Trends in Anaesthesia and Critical Care 3 (2013) 62e67

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Trends in Anaesthesia and Critical Care

journal homepage: www.elsevier.com/locate/tacc

REVIEW

Acute kidney injury in ICU

Zaccaria Ricci*
Department of Pediatric Cardiology and Cardiac Surgery, Pediatric Cardiac Intensive Care Unit, Bambino Ges Childrens Hospital, IRCCS, Piazza S.Onofrio 4, 00165 Rome, Italy

s u m m a r y
Keywords:
Acute kidney injury
RIFLE criteria
Diuretics
Prevention
Renal replacement therapy
Dialysis dose

This review will describe the new era of critical care nephrology by presenting the current literature
(and its many controversies) concerning the diagnosis, physiopathology and management of acute
kidney injury (AKI). A conventional denition for the acute changes of renal function, previously lacking
in the medical community, has recently been proposed in order to gather and compare the experiences
of different centres relating to AKI incidence and management. Such a new denition is actually a classication that describes renal damage as a spectrum of progressive damage, from mild creatinine
increase to renal injury and through to a more severe form, failure: preventive measures, medical
treatment and dialysis can now be standardized and data collected in order to improve the outcome of
critically ill patients with AKI.
2012 Elsevier Ltd. All rights reserved.

1. Introduction
Critical care nephrology has recently gained an increased interest since clinicians operating in the eld of critical illness realized that the dysfunction of the renal system in their patients was
always associated e as a victim or as a potential culprit e with
worse outcomes. Hence, several groups started intense work both
at an experimental and clinical level, in order to improve comprehension and management of acute renal dysfunction syndrome.
This review will present the most important aspects of this work,
highlighting the several controversies and unsolved problems that
will need to be addressed in the future.
2. Denition and epidemiology of AKI
Renal dysfunction is a complex syndrome, including several
different clinical pictures and aetiologies. For this reason it is only
recently that the term acute kidney injury (AKI) has been coined 1
in place of the former expression acute renal failure, and conventional denitions of acute changes in renal function have nally
been proposed.1e3 It is now clear that renal dysfunction ranges
from a low level (or risk of being injured), to an actual injury
(with reduced but still present renal function), to a denitive
failure (severely reduced or lost renal physiology): this is the idea
at the base of the RIFLE criteria.1 Such an acronym conventionally
described 3 stages of progressively higher creatinine levels or

* Corresponding author. Tel.: 39 06 6859 2449; fax: 39 06 6859 2670.

E-mail addresses: z.ricci@libero.it, zaccaria.ricci@opbg.net.
2210-8440/$ e see front matter 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tacc.2012.12.005

decreased urine output ows (risk, injury, and failure) and 2 outcomes (loss of function and end stage kidney disease). Subsequently the Acute Kidney Injury Network (AKIN) introduced small
though important modications to this classication2: a number of
comparative studies could not show signicant differences in their
diagnostic/prognostic performance.4
The recent enthusiasm of basic research on AKI diagnosis
highlighted the fact that renal dysfunction begins long before sufcient loss of excretory kidney function can be detected with
standard laboratory tests. This happens because urea and creatinine are insensitive markers of glomerular ltration rate (GFR)
and are modied by nutrition, the use of steroids, the presence of
gastrointestinal blood, muscle mass, age, gender, or muscle injury.5
Furthermore, creatinine starts increasing only when more than 50%
of GFR is lost, therefore it cannot reect GFR trends and may be
diluted after aggressive uid resuscitation.6 New techniques based
on proteomics have identied several novel biomarkers of AKI:
cystatin C (CysC), neutrophil gelatinase associated lipocalin (NGAL),
interleukin 18 (il-18), kidney injury molecule 1 (kim-1), and many
others (Table 1).7 A biochemical panel can be hypothesized based
on the different features of each of them. In many pivotal studies
biomarkers showed changes earlier than changes in serum creatinine.8 Others appeared to reect the different aetiologies of renal
injury.9 Then, they seemed to dynamically change with treatment
or recovery, which suggests that they can be used to monitor interventions.10 In recent studies subpopulations of patients who did
not have AKI according to creatinine-based criteria, but actually had
a degree of subclinical renal damage, were identied by biomarkers
and associated with worse outcomes.11 Finally, by identifying
possible mechanisms of injury, these biomarkers might increase

Z. Ricci / Trends in Anaesthesia and Critical Care 3 (2013) 62e67

Table 1
Classication of biomarkers at different sites of action.
Proximal tubules

Glomerulus

Distal
tubules

Collecting Loop of
duct
Henle

Kim-1
Clusterin
NGAL
GST-a
b2-microglobulin
a1-microglobulin
NAG
Osteopontin
Cystatin C (urinary)
Netrin-1
RBP
IL-18
HGF
Cyr61
NHE-3
Exosomal fetuin-A
L-FABP
Albumin

Total protein
Cystatin C (urinary)
b2-microglobulin
a1-microglobulin
Albumin

Osteopontin Calbindin Osteopontin

Clusterin
D28
NHE-3
GST-m/p
NGAL
H-FABP
Calbindin
D28

our understanding of the pathogenesis of AKI and/or help in the

prognosis/triaging of AKI syndrome.12 Although urinary NGAL and
CysC are probably the most studied renal biomarkers, many other
molecules are also currently being investigated. A long road lies
ahead before any positive association between the biomarkers used
(and their relative costs) and hard clinical outcomes are shown.
The recent classication effort, however, has led to an improved
perception concerning actual AKI incidence in the critically ill
population. Recently, a web-based data collection survey13 conducted in 10 Italian intensive care units (ICU) found that absolute
AKI incidence is high (more than one third of all admissions) with
30%, 20% and 50% of these patients stratied across the three AKI
severity classes, risk, injury and failure, respectively. Almost two
thirds of AKI cases were diagnosed within 24 hours of ICU admission. AKI is associated with a crude ICU mortality (28.8% vs. non-AKI
8.1%) and long ICU length of stay (median 7 days vs. non-AKI 3
days).13 According to this survey, about 12% of AKI patients were
treated with renal replacement therapy (RRT) in the ICU. Patients
were started on RRT a median of 2 (IQR 0e6) days after ICU
admission.13 60% of AKI patients had complete renal function recovery, 13.5% had partial renal recovery, while about 30% did not
recover renal function at the time of death or ICU discharge. Septic
patients had more severe AKI, and were more likely to receive RRT
with less frequency of renal function recovery. Patients with sepsis
had higher ICU mortality and a longer ICU stay.13
3. Aetiology
AKI aetiology is multifactorial and each AKI episode should be
diagnosed and managed separately. As a matter of fact a critically ill
patient may suffer a single AKI episode whose severity will be
directly proportional to the number of aetiological agents or multiple renal attacks14 for different causes in different phases of his/
her clinical history. Several variables and extremely different clinical conditions are involved in the reduction of renal function and
make it difcult to t exactly all types of AKI into a single pathophysiologic pathway. What has currently been claried, however, is
that since a renal histological diagnosis is rarely performed, a clear
distinction between the most severe forms of pre-renal AKI and
tubular damage (tubular necrosis) is never possible and it can only
be retrospectively hypothesized. A recent 10-year retrospective
multicentre French study of 77 critically ill patients with AKI who
underwent renal biopsy showed that, in spite of a relatively high

63

number of complications, only 18% were diagnosed with acute

tubular necrosis.15
The previously used pre-renal, post-renal and intra-renal AKI
classication seems today somewhat supercial and has lost its
physiopathological validity.5 Today, it seems more logical to dene/
diagnose AKI by a classication score and contextualize the aetiology in the clinical setting. Hence, the most common forms of
acute renal dysfunction are septic AKI, post-surgical AKI, postcardiosurgical AKI, isolated AKI (typically, when a primary renal
disease requires intensive care unit assistance), nephrotoxic AKI,
contrast induced nephropathy. Paediatric AKI is also a form of acute
renal dysfunction with several peculiar aspects, especially as far as
neonatal immature kidneys are concerned.
As a consequence, in this light, each type of AKI might be
viewed as a mixture of several injuries: certainly, renal hypoperfusion/hypoxia is involved in AKI pathogenesis since haemodynamically unstable patients and cardiac failure subjects are most
frequently affected by AKI. Furthermore normotensive AKI has been
described as a consequence of intra-renal haemodynamic
changes.16 A small interesting study on established septic AKI,
evaluated by cine phase-contrast magnetic resonance, concluded
that renal blood ow (RBF) fraction of cardiac output appears signicantly reduced when compared with normal healthy individuals (7% vs. 20%).17 However, measurement of RBF in patients
with established AKI depends on organ oedema, tubular injury,
back-leak and increased tubular luminal pressure5: hence, RBF
reduction may be the consequence of, rather than the mechanism
responsible for AKI. Causes of RBF reduction may be identied in
sympathetic system activation,18 kidney-specic neurohormonal
activation of the renin angiotensin system (RAAS)18 and activation
of the tubulo-glomerular feedback (TGF) system.18 In particular,
during septic AKI, infection might lead to an induction of nitric
oxide synthase and nitric oxide mediated arterial vasodilatation
and secondary activation of the sympathetic system, RAAS activity
and renal vasoconstriction.18 Arginine vasopressin seems to have
a role too, contributing to water retention.18 Complex neurohormonal feedback may also cause intra-renal shunting with
decreased GFR and ischaemia of the renal medulla. Hence, microcirculation is nally affected, suggesting that, even if one could
measure global RBF, unless the microcirculation is also assessed,
estimation of renal perfusion is signicantly limited.18 Kidney
perfusion cannot explain all AKI cases: hence, local activation of
the coagulation system, inltration of the kidney by leukocytes,
endothelial injury, expression of adhesion molecules, release of
cytokines, induction of toll-like receptors, activation of intra-renal
vasoconstrictor pathways and induction of apoptosis have been
examined.18 There are also associated changes in tubular cells with
loss or inversion of polarity and loss of adhesion to the basement
membrane.18 Unfortunately, these experimental models have never
been exactly associated with a specic clinical state or with a precise treatment algorithm.
Quite interestingly, attention is increasing on genetic factors
associated with AKI incidence. It is a common experience that different clinical pictures and outcomes frequently characterize patients with nearly identical forms of AKI. A recent multicentre study
of AKI in severe sepsis and septic shock evaluated the association
between inammatory phenotype and HLA genotype in 176 critically
ill patients19: the authors found that severe AKI" had higher levels of
plasma interleukin-10, migration inhibitory factor and interleukin-6
compared to no AKI and mild AKI. HLA-DRB genotyping, furthermore, showed a protective" effect on the presence of 4 alleles
for HLA-DRB, that were signicantly more present in patients with
severe AKI who did not receive RRT (84%) than among patients
requiring RRT (58%).19 This kind of genetic approach will presumably
guide therapy timing and type in the next future.

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Z. Ricci / Trends in Anaesthesia and Critical Care 3 (2013) 62e67

4. Prevention of AKI
Avoiding AKI occurrence is probably the best way to improve the
outcome of critically ill patients with renal dysfunction. Hence,
when possible, patients should not receive potentially nephrotoxic
drugs such as vancomycin, aminoglycosides, contrast agents and
acetyl salicylic acid, especially in patients with additive risk factors
for AKI development (elderly, diabetic, congestive heart disease or
chronic renal failure patients)20 (Table 2). Furthermore, management of renal perfusion is mandatory in the initial phases of the
shock state: typically a colloid/crystalloid 10e40 ml/kg intravenous
uid challenge is considered the rst line therapy to target a mean
arterial pressure of 65 mmHg and a central venous pressure of 12e
15 mmHg (in case of mechanical ventilation).21 An on going debate
has not fully elucidated so far (but evidence is growing in this
sense) about whether colloids can be infused and if they can be
safely used on critically ill patients, especially in light of their potential nephrotoxic role.22,23 Chloride containing crystalloid solutions, however, cannot be considered harmless as well.24,25
Unfortunately, today, no striking evidence from human data, contradictory animal studies and no understanding of the physiological
effects of uid bolus resuscitation in critically ill patients exists.26 If
restrictive uid management of haemodynamically unstable patients is considered, an early and aggressive use of vasopressors
should be recommended in order to restore adequate perfusion
pressure after an initial moderate uid administration.26 In this
light, norepinephrine seems to be the drug of choice and its benecial effects on renal perfusion have been clearly shown in an
interesting experimental model.27 Vasopressin (antidiuretic hormone) is another powerful agent for rapid and effective increase of
systemic resistances and mean arterial pressure.28 It is important to
highlight that vasopressors, when carefully titrated to the minimal
dose able to restore mean arterial pressure in critically ill patients,
are not harmful for kidney function and may be potentially
benecial.
5. Medical therapy for AKI
Medical therapy for AKI, so far, does not exist. Several specic
medications for septic AKI have been attempted in the last ten years
but their use in the clinical eld has hopelessly failed, so far. This
frustrating list includes low dose dopamine, recombinant human
insulin-like growth factor-I (rhIGF-I), recombinant human activated
protein C (rhAPC) and human atrial natriuretic peptide (ANP).18 The
reason for such negative results (usually preceded by encouraging
experimental successes and small positive clinical trials) lies partly
on low statistical power, lower than expected drug efcacy,
underestimated side effects, lack of a consensus denition of AKI in
previous trials, improper end points, difculty in timely administration of the drug, adverse effects of the drug and patient heterogeneity.18 Furthermore the complex physiopathology of septic
AKI, as detailed above, is due to the activation of multiple and not

always predictable overlapping pathways that, at the macroscopic

clinical level, converge into loss of renal function. In this light, it is
unlikely that targeting events that occur late in AKI or even a single
pathway will be effective.
Diuretics, in particular loop diuretics, exemplify the typical
symptomatic medication of critically ill patients with oliguric AKI.
Loop diuretics (furosemide and ethacrynic acid) act on the medullary thick ascending loop of Henle to inhibit the Na/K/2Cl
pump on the luminal cell membrane surface and reduce oxygen
demand. Diuretics main role is to manage volume overload and
optimize acidebase and electrolyte homeostasis. Currently, however, controversy exists as to whether or not diuretics can actually
reduce or delay RRT use and eventually improve clinical outcomes
in sepsis and septic AKI.29 Thus, although a strong rationale for their
use seems to exist, understanding how and when diuretics should
be used is limited. Most interestingly, however, a recent post hoc
analysis,30 from the Fluid and Catheter Treatment Trial (FACTT)
study, which evaluated a conservative versus liberal uid management strategy in patients with acute lung injury, showed that
a positive uid balance after AKI was associated with 60-day
mortality, that the risk of death in patients with acute lung injury
and AKI was approximately 1.6-fold higher per litre/day of uid
accumulated and, importantly, that diuretic use after AKI was
associated with decreased mortality, with the protective effect on
60-day mortality being limited after adjustment for uid balance.
This analysis suggested that the benet of furosemide in critically ill
patients was derived from the resultant optimization of uid
overload.
It might be that new strategies to treat or prevent AKI will
require compounds that target pathways that are more proximal to
onset or that affect multiple pathways rather than only one. A
detailed specication of new drugs for AKI therapy, not yet fully
evaluated in clinical trials, would go beyond the scope of this review (Table 3). Two interesting approaches, however, deserve to be
mentioned because they will reach a wider clinical application in
the future: renal remote ischaemic preconditioning and use of
mesenchymal stem cells for the treatment of AKI at the histological
level. In the rst case, ischaemic preconditioning (IPC) is a potent
protective strategy in which the application of a brief episode of
ischaemia and reperfusion results in a tolerance to subsequent
injury. The conditioning stimulus has been shown to be effective
when applied either to the target organ itself or to a remote organ
or tissue (remote IPC, RIPC). IPC was originally discovered and
practiced in the heart, and has been successfully reproduced in
a variety of other organs, e.g. the intestine, brain, liver and kidney.31
The kidney is obviously one of the major organs of interest for the
clinical application of IPC because of its particular sensitivity to
ischaemia-reperfusion injury, especially in a cardiac surgery setting. Experimental models have shown IPC to protect the kidney:
it reduces serum creatinine, blood urea nitrogen and histological
renal damage as compared to controls. Factors inuencing IPC
efcacy were the window of protection (<24 h early vs.

Table 2
Classication of different nephrotoxins at renal sites of action.
Proximal tubules

Glomerulus

Distal tubules

Collecting duct

Loop of Henle

Cyclosporine Tacrolimus
Cisplatin Vancomycin Gentamicin
Neomycin Tobramycin Amikacin
Ibandronate Zoledronate
Hydroxyethyl starch Contrast
agents Foscarnet
Cidofovir Adefovir Tenofovir
Intravenous immune Globulin

Doxorubicin (adriamycin)
puromycin gold pamidronate
penicillamine

Cyclosporine tacrolimus
sulfadiazine lithium (chronic)
amphotericin B

Amphotericin B
acyclovir lithium
(acute)

Non steroidal antiinammatory agents

(chronic)

Z. Ricci / Trends in Anaesthesia and Critical Care 3 (2013) 62e67

Table 3
Medical therapy of AKI currently under examination for clinical use.
Antiapoptosis/
necrosis

Anti-inammatory Antisepsis Growth factors Vasodilators

Caspase
inhibitors
Minocycline
Guanosine
Pithrin-alpha
PARP
inhibitor

Sphingosine 1
phosphate analog
Adenosine 2A
agonist
Alpha-MSH
IL-10
Fibrate
PPAR-gamma
agonist

iNOS
inhibitor
ethyl
pyruvate

Recombinant
erythropoietin
hepatocyte
growth factor

Endothelin
antagonist
fenoldopam

24 h late) and animal species. However, current clinical trials on

renal IPC are still lacking, and probably further standardization of
animal experiments is required before the clinical phase is
reached.31
As far as mesenchymal stem cell therapy is concerned, it has
been hypothesized that they might have been differentiating into
organ parenchymal cells and such a promising approach is currently under investigation for different organs. However, in the
kidney, benets have been attributed mainly to paracrine mechanisms: mesenchymal stem cells release a number of trophic, antiinammatory, and immune-modulatory factors that may limit
kidney injury and favour recovery. Preclinical and clinical data are
still at an early stage.32
On the clinical eld, an isolated positive investigation evaluated
the administration of bovine alkaline phosphatase (AP) in sepsis
patients with AKI.33 AP is an endogenous enzyme that acts through
dephosphorylation of endotoxins and pro-inammatory extracellular ATP with a specic local action on renal tubules. In this trial,
AP signicantly improved renal function, indicated by the authors
with a composite endpoint including endogenous creatinine
clearance, RRT requirement and duration of dialysis. The ndings of
this study were further reinforced by a signicant reduction in
some of the evaluated circulating inammatory markers (C-reactive protein, Interleukin-6, LPS-binding protein) and urinary
markers of tubular injury (KIM-1 and IL-18) in AP-treated patients
compared to placebo.
In conclusion, specic medical therapy for renal dysfunction is
not currently available in routine clinical practice. Critically ill patients primarily benet from preventive measures, aggressive
haemodynamic optimization, proper management of uid balance
and avoidance of overload. Medical (supportive) therapy for severe
AKI, so far, can be considered a strategic method to gain time before
extracorporeal renal support is decided.
6. Renal replacement therapy of AKI
Articial blood purication and renal function substitution are
indicated when kidney dysfunction is severe enough to cause acute
harm to the patient. Given this consideration, it is clear that the best
time to start RRT is controversial and difcult to establish. Several
observational studies evaluating timing described early RRT as
benecial34: as it happened for AKI diagnosis, however, currently
no standard denition of RRT timing exists and, above all, it has not
been claried in respect of what we should dene as early timing
(ICU admission? AKI diagnosis? Severe AKI diagnosis? Sepsis
occurrence? Fluid balance?).35
Once RRT is indicated, a prescription on dialysis dose has to be
made and the treatment carefully delivered. Intensity of a dialytic
treatment could be roughly indicated by the amount of dialysis/
haemoltration ow delivered to the patient: after the milestone
trial by a group in Vicenza in 2000,36 such a ow has been indexed

65

in patients body weight, in order to highlight that this variable is of

practical importance in AKI patients. Two large multicentre randomized controlled studies published in 2009 (the randomized
evaluation of normal versus augmented level (RENAL) replacement
therapy study37 and the VA/NIH Acute Renal Failure Trial Network
(ATN) study38) nally claried the concept of optimal dialysis dose.
The RENAL and ATN studies were designed to compare normal or
less intensive renal support to an augmented or intensive
therapy: in particular, the RENAL study compared 25 ml/kg per h
continuous venovenous haemodialtration (CVVHDF) to 40 ml/kg
per h; the ATN study compared 20 ml/kg per h CVVHDF or thrice
weekly intermittent dialysis to 35 ml/kg/h CVVHDF or daily intermittent dialysis. Surprisingly, both studies showed that increases in
the intensity of the RRT dose did not improve patient outcomes,
essentially confuting a large body of evidence coming from previous smaller trials. As a consequence, the denition of normal dose
is now recommended in a range of 20e30 ml/kg per h for continuous therapies and/or thrice weekly intermittent haemodialysis.
Interestingly, a recent survey conrmed that at the bedside, clinicians commonly apply these recommendations.39 An online questionnaire that included questions about RRT management in
critically ill patients with acute kidney injury was sent to the European Society of Intensive Care Medicine members in 2010. The
273 respondents reported that the median prescribed ultraltration (UF) dose during CRRT was 35 ml/kg/h (25e35). For patients
with sepsis, the respondents reported using higher UF doses than in
the general ICU population (35 ml/kg/h (35e35) vs. 35 ml/kg/h
(25e35); p 0.03). Regarding the CRRT modality, half of the respondents (50.9%) reported using preferentially CVVHDF, 40.6 %
reported using continuous venovenous haemoltration (CVVH)
and 9.0 % reported using continuous venovenous haemodialysis
(CVVHD).
No randomized controlled trials have addressed the issue of RRT
stop. Observational studies have suggested that urine output during RRT can be used to predict successful weaning. A spontaneous
urine output >500 ml/day seems to have sufcient discrimination
to be used for the purpose of considering a trial of RRT cessation.40
Furthermore uid balance has recently been claimed as a major
outcome determinant of critically ill patients with AKI: it is possible
that a negative uid balance should be targeted in CRRT patients,
once haemodynamic stability has been warranted by initial resuscitation efforts. However, it is currently impossible to recommend
a priori the net UF rate that should instead be tailored on patients
needs. The authors of the RENAL trial recently conducted a retrospective analysis of the association between daily uid balance and
several hard clinical outcomes on a cohort of more than 1400 patients previously enrolled in the RENAL study.41 Interestingly, not
only did they nd that a negative mean daily uid balance during
the study treatment was independently associated with
a decreased risk of death at 90 days, increased survival time and
increased renal replacement-free days, intensive care unit-free
days and hospital-free days, they also showed how this association remained after adjustment for propensity and all available
markers of illness severity at randomization. Such a robust association between a positive uid balance and unfavourable outcomes suggests the need to decrease, as soon as clinically possible,
uid administration in patients with AKI or to specically target
negative uid balance during RRT.
7. Summary
The future of AKI management is still open and uncertain and
much work has been done on diagnosis and prevention. However,
the mortality of critically ill patients with AKI still remains high
(about 50%). It is possible that even a short episode of AKI may

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Z. Ricci / Trends in Anaesthesia and Critical Care 3 (2013) 62e67

contribute to long-term organ and patient morbidity and mortality.

Thus, this complex syndrome should be aggressively treated. It is
possible that a simple improvement in the therapy of AKIassociated clinical pictures will be more effective than the treatment of a single organ (namely, the kidney). However, genetics,
molecular biology and regenerative medicine are currently actively
operating in the eld of critical care nephrology and some results
will be visible at the bedside within the next 10 years. When RRT
becomes necessary, it is possible that the (critically ill) patient has
a clinical picture of multiple organ failure and the probability of
survival further decreases: a correct dialysis prescription and delivery, avoidance of dialysis underdosing and prevention of harmful
complications (such as hypotension and bleeding) are currently
recommended to target standard of care. AKI survivors have to be
followed up as progression to chronic renal failure is currently
increasing.

Box 1.
It has to be remarked that a definition should not be
confused with the concept of aetiological diagnosis: RIFLE criteria, for example, was not developed to identify the
cause of AKI but only to identify it in a standardized way.
Today, a renewed interest in AKI diagnosis, prevention and
treatment was raised by this huge amount of standardized
information and awareness of actual AKI incidents in several clinical settings, and of its lethal effects (even after
milder forms of renal impairment) that have dramatically
increased and some centres have already implemented the
RIFLE score into their databases and medical records.

Box 2.
The downtime (period of unintentional treatment stop)
should be taken into account when an RRT is initially prescribed: frequent interrupted treatments (due to poor catheter performance, inadequate anti-coagulation or lack of
experienced/trained staff on site) significantly reduce the
delivery of prescribed dialysis. In this light, a slightly greater
RRT dose might be selected in order to compensate for
a future downtime. Each clinician should be aware, when
prescribing RRT, of the alertness of their staff in order to restart an interrupted treatment: the current trend to decrease
the dialysis dosage, in light of the RENAL trial results,
should not push operators to accept an under-dialysis of
their critically ill patients.

7.1. Outstanding question

A great deal of interest is currently spent on the extracorporeal
treatment of multiple organ failure, resumed by the concept of
multiple organ support therapy. It will be interesting to assist with
the future development of such therapy in order to see if it will
actually be possible to integrate extracorporeal membrane oxygenation, haemoperfusion, haemo-absorption, plasmaltration
coupled with absorption, liver support therapy in a single userfriendly platform with exible prescriptions such that it will be
possible to easily and timely apply it in the setting of severe sepsis
and multiple organ failure.

Conict of interest statement

The author has no conict of interest to declare.
Glossary

AKI
GRF
RBF
CysC
NGAL
il-18
kim-1
ICU
RRT
RAAS
TGF
AP
CVVHDF
UF
CVVH
CVVHD

acute kidney injury

glomerular ltration rate
renal blood ow
cystatin C
neutrophil gelatinase associated lipocalin
interleukin 18
kidney injury molecule 1
intensive care unit
renal replacement therapy
renin angiotensin system
tubule-glomerular feedback
alkaline phosphatase
continuous venovenous haemodialtration
ultraltration
continuous venovenous haemoltration
continuous venovenous haemodialysis

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