Renal Failure

ISSN: 0886-022X (Print) 1525-6049 (Online) Journal homepage: http://www.tandfonline.com/loi/irnf20

Septic acute kidney injury in critically ill patients

– a single-center study on its incidence, clinical
characteristics, and outcome predictors

Hoi-Ping Shum, Harriet Hoi-Yan Kong, King-Chung Chan, Wing-Wa Yan & Tak
Mao Chan

To cite this article: Hoi-Ping Shum, Harriet Hoi-Yan Kong, King-Chung Chan, Wing-Wa Yan
& Tak Mao Chan (2016): Septic acute kidney injury in critically ill patients – a single-center
study on its incidence, clinical characteristics, and outcome predictors, Renal Failure, DOI:
10.3109/0886022X.2016.1157749

To link to this article: http://dx.doi.org/10.3109/0886022X.2016.1157749

Published online: 16 Mar 2016.

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 RENAL FAILURE, 2016
http://dx.doi.org/10.3109/0886022X.2016.1157749

CLINICAL STUDY

Septic acute kidney injury in critically ill patients – a single-center study on

its incidence, clinical characteristics, and outcome predictors
Hoi-Ping Shuma, Harriet Hoi-Yan Konga, King-Chung Chanb, Wing-Wa Yana and Tak Mao Chanc
a
Department of Intensive Care, Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China; bDepartment of Anesthesia and
Intensive Care, Tuen Mun Hospital, Tuen Mun, Hong Kong SAR, China, cDepartment of Medicine, the University of Hong Kong, Queen
Mary Hospital, Pokfulam, Hong Kong SAR, China

ABSTRACT ARTICLE HISTORY

Purpose The objective of this study is to examine the incidence, clinical characteristics, and out- Received 4 October 2015
come (90-day mortality) of critically ill Chinese patients with septic AKI. Methods Patients admit- Revised 27 January 2016
ted to the ICU of a regional hospital from 1 January 2011 to 31 December 2013 were included, Accepted 17 February 2016
Downloaded by [University of Sydney Library] at 23:55 21 March 2016

excluding those on chronic renal replacement therapy. AKI was defined using KDIGO criteria. Published online 11 March
2016
Patients were followed till 90 days from ICU admission or death, whichever occurred earlier.
Demographics, diagnosis, clinical characteristics, and outcome were analyzed. Results In total, KEYWORDS
3687 patients were included and 54.7% patients developed AKI. Sepsis was the most common Acute kidney injury;
cause of AKI (49.2%). Compared to those without AKI, AKI patients had higher disease severity, epidemiology; intensive
more physiological and biochemical disturbance, and carried significant co-morbidities. Ninety-day care; prognosis; sepsis
mortality increased with severity of AKI (16.7, 27.5, and 48.3% for KDIGO stage 1, 2, and 3 AKI,
p < 0.001). Full renal recovery was achieved in 71.6% of AKI patients. Compared with non-septic
AKI, septic AKI was associated with higher disease severity and required more aggressive support.
Non-recovery of renal function occurred in 2.5% of patients with septic AKI, compared with 6.4%
in non-septic AKI (p < 0.001). Cox regression analysis showed that age, emergency ICU admission,
post-operative cases, admission diagnosis, etiology of AKI, disease severity score, mechanical venti-
lation, vasopressor support, and blood parameters (like albumin, potassium and pH) independently
predicted 90-day mortality. Conclusions AKI, especially septic AKI is common in critically ill
Chinese patients and is associated with poor patient outcome. Etiology of AKI has a significant
impact on 90-day mortality and may affect renal outcome.

Introduction contributing factor to AKI in critically ill.6 Patients with

Acute kidney injury (AKI) is a common clinical problem
in critically ill patients and is associated with increased
mortality and morbidity.1 The lack of consensus on the
definition of AKI before 2004 has resulted in a broad
range of estimated incidence in the intensive care unit
(ICU). The Acute Dialysis Quality Initiative (ADQI) pub-
lished the Risk, Injury, Failure, Loss, and End-Stage
(RIFLE) criteria in 2004 which defined AKI in terms of
changes in serum Cr from baseline and urine output.2
Subsequently, the Acute Kidney Injury Network (AKIN)
proposed a more sensitive guideline for the diagnosis of
AKI.3 The latest Kidney Disease Improving Global
Outcomes (KDIGO) definition is a combination of AKIN
and RIFLE.4 Study by Luo et al.5 showed that KDIGO
identified more patients with AKI than RIFLE or AKIN
classification system.
The etiology of AKI is often multifactorial. However,
sepsis has consistently been found to be a leading
septic AKI are generally sicker, with a higher disease
severity couple with greater abnormalities in acute physi-
ology when compared to patients with non-septic AKI.7
Moreover, septic AKI is independently associated with
higher mortality and longer hospital length of stay. Most
outcome data on septic AKI come from Caucasians. Data
among Chinese population are relatively sparse. Our
objective is to examine the incidence, clinical characteris-
tics and outcome (90-day mortality) of critically ill
Chinese patients with AKI, especially in those with sepsis.
Subjects and methods
This study was approved by the Hong Kong East Cluster
Ethics Committee. Written informed consent was waived.
It was a retrospective, single-centered, cohort study con-
ducted at the ICU of Pamela Youde Nethersole Eastern
Hospital, a 2300-bed acute care tertiary hospital. The ICU

CONTACT Dr Hoi-Ping Shum, MBBS, MRCP, FRCP, FHKAM (Medicine) shumhp@ha.org.hk Department of Intensive Care, Pamela Youde Nethersole
Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong SAR, China
ß 2016 Taylor & Francis
 2 H.-P. SHUM ET AL.
Table 1. KDIGO criteria to diagnose and grade the severity of AKI.
Classification Stage Serum creatinine criteria
KDIGO Definition: Increase in serum creatinine  26.5lmol/L
within 48 h or 50% within 7 days
1 Increased serum creatinine 26.5 lmol/L in 48 h,
or increase 1.5- to 1.9-fold from baseline
2 Increased serum creatinine 2.0- to 2.9-fold from baseline
3 Increased serum creatinine 3-fold from baseline, or increase in serum
creatinine to 353.6 lmol/L, or initiation of RRT irrespective of serum creatinine
is a 22-bed closed mixed medical-surgical unit with an
average admission of 1300 patients per year. Patients
electively or emergently admitted from 1 January 2011
to 31 December 2013 were recruited with the exclusion
of those receiving chronic renal replacement therapy
including hemodialysis, hemofiltration, or peritoneal dia-
lysis. Only the first ICU admission episode was analyzed
for recurrent ICU admission during the same hospitaliza-
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tion episode. Admissions involving the same patient in
different hospitalization episodes were treated inde-
pendently. Medical records were reviewed. Patients were
followed till 90 days from ICU admission or death, which-
ever occurred earlier. Demographics, diagnosis, clinical
characteristics, severity of kidney injury, and outcome
were recorded.
Definitions
Septic AKI was defined as the development and pro-
gression of sepsis associated AKI in severe sepsis
without other apparent cause.7–9 Severe sepsis was
defined according to the American College of Chest
Physician (ACCP)/Society of Critical Care (SCCM) crite-
ria,10 i.e. Systemic Inflammatory Response Syndrome
in the presence of suspected or known infection
which led to organ dysfunction. Cardiogenic AKI was
defined as AKI due to type I cardiorenal syndrome.11
Hypovolemia associated AKI was defined as AKI due
to volume depletion (clinical dehydration 6 hypoten-
sion) in the absence of other apparent cause of AKI.
Those defined as ‘‘others’’ included post-renal causes,
contrast induced AKI, glomerulonephritis, and other.
For patients with more than one potential causes of
AKI, the predominant cause was decided based on
clinical judgment.
We used KDIGO criteria to diagnose and grade the
severity of AKI (Table 1).4 Baseline renal function was
defined as the lowest known SCr value in the preceding
3 months before current ICU admission. It was estimated
by the Modification of Diet in Renal Disease (MDRD)
equation for those without the preceding value (assum-
ing a lower limit of normal baseline glomerular filtration
rate (GFR) of 75 mL/min).2,12 Chronic kidney disease
(CKD) was defined as CKD stage 3 or above.
Urine output criteria
<0.5 mL/kg/h for 6–12 h
<0.5 mL/kg/h for 12 h
<0.3 mL/kg/h for 24 h or anuria for 12 h
Primary outcome was 90-day mortality. Secondary
outcomes were ICU and hospital mortality, ICU and hos-
pital length of stay. Renal replacement therapy was
defined as continuous or intermittent renal replacement
therapy, which was started based on fluid, electrolyte,
and acid–base status and also the clinical progress.
Renal recovery at 90 days from ICU admission was eval-
uated. It was defined as full recovery if serum crea-
tinine 125% baseline, partial recovery if serum
creatinine >125% and 300% baseline, and non-recov-
ery if serum creatinine >300% baseline or required dia-
lysis support.2,13
Statistical analysis
Comparisons were performed between those (1) with
and without AKI, (2) with septic AKI and without AKI, (3)
septic and non-septic AKI. Results were expressed as
mean 6 standard deviation (SD) or as number of cases
and percentages as appropriate. Categorical variables
were compared using Pearson chi-square tests or
Fisher’s exact test as appropriate. Student t-test or
Mann–Whitney U test was used to compare continuous
variables. Cox regression analysis using forward stepwise
(Likelihood ratio) strategy was used to identify factors
associated with 90-day mortality in patients. Trend ana-
lysis was performed using Chi squared test for trend in
proportions. On conversion of continuous variables to
categorical variables, the appropriate cut-off values
were determined by the receiver operating characteris-
tic method. All the analyses were performed using the
Statistical Package for Social Sciences for Windows, ver-
sion 20 (SPSS Inc., Chicago, IL) and R statistical program
version 3.2 (R Foundation, http://www.r-project.org/).
Results
All patients
A total of 3809 patients were admitted into our ICU dur-
ing the study period from 1 January 2011 to 31
December 2013. One hundred and twenty two patients
(3.2%) were excluded because they were receiving
chronic renal replacement therapy before ICU admis-
sion. A total of 3687 patients were further analyzed with
 RENAL FAILURE 3

Table 2. Characteristics and laboratory results of patients with and without acute kidney injury.
All patients All AKI Septic AKI No AKI p values p values
(n ¼ 3687) (n ¼ 2018) (n ¼ 992) (n ¼ 1669) (AKI vs. no AKI) (Septic AKI vs. no AKI)
Age 64.0 6 17.2 66.2 6 16.7 67.3 6 16.1 61.3 6 17.3 <0.001 <0.001
Male (%) 2163 (58.7) 1304 (64.6) 632 (63.7) 859 (51.5) <0.001 <0.001
Body weight (kg) 58.4 6 10.8 59.3 6 10.7 58.8 6 10.6 57.4 6 10.9 <0.001 0.001
Parent specialty <0.001 <0.001
Medical 1407 (38.2) 891 (44.1) 574 (57.9) 516 (30.9) <0.001 <0.001
Surgical 1173 (31.8) 617 (30.6) 246 (24.8) 556 (33.3) 0.076 <0.001
Neurosurgical 675 (18.3) 289 (14.3) 66 (6.7) 386 (23.1) <0.001 <0.001
Others 432 (11.7) 222 (11.0) 106 (10.7) 210 (12.6) 0.136 0.154
Emergency cases 3025 (82.0) 1798 (89.1) 992 (100) 1227 (73.6) <0.001 <0.001
Post-operation 1547 (42.0) 722 (35.8) 164 (16.5) 825 (49.5) <0.001 <0.001
Comorbidities
HT 1406 (38.1) 817 (40.5) 398 (40.1) 589 (35.3) 0.001 0.013
DM 861 (23.4) 549 (27.2) 264 (26.6) 312 (18.7) <0.001 <0.001
CHF 11 (0.3) 10 (0.5) 5 (0.5) 1 (0.1) 0.016 0.030
CKD 955 (25.9) 671 (33.2) 341 (34.4) 284 (17.0) <0.001 <0.001
Malignancy 190 (5.2) 114 (5.6) 71 (7.2) 76 (4.6) 0.117 0.006
Diagnosis by system <0.001 <0.001
Cardiovascular 357 (9.7) 216 (10.7) 0 (0) 141 (8.5) 0.022 <0.001
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Respiratory 415 (11.3) 229 (11.3) 214 (21.6) 186 (11.2) 0.875 <0.001
Neurological 793 (21.5) 343 (17.0) 82 (8.3) 450 (27.0) <0.001 <0.001
Gastrointestinal 766 (20.8) 399 (19.8) 135 (13.6) 367 (22.0) 0.103 <0.001
Renal 122 (3.3) 104 (5.2) 59 (5.9) 18 (1.1) <0.001 <0.001
Sepsis 656 (17.8) 492 (24.4) 468 (47.2) 164 (9.8) <0.001 <0.001
Metabolic 276 (7.5) 91 (4.5) 6 (0.6) 185 (11.1) <0.001 <0.001
Trauma 211 (5.7) 95 (4.7) 4 (0.4) 116 (7.0) 0.004 <0.001
Others 91 (2.5) 50 (2.5) 24 (2.4) 41 (2.5) 1.000 1.000
ICU procedure
RRT 360 (9.8) 360 (17.8) 231 (23.3) N/A N/A N/A
MV 1828 (49.6) 1261 (62.5) 641 (64.6) 567 (34.0) <0.001 <0.001
Vasopressor use 1211 (32.8) 960 (47.5) 567 (57.2) 251 (15.0) <0.001 <0.001
APACHE IV
Score 69.2 6 35.4 83.3 6 37.2 88.7 6 34.5 52.2 6 23.8 <0.001 <0.001
Risk of death 0.25 6 0.27 0.35 6 0.30 0.39 6 0.29 0.13 6 0.17 <0.001 <0.001
APACHE II
Score 18.7 6 9.2 22.0 6 9.6 23.7 6 9.0 14.7 6 6.9 <0.001 <0.001
Risk of death 0.32 6 0.27 0.42 6 0.29 0.48 6 0.26 0.20 6 0.19 <0.001 <0.001
Mortality
ICU 379 (10.3) 343 (17.0) 176 (17.7) 36 (2.2) <0.001 <0.001
Hospital 619 (16.8) 542 (26.8) 278 (28.0) 77 (4.6) <0.001 <0.001
90 days 730 (19.8) 621 (30.8) 321 (32.4) 109 (6.5) <0.001 <0.001
90 days renal recovery N/A N/A N/A
Full recovery 1434 (71.0) 1434 (71.0) 694 (70.0)
Partial recovery 494 (24.5) 494 (24.5) 273 (27.5)
Non recovery 91 (4.5) 91 (4.5) 25 (2.5)
Length of stay (day)
ICU 3.7 6 6.0 5.0 6 7.6 6.1 6 9.1 2.2 6 2.6 <0.001 <0.001
Hospital 20.0 6 38.3 23.3 6 45.5 25.5 6 57.3 16.0 6 26.5 <0.001 <0.001
SCr (lmol/L)
Baseline 94.6 6 53.5 104.4 6 64.7 106.4 6 65.1 82.7 6 31.7 <0.001 <0.001
Admission 116.1 6 116.5 144.6 6 148.7 159.2 6 169.7 81.6 6 32.6 <0.001 <0.001
GFR by MDRD (mL/min/1.73 m2) 74.3 6 26.4 69.8 6 27.8 68.6 6 28.9 79.7 6 23.5 <0.001 <0.001
Potassium (mmol/L) 4.3 6 0.8 4.4 6 0.9 4.4 6 0.9 4.1 6 0.6 <0.001 <0.001
Albumin (g/L) 29.6 6 7.7 27.7 6 8.0 26.8 6 7.4 31.9 6 6.6 <0.001 <0.001
Bilirubin (lmol/L) 20.9 6 28.6 22.8 6 32.4 24.6 6 31.8 18.6 6 22.8 <0.001 <0.001
WCC (109/L) 15.3 6 15.4 15.8 6 12.7 17.4 6 16.2 14.7 6 18.1 0.037 <0.001
Hemoglobulin (g/dL) 10.6 6 2.4 10.1 6 2.5 10.2 6 2.4 11.2 6 2.2 <0.001 <0.001
Platelet (109/L) 183 6 90 173 6 96 172 6 104 194 6 81 <0.001 <0.001
pH 7.34 6 0.12 7.31 6 0.13 7.31 6 0.14 7.37 6 0.08 <0.001 <0.001
Data are presented as mean 6 standard deviation or number (percentage) unless otherwise specified.
AKI: acute kidney injury, HT, hypertension, DM, diabetes mellitus, CHF: congestive heart failure, CKD: chronic kidney disease, MV: mechanical ventilation, RRT:
renal replacement therapy, APACHE: Acute Physiology and Chronic Health Evaluation; SCr: serum creatinine; GFR: glomerular filtration rate; WCC: white cell
count.
All laboratory results refer to the worst value available within the first 24 hr of ICU admission except the baseline serum creatinine (SCr). Baseline SCr was
defined by the lowest known SCr value in the preceding 3 months before current ICU admission. They were estimated by the MDRD equation for those
without preceding results.
 4 H.-P. SHUM ET AL.

100% cardiogenic (14.1%), and others (4.4%). Among those

(A)
90% with AKI, 666 (33.0%) had KDIGO stage 1 AKI, 691
80% (34.2%) had stage 2 AKI, and 661 (32.8%) had stage 3
70% AKI. Using SCr criteria or urine output criteria alone for
60% diagnosing AKI would have underdiagnosed 707
50% Alive (35.0%) patients and 501 (24.8%) patients, respectively.
40% ICU Death The proportion of patients who required MDRD SCr esti-
30% mation were higher in those with AKI compared to
20% those without AKI (14.5% versus 10.7%, p ¼ 0.001). The
10%
percentage of patients suffered from AKI was similar
0%
across the study period (55.3% in 2011, 53.6% in 2012,
0 1 2 3
and 55.5% in 2013, p ¼ 0.872).
100%
(B) Acute kidney injury (AKI) patients were older,
90%
more likely to be male, heavier and have more sig-
80%
nificant comorbidities (including hypertension, dia-
70%
betes mellitus, CKD, and underlying malignancy)
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60%
50% Alive
40% Hospital Death
30%
20%
10%
0%
0 1 2 3
Figure 1. ICU (A) and hospital (B) mortality by KDIGO AKI
stage.
baseline characteristics shown in Table 2. Their mean
age was 64 6 17.2 years old, 58.4% were male and the
mean Acute Physiology and Chronic Health Evaluation
(APACHE) IV score was 69.2 6 35.4 corresponding to
25 6 27% predicted risk of hospital death. The most
common diagnostic categories for ICU admission were
neurological (21.5%), followed by gastrointestinal
(20.8%), and sepsis (17.8%). Baseline SCr were available
in 3217 (87.3%) patients and the rest were estimated
using MDRD equation. The mean baseline SCr was
94.6 6 53.5 lmol/L. One fourth (25.9%) of all patients
had CKD. The ICU, hospital and 90-day mortality were
10.3, 16.8, and 19.8%, respectively. The most common
causes of death included pneumonia (28.0%), cardiovas-
cular complications (17.2%), cerebral vascular complica-
tions (14.2%), sepsis other than pneumonia (16.1%),
malignancy (7.1%), trauma (6.6%), and others such as
ischemic bowel disease, gastrointestinal hemorrhage,
and suicide (10.8%).
Comparison between those with and without AKI
Of 3687 patients, 2018 (54.7%) patients developed AKI
during ICU stay. Sepsis was the most common cause of
AKI (49.2%) followed by hypovolemia (32.3%),
(Table 2). They were more likely to be emergency
admission (89.1% versus 73.6%) and came from med-
ical specialty (44.1% versus 30.9%). Sepsis (24.4%)
was the most common diagnostic category. Their
APACHE scores were higher indicating greater disease
severity. AKI patients were more likely to be on
mechanical ventilation (62.5% versus 34.0%) and
required the use of vasopressor (47.5% versus 15.0%).
Renal replacement therapy (RRT) was initiated in 360
patients (17.8%), while 83% received continuous
venovenous hemofiltration (CVVH) and 17% received
sustained low-efficiency hemodialysis or hemodiafiltra-
tion (SLED or SLED-f). AKI patients also had lower
albumin, hemoglobin, platelet count, pH and GFR,
and higher white cell count (WCC) on first 24 h of
ICU admission when compared to those without AKI
(Table 2). The ICU (17% versus 2.2%) and hospital
mortality (26.8% versus 4.6%) were higher for
patients with AKI when compared to those without
AKI. Mortality increased with severity of AKI (Figure
1). The Kaplan–Meier survival plot for 90-day mortal-
ity differed significantly between those with and
without AKI (Figure 2). The 90-day renal recovery was
good for those with AKI. Full renal recovery was
achieved in 71.6% patients and only 4.5% patients
were classified as non-recovery. The mean ICU and
hospital length of stay (LOS) for those with and with-
out AKI differed by 2.8 and 7.3 days, respectively.
Logistic regression analysis using Forward LR meth-
ods (Hosmer and Lemeshow test v2 ¼ 4.916, df ¼ 8,
p ¼ 0.767) showed that male gender, emergency ICU
admission, the presence of diabetes or CKD as
comorbidity, ideal bodyweight >60 kg,
hemoglobin <10 g/dL, albumin <27.5 g/L, APACHE IV
score >65, and requirement of mechanical ventilation
or vasopressor were independent risk factors for pre-
dicting occurrence of AKI (Table 3).
 RENAL FAILURE 5
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Figure 2. Kaplan–Meier survival plot for 90-day mortality for those with and without AKI.

Table 3. Logistic regression analysis for independent predictors Table 4. Cox regression analysis for independent predictors of
of AKI. 90-day mortality.
Factors Odds ratio 95% CI p Factors Hazard ratio 95% CI p
Male 1.282 1.012–1.624 0.039 Age 1.023 1.017–1.028 <0.001
Ideal body weight >60 kg 1.639 1.296–2.073 <0.001 Emergency admission 3.169 1.994–5.036 <0.001
Emergency admission 1.506 1.227–1.850 <0.001 Post-operative case 0.624 0.505–0.772 <0.001
Presence of DM 1.439 1.192–1.737 <0.001 Diagnosis: Genitourinary 0.471 0.276–0.806 0.006
Presence of CKD 1.512 1.252–1.826 <0.001 Diagnosis: Neurological 2.561 2.006–3.270 <0.001
Mechanical ventilation 1.599 1.357–1.884 <0.001 Diagnosis: Trauma 2.070 1.388–3.087 <0.001
Vasopressor use 2.300 1.904–2.778 <0.001 Diagnosis: Malignancy 2.674 2.069–3.456 <0.001
Hemoglobin <10 g/dL 1.324 1.107–1.583 0.002 APACHE IV score >65 2.016 1.567–2.593 <0.001
Albumin <27.5 g/L 1.371 1.139–1.649 0.001 Mechanical Ventilation 1.730 1.406–2.129 <0.001
APACHE IV score >65 2.706 2.260–3.240 <0.001 Use of vasopressor 1.675 1.389–2.019 <0.001
Other factors included within the models which are not statistically signifi- Type of AKI # <0.001
cant: age, parent specialty, post-operation, the presence of hypertension, Septic 1.819 1.423–2.324 <0.001
congestive heart failure, malignancy as comorbidity, diagnosis by system, Hypovolemic 1.993 1.514–2.623 <0.001
bilirubin level, white cell count, and platelet count. Cardiogenic 3.434 2.592–4.550 <0.001
Potassium 1.175 1.067–1.293 0.001
Albumin 1.048 1.036–1.060 <0.001
pH 5.102 2.762–9.346 <0.001
90-Day mortality #
Compared with those without AKI.
Other factors included within the models which are not statistically signifi-
Cox regression analysis showed that age, emergency cant: gender, body weight, chronic kidney disease, admission diagnosis due
ICU admission, post-operative cases, admission diagno- to cardiovascular disease/gastrointestinal disease/metabolic disease/sepsis,
requirement of renal replacement therapy, baseline glomerular filtration
sis (neurological, trauma, malignancy, and genitourinary rate, bilirubin level, white cell count, platelet count, and hemoglobin level.
cases), type of AKI, APACHE IV score, requirement of
mechanical ventilation and vasopressor support, and patients). The causes of sepsis included pneumonia (57%),
blood parameters (albumin, potassium, and pH) inde- gastrointestinal and hepato-biliary sepsis (18%), and others
pendently predicted 90-day mortality (Table 4). such as urosepsis and musculoskeletal infection (24%).
Surgical wound infection accounted for 0.3% of septic
cases. The isolated micro-organisms included Escherichia
Comparison between septic AKI and without AKI
coli (10%), Pseudomonas (9.7%), Methicillin-resistant
Among all patients, 1635 patients (44.3%) were docu- Staphylococcus aureus (MRSA) (8%), Klebsiella species
mented to have sepsis at the time of ICU admission (1224 (7.8%), Coagulase negative staphylococcus (7.7%), Candida
patients) or after ICU admission but during ICU stay (411 albicans (6.4%), Stenotrophomonas maltophilia (5.1%),
 6 H.-P. SHUM ET AL.

Table 5. Septic AKI versus non-septic AKI. Alpha hemolytic streptococci (4.9%), Staphylococcus aureus
Septic AKI Non-Septic AKI (3.3%), Acinetobacter (3.2%), Enterococcus (3%),
(n ¼ 992) (n ¼ 1026) p
Enterobacter (2.8%), and Klebsiella pneumoniae (2%).
Age 67.3 6 16.1 65.1 6 17.2 0.004
Male (%) 632 (63.7) 672 (65.5) 0.401 Among those septic patients, 1171 of them (71.6%) devel-
Body weight (kg) 58.8 6 10.6 59.7 6 10.7 0.061 oped AKI and septic AKI was regarded as the predomin-
Parent specialty <0.001 ant cause in 992 patients (84.7%). Patients were classified
Medical 574 (57.9) 317 (30.9) <0.001 as KDIGO stage 1, 2, and 3 AKI in 28.1, 32.6, and 39.3%,
Surgical 246 (24.8) 370 (36.1) <0.001
Neurosurgical 66 (6.7) 223 (21.7) <0.001 respectively. Compared with those without AKI, septic
Others 106 (10.7) 116 (11.3) 0.670 AKI patients were older, more likely to be male, had
Emergency admission 992 (100) 805 (78.5) <0.001
Post-operation 164 (16.5) 558 (54.4) <0.001 slightly higher body weight and have more significant
Comorbidities comorbidities (including hypertension, diabetes, CKD,
HT 398 (40.1) 419 (40.8) 0.743 and underlying malignancy) (Table 2). All of them were
DM 264 (26.6) 285 (27.8) 0.557
CHF 5 (0.5) 5 (0.4) 0.957
emergency ICU admission and predominantly from med-
CKD 341 (34.4) 330 (32.2) 0.292 ical specialty (57.9%). Sepsis (47.2%) was the most com-
Malignancy 71 (7.2) 43 (4.2) 0.005 mon diagnostic category. They had higher APACHE
Diagnosis by system scores indicating greater disease severity, corresponding
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Cardiovascular 0 (0) 216 (21.1) <0.001

Respiratory 214 (21.6) 15 (1.5) <0.001 to 40% predicted hospital mortality rate. AKI patients
Neurological 82 (8.3) 261 (25.4) <0.001 were more likely to be on mechanical ventilation (64.6%
Gastrointestinal 135 (13.6) 264 (25.7) <0.001
Renal 59 (5.9) 45 (4.4) 0.131 vs. 34.0%) and required use of vasopressor (57.2% vs.
Sepsis 468 (47.2) 24 (2.3) <0.001 15.0%). Up to 23.3% of patients with septic AKI required
Metabolic 6 (0.6) 84 (8.2) <0.001
Trauma 4 (0.4) 91 (8.9) <0.001
RRT. They also had lower albumin, hemoglobin, platelet
Others 24 (2.4) 26 (2.5) 0.887 count, pH, GFR, and higher WCC on first 24 h of ICU
ICU procedure admission compared with those without AKI (Table 2).
RRT 231 (23.3) 129 (12.6) <0.001 The ICU (17.7% vs. 2.2%), hospital (28.0% vs. 4.6%), and
Mechanical ventilation 641 (64.6) 620 (60.4) 0.052
Vasopressor use 567 (57.2) 392 (38.2) <0.001 90-day mortality (32.4% vs. 6.5%) were significantly
APACHE IV Score 88.7 6 34.5 78.1 6 38.9 <0.001 higher in patients with septic AKI. They also had longer
APACHE IV Risk of death 0.39 6 0.29 0.31 6 0.31 <0.001
APACHE II Score 23.7 6 9.0 20.5 6 10.0 <0.001 ICU and hospital LOS.
APACHE II Risk of death 0.48 6 0.26 0.35 6 0.29 <0.001
Mortality
ICU 176 (17.7) 167 (16.3) 0.381 Comparison between septic and non-septic AKI
Hospital 278 (28.0) 264 (25.7) 0.245
90 days 321 (32.4) 299 (29.1) 0.117 Comparing to patients with non-septic AKI, patients
90 days renal recovery with septic AKI were older, more likely to be emergency
Full recovery 694 (70.0) 740 (72.1) 0.303 admission, and were admitted from medical specialty
Partial recovery 273 (27.5) 220 (21.4) 0.002
Non recovery 25 (2.5) 66 (6.4) <0.001 (Table 5). The presence of significant comorbidities was
Length of stay (days)
similar between two groups except malignancy, which
ICU 6.1 6 9.1 3.9 6 5.5 <0.001 was more common among those with septic AKI. Septic
Hospital 25.5 6 57.3 21.1 6 29.9 0.032 AKI patients had higher APACHE scores, with 10% differ-
SCr (lmol/L) ence of the predicted risk of hospital death when com-
Baseline 106.4 6 65.1 102.5 6 64.3 0.171
Starting 159.2 6 169.7 130.3 6 123.5 <0.001 pared with non-septic AKI. Vasopressor (57.2% vs.
GFR by MDRD (mL/min/1.73 m2) 68.6 6 28.9 71.0 6 26.8 0.051 38.2%) and RRT (23.3% vs. 12.6%) was more commonly
Potassium (mol/L) 4.4 6 0.9 4.4 6 0.9 0.823
Albumin (g/L) 26.8 6 7.4 28.5 6 8.4 <0.001 adopted in septic AKI patients. Among those who
Bilirubin (lmol/L) 24.6 6 31.8 21.1 6 33.0 0.016 received RRT, CVVH was more commonly performed in
WCC (109/L) 17.4 6 16.2 14.2 6 7.5 <0.001
Hemoglobulin (g/dL) 10.2 6 2.4 10.1 6 2.6 0.784
septic AKI patients than in non-septic AKI patients (85%
Platelet (109/L) 172 6 104 174 6 86 0.605 vs. 80%, p < 0.001). Compared with non-septic AKI,
pH 7.31 6 0.14 7.31 6 0.13 0.305 patients with septic AKI had lower albumin, higher start-
Data are presented as mean 6 standard deviation or number (percentage)
unless otherwise specified.
ing SCr, bilirubin, and WCC within the first 24 h of ICU
AKI: acute kidney injury, HT, hypertension, DM, diabetes mellitus, CHF: con- admission. Despite higher APACHE score predicted risk
gestive heart failure, CKD: chronic kidney disease, MV: mechanical ventila- of death, ICU, hospital, and 90-day mortality were similar
tion, RRT: renal replacement therapy, SCr: serum creatinine, GFR:
glomerular filtration rate, MDRD: Modification of Diet in Renal Disease, between both septic and non-septic AKI patients. The
WCC: white cell count, APACHE: Acute Physiology and Chronic Health unadjusted Kaplan Meier survival plot for 90-day mortal-
Evaluation.
ity showed significant mortality difference between dif-
ferent causes of AKI (Figure 3). Full renal recovery at 90
days from ICU admission could be achieved in 70% of

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Figure 3. Kaplan–Meier survival plot for 90-day mortality for different causes of AKI.
patients with septic AKI, while 27.5% had partial recov-
ery. Non-recovery of renal function only occurred in
2.5% of patients with septic AKI compared with 6.4% for
those patients with non-septic AKI (p < 0.001). The
mean ICU and hospital LOS for those with septic and
non-septic AKI differed by 2.2 and 4.4 days, respectively.
Discussion
This study evaluated the incidence, clinical characteris-
tics, and outcome of critically ill patients with septic AKI
among local population. We found that among 3687
recruited patients, 54.7% (2018 patients) had AKI and
half of them (992 patients, 49.2% among those with AKI,
26.9% among all recruited critically ill patients) suffered
from septic AKI. Among those with documented sepsis
on ICU admission or during ICU stay, 71.6% developed
AKI and septic AKI being the predominant cause
(84.7%). Due to the varied clinical background prior to
ICU admission, we do not have accurate data on urine
output prior to ICU admission in these patients.
Nevertheless, based on serum creatinine data alone, 395
patients (10.7%) had AKI at the time of ICU admission.
We believe that this is an under-estimate of the true
prevalence. As the deterioration of renal function was
often a continuous process with many patients showing
further decline of renal function and urine output after
ICU admission, the eventual overall incidence noted at
and during ICU stay is the more clinically meaningful
RENAL FAILURE 7
and reliable parameter than the percentage prior to ICU
admission.
Globally, there are a numbers of studies that eval-
uated the epidemiology of septic AKI (Table 6) but the
majority of them examined Caucasians. Data among
Chinese population are relatively sparse. Most of the
published studies were conducted in critical care set-
ting. The largest one is by Bagshaw et al. which involved
57 Australian ICUs with >120,000 critically ill patients.7
AKI was classified according to the RIFLE system with a
modification of the urine output criteria. He reported a
septic AKI incidence of 11.7%. Wang et al. reported the
largest multi-center study among Chinese populations,
which involved 30 ICUs in Beijing with >3100 critically
ill patients.14 AKI was defined and classified according
to the KDIGO guidelines.4 Sepsis was present in 29.5%
patients and 361 patients (39.4% among those with sep-
sis and 11.6% among all recruited patients) developed
septic AKI, which is similar to that reported by Bagshaw
et al.7 The reported incidence of septic AKI from other
studies ranged from 1.6% to 16.8%, although study by
Gurjar et al. reported an exceptionally high level of 31%
(Table 6). Obviously, difference of AKI diagnostic criteria
among studies affects the reported incidence. Majority
of studies used RIFLE system for diagnosing AKI.
However, modifications of RIFLE criteria are commonly
performed7,15 which may have contributed to a mis-
classification of some patients and may influence the
overall incidence of septic AKI. In this study, we adopted
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8
H.-P. SHUM ET AL.

Table 6. Summary of major studies describing the incidence of septic AKI.

Single or Population
References Sample size multi-center studied Diagnostic criteria Incidence Mortality among those septic AKI patients
Hoste et al. (2003)28 1875 (all) 185 (septic patients) Single Critical care SCr >176 lmol/L 1.6% (all) 16.2% (septic patients) Hospital: 56.7%
Bagshaw et al. (2007)8 29269 (all) Multi Critical care u/o <200 mL over 12 h and ur 2.8% (all) Hospital: 70.2%
>30 mmol/L and/or need RRT
Bagshaw et al. (2008)7 120,123 (all) 33,375 (septic patients) Multi Critical care RIFLE 11.7% (all) 42.1% (septic patients) ICU: 19.8% Hospital: 29.7%
Oppert et al. (2008)29 3877 (all) 401 (septic patients) Multi Critical care RIFLE 4.3% (all) 41.4% (septic patients) ICU: 64.6% Hospital: 67.3%
Bagshaw et al. (2009)15 4532 (septic shock patients) Multi Critical care RIFLE 64.4% (septic shock patients) ICU: 45.2% Hospital: 51.4% 90-day: 50.1%
Lopes et al. (2009)30 335 (septic patients) Single Critical care AKIN and RIFLE 31.4% (AKIN, septic patients) 29.2% Hospital: 25.3%
(RIFLE, septic patients
Yegenaga et al. (2010)31 139 (septic patients) Single Critical care RIFLE 56.8% (septic patients) ICU: 65%
Plataki et al. (2011)32 4893 (all) 763 (septic patients) Single Critical care RIFLE 4.8% (all) 31.1 (septic patients) Hospital: 48.5%
Payen et al. (2012)33 176 (septic patients) Multi Critical care AKIN 73.3% (septic patients) 28-day: 34.1%
Kim et al. (2012)34,35 291 (septic patients) Single Critical care RIFLE AKIN 62.9% (RIFLE, septic patients) 65.6% 28-day: 58.5% (RIFLE), 57.6% (AKIN)
(AKIN, septic patients)
Gurjar et al. (2013)36 406 (all) 323 (septic patients) Single Critical care RIFLE 31.0% (all) 39.0% (septic patients) ICU: 52%
Suh et al. (2013)37 5680 (all) 992 (septic patients) Single Emergency RIFLE 10.1% (all) 57.7% (septic patients) Hospital: 16.4%
department
Poukkanen et al. (2013)9 2901 (all) 918 (septic patients) Multi Critical care KDIGO 16.8% (all) 53.2% (septic patients) Hospital: 29.3% 90-day: 38.1%
Wang et al. (2014)14 3107 (all) 917 (septic patients) Multi Critical care KDIGO 11.6% (all) 39.4% (septic patients) ICU: 44.3%
Medeiros et al. (2015)38 200 (septic patients) Single Emergency AKIN 72% (septic patients) Hospital: 51.4%
department
Shum 2015 (current study) 3687 (all) 1635 (septic patients) Single Critical care KDIGO 26.9% (all) 60.7% (septic patients) ICU: 17.7% Hospital: 28.0% 90-day: 32.4%
RIFLE: Risk, Injury, Failure, Loss, and End-stage kidney disease; AKIN: Acute Kidney Injury Network; KDIGO: Kidney Diseases – Improving Global Outcomes; ICU: intensive care unit; SCr: serum creatinine; u/o: urine
output.

KDIGO criteria. KDIGO identified more AKI due to the
addition of the criterion of an absolute increase in cre-
atinine of 26.5 lmol/L over 48 h to the RIFLE definition
and extending the time-limit from 48 h to 7 days for
percentage increase of creatinine of 50% in the AKIN
definition.16 A comparison of the performance of the
three AKI classification systems in 1900 post-cardiac sur-
gery patients showed that AKI incidence (25.9%) and
staging were identical when using KDIGO and AKIN,
while RIFLE identified fewest (24.9%) patients with AKI.17
Similar findings were also reported in a study with 3100
critically ill patients.5 KDIGO identified more patients
with AKI than RIFLE (51% vs. 46.9%; p ¼ 0.001) or AKIN
(51% vs. 38.4%; p < 0.001). Therefore, based on currently
available evidence, KDIGO is at least as good as, and in
some situations even better than the AKIN and RIFLE.
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Difference in the population studied also contributed to
variation of septic AKI incidence. Different ICU using dif-
ferent admission criteria and case-mix are highly vari-
able. Moreover, disease severity is assessed using
different tools which make it difficult to compare across
different studies.
We found that septic AKI patients differ from patients
with non-septic AKI. Septic AKI patients were older and
had greater biochemical disturbance. They had higher
disease severity that required more invasive and inten-
sive organ support. However, the ICU, hospital, and 90-
day mortality were similar between septic and non-sep-
tic AKI patients, which were unexpected. Study by
Bagshaw et al. showed that septic AKI was associated
with greater risks for both ICU and hospital death.7 We
could have a better understanding on this issue by
examining the etiologies of non-septic AKI. In fact, the
90-day mortality rate for patients with septic AKI was
32%, which was higher than those with hypovolemia
induced AKI (19%, log rank test p < 0.001) but lower
than those with cardiogenic AKI (46%, p < 0.001)
(Figure 3). This finding carries significant prognostic
implication and stresses the importance to identify the
etiology of AKI. Currently, the differentiation between
different causes of AKI is largely based on clinical judg-
ment. Utilization of multiple functional and injury bio-
markers specific for different pathways may be able to
earlier diagnose, as well as to identify the underlying eti-
ology of AKI.18
Despite more patients with septic AKI required RRT
when compared with non-septic AKI, they had better
renal recovery. This finding is actually similar to that
reported by Cruz et al. and Bagshaw et al.,8,19 signifying
a difference in the pathophysiology20–22 between septic
and non-septic AKI. Instead, Singer et al proposed the
cell cycle arrest hypothesis and mentioned that multi-
organ failure induced by critical illness is primary a
RENAL FAILURE 9
functional, rather than structural abnormality.23 His
hypothesis is supported by recent clinical studies, which
demonstrated that two G1 cell cycle arrest markers,
namely, insulin-like growth factor-binding protein 7
(IGFBP7) and tissue inhibitor of metalloproteinase 2
(TIMP-2), predicted AKI in critically ill, and cardiac surgical
patients.24–26 This adaptive response may be controlled
by mitochondria, with the aim to limit further cellular
damage and provide cells with the opportunity to
recover function.27 By shutting down some non-essential
cellular functions, remaining energy can be directed to
other functions that are required for cell survival.27
Our study has several limitations. First, this is a single
center study. Patients outcome are affected by our clin-
ical practice which may differ from other centers.
Second, the retrospective nature of this study may
potentially make it susceptible to several forms of bias.
Change of management strategies over time may alter
patients’ outcome. Third, we did not include some
potentially important variables in data collection, such
as mode and intensity of RRT, timing for initiation of
RRT, fluid status and appropriateness of antibiotic for
septic patients. Fourth, some of patients’ baseline cre-
atinine concentrations were not available (12.7%); there-
fore, we had to perform back-calculation. This may have
led to misclassification of some patients. Finally, the dur-
ation of follow-up is short and the long-term outcome
of those AKI patients is unclear.
Conclusion
We showed that incidence of AKI is high in critically
ill patients, with sepsis being the commonest eti-
ology. Patients who developed AKI were sicker, had
more physiological and biochemical disturbance, and
carried more significant co-morbidities. ICU, hospital,
and 90-day mortality increased with severity of AKI.
Compared with non-septic AKI, septic AKI patients
had more severe disease and required more aggres-
sive support in ICU. However, despite the fact that
more patients with septic AKI required RRT when
compared with non-septic AKI patients, they had bet-
ter renal recovery. This could be explained by the
difference in underlying pathophysiology between dif-
ferent types of AKI. Etiology of AKI has significant
impact on 90-day mortality. Future researches should
investigate the usefulness of biomarkers to differenti-
ate different causes of AKI and delineate the appro-
priate therapeutic strategies.
Acknowledgements
We would like to thank all nursing staff of our unit for their
cooperation and support.
 10 H.-P. SHUM ET AL.
Disclosure statement
The authors report no conflicts of interest. The authors alone
are responsible for the content and writing of the paper.
References
1. Lameire NH, Bagga A, Cruz D, et al. Acute kidney injury:
An increasing global concern. Lancet. 2013;382:
170–179.
2. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P.
Acute dialysis quality initiative w. acute renal failure –
Definition, outcome measures, animal models, fluid
therapy and information technology needs: The Second
International Consensus Conference of the Acute
Dialysis Quality Initiative (ADQI) Group. Crit Care.
2004;8:R204–R212.
3. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney
Downloaded by [University of Sydney Library] at 23:55 21 March 2016
Injury Network: Report of an initiative to improve out-
comes in acute kidney injury. Crit Care. 2007;11:R31.
4. Khwaja A. KDIGO clinical practice guidelines for acute
kidney injury. Nephron Clin Pract. 2012;120:c179–c184.
5. Luo X, Jiang L, Du B, et al. A comparison of different
diagnostic criteria of acute kidney injury in critically ill
patients. Crit Care. 2014;18:R144.
6. Zarjou A, Agarwal A. Sepsis and acute kidney injury. J
Am Soc Nephrol. 2011;22:999–1006.
7. Bagshaw SM, George C, Bellomo R, Committee ADM.
Early acute kidney injury and sepsis: A multicentre
evaluation. Crit Care. 2008;12:R47.
8. Bagshaw SM, Uchino S, Bellomo R, et al. Septic acute
kidney injury in critically ill patients: Clinical characteris-
tics and outcomes. Clin J Am Soc Nephrol.
2007;2:431–439.
9. Poukkanen M, Vaara ST, Pettila V, et al. Acute kidney
injury in patients with severe sepsis in Finnish Intensive
Care Units. Acta Anaesthesiol Scand. 2013;57:863–872.
10. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis
campaign: International guidelines for management of
severe sepsis and septic shock: 2012. Crit Care Med.
2013;41:580–637.
11. House AA, Anand I, Bellomo R, et al. Definition and clas-
sification of cardio-renal syndromes: workgroup state-
ments from the 7th ADQI Consensus Conference.
Nephrol Dial Transpl. 2010;25:1416–1420.
12. Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C. An
assessment of the RIFLE criteria for acute renal failure
in hospitalized patients. Crit Care Med. 2006;34:
1913–1917.
13. Pannu N, James M, Hemmelgarn B, Klarenbach S.
Association between AKI, recovery of renal function,
and long-term outcomes after hospital discharge. Clin J
Am Soc Nephrol. 2013;8:194–202.
14. Wang X, Jiang L, Wen Y, et al. Risk factors for mortality
in patients with septic acute kidney injury in intensive
care units in Beijing, China: A multicenter prospective
observational study. BioMed Res Int. 2014;2014:172620.
15. Bagshaw SM, Lapinsky S, Dial S, et al. Acute kidney
injury in septic shock: Clinical outcomes and impact of
duration of hypotension prior to initiation of antimicro-
bial therapy. Intensive Care Med. 2009;35:871–881.
16. Zeng X, McMahon GM, Brunelli SM, Bates DW, Waikar
SS. Incidence, outcomes, and comparisons across defini-
tions of AKI in hospitalized individuals. Clin J Am Soc
Nephrol. 2014;9:12–20.
17. Bastin AJ, Ostermann M, Slack AJ, Diller GP, Finney SJ,
Evans TW. Acute kidney injury after cardiac surgery
according to risk/injury/failure/loss/end-stage, Acute
Kidney Injury Network, and Kidney Disease: Improving
Global Outcomes classifications. J Crit Care.
2013;28:389–396.
18. Endre ZH, Kellum JA, Di Somma S, et al. Differential
diagnosis of AKI in clinical practice by functional and
damage biomarkers: Workgroup statements from the
tenth Acute Dialysis Quality Initiative Consensus
Conference. Contrib Nephrol. 2013;182:30–44.
19. Cruz MG, Dantas JG, Levi TM, et al. Septic versus non-
septic acute kidney injury in critically ill patients:
Characteristics and clinical outcomes. Rev Bras Ter
Intensiva. 2014;26:384–391.
20. Takasu O, Gaut JP, Watanabe E, et al. Mechanisms of
cardiac and renal dysfunction in patients dying of sep-
sis. Am J Respir Crit Care Med. 2013;187:509–517.
21. Langenberg C, Gobe G, Hood S, May CN, Bellomo R.
Renal histopathology during experimental septic acute
kidney injury and recovery. Crit Care Med.
2014;42:e58–e67.
22. Lerolle N, Nochy D, Guerot E, et al. Histopathology of
septic shock induced acute kidney injury: Apoptosis
and leukocytic infiltration. Intensive Care Med.
2010;36:471–478.
23. Singer M, De Santis V, Vitale D, Jeffcoate W. Multiorgan
failure is an adaptive, endocrine-mediated, metabolic
response to overwhelming systemic inflammation.
Lancet. 2004;364:545–548.
24. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and
validation of cell cycle arrest biomarkers in human
acute kidney injury. Crit Care. 2013;17:R25.
25. Meersch M, Schmidt C, Van Aken H, et al. Urinary TIMP-
2 and IGFBP7 as early biomarkers of acute kidney injury
and renal recovery following cardiac surgery. PLoS One.
2014;9:e93460.
26. Meersch M, Schmidt C, Van Aken H, et al. Validation of
cell-cycle arrest biomarkers for acute kidney injury after
pediatric cardiac surgery. PLoS One. 2014;9:e110865.
27. Gomez H, Ince C, De Backer D, et al. A unified theory of
sepsis-induced acute kidney injury: Inflammation, micro-
circulatory dysfunction, bioenergetics, and the tubular
cell adaptation to injury. Shock. 2014;41:3–11.
28. Hoste EA, Lameire NH, Vanholder RC, Benoit DD,
Decruyenaere JM, Colardyn FA. Acute renal failure in
patients with sepsis in a surgical ICU: predictive factors,
incidence, comorbidity, and outcome. JASN.
2003;14:1022–1030.
29. Oppert M, Engel C, Brunkhorst FM, et al. Acute renal
failure in patients with severe sepsis and septic
shock––a significant independent risk factor for mortal-
ity: results from the German Prevalence Study.
Nephrology, Dialysis, Transplantation. 2008;23:904–909.
30. Lopes JA, Jorge S, Resina C, et al. Acute kidney injury in
patients with sepsis: a contemporary analysis. Intl J
Infect Dis.: IJID. 2009;13:176–181.

31. Yegenaga I, Tuglular S, Ari E, et al. Evaluation of sepsis/
systemic inflammatory response syndrome, acute kid-
ney injury, and RIFLE criteria in two tertiary hospital
intensive care units in Turkey. Nephron. Clin Practice.
2010;115:c276–282.
32. Plataki M, Kashani K, Cabello-Garza J, et al. Predictors of
acute kidney injury in septic shock patients: an observa-
tional cohort study. Clin J Am Soc Nephrol.: CJASN.
2011;6:1744–1751.
33. Payen D, Lukaszewicz AC, Legrand M, et al. A
multicentre study of acute kidney injury in severe
sepsis and septic shock: association with
inflammatory phenotype and HLA genotype. PloS One.
2012;7:e35838.
34. Kim WY, Huh JW, Lim CM, Koh Y, Hong SB. Analysis of
progression in risk, injury, failure, loss, and end-stage
renal disease classification on outcome in patients with
Downloaded by [University of Sydney Library] at 23:55 21 March 2016
RENAL FAILURE 11
severe sepsis and septic shock. J Crit Care. 2012;27:104
e101–107.
35. Kim WY, Huh JW, Lim CM, Koh Y, Hong SB. A compari-
son of acute kidney injury classifications in patients
with severe sepsis and septic shock. Am J Med Sci.
2012;344:350–356.
36. Gurjar M, Baronia AK, Azim A, et al. Septic acute kidney
injury in critically ill Indian patients. Ind J Crit Care Med.
2013;17:49–52.
37. Suh SH, Kim CS, Choi JS, Bae EH, Ma SK, Kim SW. Acute
kidney injury in patients with sepsis and septic shock:
risk factors and clinical outcomes. Yonsei Med J.
2013;54:965–972.
38. Medeiros P, Nga HS, Menezes P, Bridi R, Balbi A, Ponce
D. Acute kidney injury in septic patients admitted to
emergency clinical room: risk factors and outcome. Clin
Exp Nephrol. 2015;19:859–866.