MINERVA MEDICA COPYRIGHT®

may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which

not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary

O R I G I N A L A RT I C L E

Prospective multicenter study on epidemiology

of acute kidney injury in the ICU: a critical care
nephrology Italian collaborative effort (NEFROINT)
P. PICCINNI 1*, D. N. CRUZ 2, 3*, S. GRAMATICOPOLO 1, F. GARZOTTO 1, 2, 3,
M. DAL SANTO 1, G. ANELONI 3, M. ROCCO 4, E. ALESSANDRI 4, F. GIUNTA 5,
V. MICHETTI 6, M. IANNUZZI 7, C. BELLUOMO ANELLO 8, N. BRIENZA 9, M. CARLINI 10,
P. PELAIA 11, V. GABBANELLI 11, C. RONCO 2, 3 on behalf of the NEFROINT investigators
1Department of Intensive Care and Anesthesiology, S. Bortolo Hospital, Vicenza, Italy; 2Department of Nephrology, Dialysis

and Transplantation, S. Bortolo Hospital, Vicenza, Italy; 3International Renal Research Institute Vicenza (IRRIV), Vicenza,
Italy; 4Department of Anesthesiology and Intensive Care, “La Sapienza” University of Rome, Rome, Italy; 5Division of
Anesthesiology and Intensive Care, Department of Surgery, University of Pisa, Pisa, Italy; 6Department of Intensive Care
and Anesthesiology, Sacro Cuore Catholic University, Rome, Italy; 7Intensive Care Unit, Department of Anesthesia and
Resuscitation, Federico II University Hospital, Naples, Italy; 8Department of Anesthesia and Intensive Care, San Giovanni
di Dio Hospital, Florence, Italy; 9Department of Anesthesia and Intensive Care, Emergency and Organ Transplantation,
University of Bari, Bari, Italy; 10Department of Anesthesia and Intensive Care, A.O.U.I. University of Verona, Verona, Italy;
11Intensive Care Unit, University Hospital Umberto I, G.M. Lancisi, G. Salesi,Torrette, Ancona, Italy

ABSTRACT
Acute kidney injury (AKI) is an independent risk factor for mortality in critically ill patients whose epidemiology has
been made unclear in the past by the use of different definitions across various studies. The RIFLE consensus defini-
tion has provided a unifying definition for AKI leading to large retrospective studies in different countries. The present
study is a prospective observational multicenter study designed to prospectively evaluate all incident admissions in 10
Intensive Care Units (ICUs) in Italy and the relevant epidemiology of AKI. A simple user-friendly web-based data col-
lection tool was created with the scope to serve for this study and to facilitate future multicenter collaborative efforts.
We enrolled 601 consecutive patients into the study; 25 patients with End-Stage Renal Disease were excluded leaving
576 patients for analysis. The median age was 66 (IQR 53-76) years, 59.4% were male, while median SAPS II and
APACHE II scores were 43 (IQR 35-54) and 18 (IQR 13-24), respectively. The most common diagnostic categories
for ICU admission were: respiratory (27.4%), followed by neurologic (17%), trauma (14.4%), and cardiovascular
(12.1%). Crude ICU and hospital mortality were 21.7% and median ICU length of stay was 5 days (IQR 3, 14). Of
576 patients, 246 patients (42.7%) had AKI within 24 hours of ICU admission while 133 developed new AKI later
during their ICU stay. RIFLE-initial class was Risk in 205 patients (54.1%), Injury in 99 (26.1%) and Failure in 75
(19.8%). Progression of AKI to a worse RIFLE class was seen in 114 patients (30.8% of AKI patients). AKI patients
were older, with higher frequency of common risk factors. 116 AKI patients (30.6%) fulfilled criteria for sepsis dur-
ing their ICU stay, compared to 33 (16.7%) of non-AKI patients (P<0.001). 48 patients (8.3%) were treated with
renal replacement therapy (RRT) in the ICU. Patients were started on RRT a median of 2 (IQR 0-6) days after ICU
admission. Among AKI patients, they were started on RRT a median of 1 (IQR 0-4) days after fulfilling criteria for
AKI. Median duration of RRT was 5 (IQR 2-10) day. AKI patients had a higher crude ICU mortality (28.8% vs.
non-AKI 8.1%, P<0.001) and longer ICU length of stay (median 7 days vs. 3 days [non-AKI], P<0.001). Crude
ICU mortality and ICU length of stay increased with greater severity of AKI. Two hundred twenty five patients
(59.4% of AKI patients) had complete recovery of renal function, with a SCr at time of ICU discharge which was
≤120% of baseline; an additional 51 AKI patients (13.5%) had partial renal recovery, while 103 (27.2%) had not
recovered renal function at the time of death or ICU discharge. Septic patients had more severe AKI, and were more
tion of the Publisher.

*Both authors contributed equally to the paper.

1072 MINERVA ANESTESIOLOGICA November 2011

 MINERVA MEDICA COPYRIGHT®
PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU Piccinni
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which

not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary

likely to receive RRT with less frequency of renal function recovery. Patients with sepsis had higher ICU mortality
and longer ICU stay. The study confirms previous analyses describing RIFLE as an optimal classification system to
stage AKI severity. AKI is indeed a deadly complication for ICU patients where the level of severity correlated with
mortality and length of stay. The tool developed for data collection resulted user friendly and easy to implement.
Some of its features including a RIFLE class alert system, may help the treating physician to collect systematically
AKI data in the ICU and possibly may guide specific decision on the institution of renal replacement therapy.
(Minerva Anestesiol 2011;77:1072-83)
Key words:  Cardiac, physiology - Hemodilution - Resuscitation - Shock, hemorrhagic - Catheter, indwelling.

A cute kidney injury (AKI) is an important

clinical issue, especially in the critical care
setting. It has been shown in multiple studies to
be a key independent risk factor for mortality,
even after adjustment for demographics, severity
of illness and other relevant factors.1, 2 A clear
understanding of the epidemiology of AKI had
previously been hampered by the use of different
AKI definitions across various studies. The con-
sensus definitions RIFLE (risk, injury, failure,
loss of function, end stage renal disease) 2 was
created to provide a unifying definition for AKI
literature, in much the same way that consensus
definitions for sepsis, acute respiratory distress
syndrome and acute lung injury have done.
RIFLE defines and stages AKI using serum
creatinine (SCr) and urine output (UO), mak-
ing it simple to apply in a variety of clinical and
Participating centres and investigators
Department of Anesthesiology and Intensive Care - St Bortolo Hospi-
tal, Vicenza, Italy (Silvia Gramaticopolo, Marzia Dal Santo, Pasquale
Piccinni)
Department of Cardiocirculatory Physiopathology, Anesthesiology and
Chirurgical, University of Rome “ La Sapienza”, Rome, Italy (Monica
Rocco, Elisa Alessandri)
Division of Anesthesiology and Intensive Care, Department of Surgery
- University of Pisa, Italy (Francesco Giunta);
Department of Intensive Care and Anesthesiology - Catholic Univer-
sity of Sacred Heart, Rome, Italy (Vincenzo Michetti);
Intensive Care Unit, Department of Anesthesia and Resuscitation, Fed-
erico II University Hospital, Napoli (Michele Iannuzzi);
Intensive Care Unit, Emergency Department of Anesthesiological and
Chirurgical Science 2 (SUN), University Hospital, Napoli (Clara Bel-
luomo Anello);
Department of Anaesthesia and Intensive Care, San Giovanni di Dio
Hospital, Florence, Italy (Giorgio Tulli)
Anesthesia and Intensive Care Division, Emergency and Organ Trans-
plantation Department -University of Bari, Italy (Nicola Brienza);
Department of Anaesthesia and Intensive Care, University of Verona,
Azienda Ospedaliera Universitaria Integrata (AOUI), Italy (Mauro
Carlini);
Intensive Care Unit, University Hospital, Ospedali Riuniti Umberto
I - G.M. Lancisi - G. Salesi,Torrette, Ancona, Italy. (Paolo Pelaia, Vin-
cenzo Gabbanelli);
Department of Cardiothoracic Anesthesia and Intensive Care, Vita-
Salute San Raffaele University, San Raffaele Scientific Institute, Milan,
tion of the Publisher.
research settings.3 The use of such definitions in
the literature has increased gradually over the last
six years.4 Indeed, recent large retrospective stud-
ies have utilized RIFLE to describe the epidemi-
ology of AKI among critically ill patients in the
United Kingdom and Germany,5 Australia and
New Zealand,6 and in the United States.7 As is
the norm with secondary analyses of large data-
bases, the investigators used the serum creatinine
criteria only. Six- and 12-hour urine outputs,
which are the criteria used for Risk and Injury,
were not routinely collected in such registries.
Thus, there is a need for prospective studies.8 So
far, there have been few studies describing the
epidemiology of AKI in Italy. In a single center
study, Fiaccadori et al. studied 427 patients con-
secutively admitted for acute renal failure to the
nephrology and internal medicine wards, with
the aim of comparing 3 severity of illness scores
with regards to prediction of patient outcome.9
Cruz et al. performed a prospective multicenter
observational study of patients who fulfilled RI-
FLE criteria for AKI in 19 intensive care units
(ICUs) in northeastern Italy (10). Among 234
AKI patients, 19% were classified as Risk, 35%
as Injury, and 46% as Failure. Crude ICU mor-
tality increased progressively with severity of
AKI; 20% in Risk, 29.3% in Injury, 49.5% in
Failure. In this study, independent risk factors
for mortality included RIFLE class, sepsis, and
need for renal replacement therapy (RRT). It re-
mains to date the best description of AKI among
critically ill patients in Italy. However, similar to
a multinational multicenter study on AKI,11 this
study collected detailed data only on the AKI pa-
tients, precluding direct comparison with non-

Italy (Tiziana Bove). AKI patients.

Vol. 77 - No. 11 MINERVA ANESTESIOLOGICA 1073

 MINERVA MEDICA COPYRIGHT®
Piccinni PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which
not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary
The present study is a prospective observa-
tional multicenter study designed to evaluate all
admissions to participating ICUs in Italy. Our
objectives were to determine the incidence of
AKI among critically ill patients using consensus
definitions, to characterize etiology and timing
of AKI, and to evaluate clinical outcomes associ-
ated with AKI. For this purpose we developed
and refined a simple user-friendly web-based
data collection tool to facilitate the current and
future multicenter collaborative efforts.
Methods
Study design and setting
This was a prospective observational study of
adult patients (age ≥18 years) admitted to 10
ICUs in Italy from September 2009 to April
2010 (participating centers are listed at the end
of the article). The study protocol was reviewed
by the ethics committees or institutional review
boards of the participating centers. Because of
the anonymous and non-interventional nature
of the study, the ethics committees of study cent-
ers waived the need for informed consent.
Definition of AKI
AKI was defined using both the creatinine
and urine output criteria of the RIFLE classifi-
cation.2 A patient was considered to have AKI
when he had an increase in SCr of at least 50%
from baseline, or a reduction in urine output to
<0.5 mL/kg per hour for more than six hours
(i.e. fulfilling at least class risk). Clinical charts
were reviewed for previous SCr values. Baseline
renal function was defined as the lowest known
SCr value during the preceding 3 months. For
patients without known prior SCr, the baseline
SCr was estimated by solving the Modification
of Diet in Renal Disease (MDRD) equation,
assuming a glomerular filtration rate of 75 mL/
min/1.73m2, as recommended by the ADQI
Working Group 2 and previously applied.10, 12
Patients were classified daily using the RIFLE
criteria. RIFLE-initial refers to their RIFLE class
on the first day of AKI. RIFLE-max refers to the
tion of the Publisher.
worst RIFLE class reached by a patient during
1074 MINERVA ANESTESIOLOGICA November 2011
his ICU stay. Patients were considered as having
new AKI if they did not have AKI on ICU ad-
mission, but subsequently reached at least class
Risk during their follow-up. AKI patients were
considered as having worsening AKI if they later
reached higher RIFLE-max class compared to
RIFLE-initial (i.e. Risk to Injury or Failure; or
Injury to Failure) at any time during their ICU
stay. Patients with RIFLE-initial class of Failure
were considered as having worsening AKI if they
later required RRT. RRT was initiated and con-
ducted at the discretion of the responsible physi-
cians. There were no standardized criteria to start
or end RRT. For AKI patients, renal outcome at
ICU discharge or death was defined as follows:
complete recovery if discharge SCr was within
120% of baseline; partial recovery if discharge
SCr was 121-150% of baseline; and non-recov-
ery if discharge SCr was >150% of baseline or
still receiving RRT.
Sepsis and severity of illness scores
Sepsis and systemic inflammatory response
syndrome (SIRS) were diagnosed according to
the definitions of the American College of Chest
Physicians/Society of Critical Care Medicine.13
Patients who fulfilled these criteria during their
ICU admission were classified accordingly. The
individual data elements for the Acute Physiol-
ogy and Chronic Health Evaluation (APACHE)
II score,14 Sequential Organ Failure Assessment
(SOFA) score 15 and Simplified Acute Physiol-
ogy Score (SAPS) II 16 were recorded on the day
of ICU admission, and scores were automatically
calculated. SOFA was calculated daily.
Data collection
Data from enrolled patients were entered into
electronic case report forms resident on a pass-
word-protected web application. Centers could
only have access to data relevant to their patients.
Multiple data elements were collected for each
patient. After usability test, a web-based system
was designed based on an open source frame-
work Ruby on Rails. Data were collected into a
Mysql database. A web-based system was cho-
sen to offer investigators the convenience of col-
 MINERVA MEDICA COPYRIGHT®
PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU Piccinni
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which

not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary

Figure 1.—Screenshot of the NEFROINT database in which a patient has reached RIFLE class Risk during ICU stay. This simple
alarm mechanism, may induce and guide therapeutic interventions or the start of RRT.

lecting and entering information from various
locations within their own centers in a rapid, effi-
cient and accurate manner. The web further offers
the advantages of both centralization of informa-
tion and coordination of multiple clinical trial
processes. An automatic data verification system
for each data field screens for missing or out-of-
range values and data inconsistencies, and gener-
ates a visual user-alert. The user is identified of the
error and is asked to correct it in real-time. The
web tool is organized in 8 distinct sections, with
easy navigability from one section to the other: 1)
demographics, anthropometrics, and admission
diagnoses; 2) comorbidities; 3) first ICU day; 4)
daily vital signs and laboratory values; 5) AKI;
6) RRT; 7) sepsis; and 8) outcomes/case closure.
In the “Comorbidities” section, a history of ex-
posure to nonsteroidal anti-inflammatory drugs,
angiotensin-converting enzyme inhibitors (ACE-
I), angiotensin-2-receptor blockers (ARB), ami-
noglycosides or iodinated contrast media prior to
ICU admission was also recorded. Data from the
“First ICU day” section are used to automatically
calculate APACHE II, SAPS II and SOFA scores.
In the “Daily vital signs and laboratory” section,
tion of the Publisher.
hour UO, the worst 6-hour UO, and the worst
SCr for that day are entered. The system then au-
tomatically displays the following items: the ratio
of the day’s SCr to the baseline SCr, the ratio of
the day’s SCr to the SCr within the previous 48
hour window, and the UO expressed as ml/kg/
hour. These aid the investigator in selecting the
appropriate RIFLE stage in the “AKI” section. An
optional alert can be activated when the patient
reaches at least RIFLE class Risk (Figure 1). Use
of diuretics was also recorded. In the “AKI” sec-
tion, the suspected factors contributing to AKI
are entered. The “RRT” section records indication
for RRT, details of RRT prescription and deliv-
ery. In the “sepsis” section, the microorganism(s)
and suspected source of infection are recorded.
For “outcome”, all-cause ICU and hospital (when
available) mortality are entered. Periodic audits
were performed to establish the accuracy of data
capture and transfer into the database. An email
and/or telephone contact was made to the partici-
pating investigators requesting completion, cor-
rection, or verification of specific data items. Edit
messages are retained in the file indicating the
questionable data and any changes made when

the 24 hour urine output (UO), the worst 12- the requested information is returned. Audits re-

Vol. 77 - No. 11 MINERVA ANESTESIOLOGICA 1075

 MINERVA MEDICA COPYRIGHT®
Piccinni PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which

not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary

Table I.—Characteristics of the cohort by acute kidney injury (AKI).

  All AKI Non-AKI P
N. 576 379 197  
Male sex (%) 352 (59) 237 (62) 105 (53) 0.039
Age (y) 66 (53-76) 69 (58-78) 59 (43-72) <0.001
Body weight (kg) 75 (65-80) 75 (65-85) 70 (60-80) <0.001
Height (cm) 170 (160-175) 170 (160-175) 170 (162-175) 0.274
BMI (kg/m2) 25.0 (22.9-27.8) 25.7 (23.4-28.7) 24.2 (22.1-26.3) <0.001
BMI>30 (%) 85 (15.1) 68 (18) 17 (9) 0.003
Hypertension (%) 270 (47) 198 (52) 72 (37) 0.001
Diabetes (%) 108 (19) 79 (21) 29 (15) 0.2
Cardiovascular disease (%) 249 (43) 183 (48) 66 (34) 0.003
History of chronic kidney disease (%) 36 (6) 26 (7) 10 (5) 0.471
History of proteinuria or hematuria (%) 12 (2) 11 (3) 1 (0.5) 0.067
Baseline creatinine (mg/dL) 1.0 (0.8-1.1) 1.0 (0.8-1.1) 1.0 (0.8-1.2) 0.457
Medications        
NSAID (%) 56 (10) 38 (10) 18 (9) 0.769
ACE-I or ARB (%) 95 (17) 71 (19) 24 (12) 0.045
Patient Type        
Medical (%) 273 (847) 194 (51) 79 (40) 0.014
Elective surgery (%) 117 (20) 73 (19) 44 (22) 0.385
Emergency surgery (%) 186 (32) 112 (30) 74 (38) 0.06
Admission Diagnosis        
Respiratory (%) 158 (27) 115 (30) 43 (22) 0.031
Neurologic (%) 98 (17) 50 (13) 48 (24) 0.001
Trauma (%) 83 (14) 44 (12 39 (20) 0.012
Cardiovascular (%) 70 (12) 60 (16) 10 (5) <0.001
Gastrointestinal (%) 32 (6) 22 (6) 10 (5) 0.849
ICU Admission        
SOFA 5 (3-7) 6 (4-8) 4 (3-6) <0.001
SAPS II 43 (35-54) 44 (37-55) 42 (32-53) 0.0023
APACHE II 18 (13-24) 19 (14-25) 17 (12-21) <0.001
SOFA (without renal component) 5 (3-7) 5 (3-7) 4 (3-6) 0.001
SAPS II (without renal component) 41 (33-51) 42 (34-51) 39 (29-50) 0.001
APACHE II (without renal component) 16 (12-22) 17 (13-22) 16 (11-20) 0.017
Creatinine (mg/dL) 0.9 (0.7-1.4) 1.1 (0.8-1.6) 0.8 (0.6-1.0) <0.001
Urea (mg/dL) 41 (27-64) 50 (32-78) 33 (22-44) <0.001
Urine output first ICU day (ml) 925 (500-1635) 800 (450-1380) 1250 (750-1950) <0.001
Na + (meq/L) 140 (137-143) 140 (137-144) 139 (137-142) 0.0232
K+ (meq/L) 3.8 (3.5-4.2) 3.9 (3.6-4.4) 3.7 (3.5-4.0) <0.001
Bilirubin (mg/dL) 0.7 (0.5-1.1) 0.7 (0.5-1.0) 0.7 (0.5-1.2) 0.672
Hematocrit (%) 32 (28-36) 32 (28-36) 32 (28-35) 0.913
WBC (/mm3) 11 (8-16) 11 (8-16) 10 (8-15) 0.515
Platelets (x1000/mm3) 188 (127-250) 184 (124-248) 191 (138-253) 0.383
pH 7.40 (7.33-7.45) 7.39 (7.32-7.45) 7.40 (7.36-7.47) <0.001
PaCO2 (mmHg) 38 (33-45) 38 (33-45) 38 (32-43) 0.072
PaO2 (mmHg) 114 (82-156) 110 (79-150) 122 (88-161) 0.026
HCO3 (meq/L) 23 (21-26) 23 (20-26) 23 (21-26) 0.30
PaO2 /FiO2 253 (161-366) 230 (156-342) 286 (189-420) <0.001
Mechanical ventilation (%) 532 (92) 353 (93) 179 (91) 0.326
Use of vasopressors (%) 148 (26) 115 (30) 33 (17) <0.001
Dopamine/ dobutamine ≤5 mcg/kg/min 45 (8) 37 (10) 8 (4) 0.014
Dopamine/ dobutamine ≤5 or Epinephrine/
norepinephrine ≤0.1 mcg/kg/min 45 (8) 31 (8) 14 (7) 0.744
Epinephrine/ norepinephrine >0.1 mcg/kg/min 58 (10) 47 (12) 11 (6) 0.009
Use of diuretics on 1st ICU day (%) 214 (37) 156 (41) 58 (29) 0.006
Sepsis (%) 149 (26) 116 (31) 33 (17) <0.001
Outcome        
ICU mortality (%) 125 (22) 109 (29) 16 (8) <0.001
ICU length of stay (days) 5 (3-14) 7 (3-16) 3 (2-8) <0.001
tion of the Publisher.

1076 MINERVA ANESTESIOLOGICA November 2011

 MINERVA MEDICA COPYRIGHT®
PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU Piccinni
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which

not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary

ICU admission
(escluding ESRD)
576

No AKI on admission AKI on admission

330 246
(57.3% of all ICU pts) (42.7% of all ICU pts)

New AKI
133
(40.3% of pts without AKI on admit)

Never develop AKI Ever AKI

197 225
(34.2% of all ICU pts) (65.8% of all ICU pts)

Complete renal Complete renal Complete renal

recovery* recovery* recovery*
225 (59.4% of AKI pts) 51 (13.5% of AKI pts) 103 (27.2% of AKI pts)

Figure 2.—Acute kidney injury in the study population. *At ICU discharge or death.

vealed a <3% error rate, predominantly related
to errors in entry of heights and weights. These
were quickly noted, and verified with the respec-
tive centers. In one case, the investigator was un-
able to update the discharge status of his patient.
He communicated this via phone, and this was
resolved immediately. The final data were then
imported into a statistical program for analysis.
Statistical analyses
Continuous variables are expressed as mean
± standard deviation or median (interquartile
range) and compared between any two groups
using t-test or the Mann Whitney U test, and
among three groups using analysis of variance
(general linear models with adjustment for mul-
tiple comparisons), as appropriate. Categorical
variables are expressed as proportions and com-
pared with the Mantel-Haenszel χ2 test or Fisher
tion of the Publisher.
14.0 (SPSS Inc, Chicago, IL, USA) software
package, with two-sided P value <0.05 consid-
ered as statistically significant.
Results
Patient demographics
We enrolled 601 consecutive incident patients
into the study; we excluded 25 patients with
endstage renal disease on chronic RRT, leaving
576 patients for analysis. Patient characteristics
are shown in Table I. The median age was 66
(IQR 53-76) years, 59.4% were male, while
median SAPS II and APACHE II scores were
43 (IQR 35-54) and 18 (IQR 13-24), respec-
tively. The most common diagnostic categories
for ICU admission were: respiratory (27.4%),
followed by neurologic (17%), trauma (14.4%),
and cardiovascular (12.1%). Serum creatinine
values prior to hospitalization were available for

exact test. Data were analyzed using the SPSS only 45.8% of patients; for the rest, the baseline

Vol. 77 - No. 11 MINERVA ANESTESIOLOGICA 1077

 MINERVA MEDICA COPYRIGHT®
Piccinni PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which
not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary
Figure 3.—Progression of acute kidney injury.
SCr was estimated using MDRD. The propor-
tion of patients in which the MDRD estimation
was used was similar among AKI and non-AKI
patients. The median baseline pre-morbid SCr
was 1.0 (IQR 0.8-1.1) mg/dL. Crude ICU and
hospital mortality were 21.7% and median ICU
length of stay was 5 days (IQR 3, 14).
AKI
Of 576 patients, 246 patients (42.7%) had
AKI within 24 hours of ICU admission while 133
developed new AKI later during their ICU stay
(Figure 2). The most commonly reported factors
contributing to AKI were hypovolemia (29.5%),
septic shock (13.5%), major surgery (12.1%)
and cardiogenic shock (11.8%). RIFLE-initial
class was Risk in 205 patients (54.1%), Injury
tion of the Publisher.
in 99 (26.1%) and Failure in 75 (19.8%). Pro-
1078 MINERVA ANESTESIOLOGICA November 2011
gression of AKI to a worse RIFLE class was seen
in 114 patients (30.8% of AKI patients) (Figure
3). Among these patients, it took a median of
2 (IQR 1-6) days to attain their maximum RI-
FLE class. RIFLE-max was Risk in 127 patients
(33.5%), Injury in 130 (34.3%) and Failure in
122 (32.2%).
AKI patients were older, more likely to be
male, and have a history of cardiovascular dis-
ease and hypertension, and to have had exposure
to ACE-I or ARBs prior to their hospitalization.
The proportion of obese patients (BMI>30)
was higher in the AKI group (17.9% vs non-
AKI 8.6%, P=0.003). They were more likely to
have a respiratory or trauma diagnosis on ICU
admission, and had higher APACHE II, SAPS
II, and SOFA scores. The latter finding was con-
sistent whether the scores were calculated with
or without the renal component. On their first

PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU Piccinni
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which
not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary
100
Crude ICU mortality (%)
80
60
40
20
0 0
Non-AKI All AKI
RIFLE Max
Figure 4.—ICU mortality by RIFLE-max class.
ICU day, AKI patients were more likely to be
on vasopressors and to have been given diuret-
ics, but the proportion of patients on mechanical
ventilation was similar between the two groups.
AKI patients also had lower mean arterial pres-
sure (MAP), urine output, pH, PO2 and PaO2/
FiO2 values, and higher urea and SCr values on
ICU admission. One hundred sixteen AKI pa-
tients (30.6%) fulfilled criteria for sepsis during
their ICU stay, compared to 33 (16.7%) of non-
AKI patients (P<0.001).
Forty eight patients (8.3%) were treated with
RRT in the ICU; 2/48 did not fulfill criteria for
AKI and received RRT for non-renal indica-
tions. Overall, patients were started RRT a me-
dian of 2 (IQR 0-6) days after ICU admission.
Among AKI patients, they were started on RRT
a median of 1 (IQR 0-4) days after fulfilling
criteria for AKI. The initial RRT modality was
continuous RRT (CRRT) in 46 (96%) of cases,
specifically continuous venovenous hemodiafil-
tration (N.=30), continuous venovenous hemo-
filtration (CVVH) (N.=9), CVVH with coupled
plasma filtration adsorption (N.=2), continuous
venovenous hemodialysis (N.=4) and pulse high
volume hemofiltration (N.=1). In 2 patients, the
initial modality was intermittent hemodialysis
(HD). Median duration of RRT in the ICU was
5 (IQR 2-10) days.
AKI patients had a higher crude ICU mortal-
ity (28.8% vs. non-AKI 8.1%, P<0.001) (Figure
4) and longer ICU length of stay (median 7 days
vs. 3 days [non-AKI], P<0.001). Crude ICU
mortality and ICU length of stay increased with
greater severity of AKI. Two hundred twenty five
tion of the Publisher.
patients (59.4% of AKI patients) had complete
Vol. 77 - No. 11 MINERVA ANESTESIOLOGICA 1079
MINERVA MEDICA COPYRIGHT®
10
9
ICU length of stay (days)
8
7
6
5
4
3
2
1
Risk Injury Failure Non-AKI All AKI Risk Injury Failure
RIFLE Max
Figure 5.—ICU length of stay by RIFLE-max class.
recovery of renal function, with a SCr at time
of ICU discharge or death which was ≤120% of
baseline; an additional 51 AKI patients (13.5%)
had partial renal recovery, while 103 (27.2%)
had not recovered renal function at the time
of death or ICU discharge (Figure 2). Among
AKI patients who had complete renal recovery,
33/225 (14.7%) nevertheless died in the ICU.
The crude ICU mortality among patients with
partial versus no renal recovery were 35.3% and
56.3%, respectively.
AKI and sepsis
Sepsis events were recorded throughout pa-
tient’s stay in the ICU; 149 patients (25.9%)
fulfilled criteria for sepsis. Of these, 116/149
(77.8%) had AKI, compared to 263/427 (61.6%)
non-septic patients (P<0.001). Among septic AKI
patients, they tended to fulfill criteria for both sep-
sis and AKI on the same day; in a few cases, sepsis
preceded AKI (median days from sepsis criteria
to AKI criteria, 0, IQR 0-1). Septic patients had
more severe AKI, and were more likely to receive
RRT (Table II). The duration of RRT was similar
among septic and non-septic patients; however,
septic AKI patients were less likely to recover re-
nal function. Patients with sepsis had higher ICU
mortality and longer ICU stay.
Discussion
Key findings and comparison with literature
AKI is a deadly complication for ICU patients.
The level of severity correlates with mortality
 MINERVA MEDICA COPYRIGHT®
Piccinni PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which

not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary

Table II.—Selected characteristics of the cohort by sepsis.

  Sepsis No Sepsis P
N 149 427  
Male sex (%) 95 (64) 247 (58) 0.21
Age (y) 66 (54 to 76) 67 (52 to 77) 0.537
Patient type      
Medical (%) 88 (59) 185 (43) 0.001
Elective surgery (%) 13 (88) 104 (24) <0.001
Emergency surgery (%) 48 (32) 138 (32) 1
Admission diagnosis      
Respiratory (%) 54 (36) 104 (24) 0.007
Neurologic (%) 15 (10) 83 (19) 0.008
ICU Admission      
SOFA 6 (4 to 9) 5 (3 to 7) <0.001
SAPS II 45 (39 to 55) 42 (34 to 54) 0.009
APACHE II 20 (15 to 25) 17 (13 to 23) 0.004
Creatinine (mg/dL) 1.0 (0.7 to 1.6) 0.9 (0.7 to 1.3) 0.725
Urea (mg/dL) 50 (30 to 76) 40 (27 to 62) 0.006
Urine output first ICU day (ml) 900 (400 to 1600) 970 (515 to 1640) 0.238
Mechanical ventilation (%) 141 (95) 391 (92) 0.283
Use of vasopressors (%) 55 (37) 93 (22) <0.001
Acute kidney injury      
AKI (%) 116 (78) 263 (62) <0.001
RIFLE initial      
Risk (%) 59 (40) 146 (34)
Injury (%) 25 (17) 74 (17) <0.001
Failure (%) 32 (22) 43 (10)
RIFLE maximum      
Risk (%) 32 (22) 95 (22)
Injury (%) 29 (20) 101 (24) <0.001
Failure (%) 55 (37) 67 (16)
RRT      
RRT (%) 34 (23) 14 (3) <0.001
Duration of RRT (days) 4 (2 to 10) 5 (3 to 13) 0.632
Recovery of renal function      
Complete (%) 92 (68) 321 (75)
Partial (%) 12 (8) 46 (11) <0.001
None (%) 45 (30) 60 (14)
Outcome      
ICU mortality (%) 56 (38) 69 (16) <0.001
ICU length of stay (days) 13 (7 to 24) 4 (2 to 8) <0.001
Data are expressed as mean (standard deviation) or as median (interquartile range).

and length of stay in the ICU. Epidemiology of
Aki represents an important aspect to consider
in critically ill patients in order to establish and
implement potential strategies for prevention
and effective treatment.
Different definitions of AKI have been used
tion of the Publisher.
lack of clarity and inconsistent results. Recent
advances on classification and definition of AKI
syndrome have permitted a more integrated and
comprehensive approach to epidemiology. Sev-
eral studies have been performed in Europe and
US leading to a clearer understanding of the im-

in the past and this fact has contributed to the plications of the syndrome in the ICU.

1080 MINERVA ANESTESIOLOGICA November 2011

 MINERVA MEDICA COPYRIGHT®
PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU Piccinni
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which
not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary
The incidence of AKI resulted similar to that
observed in other databases. Almost 50% of pa-
tients displayed some form of AKI at ICU admis-
sion. Considering the number of patients devel-
oping AKI at any time during ICU stay, the final
proportion of ICU patients with AKI resulted
65.8% demonstrating that critical care nephrol-
ogy is a significant component of modern criti-
cal care. Of these patients, approximately 60%
recovered renal function while 13.5% had par-
tial recovery and 27.2% had no recovery of renal
function. Considering that more than 50% of
the AKI population started with a RIFLE Class
R, it is interesting to note that almost half of
them evolved into RIFLE class I or F. The initial
group with Class F, required RRT in only 25%
of the cases. As in other populations studied, the
presence of sepsis represents an important factor
affecting outcome and severity of other clinical
disorders such as AKI.
Insofar the vast majority of studies conducted
to evaluate the incidence and prevalence of AKI
have been retrospective and involving large pop-
ulation of hospitalized patients. On the opposite
NEFROINT has its originality in the fact that it
is a prospective multicenter study, that explores
AKI has it happens in a real-world intensive
care environment, and as it is perceived by the
clinician in charge. As it has been pointed out
by Lafrance and Miller in a recent paper 17 AKI
classification systems depend on the definition
of baseline creatinine and increase in creatinine.
But it is important to notice that often to the
clinician in charge in an intensive care the in-
formation on a precedent creatinine level is not
given, so this kind of “real life” AKI estimation
has never been explored.
In the same study the author points out that
AKI classification varies whether creatinine in-
crease is calculated by employing ratios or differ-
ences. Such differences are at the root of the dis-
tinction between Acute Kidney Injury Network
(AKIN) and RIFLE classification. Comparison
of these data in the NEFROINT database will
be the object of a future paper.
Significance of study findings
The study confirms previous analyses describ-
tion of the Publisher.
ing RIFLE as an optimal classification system to
Vol. 77 - No. 11 MINERVA ANESTESIOLOGICA 1081
stage AKI severity. The tool developed for data
collection resulted user friendly and easy to im-
plement. Some of its features including a RIFLE
class alert system, may help the treating physi-
cian to collect systematically AKI data in the
ICU and guide specific decision on the institu-
tion of renal replacement therapy (Figure 1). In
this way, early or late therapy will result referred
to a specific AKI severity class rather than a sub-
jective concept of renal impairment.
Strengths and limitations
The NEFROINT platform was implemented
with the purpose of collecting epidemiological
data about patients in intensive care units, but
was thought as well as a tool for intensivists to
help to detect AKI as soon as it occurs and grade
it. Therefore developing a friendly user interface
has been demanding and time consuming. The
approach was consistent with the current view
that data base entry methodology should be sim-
ple and easy to correct and control. Physicians
and nurses in the ICU have very little time to
comply with complicated studies requiring time
consuming procedures for data input. The cur-
rent version of the NEFROINT database seems
to respond to the requirements of simplicity to-
gether with internal accurate and sophisticated
management of data. We feel that this approach
may represent a potential pathway towards large
multicenter studies to be undertaken in the near
future.
However, the effort of simplifying data col-
lection had as a consequence that evaluation
of patient’s clinical condition as sepsis, septic
shock, hypovolemia were at the discretion of the
clinician in charge of the patient. For example,
as RRT was initiated at the discretion of the
physician in care of the patient, this may have
influenced outcome, but this is true of any ob-
servational study on RRT in AKI. Moreover, at
the moment there is no standard of care indicat-
ing the exact time for initiation of RRT in criti-
cal patients. Such practice often depends strictly
on available technique and staff and the clinician
expertise. For this reason it is very important to
be able to correlate AKI stages and RRT practice
and see how it influences patient outcome.18, 19
 MINERVA MEDICA COPYRIGHT®
Piccinni PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which
not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary
For the same reasons explained above, hypovo-
lemia as a cause of AKI depended on the judgment
of the clinician in charge, not on set parameters
of central venous pressure (CVP) or fluid balance
or other parameters. It is a limitation of the study
but on the other side it shows what is the clini-
cian’s perception on possible causes of AKI.
Future studies
There is an emerging consensus that early or
late initiation of therapy, is a completely subjec-
tive definition unless a specific parameter with
characteristic thresholds or cut off values is es-
tablished. In this case, AKI staged by RIFLE can
be considered a mean to define early or late in-
tervention based on creatinine or urine output
criteria and be specifically used in prospective
trials. New biomarkers may also become inter-
esting criteria to define early or late initiation of
therapy.
In these circumstances, it would also be inter-
esting to know if new biomarkers for early diag-
nosis of AKI would have modified the evolution
of the syndrome and would have permitted an
earlier application of preventive measures mod-
ifying the outcome of the syndrome. It is our
impression that the present study represents an
important staring point to assess prospectively
epidemiology of AKI in a specific population
and at the same time, it may represent a future
approach for new prospective trials designed to
establish biomarker or preventive therapies util-
ity in the natural history of AKI in critically ill
patients admitted to ICU.
To anticipate AKI diagnosis the concept of
“renal angina” 20 has been developed and the
pharmaceutical industry is offering diagnostic
panel kits that may be employed in sequential
testing of biomarkers, with an approach simi-
lar to the cardiac syndrome. The sensitivity and
specificity of novel biomarkers may be tested
in conjunction with the collection of complete
epidemiological data collected from a simple
and user-friendly database as NEFROINT.21, 22
The same considerations may be applied to test
the efficacy of preventive measures for AKI in
patients subgroups as for example those who
tion of the Publisher.
undergo cardiac or major surgery; as it has been
1082 MINERVA ANESTESIOLOGICA November 2011
pointed out, clinicians are tempted to discover
and employ a “magic bullet” that may resolve
or prevent AKI whenever it occurs; however the
complex pathophysiology of AKI makes it com-
pelling to confront any new molecule employed
to the complex picture offered by patients in in-
tensive care and this can be done only with an
instrument that allows collection of biochemi-
cal data and analyzing cardiac, respiratory, renal
and sphlancnic system on a daily basis.23 It is our
impression that the present study represents an
important starting point to assess prospectively
epidemiology of AKI in a specific population
ad at the same time, it may represent a future
approach for new prospective trials designed to
establish biomarker or preventive therapies util-
ity in the natural history of AKI in critically ill
patients admitted to ICU. A study performed in
Italy, suggests that plasma neutrophil gelatinase-
associated lipocalin (NGAL) appears to be a use-
ful early marker for the development of AKI in
a large heterogenous adult ICU population, al-
lowing the diagnosis of AKI up to 48 hours prior
to a clinical diagnosis based on AKI consensus
definitions. It is also a good predictor of need for
RRT and correlates with AKI severity and over-
all severity of illness.24
NEFROINT is a flexible and adaptable in-
strument that may be integrated with other ex-
perimental system of analysis that recently have
been proposed for a new insight in renal patho-
physiology and its correlation with cardiac and
pulmonary function.25
Data collected by the NEFROINT data-base
will allow to confront AKI and non-AKI pa-
tients exposure to nephrotoxic drugs, diuretics,
mechanical ventilation, vasopressor drugs dur-
ing their ICU stay, and this will be object of fu-
ture studies
References
  1. Cruz DN, Ronco C. Acute kidney injury in the intensive
care unit: current trends in incidence and outcome. Crit
Care 2007;11:149.
  2. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. 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:R204-12.
  3. Cruz DN, Ricci Z, Ronco C. Clinical review: RIFLE and
AKIN-time for reappraisal. Crit Care 2009;13:211.
 MINERVA MEDICA COPYRIGHT®
PROSPECTIVE MULTICENTER STUDY ON EPIDEMIOLOGY OF ACUTE KIDNEY INJURY IN THE ICU Piccinni
may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either
sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which

not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary

  4. Ricci Z, Cruz D, Ronco C. The RIFLE criteria and mortal-
ity in acute kidney injury: A systematic review. Kidney Int
2008;73:538-46.
  5. Ostermann M, Chang RW. Acute kidney injury in the
intensive care unit according to RIFLE. Crit Care Med
2007;35:1837-43; quiz 1852.
  6. Bagshaw SM, George C, Dinu I, Bellomo R. A multi-cen-
tre evaluation of the RIFLE criteria for early acute kidney
injury in critically ill patients. Nephrol Dial Transplant
2008;23:1203-10.
  7. Hoste EA, Clermont G, Kersten A, et al. RIFLE criteria
for acute kidney injury are associated with hospital mor-
tality in critically ill patients: a cohort analysis. Crit Care
2006;10:R73.
  8. Cruz DN, Garzotto F, de Cal M, Piccinni P, Ronco C.
Diagnostic and staging criteria for acute kidney injury: do
we need prospective studies? Minerva Anestesiol 2008;74
Suppl 1:303-305.
  9. Fiaccadori E, Maggiore U, Lombardi M, Leonardi S, Rotelli
C, Borghetti A. Predicting patient outcome from acute re-
nal failure comparing three general severity of illness scoring
systems. Kidney Int 2000;58:283-92.
10. Cruz DN, Bolgan I, Perazella MA, Bonello M, de Cal M,
Corradi V et al. North East Italian Prospective Hospital Re-
nal Outcome Survey on Acute Kidney Injury (NEiPHROS-
AKI): targeting the problem with the RIFLE Criteria. Clin
J Am Soc Nephrol 2007;2:418-25.
11. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H,
Morgera S et al. Acute renal failure in critically ill patients:
a multinational, multicenter study. JAMA 2005;294:813-8.
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;34:1913-7.
13. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D,
Cook D et al. 2001 SCCM/ESICM/ACCP/ATS/SIS In-
ternational Sepsis Definitions Conference. Crit Care Med
2003;31:1250-6.
14. Knaus WA, Draper EA, Wagner DP, Zimmerman JE.
APACHE II: a severity of disease classification system. Crit
Care Med 1985;13:818-29.
15. Vincent JL, de Mendonça A, Cantraine F, Moreno R,
Takala J, Suter PM et al. Use of the SOFA score to assess
the incidence of organ dysfunction/failure in intensive care
units: results of a multicenter, prospective study. Working
group on “sepsis-related problems” of the European Society
of Intensive Care Medicine. Crit Care Med 1998;26:1793-
800.
16. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified
Acute Physiology Score (SAPS II) based on a European/
North American multicenter study. JAMA 1993;270:2957-
63.
17. Lafrance JP, Miller DR. Defining acute kidney injury in
database studies: the effects of varying the baseline kidney
function assessment period and considering CKD status.
Am J Kidney Dis 2010;56:651-60.
18. Cruz DN, Ricci Z, Bagshaw SM, Piccinni P, Gibney N,
Ronco C. Renal replacement therapy in adult critically ill
patients: when to begin and when to stop. Contrib Nephrol
2010;165:263-73.
19. Bagshaw SM, Cruz DN, Gibney RN, Ronco C. A proposed
algorithm for initiation of renal replacement therapy in
adult critically ill patients. Crit Care 2009;13:317.
20. Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Ne-
phrol 2010;5:943-9.
21. Cala K. Biomarkers of acute kidney injury: early recogni-
tion and timely intervention is a need of the hour. Minerva
Anestesiol 2010.
22. Moore E, Bellomo R, Nichol A. Biomarkers of acute kidney
injury in anesthesia, intensive care and major surgery: from
the bench to clinical research to clinical practice. Minerva
Anestesiol 2010;76:425-40.
23. Biancofiore G. Postoperative renal dysfunction. Have
we emerged from the labyrinth? Minerva Anestesiol
2010;76:239-40.
24. Cruz DN, de Cal M, Garzotto F, Perazella MA, Lentini P,
Corradi V et al. Plasma neutrophil gelatinase-associated
lipocalin is an early biomarker for acute kidney injury in an
adult ICU population. Intensive Care Med 2010;36:444-51.
25. Caironi P, Langer T, Taccone P, Bruzzone P, De Chiara S,
Vagginelli F et al. Kidney instant monitoring (K.IN.G): a
new analyzer to monitor kidney function. Minerva Aneste-
siol 2010;76:316-24.

Fundings.—The study was supported by the national project “Programma strategico: “Costituzione di un network mutiregionale per
la prevenzione della malattia renale e migliorare il management clinico del paziente nefropatico” of the Italian Ministry of health (San
Bortolo Hospital Institutional Grant number 222/2009-2010).
Acknowledgements.—We acknowledge the “Programma strategico: “Costituzione di un network mutiregionale per la prevenzione della
malattia renale e migliorare il management clinico del paziente nefropatico” of the Italian Ministry of health and the San Bortolo Hospi-
tal Institutional Grant number 222/2009-2010 for the support given to the present study.
Received on November 15, 2010 - Accepted for publication on March 31, 2011.
Corresponding authors: P. Piccinni, Department of Intensive Care and Anesthesiology, St. Bortolo Hospital, 36100 Vicenza, Italy.
E-mail: pasquale.piccinni@ulssvicenza.it; C. Ronco, Department of Nephrology, St. Bortolo Hospital, 36100 Vicenza, Italy.
E-mail cronco@goldnet.it
tion of the Publisher.

Vol. 77 - No. 11 MINERVA ANESTESIOLOGICA 1083