (PD) was the preferred modality
of dialysis therapy in AKI equaling 70.9% of dialysis
treatment. Patients classified as Failure at presentation
according to pRifle criteria were significantly more likely
to need dialysis (27/50, p = 0.00001) in comparison to
those presenting with classification Injury (12/57) or Risk
(6/60).
Causes of AKI
Diarrhea-associated Hemolytic uremic syndrome
(D+HUS) was the most frequent cause of AKI (20.3 %,
34 cases), followed by congenital cardiac surgery (13.7%,
25 cases), medication-related nephrotoxicity (13.2%, 23
cases), and glomerulonephritis (12%, 22 cases) (Fig. 1
and Table 2).
D+HUS was confirmed by positive fecal culture and
PCR identification of Shiga toxin producing Escherichia
coli (STEC) in 47% of cases. In 93.7% (15/16) of these con-
firmed cases the STEC O157H7 was the culprit. D+HUS
cases were seen year round but predominantly during
the summer months (Fig. 2). No children with D+HUS
died but they did develop significant complications such
as neurologic dysfunction (5/34), pancreatitis (3/34) and

Table 2  Underlying diagnoses, mortality, CKD, staging, PICU stay in children with AKI.

Failure(F)
Total Mortality CKD at presentation PICUstay
N = 167
Underlying diseases N (%) N (%) N (%) N (%) Days/year
Hemolytic uremic syndrome
D+HUS 34(20.3) 0 10(37) 21(46.7) 56
AHUS*/strept. HUS** 3(1.8) 0 1(3.7) 0 4.4
Cardiac surgery 25(15) 10(40) 1(3.7) 3(6.7) 53.8
Nephrotoxicity(medication) 23(13.7) 5(20) 7(25.9) 1(2.2) 13.7
Glomerulonephritis 21(12.6) 0 4(14.8) 3(6.7) 7.8
Sepsis 14 (8.4) 4(16) 0 4(8.9) 35.5
Obstructive uropathy 10 (6) 0 1(3.7) 3(6.7) 3
Gastroenteritis/Dehydration 16(9.5) 2(8) 0 6(13.3) 6
Others*** 21(12.6) 4(16) 3(11.1) 4(8.9) 23.1
Total 167(100%) 25 27 45 203.3
Notes: AHUS*: Atypical Hemolytic uremic syndrome.
Strept. HUS**: Streptococcus-Associated Hemolytic uremic syndrome.
Others***: Tubulo interstitial nephritis (2), renal trauma (4), contrast nephropathy (1), Rhabdomiolysis (2), acute pyelonephritis (3 cases),
Tumorlysis (2), congestive heart failure (1), malaria (1), hyper IgM disease (1), Graft versus Host disease (1), status epilepticus (1) unknown
cause (2).

Figure 1  Annual causes of AKI.

 Acta Clinica Belgica  2017 3

Keenswijk et al.  Epidemiology and outcome of acute kidney injury in children
Figure 2  DHUs cases 2008–2014.
Figure 3  Outcome of AKI related to underlying etiology.
pericarditis (1/34) and development of CKD (10/34).
Two cases of atypical HUS were noted and one case of
Streptoccocal-associated HUS. Cardiac surgery accounted
for 13.7 % of cases of AKI. All of these cases concerned
children undergoing surgery for correction of congeni-
tal cardiac anomalies such as Tetralogy of Fallot (TOF),
Double Outlet right ventricle (DORV), Transposition of
Great Arteries (TGA), and other complex cardiac defects.
Nephrotoxicity accounted for 22 cases (13.2 %) and was
mostly seen in oncologic patients receiving chemotherapy
(e.g. vincristin, methotrexate) or immune suppression (e.g.
tacrolimus) sometimes in association with nephrotoxic
antibiotics (e.g. aminoglycosides, vancomycin). Acute
Glomerulonephritis (GN) responsible for 22 cases was
in 50% (11 cases) caused by post-infectious GN. Lupus
nephritis accounted for two cases of acute GN.
Mortality
Twenty five children (Fig. 3) died from AKI related con-
ditions with congenital cardiac surgery (10 cases, 40%)
accounting for most cases followed by nephrotoxicity
(5 cases, 25%) and sepsis (4 cases, 18.2%) (Table 2).When
4 Acta Clinica Belgica   2017
compared with children that made a full recovery, mor-
tality was significantly associated to oliguria (p = 0.0001)
(Table 3) within the first 48 hours of AKI diagnosis and
lowest platelet count (p = 0.002). Serum creatinine and ‘F’
classification according to pRifle criteria at AKI presenta-
tion were not indicative of a higher risk of mortality. A sub-
analysis of mortality in children who underwent congenital
cardiac surgery and developed AKI, showed a correlation
between mortality and oliguria, (p = 0.01) (Table 4), but
not with higher serum creatinine or classification as ‘F’
within the first 48 hours after surgery.
Chronic kidney disease
27 children (16.2%) developed CKD of whom14 were
boys and 13 were girls (Table 3).
In comparison with children who made a full recovery,
CKD development was significantly associated with hyper-
tension (p = 0.0001), higher serum creatinine (p = 0.0001)
and lower eCCl (p = 0.002) at AKI diagnosis. In addition
higher maximum serum creatinine (p = 0.0001), classifica-
tion as ‘F’ (p = 0.03) at presentation and need for dialysis
were also significantly related to CKD.
 Keenswijk et al.  Epidemiology and outcome of acute kidney injury in children

Table 3  Independent variables and outcome.

Full recovery CKD Mortality

N = 115(68.8%) N = 27(16.2%) N = 25(15%)
Independent variables Group I Group II Group III P value
Male (%) 61 (36.5) 14 (8.4) 10 (6)
Female (%) 54 (32.3) 13 (7.8) 15 (9)
Age 6.1 (0.1–17) 7.9 (0.1−16) 4.5 (0.1–16) 0.059
Hypertension*(%) 24 (20.8) 15 (55.5)a 5 (20) 0.0001
Oliguria*(%) 23 (20) 13 (48.1) 16 (64)b 0.0001
Hb(g/dl)* 10.4 (3.6–18.7) 9.7 (6.5−16.5) 10 (3.5–16.5) 0.645
Leukocytes * 11.5 (0.1–46.8) 13.7(0.94–18.6) 39.5 (0.2–687) 0.053
Lowest Platelet count 148 (5.0–496) 149 (4–548) 55 (3–238)c 0.002
BUN (mg/dl)* 73.8 (10–539) 95.2 (8.3–327) 50 (16–224) 0.06
SCr* 1.3 (0.33–11.0) 2.7 (0.49–9.27)d 0.9 (0.45–4.34) 0.0001
Max.Scr 1.7 (0.35–11) 4.2 (0.59–15.2)e 1.6 (0.5–4.34) 0.0001
Sodium(mmol/l* 138 (115–161) 135 (122–143) 143 (128–179)f 0.01
Potassium(mmol/l)* 4.6 (2.5–8.8) 4.9 (3.0–6.8) 4.4 (2.6–6.7) 0.091
Admission eCCl 53.1(7.1–123) 33.5 (4.8–78) 53.7 (14–78.8) 0.002
Worst eCCl 44 (4–116) 25.9 (3–68)g 31.1 (13–66) 0.003
RIFLE category ‘F’*(%) 31 (27) 15 (55.5)h 4 (16) 0.03
Received dialysis (%) 22 (19.1) 13 (48.1)i 10 (40) 0.002
*
at admission or AKI presentation
a
significant vs. group I and III.
b
significant vs. group I.
c
significant vs. group I and II.
d
significant vs. group I and III.
e
significant vs. group I and III.
f
significant vs. group II.
g
significant vs. group I.
h
significant vs. group I and III.
i
significant vs. group I and III.

Table 4  Comparison of outcome with AKI after congenital cardiac surgery.

Survived Deceased
Total number of patients N = 25 N = 15 N = 10 P-value
Male (%) 7 (28) 5 (20)
Female(%) 8 (32) 5 (20)
Age in years 1.6 (0.1–10) 2.4 (0.2–10) 0.474
Hypertension* 0 0
Oliguria*(%) 4 (26.6) 9 (90) 0.022
Hb(g/dl)* 12.1 (8.4–18.7) 11.8 (8.5–16.5) 0.643
Leukocytes * 14.1 (5.1–22.1) 14.6 (4.3-33.6) 0.135
Lowest Platelet count 130 (28–357) 55.8 (3–238) 0.052
SCr* 0.64 (0.43–1.1) 0.62 (0.46–0.91) 0.837
Max.Scr 1.3 (0.43–2.79) 1.8 (0.59–3.44) 0.583
BUN(mg/dl)* 40.9 (11–122) 46.9 (16–107) 0.99
Sodium(mmol/l* 141.9 (132–150) 143.5(130–154) 0.081
Potassium(mmol/l)* 4.9 (3.6–6.0) 4.6 (3.4–5.6) 0.441
Admission eCCl 50.4 (18–84) 51.2 (14–78.8) 0.688
Received dialysis 5 6
*
at AKI presentation.

Discussion
D+HUS is the most frequent cause of AKI in our pediatric
population with a clear peak during the summer months
(June-August). No patients died in this group, but the con-
dition was associated with a high risk (10/34) of CKD
development. Overall the mortality related to D+HUS
in other studies has shown to be between 3–5% [8.9].
The average age of children developing D+HUS was 4.8
years (range 20 months–15 years). D+HUS is usually
preceded by STEC-induced gastroenteritis, usually from
the O157: H7 serotype. Several other Shiga-toxin produc-
ing Enterohemorrhagic E. coli (STEC) serotypes such as
the O103, O111, O26:H11, and O104:H4 can also induce
D+HUS.10 STEC typically colonizes the bovine intesti-
nal tract but has also been found in sheep, goats, horses,
and dogs.11,12 Humans are infected via several routes, for
example by consumption of contaminated undercooked
beef, unpasteurized dairy products, or contaminated fruits
and vegetables, by human to human transmission and by
ingesting contaminated water (swimming). STEC pro-
duces toxins, known as Verocytotoxins or Shiga-toxins
which can induce HUS symptoms via endothelial damage
and related vasculitis in e.g. kidneys, lungs, pancreas, liver,
and brains. Patients typically < 5 years present with bloody

 Acta Clinica Belgica  2017 5

Keenswijk et al.  Epidemiology and outcome of acute kidney injury in children
diarrhea and develop signs of renal failure and thrombotic
microangiopathy 5–7 days thereafter.11,12
A national study (Belgium) performed in 2007 showed
that 37.8 % of all cattle ranches were contaminated with
the STEC O157:H7.13 About 1 % of cattle carcasses was
positive for STEC with 0.1 % of commercial beef ending
up positive after processing.
In the summer months, increased consumption of
undercooked beef (e.g. barbecue, hamburgers, steak tar-
tare) with an increase in swimming in natural water reser-
voirs and farm visits (e.g. farm vacations) might explain
the peak in D+HUS cases. There are no recent data on
the annual incidence of D+HUS in Belgium and the last
national D+HUS study dates back to 199614 showing an
incidence of 4.3/100,000 children  <  5years of age. An
obvious issue in Belgium is the fact that no mandatory
reporting of cases of EHEC infections or D+HUS cases
exists. Although EHEC can easily be cultured and detected
in feces, based on their biochemical characteristics,13 most
hospitals and laboratories do not perform fecal testing for
EHEC because this is not covered by basic health insur-
ance. This evidently increases the risk of under-reporting
new cases. To reduce rates of EHEC infections and pro-
tect the public, effective surveillance of EHEC infection
and D+HUS cases is essential. This might allow for early
source detection and would be useful in setting up pre-
ventive measures in a timely manner. The catastrophic
outbreak in Germany in 2011, caused by EHEC O104:H4
contamination of vegetables which led to 3842 cases of
EHEC infections with 850 D+HUS cases and 53 deaths
(mostly adults),15 highlights the need for an early warn-
ing system. In Limburg (Belgium) in 2012 an outbreak
of 24 cases of EHEC with 5 HUS cases leading to 16
hospitalizations was seen.16 In several European countries
such as Austria, Finland, Sweden, and Norway intensive
surveillance systems are put in place with mandatory
reporting of new STEC infections and D+HUS cases to
health care authorities is done.2,17,18 This however is not
the case in countries such as Belgium, France, and Italy.19
D+HUS was shown to be the most frequent cause of AKI
in our pediatric population which is in line with studies
performed in other Western European countries.20,21 It was
also the most common underlying diagnosis of AKI-related
admission to the PICU and the authors recommend that
effective surveillance with mandatory reporting should be
implemented anywhere D+HUS is a threat to the public
health. In the United States a clear decrease in D+HUS-
related fatalities was noted after 1980, likely related to the
fact that STEC infections were more often reported and
awareness had increased22 In addition, we also suggest
that preventive measures such as education of the general
public concerning adequate preparation of high risk foods,
personal hygiene, and risk of swimming in natural reser-
voirs should be intensified.
The second most common cause of AKI and most
important underlying factor of AKI-related mortality was
6 Acta Clinica Belgica   2017
congenital cardiac surgery. Congenital cardiac surgery is
recognized as an important cause of AKI and factors such
as younger age at surgery and duration of cardiopulmo-
nary bypass time (CPB time)23 have been associated with
a higher risk of AKI development. In a subanalysis of
patients with AKI after cardiac surgery (Table 4) in our
study, oliguria was found to be significantly associated
with mortality. Maximum serum creatinine and serum cre-
atinine at AKI detection however were not significantly
higher in children that died in comparison to survivors. A
possible explanation is that oliguria in combination with
extra fluids given post-surgery could have predisposed
these patients to fluid overload which is negatively related
to survival.24 Fluid overload could also have masked the
rise in serum creatinine with possible underestimation and/
or late detection of AKI.25–27 It should be noted that factors
related to the severity of the underlying cardiac defect and
to the surgery itself such as increased CPB time could also
explain a higher rate of oliguria, and thus higher mortality
in these patients.
We also assume this central role of underlying pathol-
ogy (such as sepsis, hematologic diseases) in other AKI-
related case fatalities.
The authors conclude that a limitation in this trial
was the low number of included patients (25) with AKI
related to cardiac surgery. This in addition to the retro-
spective nature of the trial, limits the possibility to asses
these types of cause–effect relationships. Efforts aimed
at early detection of AKI after cardiac surgery to enable
early treatment have been undertaken (e.g. the usefulness
of early biomarkers).28,29 Another important cause of AKI
with significant morbidity and mortality was nephrotoxic-
ity which was mostly related to chemotherapy associated
with oncologic conditions such as leukemia (8/23) and
solid tumors (5/23). Many chemotherapeutic agents such
as vincristine, cisplatin, and methotrexate are known to be
nephrotoxic.30,31 In addition these drugs also induce immu-
nosuppression resulting in higher rates of serious infec-
tions in these patients. We found that in two fatal cases a
combination of chemotherapeutic agents and nephrotoxic
antibiotics (vancomycin, amikacin) were probably respon-
sible for AKI. Authors propose that for children receiving
nephrotoxic chemotherapeutic agents, nephrotoxic antibi-
otics, and drugs (e.g. NSAIDS, Ace-inhibitors) should be
avoided as much as possible. In case of infection, antibiot-
ics such as amoxicillin-clavulanate, flucloxacillin, cefuro-
xim, and cefalexin with a less toxic renal profile should be
preferred over those (e.g. aminoglycosides, vancomycin)
strongly associated with nephrotoxicity.32,33 In addition,
close surveillance of renal function in patients receiving
nephrotoxic medication is warranted since this can ena-
ble timely treatment and drug dosage adjustments avoid-
ing toxic drug levels in light of the falling GFR. Other
important causes of AKI were Acute GN (21 cases) and
Sepsis (14 cases). Acute Glomerulonephritis was mostly
attributed to post-infectious GN (50%) with four patients

developing CKD while septic AKI was diagnosed in four
children who eventually died.
Long term outcomes of AKI in children are unknown.
However recent studies suggest a higher risk of developing
CKD in this population even after initial complete normal-
ization of renal function.34 This emphasizes the importance
of long term follow-up of children with AKI regardless of
initial outcome.
Our current study has some limitations. This is a single
center study performed in a tertiary hospital which means
that a certain degree of selection bias in favor of more
severe cases can be expected. The retrospective design
of the study by definition does not allow to demonstrate
causal associations. This study does provide data on the
incidence of AKI in hospitalized children and underly-
ing conditions, AKI staging at presentation with outcome
reporting (mortality and CKD development). It is the first
of its kind in Belgium and we do believe that it is repre-
sentative of AKI in the Belgian pediatric population. This
study also provides data which can be used as a base for
future prospective studies (e.g. evaluating the role of olig-
uria and fluid overload as an early predictor of AKI-related
mortality and morbidity after cardiac surgery). In Belgium
and other European countries, measures aimed at reducing
D+HUS incidence should be taken (e.g. effective STEC
surveillance, mandatory reporting of D+HUS cases). More
and broader pediatric AKI studies are needed providing
epidemiologic data which in turn increases insight and
awareness among policy-makers, health care professionals,
and the general public. Clinicians need to be aware of the
relatively high incidence of pediatric D+HUS especially
in children < 5 years and the need for follow-up of renal
function in cases of unspecified bloody diarrhea. Timely
evaluation of renal function is highly recommended in
patients at risk for AKI e.g. with sepsis, post-cardiac sur-
gery, or receiving chemotherapeutic agents. Pediatric AKI
continues to impose a huge burden on patients and families
with significant mortality and short and long term morbid-
ity. Dialysis treatment, PICU admissions, long term CKD
follow-up with possible transplantation, and increased risk
of cardiovascular disease all impose an enormous eco-
nomic burden on the society as a whole, emphasizing the
importance of preventive measures, timely recognition,
and treatment of this condition.
Notes on Contributors
Werner Keenswijk, PhD, is a last year fellow pediat-
ric nephrology and a doctoral candidate attached to the
Pediatric Department of the Ghent University Hospital
and Ghent University with a strong research interest in
Acute Kidney Injury.
Jill Vanmassenhove, PhD, is a nephrologist attached to
the adult renal unit of the Ghent University Hospital with
 Acta Clinica Belgica  2017
Keenswijk et al.  Epidemiology and outcome of acute kidney injury in children
a strong interest in acute kidney injury and several inter-
esting papers in this field.
Ann Raes, PhD, is a pediatric nephrologist attached to the
Pediatric Department of the Ghent University Hospital
with over 15 years of experience and strong research
interests in acute and chronic kidney diseases and urinary
incontinence/enuresis.
Evelyn Dhont, PhD, is a pediatric intensivist
attached to the Pediatric Intensive care of the Ghent
University Hospital with a strong interest in Acute
Kidney Injury.
Johan VandeWalle, PhD, is the head of the pediatric renal
unit of the Ghent University Hospital with more than 30
years of experience and strong research interests in acute
and chronic kidney diseases, nephhrotic syndrome and
urinary incontinence/enuresis.
Conflicts of interest
The authors report no declarations of interest.
Funding source
None.
Acknowledgements
We would like to thank and acknowledge Ghent University
for their ongoing support and the facilitation of this
research project.
ORCID
Werner Keenswijk    http://orcid.org/0000-0001-5576-
169X
Ann Raes   http://orcid.org/0000-0001-7809-2505
Evelyn Dhont   http://orcid.org/0000-0002-8969-2941
Johan VandeWalle    http://orcid.org/0000-0001-9700-
5358
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