Cardiovascular Pathophysiology and Outcomes

E   Original Clinical Research Report

A Multinational Observational Study Exploring

Adherence With the Kidney Disease: Improving Global
Outcomes Recommendations for Prevention of Acute
Kidney Injury After Cardiac Surgery
Mira Küllmar, MD,* Raphael Weiß, MD,* Marlies Ostermann, MD,† Sara Campos, MD,†
Neus Grau Novellas, MD,† Gary Thomson, MD,† Michael Haffner, MD,† Christian Arndt, MD,‡
Hinnerk Wulf, MD,‡ Marc Irqsusi, MD,§ Fabrizio Monaco, MD,║ Ambra Licia Di Prima, MD,║
Downloaded from http://journals.lww.com/anesthesia-analgesia by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC1y0abggQZXdgGj2MwlZLeI= on 10/10/2021

Mercedes García-Alvarez, MD,¶ Stefano Italiano, MD,¶ Mar Felipe Correoso, MD,¶
Gudrun Kunst, MD,# Shrijit Nair, MD,# Camilla L’Acqua, MD,** Eric Hoste, MD,††
Wim Vandenberghe, MD,†† Patrick M. Honore, MD,‡‡ John A. Kellum, MD,§§ Lui Forni, MD,║║
Philippe Grieshaber, MD,¶¶ Carola Wempe, MSc,* Melanie Meersch, MD,* and
Alexander Zarbock, MD*

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recom-
mend a bundle of different measures for patients at increased risk of acute kidney injury (AKI).
Prospective, single-center, randomized controlled trials (RCTs) have shown that management in
accordance with the KDIGO recommendations was associated with a significant reduction in the
incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle
in routine clinical practice is unknown.
METHODS: This observational prevalence study was performed in conjunction with a prospec-
tive RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac sur-
gery. A 2-day observational prevalence study was performed in all participating centers before
the RCT to explore routine clinical practice. The participating hospitals provided the following
data: demographics and surgical characteristics, AKI rates, and compliance rates with the indi-
vidual components of the bundle.
RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within
72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully com-
pliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients,
volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemody-
namic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2%
of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast
agents. The patients received on average 3.4 (standard deviation [SD] ±1.1) of 6 supportive mea-
sures as recommended by the KDIGO guidelines. There was no significant difference in the number
of applied measures between AKI and non-AKI patients (3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347).
CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations
was low in routine clinical practice. (Anesth Analg 2020;130:910–6)

KEY POINTS
• Question: Is the Kidney Disease: Improving Global Outcomes (KDIGO) bundle consisting of
different supportive measures already implemented in routine clinical practice?
• Findings: A total of 5.3% of patients received the complete recommended bundle consist-
ing of 6 supportive measures (52.6% discontinuation of nephrotoxic drugs, 70.5% volume
optimization, 52.6% functional hemodynamic monitoring, 24.2% close monitoring of serum
creatinine and urine output, 41.1% avoidance of hyperglycemia, no patient received radiocon-
trast agents).
• Meaning: Compliance with the KDIGO bundle is low in daily practice; efforts should focus on
increasing compliance to reduce the incidence of AKI.

From the *Department of Anaesthesiology, Intensive Care Medicine and Pain
Medicine, University Hospital Münster, Münster, Germany; †Department of
Critical Care, Guy’s & St Thomas’ NHS Foundation Hospital, London, United
Kingdom; ‡Department of Anaesthesiology and Intensive Care Medicine,
University Hospital Marburg, Marburg, Germany; §Department of Cardiac
Surgery, University Hospital Marburg, Marburg, Germany; ║Department
of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute,
Milan, Italy; ¶Department of Anesthesiology, Hospital de la Santa Creu i
Copyright © 2020 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000004642
Sant Pau, Barcelona, Spain; #Department of Anaesthetics, King’s College
Hospital, Denmark Hill, London, United Kingdom; **Centro Cardiologico
Monzino IRCCS, Milan, Italy; ††Department of Intensive Care Medicine,
University Hospital Gent, Gent, Belgium; ‡‡Department of Intensive Care,
CHU Brugmann University Hospital, Brussel, Belgium; §§Center for Critical
Care Nephrology, Department of Critical Care Medicine, University of
Pittsburgh, Pennsylvania; ║║Department of Intensive Care Medicine, Royal
Surrey County Hospital, Guildford, United Kingdom; and ¶¶Department of
Cardiac Surgery, University Hospital Giessen, Giessen, Germany.
Accepted for publication December 12, 2019.

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 EE Original Clinical Research Report

GLOSSARY
ARDS = acute respiratory distress syndrome; AKI = acute kidney injury; CABG = coronary artery
bypass graft; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease;
CONSORT = Consolidated Standards of Reporting Trials; CreaPre = preoperative serum creatinine;
EF = ejection fraction; GFR = glomerular filtration rate; ICU = intensive care unit; KDIGO = Kidney
Disease: Improving Global Outcomes; MAP = mean arterial pressure; PAC = pulmonary artery cath-
eter; PICCO = pulse contour cardiac output; PrevAKI = Prevention of cardiac surgery–associated
AKI by implementing the KDIGO guidelines in high-risk patients identified by biomarkers; RCT =
randomized controlled trial; SCr/UO = serum creatinine/urine output; SD = standard deviation

A
mong different types of perioperative organ
injury, acute kidney injury (AKI) is particu-
larly challenging and prominent. AKI is par-
ticularly high in cardiac surgery patients, reaching
50% depending on criteria used.1–3 The mortality rate
in this patient population is 1%–5% with a further rise
up to 24% in patients who require renal replacement
therapy.3 Survival of cardiac surgery patients with
renal injury decreases progressively with the degree
of renal damage.4 In addition, patients surviving an
episode of AKI are at high risk for developing chronic
kidney as well as heart diseases.4 AKI has been shown
to be an independent predictor of mortality and con-
tributor to health care costs.5,6 It is estimated that AKI
costs 300,000 lives, contributes to 300,000 advanced
chronic kidney diseases, and costs an estimated $1
billion annually.7 Especially in the cardiac surgical
setting, inflammatory reactions caused by ischemia-
reperfusion injury are the main contributing factors
for AKI development.8,9 Several trials have been per-
formed investigating different measures to prevent or
treat AKI, however, without any success.10
In 2012, the Kidney Disease: Improving Global
Outcomes (KDIGO) AKI guidelines were published.11
They include recommendations based on expert opin-
ion to initiate various different supportive measures
related to volume management, hemodynamics, and
judicious avoidance of nephrotoxins in patients at
high risk for AKI.11 Since then, 2 prospective, single-
center, randomized controlled trials showed that the
implementation of the KDIGO bundle in high-risk
patients significantly reduced the occurrence of AKI
after surgery, while one other study did not show a
benefit of such a strategy.12–14
Funding: The trial was supported by the European Society of Intensive Care
Medicine and by the German Research Foundation (ZA428/14-1, KFO 342/1,
ZA 428/18-1, ZA 428/10-1, ME 5413/1-1). The content of this article is solely
the responsibility of the authors and does not necessarily represent the offi-
cial views of the funding agency.
Conflicts of Interest: See Disclosures at the end of the article.
M. Küllmar and R. Weiß contributed equally and share first authorship.
M. Meersch and A. Zarbock contributed equally and share last authorship.
The trial was registered at clinicaltrials.gov (NCT 03244514).
Reprints will not be available from the authors.
Address correspondence to Alexander Zarbock, MD, Department of Anes-
thesiology, Intensive Care and Pain Medicine, University Hospital Münster,
Albert-Schweitzer-Campus 1, Gebäude A1, 48149 Münster, Germany. Ad-
dress e-mail to zarbock@uni-muenster.de.
Compliance with the KDIGO bundle in routine
clinical practice is unknown. We therefore performed
a multinational observational study to investigate the
compliance rate with the different components of the
KDIGO bundle.
METHODS
Study Design and Ethics
The prevention of cardiac surgery–associated AKI
by implementing the KDIGO guidelines in high-
risk patients identified by biomarkers (PrevAKI)
multicenter trial is a 2-phase observational and ran-
domized controlled multicenter trial conducted in
12 centers across Europe (Belgium, Germany, Italy,
Spain, United Kingdom). The observational cohort
study was performed during a 2-day period before the
randomized controlled intervention study between
November 2017 and October 2019. The trial was
approved by the Ethics Committee of the Chamber
of Physicians Westfalen-Lippe and the Westfalian
Wilhelm University Muenster (2017-291-f-S) and the
corresponding ethical review boards of all participat-
ing centers. The trial was registered at clinicaltrials.
gov before patient enrolment (NCT 03244514, princi-
pal investigator: Alexander Zarbock, date of registra-
tion: September 8, 2017) and followed Consolidated
Standards of Reporting Trials (CONSORT). It was con-
ducted according to the principles of the Declaration
of Helsinki (version Fortaleza, 2013).
Patient Recruitment
With written informed consent, patients undergoing
cardiac surgery with cardiopulmonary bypass were
included during a 2-day period before the interven-
tion phase. There was no change in clinical manage-
ment. Every patient was treated according to the
practice and standards of the respective centers.
Data Collection and End Points
Clinical data included patient demographics and sur-
gical data, AKI rates, and compliance rates with the
individual KDIGO bundle components.
The primary end point of this observational study
was the adherence with the KDIGO bundle up to 72
hours postoperatively during intensive care unit (ICU)
stay consisting of (1) discontinuation of nephrotoxic

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 PrevAKI Multicenter Observational Trial
agents, (2) optimization of volume status and hemo-
dynamics, (3) functional hemodynamic monitoring,
(4) close monitoring of serum creatinine and urine
output, (5) avoidance of hyperglycemia, and (6) avoid-
ance of radiocontrast agents. The specific parameters
were defined as follows: optimization of volume sta-
tus and hemodynamic parameters, target mean arte-
rial pressure (MAP) ≥65 mm Hg (not fulfilled if MAP
was <65 mm Hg and no treatment was initiated to
achieve this goal); application of functional hemody-
namic monitoring including echocardiography, pulse
contour cardiac output (PICCO), or pulmonary artery
catheter (PAC); close monitoring of serum creatinine
every 12 hours and urine output hourly; hyperglyce-
mia was defined as blood glucose levels >150 mg/dL
or >8.3 mmol/L for more than 2 consecutive hours.
Secondary outcomes include the incidence and the
severity of AKI as defined by the KDIGO criteria
(serum creatinine and urinary output) within 72 hours.
Statistical Analysis
No power analysis was performed for this observational
cohort study. The primary end point was the binary
indicator of whether the KDIGO bundle was com-
pletely fulfilled at all time or not. Descriptive statistics
are summarized for categorical variables as frequency
(%) and were compared between groups with χ2 test.
Continuous variables, expressed as mean (standard
deviation [SD]), were compared between groups with
an unpaired Student t test. Continuous variables which
were not normally distributed were analyzed using
nonparametric test (Mann-Whitney U and Wilcoxon for
unpaired and paired observations, respectively). No for-
mal statistical hypothesis was tested. Statistical analyses
were performed with IBM SPSS Statistics (Version 25).
RESULTS
A total of 95 patients were enrolled (Figure 1). Baseline
characteristics of the AKI and non-AKI patients are
provided in the Table. There were no differences in
baseline characteristics, except that more patients in
the AKI group had congestive heart failure (P = .021).
Twenty-three patients (24.2%) developed postoper-
ative AKI as defined by the KDIGO criteria (AKI stage
1 [n = 16; 16.8%], AKI stage 2 [n = 5; 5.2%], and AKI
stage 3 [n = 2; 2.1%]).
A total of 5.3% of all patients were managed
according to all 6 supportive measures of the bun-
dle. Nephrotoxic drugs were discontinued in 52.6%
patients, volume optimization was performed in
70.5%, 52.6% of patients received functional hemo-
dynamic monitoring, close monitoring of serum cre-
atinine every 12 hours and urine output every hour
was performed in 24.2% of patients, hyperglycemia
was avoided in 41.1% of the patients, and no patient
received radiocontrast agents (Figure 2).
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Figure 1. Participant flow.
Patients received on average 3.4 (SD ±1.1) measures
out of 6 supportive measures as recommended by the
KDIGO guidelines (Figure 3). In AKI patients, neph-
rotoxic drugs were discontinued in 39.1% patients,
volume optimization was performed in 73.9%, 60.8%
of the patients received functional hemodynamic
monitoring, close monitoring of serum creatinine and
urine output was performed in 13%, hyperglycemia
was avoided in 34.7% of the patients, and no patients
received radiocontrast agents (Figure 2). AKI patients
received the same number of supportive measures
compared to patients who did not develop an AKI
(3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347).
DISCUSSION
The KDIGO guidelines recommend a bundle of sup-
portive measures in patients at increased risk for
AKI.11 However, adherence with the KDIGO bundle
in routine clinical practice is unknown. In this mul-
tinational observational cohort study, we investi-
gated the adherence rate in cardiac surgery patients
and demonstrated that compliance with the whole
KDIGO bundle was low. All 6 measures of the bundle
were applied to only 5.3% of patients, and in 37.9% of
patients, only 3 elements were applied. Furthermore,
adherence with the KDIGO bundle was not different
between patients with and without AKI after cardiac
surgery.
Patients undergoing cardiac surgery are particu-
larly susceptible to the development of AKI. Even
small increases of serum creatinine indicating mild
disruptions of kidney function have been shown to be
associated with the development of AKI.15 There are
some molecular approaches that might be effective
in the prevention or treatment of AKI.16–18 However,
implementing simple preventive measures as recom-
mended by the KDIGO guidelines prevents the appli-
cation of substances with potential side effects and
represents a safer option. Most critically ill patients
have several concurrent medical problems. As a result,
clinicians are often expected to follow several different
guidelines simultaneously. In general, the compliance
ANESTHESIA & ANALGESIA
 EE Original Clinical Research Report

Table. Demographics and Operative Characteristics

Overall Non-AKI AKI
(n = 95) (%) (n = 72) (%) (n = 23) (%) P
Sex .466
Female 35 (36.8) 25 (34.7) 10 (43.5)
Male 60 (63.2) 47 (65.3) 13 (56.5)
Congestive heart failure 20 (21.1) 11 (15.3) 9 (39.1) .021
EF < 35% 6 (6.3) 4 (5.6) 2 (8.7) .630
CKD (GFR >30 mL/min) 95 (100) 72 (100) 23 (100) …
Creapre 1.2–2 mg/dL 18 (18.9) 12 (16.7) 6 (26.1) .363
Creapre >2.1 mg/dL 0 (0.0) 0 (0.0) 0 (0.0) …
COPD 5 (5.3) 2 (2.8) 3 (13.0) .090
Insulin-dependent diabetes mellitus 8 (8.4) 6 (8.3) 2 (8.7) 1.000
Previous heart surgery 12 (12.6) 7 (9.7) 5 (21.7) .155
Emergency surgery 5 (5.3) 2 (2.8) 3 (13.0) .90
Type of surgery
CABG 22 (23.2) 19 (26.4) 4 (17.4) .260
Valve 48 (50.5) 32 (44.4) 14 (60.9) .339
CABG + valve 9 (9.5) 7 (9.7) 2 (8.7) 1.000
Other surgery 17 (17.9) 14 (19.4) 3 (13.0) .750
Abbreviations: AKI, acute kidney injury; EF, ejection fraction; CABG, coronary artery bypass graft; CKD, chronic kidney disease; COPD, chronic obstructive
pulmonary disease; CreaPre, preoperative serum creatinine; GFR, glomerular filtration rate; SCr/UO, serum creatinine/urine output.

Figure 2. Implementation of the bundles as recommended by the KDIGO guidelines in all patients (black bars) and in patients with AKI (grey
bars). AKI indicates acute kidney injury; KDIGO, Kidney Disease: Improving Global Outcomes; SCr/UO, serum creatinine/urine output.

rate with guidelines ranges approximately between
1% and 75% in critically ill patients but may drop
further if multiple bundles have to be applied at the
same time.19 It is important to note that the compli-
ance rate is not influenced by the complexity of the
implemented measure. An observational trial demon-
strated that only 34% of septic patients were treated
according to the sepsis guidelines. Similarly, a sim-
ple measure such as the use of low tidal ventilation
in acute respiratory distress syndrome (ARDS) was

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 PrevAKI Multicenter Observational Trial
Figure 3. Number of supportive measures applied in the cohort.
applied in only one-third of patients.19 Importantly,
increased compliance with guidelines was associated
with significantly better patients’ outcomes.20
The KDIGO recommendations specifically empha-
size that the supportive measures should be followed
in patients with increased risk for AKI but not neces-
sarily in all patients.11 The reason for this notion is that
some of the recommended supportive measures are
also associated with potential adverse events, includ-
ing bleeding, thrombosis, arrhythmias, ischemia, and
hypoglycemia.21,22 In addition, it is not feasible to
implement the KDIGO bundles in all patients because
this is time consuming and cost-intensive.
Although the KDIGO guidelines suggest to man-
age the patients with AKI according to the stage and
cause, this recommendation was not graded, mainly
because at the time of publication, there were no stud-
ies confirming the benefits of this approach. However,
since then, several trials have demonstrated that the
implementation of the KDIGO bundle in high-risk
patients as identified by biomarkers significantly
reduced the occurrence of AKI.12,13 As recommended
in the KDIGO guideline, optimizing volume status
and hemodynamics are 2 important measures that
may prevent renal impairment and reduce the need
for renal replacement therapy.23,24 Both approaches
aim to increase oxygen delivery to prevent or cor-
rect deficiency in oxygen delivery. These goals can be
achieved in different ways, and the participating cen-
ters used different devices and different methods to
achieve these goals. Therefore, the results might rep-
resent differences in clinical practice.
The study has some notable strengths. To date, this
is the first study that investigates compliance with 6
supportive measures that are recommended in the
KDIGO AKI guidelines. Our findings demonstrate
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that the adherence rate in daily clinical practice is low,
although single-center trials have shown a reduced
AKI rate in high-risk patients.12,13 Finally, if future
multicenter studies confirm that the KDIGO bundle
can prevent AKI, then the KDIGO bundle will become
one of the most powerful interventions in clinical care.
We recognize that the study has also some limi-
tations. First, the nature of this observational study
may have led to some unknown bias that, rather than
interventions, may actually be the cause of the differ-
ences in compliance with interventions. Second, we
did not differentiate between different etiologies of
AKI. It is certainly possible that the response to the
KDIGO bundle varies in different types of AKI (eg,
glomerulonephritis). Finally, the sample size was
small and may explain why we failed to demonstrate
an association between compliance with the KDIGO
bundle and AKI occurrence.
These pilot data suggest that compliance with the
KDIGO bundle is low in routine clinical practice and
that the bundle is not specifically applied to patients
with an increased risk for AKI or patients with an
already established AKI. Efforts to improve outcome
from AKI should focus on increasing compliance with
these evidence-based interventions in appropriate
patients. E
ACKNOWLEDGMENTS
The authors thank all the participating centers and cor-
responding staff members involved in this trial.
DISCLOSURES
Name: Mira Küllmar, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Raphael Weiß, MD.
ANESTHESIA & ANALGESIA
 EE Original Clinical Research Report
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Marlies Ostermann, MD.
Contribution: This author helped design the trial; perform the
study; and draft the manuscript, and read and approved the
manuscript.
Conflicts of Interest: M. Ostermann has received lecture fees
from Biomerieux, Fresenius Medical, and Baxter.
Name: Sara Campos, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Neus Grau Novellas, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Gary Thomson, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Michael Haffner, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Christian Arndt, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: C. Arndt has received lecture fees from
Baxter.
Name: Hinnerk Wulf, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Marc Irqsusi, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Fabrizio Monaco, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Ambra Licia Di Prima, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Mercedes García-Alvarez, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Stefano Italiano, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Mar Felipe Correoso, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Gudrun Kunst, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Shrijit Nair, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Camilla L’Acqua, MD.
April 2020 • Volume 130 • Number 4
Copyright © 2020 International Anesthesia Research Society. Unauthorized reproduction of this article is prohibited.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Eric Hoste, MD.
Contribution: This author helped design the trial; perform the
study; and draft the manuscript, and read and approved the
manuscript.
Conflicts of Interest: E. Hoste has received traveling and lecture
fees from Astute Medical, Alexion, Sopachem, and AM Pharma.
Name: Wim Vandenberghe, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Patrick M. Honore, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: John A. Kellum, MD.
Contribution: This author helped design the trial and draft the
manuscript, and read and approved the manuscript.
Conflicts of Interest: J. A. Kellum has received lecture fees from
Astute Medical, Fresenius and Baxter, unrelated to the current
study and received grant support from Astute Medical, unre-
lated to the current study.
Name: Lui Forni, MD.
Contribution: This author helped design the trial and draft the
manuscript, and read and approved the manuscript.
Conflicts of Interest: L. Forni has received research funding
from Baxter and Ortho Clinical Diagnostics, consultancy fees
from Medibeacon/La Jolla Pharmaceuticals, and honoraria
from Biomerieux/Astute.
Name: Philippe Grieshaber, MD.
Contribution: This author helped perform the study and draft
the manuscript, and read and approved the manuscript.
Conflicts of Interest: None.
Name: Carola Wempe, MSc.
Contribution: This author helped design the trial; perform
study coordination; and draft the manuscript, and read and
approved the manuscript.
Conflicts of Interest: None.
Name: Melanie Meersch, MD.
Contribution: This author helped conceive the study; design
the trial; perform study coordination; and draft the manuscript,
and read and approved the manuscript.
Conflicts of Interest: M. Meersch has received lecture fees from
Astute Medical, Fresenius, and Baxter, unrelated to the current
study.
Name: Alexander Zarbock, MD.
Contribution: This author helped conceive the study; design
the trial; and draft the manuscript, and read and approved the
manuscript.
Conflicts of Interest: A. Zarbock has received lecture fees from
Astute Medical, Fresenius, and Baxter, unrelated to the current
study and received grant support from Astute Medical, unre-
lated to the current study.
This manuscript was handled by: Jean-Francois Pittet, MD.
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