Research Article
Blood Purif
DOI: 10.1159/000502081
Acute Kidney Injury in Critically Ill
Children: A Retrospective Analysis
of Risk Factors
Francesca De Zan a Angela Amigoni b Roberta Pozzato b Andrea Pettenazzo b
Luisa Murer a Enrico Vidal c
a Nephrology, Dialysis and Transplant Unit, Department of Woman’s and Child’s Health, University Hospital of
Padova, Padova, Italy; b Pediatric Intensive Care Unit, Department of Woman’s and Child’s Health, University
Hospital of Padova, Padova, Italy; c Division of Pediatrics, Department of Medicine, University of Udine, Udine, Italy
Keywords
Acute kidney injury · Critically ill children · Pediatric
intensive care unit · Kidney Disease: Improving Global
Outcome · Outcome
Abstract
Introduction: Children admitted to paediatric intensive care
unit (PICU) are at risk of acute kidney injury (AKI). However,
few paediatric studies have focused on the identification of
factors potentially associated with the development of this
condition. The aim of our study was to assess the incidence
rate of AKI, identify risk factors, and evaluate clinical out-
come in a large sample of critically ill children. Methods: This
retrospective observational study was conducted including
patients admitted to our PICU from January 2014 to Decem-
ber 2016. AKI was defined according to Kidney Disease: Im-
proving Global Outcome criteria. Results: A total of 222 PICU
patients out of 811 (27%) had AKI (stage I 39%, stage II 24%,
stage III 37%). The most common PICU admission diagnoses
in AKI cases were heart disease (38.6%), respiratory failure
(16.8%) and postsurgical non-cardiac patients (11%). Hypox-
© 2019 S. Karger AG, Basel
E-Mail karger@karger.com
www.karger.com/bpu
Received: April 2, 2019
Accepted: July 11, 2019
Published online: August 5, 2019
ic-ischaemic was the most frequent cause of AKI. Significant
risk factors for AKI following multivariate analysis were age
>2 months (OR 2.43; 95% CI 1.03–7.87; p = 0.05), serum cre-
atinine at admission >44 µmol/L (OR 2.23; 95% CI 1.26–3.94;
p = 0.006), presence of comorbidities (OR 1.84; 95% CI 1.03–
3.30; p = 0.04), use of inotropes (OR 2.56; 95% CI 1.23–5.35;
p = 0.012) and diuretics (OR 2.78; 95% CI 1.49–5.19; p = 0.001),
exposure to nephrotoxic drugs (OR 1.66; 95% CI 1.01–2.91;
p  = 0.04), multiple organ dysfunction syndrome (OR 2.68;
95% CI 1.43–5.01; p = 0.002), and coagulopathy (OR 1.89;
95% CI 1.05–3.38, p = 0.03). AKI was associated with a sig-
nificant longer PICU stay (median LOS of 8 days, interquartile
range [IQR] 3–16, versus 4 days, IQR 2–8, in non-AKI patients;
p < 0.001). The mortality rate resulted tenfold higher in AKI
than non-AKI patients (12.6 vs. 1.2%; p < 0.001). Conclusions:
The incidence of AKI in critically ill children is high, with an
associated increased length of stay and risk of mortality. In
the PICU setting, risk factors of AKI are multiple and mainly
associated with illness severity. © 2019 S. Karger AG, Basel
F.D.Z. and A.A. authors contributed equally to this work.
130.241.16.16 - 8/6/2019 12:40:15 PM
Enrico Vidal
Division of Pediatrics, Department of Medicine, University of Udine
Piazzale Santa Maria della Misericordia, 15
Göteborgs Universitet
33100 Udine (Italy)
Downloaded by:
E-Mail enrico.vidal @ inwind.it
 Introduction
Acute kidney injury (AKI) is one of the most common
syndromes in critically ill patients and results in adverse
outcomes including prolonged mechanical ventilation,
increased length of stay in intensive care units (ICUs) and
increased mortality risk. Previous studies have shown
that the incidence of AKI in adults admitted to ICUs
ranges from 6 to 60% [1–3]. This variability in incidence
is due to both different hospitals settings and the evolu-
tion in the definition of AKI, from the RIFLE consensus
classification to the Kidney Disease: Improving Global
Outcome (KDIGO) guidelines [4–6]. The historical dis-
crepancy of definitions for AKI has further complicated
measures of incidence and prevalence over time in the
special setting of paediatric age. Very recently, the Assess-
ment of Worldwide AKI, Renal Angina and Epidemiol-
ogy (AWARE) study found that the overall incidence of
AKI in 4,683 critically ill children admitted to intensive
care settings in 32 hospitals throughout Asia, Australia,
Europe and North America was 26.9%, and the incidence
of severe AKI (KDIGO Stage 2 or 3) was 11.6% [7, 8]. Di-
agnosis of severe AKI conferred an increased risk of mor-
tality by an adjusted odd ratio of 1.77 (95% CI 1.17–2.68),
with a mortality rate of 11 vs. 2.5% (p < 0.001) in patients
without severe AKI. Given the high incidence of AKI in
the ICU setting and its association with adverse out-
comes, preventive strategies should be directed towards
the prompt identification of patients at risk. The identifi-
cation of children who are at risk of AKI is necessary in
order to target interventions to minimize morbidity and
mortality in this patient population. Few paediatric stud-
ies have focused on the identification of factors poten-
tially associated with the development of acute kidney
dysfunction: Bailey et al. [9] demonstrated that AKI in
critically ill children is the result of exposure to multiple
risk factors, which are often present before paediatric
ICU (PICU) admission.
The aims of this study were to investigate the incidence
of AKI in critically ill children admitted to a tertiary refer-
ral PICU, to identify risk factors and to evaluate their
short-term outcome.
Methods
We conducted a retrospective observational study enrolling all
patients between 0 and 20 years of age, admitted to the PICU in the
University-Hospital of Padua, Italy, for 3 consecutive years, from
January 2014 to December 2016. Charts of patients were reviewed
retrospectively for the presence of AKI based on both serum cre-
2 Blood Purif
DOI: 10.1159/000502081
atinine elevation and urinary output, according to the KDIGO cri-
teria and staging. Patients were excluded if they had a known his-
tory of end-stage renal disease, had received a recent kidney trans-
plant, had <3 serum creatinine determinations during admission,
their serum creatinine levels had returned to baseline within 48 h,
or they were admitted for nephrectomy or dialysis initiation. The
local Ethics Committee approved the study.
Patients with and without AKI were compared for a series of
risk factors at admission and during the PICU stay. The presence
or absence of each potential risk factor was assessed once daily for
each case, using data extracted from the hospital chart. Risk factors
were recorded until development of AKI, discharge from PICU or
death.
Diagnoses at PICU admission were categorized into the follow-
ing groups: respiratory failure, shock (hypovolemic and haemor-
rhagic shock), cardiac disease (cardiogenic shock, congenital car-
diopathy, and elective cardiac surgery), infection (septic shock,
bacterial and viral infection), trauma (trauma, severe head injury,
burns), postsurgical (elective and urgent non cardiac surgery), and
other. Possible risk factors during PICU stay included hypoten-
sion, defined as a decrease in systolic blood pressure below 2 SDS
of the normal value for the age of the patient; multiple organ dys-
function syndrome (MODS), defined as the presence of dysfunc-
tion of 2 or more systems (including respiratory, cardio-vascular,
hematologic, neurologic, gastrointestinal, and hepatic as defined
by Proulx et al. [10]); coagulopathy, defined as the presence of in-
ternational normalized ratio >2, prothrombin time <20 s, activat-
ed partial thromboplastin time > 60 s, or D-dimer > 0.5 mg/mL;
thrombocytopenia, defined as a platelet level <50,000/mm3. Final-
ly, the use of inotropes and exposure to nephrotoxic drugs includ-
ing iodinated contrast, non-steroidal anti-inflammatory drugs,
aminoglycosides and glycopeptides, was evaluated.
Categorical data is presented as counts and percentages and
were analysed with the chi-square test. Continuous variables were
expressed as median and interquartile range (IQR) and analysed
by non-parametric tests. Univariate analysis was used to screen for
parameters potentially associated with high risk for AKI. Param-
eters significantly associated with a high risk for AKI (p < 0.05 by
univariate analysis) were selected for stepwise logistic regression
analysis. Where necessary, pooled median values were employed
to dichotomize continuous variables. For each variable significant-
ly associated with a high risk for AKI by multivariate analysis, the
odd ratio was calculated with the corresponding 95% CI. Statistical
analysis was performed with SPSS version 11.0 statistic software
package (IBM SPSS Statistics, IBM Corporation, Chicago, IL,
USA).
Results
A total of 1,384 patients were evaluated and 811 (58%)
met the inclusion criteria (Fig. 1). AKI was identified in
27% of all patients and in 18% of infants (≤1 month of
age). Of the 222 patients with AKI, 87 developed stage I
(39%), 53 stage II (24%) and 82 stage III AKI (37%). At
ICU admission, patients with AKI were significantly old-
er (median age of 5 [IQR 0–67] vs. 1 month [IQR 0–41];
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De Zan/Amigoni/Pozzato/Pettenazzo/
Murer/Vidal
Göteborgs Universitet
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573
patients fulfilled
exclusion criteria
Fig. 1. Flowchart of the study selection pro-
cess, from screening to the assessment of
the primary outcome. PICU, paediatric in-
tensive care unit; AKI, acute kidney injury.
p < 0.001) and sicker (median PIM3 score of 0.025 [IQR
0.093–0.066] vs. 0.017 [IQR 0.007–0.346]; p < 0.001) as
compared with non-AKI cases (Table 1). As compared
with non-AKI, AKI cases were more frequently hospital-
ized for a cardiac (40.5 vs. 33.5%), oncologic (10 vs.
6.3%), metabolic (3.2 vs. 1%) or renal disease (3.6 vs. 0%),
and then admitted to ICU because of cardiac dysfunc-
tion, shock or infection. Conversely, those patients with-
out AKI during the ICU course were more commonly
hospitalized because of a respiratory disease (30.1 vs.
14.1%) and admitted to ICU with respiratory failure. In
the AKI cohort, renal dysfunction was mainly ischaemic
(n = 114; 51%), due to sepsis with MODS (n = 32; 14.5%),
drug-induced (n = 26; 12%), or multifactorial (n = 21;
9.5%).
All factors included in the univariate analysis resulted
significantly associated with risk of AKI (Table 2). In a
stepwise logistic regression analysis, independent risk
factors for the development of AKI resulted when age
at the time of ICU admission >2 months (OR 2.43; 95%
CI 1.03–7.87; p = 0.05), serum creatinine at admission
>44 µmol/L (OR 2.23; 95% CI 1.26–3.94; p = 0.006), pres-
ence of at least one comorbidity (OR 1.84; 95% CI 1.03–
3.30; p = 0.04), use of 2 or more inotropes (OR 2.56; 95%
CI 1.23–5.35; p = 0.012), use of diuretics (OR 2.78; 95%
CI 1.49–5.19; p = 0.001), exposure to nephrotoxic drugs
(OR 1.66; 95% CI 1.01–2.91; p = 0.04), MODS (OR 2.68;
95% CI 1.43–5.01; p = 0.002) and coagulopathy (OR 1.89;
95% CI 1.05–3.38, p = 0.03).
The median length of stay in PICU resulted longer in
AKI as compared with non-AKI cases (8 [IQR 3–16] vs.
4 days [IQR 2–8]; p < 0.001). Thirty-one (38%) out of 82
patients with stage III AKI required dialysis during their
stay in the ICU. Twenty of these survived at ICU dis-
charge; in 13 patients estimated glomerular filtration rate
Incidence of AKI in Pediatric ICU
1,384 patients
admitted to PICU
811
patients included
in the study
589 non-AKI 222 AKI
(73%) (27%)
87 stage I 53 stage II 82 stage III
(39%) (24%) (37%)
resulted >80 mL/min/1.73 m2 at ICU discharge, whereas
7 patients still showed impairment in renal function, with
subsequent need for chronic dialysis in 2 cases. Renal
functions were normal at discharge in all patients with
stage I and II AKI, whereas 6 out of 51 children with stage
III AKI not requiring dialysis, still exhibited an impaired
renal function at PICU discharge. Crude mortality rate in
the overall cohort of patients with AKI resulted tenfold
higher as compared with the non-AKI counterpart (12.6
vs. 1.2%, p < 0.001; Fig. 2): 5 deaths occurred in the AKI
stage I group (18%), 4 in the stage II group (14%) and 19
in the stage III group (68%).
Discussion
Our retrospective study has considered a large cohort
of paediatric patients and showed that AKI occurred in
about one third of critically ill children after admission to
PICU. In this setting, AKI resulted as a strong surrogate
marker for illness severity and confirmed its association
with patient mortality.
Previous studies reported a considerable variation in
the incidence of AKI among children as a consequence of
different AKI definitions and staging, ICU settings and
coexisting comorbidities [11–14]. Since the adoption of
the KDIGO definition, the reported incidence of AKI in
critically ill children has ranged from 10 to 40% [13, 14].
In the recent large-cohort AWARE study, the incidence
rate of AKI was 26.9% [7], a figure corresponding to our
data. In our cohort, cardiac and oncologic diseases repre-
sented the most frequent diagnosis at admission in AKI
patients. This differs from other studies conducted in set-
tings where post-operative cardiac patients are not ad-
mitted to PICU, but is in line with that reported in a ret-
130.241.16.16 - 8/6/2019 12:40:15 PM
Blood Purif 3
DOI: 10.1159/000502081
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Table 1. Patient demographic and clinical characteristics of included cases at admission and during ICU stay

Variable AKI, n (%) Non AKI, n (%) p value

Number 222 (27.4) 589 (73,6)

Gender, male 127 (57.2) 337 (57.2) 1
@PICU admission
Age, months, median (IQR) 5 (0–67) 1 (0–41) <0.001
Body weight, g, median (IQR) 5,000 (3,300–17,862) 3,825 (2,973–12,100) 0.004
PIM3 score, median (IQR) 0.025 (0.093–0.066) 0.017 (0.007–0.346) <0.001
Diagnosis
Respiratory 37 (16.8) 195 (33.2) <0.001
Shock 6 (2.7) 4 (0.7)
Cardiac 85 (38.6) 178 (30.3)
Sepsis 21 (9.5) 20 (3.4)
Trauma 5 (2.3) 17 (2.9)
Postoperative 24 (11) 94 (16)
Other 42 (19.1) 79 (13.5)
Serum creatinine, μmol/L, median (IQR) 52 (31–88) 41 (25–62) <0.001
Comorbidities ≥1, median (IQR) 127 (57.2) 258 (43.8) 0.001
During ICU course
Inotropes
0 89 (41.2) 471 (81.5) <0.001
1 59 (27.3) 75 (13)
2 43 (19.9) 29 (5)
3 17 (7.9) 1 (0.2)
4 8 (3.7) 2 (0.3)
Diuretics 176/213 (82.6) 284/556 (51.1) <0.001
NSAIDs 36/212 (17) 65/557 (11.7) 0.051
Nephrotoxic drugs 148/215 (68.8) 263/566 (46.5) <0.001
ICCM 50/181 (27.6) 92/497 (18.5) 0.023
Hypotension 123/213 (57.7) 167/549 (30.4) <0.001
MODS 140/202 (69.3) 126/498 (25.3) <0.001
Coagulopathy 117/222 (52.7) 147/589 (25) <0.001
PLTs <50,000/mm3 61/222 (27.5) 28/589 (4.8) <0.001
Fluid overload, % (IQR) 3 (0–8) 0.6 (0–4) <0.001
Lenght of stay, days 8 (3–16) 4 (2–8) <0.001
Mortality, median (IQR) 28/222 (12.6) 7/589 (1.2) <0.001

ICU, intensive care unit; AKI, acute kidney injury; PICU, paediatric ICU; PIM 3, pediatric index of mortality 3; NSAIDs, nonsteroi-
dal anti-inflammatory drugs; ICCM, iodine-containing contrast media; MODS, multi-organ dysfunction syndrome; PLTs, platelet
count.

rospective examination of clinical data conducted over a
20-year period, which underlines how haematologic and
oncologic diagnosis are more frequently associated with
the development of AKI in recent years [15].
Consistent data in adult case-series found an associa-
tion between AKI staging and risk of death [1–3]. Never-
theless, even mild forms of AKI have an impact on mor-
bidity and mortality in critically ill patients [16]. This un-
derlines the importance of an early identification of
patients at risk to promptly set up strategies and thera-
peutic interventions aimed at preventing development
and progression of AKI.
In our study, we found a series of risk factors indepen-
dently associated with AKI. MODS and coagulopathy are
related with the severity of the disease and have been pre-
viously found as strong predictors of AKI in adult studies
[17, 18], and in 2 cohorts of children [9, 19].
Data from the prospective observational FINNAKI
study suggest that hypotensive episodes are associated
with the progression of AKI in critically ill adults [20]. A
Colombian retrospective study of paediatric patients ad-
mitted to a tertiary PICU found that the need of vasopres-
sor support was independently associated with the devel-
opment of AKI [19]. Similarly, in our study, the risk of
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4 Blood Purif De Zan/Amigoni/Pozzato/Pettenazzo/

DOI: 10.1159/000502081 Murer/Vidal
Göteborgs Universitet
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Table 2. Results of bivariate and multivariate logistic regression analysis of risk factors for AKI

Bivariate analysis Multivariate analysis

OR 95% CI p value OR 95% CI p value

Gender, male 1 0.73–1.37 1

Age >2 months 1.87 1.37–2.57 <0.001 2.43 1.03–7.87 0.05
Body weight >4,000 g 1.60 1.16–2.21 0.004 0.88 0.35–2.20 0.79
PIM3 >0.0187 1.61 1.14–2.26 0.006 1.19 0.71–1.99 0.50
Serum creatinine >44 μmol/L 1.67 1.19–2.34 <0.001 2.23 1.26–3.94 0.006
Comorbidities >1 1.71 1.26–2.34 0.001 1.84 1.03–3.30 0.04
Inotropes >1 6.28 4.46–8.85 <0.001 2.56 1.23–5.35 0.012
Diuretics 4.56 3.08–6.74 <0.001 2.78 1.49–5.19 0.001
NSAIDs 1.54 0.99–2.41 0.051 0.78 0.39–1.56 0.48
Nephrotoxic drugs 2.54 1.82–3.55 <0.001 1.66 1.01–2.91 0.04
ICCM 1.68 1.13–2.50 0.023 0.93 0.51–1.71 0.83
Hypotension 3.13 2.25–3.34 <0.001 0.63 0.30–1.33 0.23
MODS 6.67 4.65–9.56 <0.001 2.68 1.43–5.01 0.002
Coagulopathy 3.35 2.43–4.63 <0.001 1.89 1.05–3.38 0.03
PLTs <50,000 7.59 4.69–12.27 <0.001 1.59 0.70–3.63 0.27
Fluid overload >2% 1.63 1.18–2.25 <0.001 1.64 0.94–2.85 0.08

AKI, acute kidney injury; PIM3, pediatric index of mortality 3; NSAIDs, nonsteroidal anti-inflammatory drugs; ICCM, iodine-containing
contrast media; MODS, multi-organ dysfunction syndrome; PLTs, platelet count.

AKI was positively associated with the number of inotro-

1.0
pes, a potential surrogate marker for both hypotension
and disease severity.
Findings from the international AWAKEN study
showed that 606 (30%) out of 2,162 infants had AKI, a
0.8 percentage that is similar to that found by both the
AWARE and our study [21]. The authors found similar
epidemiology and effects of AKI in the overall cohort of
neonates as compared with paediatric and adult patients;
Cumulative survival

0.6
however, incidence rates varied significantly by gestation-
al age groups, ranging from 48% in extremely low gesta-
tional age newborns to 37% in neonates ≥36 weeks. This
0.4 last finding differs from what we have found in our study
cohort, where 18% of infants resulted to have AKI. The
lower incidence of AKI in our neonatal population might
0.2
be due to a selection bias depending on specific PICU ad-
mission criteria. A study from Taiwan also found that AKI
was a very common event (56%) in extremely low-birth-
weight infants and was associated with a lower gestation-
0 al age, high-frequency ventilation support, the presence of
patent ductus arteriosus and inotropic agent use [22]. In
0 20 40 60 80 100
our study, age >2 months resulted an independent risk
Length of ICU stay, days
factor of AKI. Our specific PICU population might bias
this finding, as only children with a body weight >1,500 g
Fig. 2. Kaplan-Meier survival curves for AKI (dotted line) and and/or a gestational age >32 weeks are admitted.
non-AKI (continuous line) patients. Comparison by log-rank test Exposure to nephrotoxic medication, including iodin-
results in a p value < 0.001. ICU, intensive care unit.
ated contrast, nonsteroidal anti-inflammatory drugs,
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Incidence of AKI in Pediatric ICU Blood Purif 5

DOI: 10.1159/000502081
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aminoglycosides and glycopeptides, is among the most
common causes of AKI in hospitalized patients. Their use
should be carefully monitored especially in critically ill
children with major comorbidities. The NINJA project
piloted in 2011 at the Cincinnati Children’s Hospital
Medical Center and now in use at >15 children’s hospitals
throughout the United States has provided a translatable
framework for near real-time risk stratification and pre-
vention of AKI in the hospital setting [23]. Under this
paradigm, a hospital pharmacist who rounds with the in-
patient care team receives a daily report (via automated
data mining of the hospital’s electronic health record) of
the patients receiving >3 nephrotoxic medications con-
currently or at least 3 consecutive days of intravenous
aminoglycoside therapy. This information is then utilized
during team rounds, so that daily monitoring of serum
creatinine levels can be optimized and nephrotoxin expo-
sure minimized as clinically appropriate.
In our cohort, all patients with stage I and II AKI were
discharged from ICU with normal serum creatinine val-
ues. On the contrary, 13 out of 82 patients with stage III
AKI still exhibited impaired renal function at discharge,
with eGFR lower than 80 mL/min/1.73 m2.
Recent epidemiological and preclinical mechanistic
studies provide strong evidence that AKI and chronic
kidney disease (CKD) form an interconnected syndrome
[24]. Injured kidneys undergo a coordinated reparative
process with an engagement of multiple cell types after
injury; however, maladaptation to the injury subjects kid-
neys to a vicious cycle of fibrogenesis and nephron loss.
Coca et al. [25] demonstrated that the risk of CKD or
ESRD increases in a graded fashion with the severity of
AKI, remaining still significant in mild AKI as compared
with non-AKI cases (adjusted HR 2.0, 95% CI 1.4–2.8).
We recognize that our study has some limitations.
First, it is a single tertiary-centre study, albeit we have
screened a heterogeneous group of critically ill children
and our results could be applied to other PICUs. Second,
it is retrospective in nature and therefore, presents limita-
tions related to the non-prospective data collection. Even
if the development of AKI was established following new
KDIGO guidelines, in some cases, it was not possible to
regain some missing data.
In conclusion, the incidence of AKI in critically ill chil-
dren is high, with an associated increased length of stay
and risk of mortality. About one third of children experi-
enced a severe and 40% a mild form of AKI, which is also
associated with subsequent risk of CKD and should be
promptly identified. In the PICU setting, risk factors of
AKI are multiple, associated with both potentially modi-
fiable factors and illness severity. Preventive strategies
should be adopted after admission to PICU especially in
children with cardiac, oncologic diseases, and in those
having comorbidities.
Statement of Ethics
Informed consent for data collection and description was ob-
tained from the patient’s parents.
Disclosure Statement
The authors declare that they have no conflicts of interest to
disclose.
Author Contributions
F.D.Z., A.A. and E.V. collected data, analyzed data and
­ rafted the paper. R.P., A.P. and L.M. collected data and draft-
d
ed  the paper. All authors read and approved the final manu-
script.

References
 1 Uchino S, Kellum JA, Bellomo R, Doig GS,
Morimatsu H, Morgera S, et al.; Beginning and
Ending Supportive Therapy for the Kidney
(BEST Kidney) Investigators. Acute renal fail-  
ure in critically ill patients: a multinational, mul-
ticenter study. JAMA. 2005 Aug;294(7):813–8.
  2 Hoste EA, Bagshaw SM, Bellomo R, Cely CM,
Colman R, Cruz DN, et al. Epidemiology of
acute kidney injury in critically ill patients: the
multinational AKI-EPI study. Intensive Care
Med. 2015 Aug;41(8):1411–23.
  3 Chertow GM, Burdick E, Honour M, Bonven-  
tre JV, Bates DW. Acute kidney injury, mor-
tality, length of stay, and costs in hospitalized
patients. J Am Soc Nephrol. 2005 Nov;16(11):
3365–70.
4 Bellomo R, Ronco C, Kellum JA, Mehta RL,  
Palevsky P; Acute Dialysis Quality Initiative
workgroup. Acute renal failure - definition,  
outcome measures, animal models, fluid ther-
apy and information technology needs: the
Second International Consensus Conference
of the Acute Dialysis Quality Initiative (ADQI)
Group. Crit Care. 2004 Aug;8(4):R204–12.
5 Akcan-Arikan A, Zappitelli M, Loftis LL,
Washburn KK, Jefferson LS, Goldstein SL.
Modified RIFLE criteria in critically ill chil-
dren with acute kidney injury. Kidney Int.
2007 May;71(10):1028–35.
6 Section 2: AKI Definition. Kidney Int Suppl
(2011). 2012 Mar;2(1):19–36.
7 Basu RK, Kaddourah A, Goldstein SL, Akcan-
Arikan A, Arnold M, Cruz C, et al.; AWARE
Study Investigators. Assessment of a renal an-
gina index for prediction of severe acute kid-
ney injury in critically ill children: a multicen-
tre, multinational, prospective observational
study. Lancet Child Adolesc Health. 2018 Feb;
2(2):112–20.
130.241.16.16 - 8/6/2019 12:40:15 PM

6 Blood Purif De Zan/Amigoni/Pozzato/Pettenazzo/

DOI: 10.1159/000502081 Murer/Vidal
Göteborgs Universitet
Downloaded by:
  8 Kaddourah A, Basu RK, Bagshaw SM, Gold-
stein SL; AWARE Investigators. Epidemiolo-
gy of Acute Kidney Injury in Critically Ill
Children and Young Adults. N Engl J Med.
2017 Jan;376(1):11–20.
 9 Bailey D, Phan V, Litalien C, Ducruet T,
Mérouani A, Lacroix J, et al. Risk factors of
acute renal failure in critically ill children: A
prospective descriptive epidemiological
study. Pediatr Crit Care Med. 2007 Jan; 8(1):
29–35.
10 Proulx F, Fayon M, Farrell CA, Lacroix J,
Gauthier M. Epidemiology of sepsis and mul-
tiple organ dysfunction syndrome in chil-
dren. Chest. 1996 Apr;109(4):1033–7.
11 Schneider J, Khemani R, Grushkin C, Bart R.
Serum creatinine as stratified in the RIFLE
score for acute kidney injury is associated
with mortality and length of stay for children
in the pediatric intensive care unit. Crit Care
Med. 2010 Mar;38(3):933–9.
12 Sutherland SM, Ji J, Sheikhi FH, Widen E,
Tian L, Alexander SR, et al. AKI in hospital-
ized children: epidemiology and clinical as-
sociations in a national cohort. Clin J Am Soc
Nephrol. 2013 Oct;8(10):1661–9.
13 Selewski DT, Cornell TT, Heung M, Troost
JP, Ehrmann BJ, Lombel RM, et al. Validation
of the KDIGO acute kidney injury criteria in
a pediatric critical care population. Intensive
Care Med. 2014 Oct;40(10):1481–8.
Incidence of AKI in Pediatric ICU
14 Sutherland SM, Byrnes JJ, Kothari M, Long-
hurst CA, Dutta S, Garcia P, et al. AKI in hos-
pitalized children: comparing the pRIFLE,
AKIN, and KDIGO definitions. Clin J Am Soc
Nephrol. 2015 Apr;10(4):554–61.
15 Williams DM, Sreedhar SS, Mickell JJ, Chan
JC. Acute kidney failure: a pediatric experi-
ence over 20 years. Arch Pediatr Adolesc
Med. 2002 Sep;156(9):893–900.
16 Sanchez-Pinto LN, Goldstein SL, Schneider
JB, Khemani RG. Association between pro-
gression and improvement of acute kidney in-
jury and mortality in critically ill children. Pe-
diatr Crit Care Med. 2015 Oct;16(8):703–10.
17 Cartin-Ceba R, Kashiouris M, Plataki M, Kor
DJ, Gajic O, Casey ET. Risk factors for devel-
opment of acute kidney injury in critically ill
patients: a systematic review and meta-analy-
sis of observational studies. Crit Care Res
Pract. 2012;2012:691013.
18 Kane-Gill SL, Sileanu FE, Murugan R, Triet-
ley GS, Handler SM, Kellum JA. Risk factors
for acute kidney injury in older adults with
critical illness: a retrospective cohort study.
Am J Kidney Dis. 2015 Jun;65(6):860–9.
19 Serna-Higuita LM, Nieto-Ríos JF, Contreras-
Saldarriaga JE, Escobar-Cataño JF, Gómez-
Ramírez LA, Montoya-Giraldo JD, et al. Risk
factors for acute kidney injury in a pediatric
intensive care unit: a retrospective cohort
study. Medwave. 2017 Apr;17(3):e6940.
Blood Purif
DOI: 10.1159/000502081
20 Poukkanen M, Wilkman E, Vaara ST, Pettilä
V, Kaukonen KM, Korhonen AM, et al.;
FINNAKI Study Group. Hemodynamic vari-
ables and progression of acute kidney injury
in critically ill patients with severe sepsis: data
from the prospective observational FINNAKI
study. Crit Care. 2013 Dec;17(6):R295.
21 Jetton JG, Boohaker LJ, Sethi SK, Wazir S, Ro-
hatgi S, Soranno DE, et al.; Neonatal Kidney
Collaborative (NKC). Incidence and out-
comes of neonatal acute kidney injury
(AWAKEN): a multicentre, multinational,
observational cohort study. Lancet Child Ad-
olesc Health. 2017 Nov;1(3):184–94.
22 Lee CC, Chan OW, Lai MY, Hsu KH, Wu TW,
Lim WH, et al. Incidence and outcomes of acute
kidney injury in extremely-low-birth-weight
infants. PLoS One. 2017 Nov;12(11):e0187764.
23 Goldstein SL, Mottes T, Simpson K, Barclay
C, Muething S, Haslam DB, et al. A sustained
quality improvement program reduces neph-
rotoxic medication-associated acute kidney
injury. Kidney Int. 2016 Jul;90(1):212–21.
24 Chawla LS, Eggers PW, Star RA, Kimmel PL.
Acute kidney injury and chronic kidney dis-
ease as interconnected syndromes. N Engl J
Med. 2014 Jul;371(1):58–66.
25 Coca SG, Singanamala S, Parikh CR. Chronic
kidney disease after acute kidney injury: a sys-
tematic review and meta-analysis. Kidney Int.
2012 Mar;81(5):442–8.
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