Neurocrit Care (2011) 14:377–381
DOI 10.1007/s12028-011-9511-1
ORIGINAL ARTICLE
Acute Kidney Injury in Patients with Severe Traumatic Brain
Injury: Implementation of the Acute Kidney Injury Network
Stage System
Ning Li • Wei-Guo Zhao • Wei-Feng Zhang
Published online: 5 February 2011
Ó Springer Science+Business Media, LLC 2011
Abstract
Background There is limited information on the inci-
dence and effect of acute kidney injury (AKI) in patients
with severe traumatic brain injury (TBI), although AKI
may affect outcome. Recently, acute kidney injury network
(AKIN) classification has been widely accepted as a con-
sensus definition for AKI. The aim of this study is to
estimate the frequency and level of severity of AKI in
patients with severe TBI by using AKIN criteria and to
study whether AKI affects outcome.
Methods The authors retrospectively identified a total of
136 patients with severe TBI admitted to the neurosurgical
center during a 3-year period ending May 2010. Demo-
graphic data, severity of TBI, serum creatinine, urine
output, outcome at 6 month, and death were collected.
Renal function was assessed by using AKIN criteria.
Results Thirty-one patients (23%) were classified as
having AKI by using AKIN criteria during their hospital-
ization. Of them, 21 patients (68%) were stratified as stage
1, 7 patients (22%) as stage 2, and 3 patients (10%) as stage
3. Patients who developed AKI were older, had lower
Glasgow coma scale at admission, and had higher level of
admission serum creatinine and blood urea nitrogen.
Patients with AKI had higher mortality and worse outcome
when compared with patients with normal renal function.
N. Li  W.-G. Zhao (&)  W.-F. Zhang
Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao
Tong University, Shanghai 200025, People’s Republic of China
e-mail: rjneurosurgery@yahoo.com.cn
N. Li
e-mail: lining930@yahoo.com
W.-F. Zhang
e-mail: zhangwf198@163.com
Furthermore, patients with mild renal dysfunction (stage 1
AKI) are also found having increased mortality and worse
long-term outcome, compared with patients without renal
dysfunction.
Conclusion It is demonstrated using the newly defined
AKIN criteria for renal dysfunction that AKI is a relatively
common feature in patients with severe TBI, and even
seemingly insignificant decrease in renal function may be
associated with worse outcome. This study highlights the
importance of close surveillance of renal function and
stresses the value of renal hygiene in the severe TBI
population.
Keywords Acute kidney injury  Renal dysfunction 
Traumatic brain injury  Outcome 
Acute kidney injury network (AKIN)
Introduction
Traumatic brain injury (TBI) remains a leading cause of
death and persistent neurocognitive impairment in civilian
and military casualties. With improvement in neurocritical
care and treatment, focus has gradually shifted to the role of
non-neurological complications on outcome after TBI. In
fact, these complications can rival the frequency of mor-
bidity and mortality from neurological complications.
Recent studies of patients with brain trauma and aneurysmal
subarachnoid hemorrhage (aSAH) have demonstrated that
nearly 80% of these patients develop dysfunction of at least
one non-neurological organ system [1, 2]. Not surprisingly,
non-neurological organ dysfunction correlates with the
severity of neurological impairment. Among non-neuro-
logical complications, cardiopulmonary complications and
hematologic abnormalities have been explored at length;
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however, little has been done to evaluate the effect of renal
dysfunction after TBI.
There is limited information on the incidence of renal
dysfunction in patients with TBI. A few studies have
broadly investigated non-neurological complications in
TBI, and reported a low incidence of ‘‘renal failure’’ in TBI
patients, about 0.45–1.9% [3–7]. However, these studies
used sequential organ failure assessment (SOFA) [8] or
multiple organ dysfunction score (MODS) [9] to identify
the presence of renal dysfunction and classify its severity.
These classifications have not been validated for acute
kidney injury (AKI) and use serum creatinine (sCr) or
blood urea nitrogen cutoffs to classify renal function,
which likely only identify patients with severe renal dys-
function. Recently, it has been recognized that early,
modest changes in renal function may affect patient’s
outcome [10, 11]. Therefore, early recognition of subtle
renal changes and stratification of patients with renal dys-
function may allow identification of patients at risk for
significant morbidity and mortality.
The acute kidney injury network (AKIN), a panel of
international experts in nephrology and critical care med-
icine, has proposed a new diagnostic staging system for
AKI (Table 1) [12]. This system has several advantages. It
appears sensitive to the early changes in kidney function,
and allows monitoring of progression of AKI. The AKIN
criteria have been validated in medical intensive care unit
patients, showing that AKIN categorization predicts clini-
cal outcome and therefore may improve prognostic
information and treatment [12–14]; however, the clinical
outcome of TBI patients using AKIN criteria stratifying
renal dysfunction has not been identified.
The primary aim of this study was to provide a more
reliable estimate of the incidence of AKI as classified by
AKIN criteria in patients with severe TBI. In addition, the
authors investigated the risk factors for AKI and associa-
tion between AKI (especially the mild renal dysfunction)
and outcome. And to the author’s knowledge, this is the
first study focusing on AKI as defined by the AKIN criteria
in the TBI population.
Table 1 AKIN staging criteria [12]
Stage Serum creatinine criteria
1 Increase serum creatinine C0.3 mg/dl or > 1.5- to 2-fold from baseline
2 Increase in serum creatinine >2- to 3-fold from baseline
3 Increase in serum creatinine C4 mg/dl with
an acute increase of at least 0.5 mg/dl or >3-fold from baseline
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Neurocrit Care (2011) 14:377–381
Patients and Methods
The Rui Jin Hospital Ethics Committees approved this
study and waived the need for informed consent. This
retrospective study reviewed all severe TBI patients
(Glasgow coma scale of 8 or less at admission) admitted to
the neurosurgical ICU (NICU) at the Shanghai JiaoTong
University, Rui Jin Hospital, Department of Neurosurgery
during a 3-year period from January 2007 to May 2010.
Exclusion criteria included: (1) patient with age less than
16; (2) patient whose hospital stay less than 48 h; (3)
patient with pre-existing kidney disease; or (4) patient with
co-existing severe extracerebral injury.
Data obtained included demographics, type of TBI
identified by CT scanning, Glasgow coma scale (GCS),
admission vital signs, daily pupil reactivity, surgical
interventions, and hospital death. In addition, hourly urine
output was recorded while in NICU and serum creatinine
level was measured every 48 h to identify and classify
patients with renal dysfunction based on AKIN criteria
(Table 1). Under the AKIN criteria, diagnosis of AKI is
categorized as an abrupt (within 48 h) reduction in kidney
function defined as an absolute increase in serum creatinine
>0.3 mg/dl, a percentage increase in serum creatinine
>50%, or a reduction in urine output (UO) <0.5 ml/kg/h
for >6 h. AKI patients were classified into classes 1–3,
according to the highest class reached during their hospital
stay. Outcome was assessed at 6 months using the Glasgow
outcome scale (GOS). Outcome was dichotomized into
favorable outcome (GOS40 –50 : moderate disability, good
outcome) and poor outcome (GOS10 –30 : death, vegetative
state and severe disability).
Continuous variables were expressed as means ± stan-
dard deviations for normal distributed variables, and
categorical variables were expressed as absolute and rela-
tive frequencies. Pearson chi-square was used to analyze
categorical data, t-test were used for variables with normal
distribution. A P-value of <0.05 was considered statistical
significant. Analysis was performed with the statistical
software package SPSS 15.0 for Windows.
Urine output criteria
Less than 0.5 ml/kg/h for more than 6 h
Less than 0.5 ml/kg/h for more than 12 h
Less than 0.3 ml/kg/h for 24 h anuria for 12 h
Neurocrit Care (2011) 14:377–381 379

Result patients required renal replacement therapy. Of 31 patients

A total of 151 consecutive patients with severe TBI were
admitted to the neurosurgical center during the study per-
iod. Of those, 15 patients were excluded according to the
exclusion criteria, leaving 136 patients evaluated in this
study. Using AKIN criteria, there were 31 patients identi-
fied with AKI with an incidence of 23%. Of 31 AKI
patients, 29 patients (94%) developed AKI in the first week
after TBI.
Patients characteristics, outcomes, and comparison
between AKI and no AKI group were summarized in
Table 2. Patients with AKI were older (49.9 ± 14.6 years)
than patients with normal renal function (42.9 ± 14.9 years,
P = 0.0127). The severity of TBI (assessed by GCS) was
higher in AKI group (5.6 ± 1.5), compared with no AKI
group (6.7 ± 1.4, P = 0.0005). The incidence of tentorial
herniation was also found higher in AKI group (65% vs.
41%, P = 0.0207). Patients with AKI had higher level of
admission sCr (1.21 ± 0.44 mg/dl vs. 0.91 ± 0.25 mg/dl,
P <0.0001) and admission BuN (6.66 ± 2.75 vs. 5.64 ±
1.96, P = 0.0303). No differences in gender, admission
glucose level, admission systolic blood pressure (SBP), and
mean blood pressure (MBP) were found between patients
with and without AKI.
Of 31 patients meeting AKIN criteria, 21 patients (68%)
were stratified as stage 1, 7 patients (22%) as stage 2, and 3
patients (10%) as stage 3. There was no significant dif-
ference found between stage 1 group and stage 2–3 groups,
as shown in Table 3.
In term of outcome, all AKI patients that survived
returned to normal level of creatinine at discharge, and no
meeting AKIN criteria, there were 17 deaths (55%), com-
pared with 11 deaths (11%) in the group of normal renal
function, (P <0.0001). Patients with AKI had a higher
incidence of poor outcome (74%) when compared with
patients without renal dysfunction (32%, P <0.0001).
Furthermore, when stratified by AKIN staging, patients
with stage 1 AKI trended to have higher mortality (48% vs.
11%, P <0.0001) and higher incidence of poor outcome
(67% vs. 32%, P = 0.0031) than patients without renal
dysfunction. Although mortality and incidence of poor
outcome tended to increase with severity of AKI, the dif-
ferences had no statistical significance.
Discussion
Nowadays, the consensus definition for AKI is not just
acute renal failure; it encompasses the entire spectrum
from severe to mild conditions, recognizing that even
small changes in renal function may also affect patients’
short- and possibly long-term outcomes [15]. Recently,
the AKIN group has proposed a new diagnostic staging
system for AKI that may better identify patients with a
clinically significant decrease in renal function [12]. This
new staging system precisely classifies renal dysfunction
according to the degree of impairment. AKIN criteria,
which have several advantages including providing diag-
nostic definition for stage 1 AKI when kidney injury can
still be prevented, have been tested in clinical practice
and widely been accepted as consensus definition for AKI
[12–14].

Table 2 Population characteristics

Characteristics Total (n = 136) No AKI (n = 105, 77%) AKI P (n = 31, 23%) P

Gender, n (%)
Male 104 (77) 79 (75) 25 (81) 0.533
Female 32 (23) 26 (25) 6 (19)
Age (years) 44.5 ± 15.1 42.9 ± 14.9 49.9 ± 14.6 0.0127
Admission GCS 6.5 ± 1.5 6.7 ± 1.4 5.6 ± 1.5 0.0005
Tentorial herniation, n (%) 63 (46) 43 (41) 20 (65) 0.0207
Admission SBP 139.6 ± 30.5 136.8 ± 23.1 144.8 ± 36.1 0.1250
Admission MBP 100.6 ± 22.8 98.1 ± 15.2 103 ± 24.1 0.1479
Admission glucose (mmol/l) 9.2 ± 3.5 8.9 ± 3.6 9.8 ± 3.2 0.0959
Admission sCr (mg/dl) 0.97 ± 0.32 0.91 ± 0.25 1.21 ± 0.44 <0.0001
Admission BuN (umol/l) 5.87 ± 2.19 5.64 ± 1.96 6.66 ± 2.75 0.0303
Outcome
Hospital mortality, n (%) 28 (21) 11 (11) 17 (55) <0.0001
6 month GOS, n (%)
GOS40 –50 79 (58) 71 (68) 8 (26) <0.0001
GOS10 –30 57 (42) 34 (32) 23 (74)

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Table 3 AKI patient’s

Characteristics Stage 1 (n = 21, 68%) Stage 2–3 (n = 10, 32%) P
characteristics
Gender, n (%)
Male 17 (81) 8 (80) 0.672
Female 4 (19) 2 (20)
Age (years) 51.5 ± 14.5 46.2 ± 14.9 0.197
Admission GCS 5.7 ± 1.5 5.8 ± 1.3 0.476
Tentorial herniation, n (%) 13 (62) 7 (70) 0.659
Admission SBP 143.1 ± 37.8 148.7 ± 34.3 0.339
Admission MBP 102.0 ± 25.9 104.3 ± 20.9 0.414
Admission glucose (mmol/l) 9.8 ± 2.9 9.9 ± 3.9 0.491
Admission sCr (mg/dl) 1.11 ± 0.39 1.33 ± 0.59 0.189
Admission BuN (umol/l) 6.16 ± 2.92 7.71 ± 2.10 0.053
Outcome
Hospital mortality, n (%) 10 (48) 7 (70) 0.433
6 month GOS, n (%)
GOS40 –50 7 (33) 1 (10) 0.343
GOS10 –30 14 (67) 9 (90)

In recent studies, AKI was found to frequently occur in
critically ill patients admitted to SICU, with an incidence
of 29.8–43.2% as defined by AKIN criteria [13, 16]. In this
study, defined by AKIN criteria, patients with severe TBI
have a higher AKI incidence of 23%, compared with pre-
vious studies using traditional criteria [3–7]. The AKIN
criteria, by nature of its set threshold, identify more renal
dysfunction than the previously used criteria with the
higher threshold. It is not surprising that the AKIN criteria
effectively increase the sensitivity of identifying AKI. The
natural follow-up question is to address whether this new
system of renal dysfunction stratification carries any
medical significance. Recently, Zacharia reported an inci-
dence of AKI in 23% of patients with aneurysmal SAH
[17], and Moore reported an incidence of AKI in 9% of
TBI patients with GCS less than 13 [18]. Importantly, these
AKI patients had an increased risk of MOF and death. In
this study, patients meeting criteria for AKI have an
increased incidence of death and worse outcome, compared
with patients with normal renal function. More impor-
tantly, increased mortality and worse outcome are found in
patients with just stage 1 AKI, compared with no AKI
patients. Patients with stage 1 AKI have only a small
decrease in renal function that would not be captured by
previously used criteria and may not draw much concern
clinically. The finding of this study indicates the impact of
minor changes in renal function in patients with severe
TBI, and highlights the need of capture these patients in
future studies.
Although this study suggests that stratification of severe
TBI patients using AKIN criteria may be beneficial, it is
recognized that there are several limitations in this study,
including its retrospective nature and the data reflect the
experience of single institution. The retrospective analysis
of prospectively collected data has many of the methodo-
logical shortcomings of purely retrospective studies and it
remains difficult to accurately assess causality between the
development of AKI and outcome of TBI. Whether AKI is
merely a marker of disease severity or an independent pre-
dictor of poor outcome can be elucidated in the future
research with a prospective design. Also given the retro-
spective nature of the analysis, the authors did not have
intracranial pressure monitoring data and pre-trauma infor-
mation in most patients, such as previous creatinine values
and whether patient had pre-existing disease in other organ
systems. Furthermore, what is also unknown is the risk of
severe TBI patients, meeting AKIN criteria, developing
chronic renal insufficiency well after the trauma hospital-
ization. There is debate in the literature regarding the
long-term effects on renal function after an episode of AKI
[19–21], especially in the patients with mild AKI.
Regardless, it is felt that the findings of this study are of
significant clinical interest. The observation that about 90%
of AKI occurs within first 7 days after severe brain injury,
and patients with older age, low admission GCS, occurrence
of transtentorial herniation, and high level of admission sCr
and BuN being at a greater risk of development of AKI
suggests the need to be particularly focused on the resus-
citation effects of this group of patients at early stage of
severe TBI. This study highlights the importance of early
recognition of renal risk and prompts clinician to practice
renal hygiene. That is, adequate hydration and renal pro-
tection strategies, and frequent screening of medication list
for potentially nephrotoxic drugs and dose adjustment for
those with renal impairment (especially the administration
of hyperosmolar therapy and nephrotoxic antibiotics).

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Furthermore, investigation of urinary and serum proteins
(e.g., NGAL) as early biomarker and predictor of acute
renal failure will be important in early detection of patients
at risk of renal dysfunction. And recent experimental study
reveals that some pharmacological interventions can
simultaneously protect brain and kidney and decrease the
incidence of AKI in neurotrauma. Erythropoietin and
carbamylated erythropoietin are two such treatments which
have been shown to protect brain and kidney by inhibition
of the inflammatory processes caused by brain injury [22].
Their potential for a similar dual effect in patients with TBI
is worthy of further investigation.
Conclusion
In this study, the authors demonstrated, using the newly
defined AKIN classification, that severe TBI patients are
frequently complicated by AKI, and even seemingly insig-
nificant decrease in renal function may affect outcome. Future
research, with a prospective design addressing etiology and
time course of AKI, is needed to help in the discussion of the
relationship between AKI and outcome in severe TBI
patients. Nevertheless, this study highlights the importance of
close surveillance of renal function and stresses the value of
renal hygiene in the severe TBI population.
Acknowledgment The authors would like to thank Yu Ting MD
(Abbott diagnostics division, China) for statistical advice.
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