Annals of Burns and Fire Disasters - vol. XXVI - n.

1 - March 2013

RENAL DYSFUNCTION IN BURNS: A REVIEW

Ibrahim A.E.,1* Sarhane K.A.,2 Fagan S.P.,1 Goverman J.1

Department of Surgery, Division of Burns, Massachusetts General Hospital, Harvard Medical School; Boston, Massachusetts, USA
1

Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine; Baltimore, Maryland, USA
2

SUMMARY. Acute kidney injury (AKI), although rare, is a major complication of burn injury that commonly leads to mortality.
It results from a complex interplay of various cellular and neuro-humoral changes affecting burn patients. Guidelines for the treat-
ment of this entity are still not well defined; therefore, prevention and early diagnosis are key to avoid the unfavorable prognosis
of AKI. These entail a comprehensive understanding of the global physiologic changes underlying the condition of burn patients
and a judicious interpretation of their continuous homeostatic alterations. The aim of this review is to present the salient features
in burn patient physiology that contribute to AKI. Strategies for identifying early AKI are presented. Finally, the different treat-
ment modalities are revisited.

Keywords: renal failure in burns, kidney dysfunction in burns, dialysis in burns, classification of kidney injury, treatment of renal
failure

Introduction these high risk patients requires a comprehensive under-

Acute kidney injury (AKI) is one of the most com-
mon serious complications in critically ill patients. Severe
AKI occurs in more than one of every twenty patients re-
quiring intensive care unit (ICU) care,1 and has been as-
sociated with mortality rates ranging from 50% to more
than 70%.1-4 In burn patients, AKI is a growing health con-
cern as it is associated with both short and long term ad-
verse events.5,6 These frequently lead to extended intensive
care unit stays and high mortality rates.7-11 Although kid-
ney function returns to normal for most burn survivors, a
minority require long-term dialysis. Despite decades of re-
search on the etiopathogenesis of AKI in thermal injury,
the treatment of this entity is still not well defined. Its
management remains supportive, focused on optimizing
fluid balance, treating acid-base and other electrolyte dis-
turbances, adjusting the dose of medications, and avoid-
ing secondary hemodynamic and nephrotoxic injury. De-
spite these conservative measures, renal replacement ther-
apy (RRT) using one or more of the multiple modalities
of dialysis and hemofiltration is often required.12 It is un-
clear, however, whether RRT during the resuscitation pe-
riod can ameliorate long-term morbidity and mortality.
Hence, the key strategy for dealing with AKI is preven-
tion. This will obviate the need for RRT (and its associ-
ated cost and side effects) and enable more targeted and
standing of the pathophysiology of renal dysfunction in
burns. The aim of the present article is to review the salient
features underlying the etiology and pathogenesis of AKI
associated with thermal injury and to summarize the effi-
cacy of the available diagnostic and treatment modalities.
Definition
Over the past few decades, definitions used to describe
AKI have varied widely; however, the common underly-
ing theme is an abrupt reduction in glomerular filtration
rate (GFR) with failure of the kidneys to regulate volume
and electrolyte homeostasis. In an effort to standardize the
definition of renal insufficiency, the International Acute
Dialysis Quality Initiative (ADQI) group developed the RI-
FLE criteria (Table I).10 This classification system relies
on a reduction in GFR or urine output as a means to de-
fine increasing levels of renal insufficiency. There are three
grades of increasing severity of renal insufficiency (Risk,
Injury, Failure) based on changes in either serum creati-
nine or urine output, as well as two outcome categories
(Loss and End-stage kidney disease). This system has been
validated in burn injuries where increasing grades corre-
spond to increasing mortality. The ADQI has since mod-
ified the RIFLE criteria to the Acute Kidney Injury Net-
work (AKIN) criteria, which incorporates a time compo-
nent to the changes in creatinine (Table I). The AKIN
13

effective therapies in high risk patients. Identification of criteria may permit earlier recognition of AKI in the ICU

* Corresponding author: Dr. Amir Ibrahim, Division of Burn Surgery, Massachusetts General Hospital, MGH-GRB 1303A, 55 Fruit Street, Boston, MA 02114-2696, USA.
E-mail: album78@hotmail.com

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 Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013

Table I - RIFLE & AKIN criteria: Increase: ↑; decrease: ↓ .13,15

Kidney dysfunction RIFLE criteria AKIN criteria

Parameter Risk Injury Failure Stage 1 Stage 2 Stage 3

Serum creatinine (Crs) ↑ in Crs ↑ in Crs ↑ in Crs ≥3.0X ↑ in Crs ≥26.2 ↑ in Crs to ↑ in Crs to ≥300%
≥1.5X ≥2.0X baseline µmol/L 200-299% (≥ 3-fold) from baseline
baseline baseline Or Or (> 2-2.9 fold) Or
Or Or ↓ in GFR ≥75% ↑ in Crs from baseline Crs ≥354 µmol/L with
↓ in GFR ↓ in GFR Or ≥150-199% an acute rise of at least
≥25% ≥50% Crs ≥354 µmol/L (1.5- to 44 µmol/L or an
with an acute rise of 1.9-fold) from initiation of RRT
at least 44 µmol/L baseline

Urine output <0.5 mL/kg/h <0.5 mL/kg/h <0.3 mL/kg/h for <0.5 mL/kg/h <0.5 mL/kg/h <0.3 mL/kg/h for ≥24 h
for ≥6 h for ≥12 h ≥24 h for ≥6 h for ≥12 h Or
Or anuria ≥12 h
anuria ≥12 h

setting since AKI is defined as an abrupt decrease in kid-
ney function (≤ 48 h).14 Currently there is no evidence to
support the use of one system over the other;15 neverthe-
less, these two consensus definitions have facilitated com-
parisons between studies analyzing AKI in burn injuries.
Etiology
Multiple conditions contribute to early AKI (first 24
h16) in the burn patient: hypovolemia, cardiac dysfunction,
release of inflammatory mediators and denatured proteins
(from extensive tissue destruction), and nephrotoxic
drugs.17-19 Late AKI usually falls within the multi-organ dys-
function syndrome (MODS) frequently associated with se-
vere sepsis.20,21 Hypovolemia and under-resuscitation have
classically been thought of as the primary causes of early
AKI; however, recent studies suggest that AKI can devel-
op despite adequate resuscitation.
Furthermore, recent studies in critically ill patients, in-
cluding burn patients, have suggested that a positive fluid
balance may have a negative influence on kidney function
Hypervolemia and Abdominal Compartment Syndrome
Following thermal injury plasma losses are in excess
of 4 ml per kg of body weight per h in a burn exceeding
30% TBSA. This is sufficient to cause decreased renal per-
fusion.31 Kim et al. observed that burn size was an inde-
pendent predictor of acute renal failure in the burn popu-
lation.8 This depressed renal blood flow, which is com-
pounded by local and systemic cytokine storms, and re-
sults in ischemia, cellular death, and subsequent release of
oxygen free radicals. These mediators cause direct tubular
damage and disrupt tight junctions, leading to obstructive
nephropathy which further reduces GFR. The ischemia time
is a critical determinant of AKI occurrence. Aggressive
and early fluid replacement protects from renal failure.32
The Shriners Burn Institute for Children (Galveston)
showed that the time to fluid resuscitation initiation was
directly related to the incidence of renal dysfunction and
overall mortality. They advocated early aggressive fluid
resuscitation which might prevent renal injury and hence
improve overall outcomes.
33

and mortality. All these observations suggest that AKI While older data clearly demonstrated an association
22-24

is more likely dependent on the degree of shock caused
by the initial injury, and the subsequent release of injuri-
ous inflammatory mediators. Global indicators of tissue
perfusion (i.e. lactate and base deficit) may be adequate
predictors of AKI in this setting, as they have been shown
to predict increased risk of systemic inflammatory response
syndrome (SIRS), acute respiratory distress syndrome
(ARDS), multi-organ dysfunction syndrome (MODS), and
mortality.16,25-29 Base deficit may also be a better marker of
poor perfusion than serum lactate because it represents the
combined sum of lactate and all other metabolic acids re-
leased during tissue hypoxia.28.30
between renal failure and a delay in resuscitation, more re-
cent data suggest that aggressive fluid replacement does not
eliminate the occurrence of AKI. AKI can develop in burn
patients despite normal to average urine output (0.5-1.0
ml/kg/h), and even when fluid resuscitation exceeds the
Parkland formula recommendations.16,34 In fact, it has be-
come clear that during resuscitation of patients with ther-
mal trauma, parameters such as urine output and mean ar-
terial pressure may not independently accurately reflect
perfusion of organs at the cellular level. A state of poor
perfusion can exist despite acceptable urine output and
blood pressure chartings,35,36 and the use of urine output

17
Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013
alone as a primary measure of adequacy of resuscitation
is not recommended by the authors. Klein et al. recently
reviewed data from the Glue Grant and found that the ma-
jority of patients with AKI were adequately resuscitated;
early AKI was therefore probably the result of the in-
flammatory mediators storm.
37,38
Conversely, the risk of over-resuscitation and fluid
creep exists and warrants close monitoring.39 Over-resusci-
tation increases the risk of pneumonia, pulmonary edema,
ARDS, and compartment syndromes (orbital, abdominal,
extremity) and ultimately contributes to an increase in mor-
tality.39-41 In spite of all efforts to monitor endpoints of re-
suscitation, intercompartmental fluid shifts occur,42 and
these can be especially hazardous if involving fascial bound
compartments such as the peritoneal cavity. Intra-abdom-
inal hypertension (IAH) then leads to splanchnic edema
with subsequent increase in gut permeability and bacteri-
al translocation. IAH, as defined by an intra-abdominal
pressure (IAP) > 12 mmHg, has numerous adverse effects
on visceral perfusion, and the occurrence of IAH in crit-
43-45
ically ill patients is an independent predictor of increased
mortality.46 In the thermally injured patient, abdominal com-
partment syndrome (ACS) is defined as an IAP > 20 mmHg
with at least one concomitant organ failure.47-49 It has been
suggested that a crystalloid rate over 20 ml/kg/h during
the initial 24 h of resuscitation should alert physicians to
possible IAH/ACS.46 There should be close monitoring for
the signs of ACS (decreased cardiac output, decreased lung
compliance, decreased urine output) in all massive burn
patients. In general, as resuscitation volumes approach 6
ml/kg/h, or as signs of IAH arise, the addition of colloid,
in the form of albumin, has been shown to decrease fluid
requirements and edema.50-54 A “permissive hypovolemia”
approach to resuscitation after severe burns was advocat-
ed, and may be highly appropriate in certain cases since
it was associated with significantly lower multiple-organ
dysfunction score (MODS) than resuscitation following the
Parkland formula.55 Considering the negative impact on
kidney perfusion of under-resuscitation (ischemic injury)
and over-resuscitation (fluid creep and ACS), burn sur-
geons need to personalize fluid therapy according to the
evolution of the patient’s general physiologic condition.
Cardiac dysfunction
Burn injury produces substantial hemodynamic and
cardiodynamic derangements;56 compromised cardiac func-
tion results in global hypoperfusion and reduced renal blood
flow contributing to AKI.57 While it was previously sug-
gested that depressed cardiovascular function in burn shock
was primarily a sequel of vascular fluid loss,58 recent da-
ta point toward direct myocardial suppression, possibly
caused by elevated plasma levels of catecholamines, va-
sopressin, angiotensin-II, neuropeptide-Y,59-61 and various
cytokines (TNF-α, IL-1β, IL-2, IL-6 and IFN-gamma).62,63
18
This occurs despite adequate fluid resuscitation (assessed
by normal central venous pressure, pulmonary capillary
wedge pressure, and mean arterial pressure). In addi-
64-67
tion, large burn areas (>50% TBSA) may result in car-
diac infections from the wounded skin, further compro-
mising organ perfusion. The incidence of bacterial endo-
carditis in such patients is six times higher than in the
general population, with mortality rates reaching up to
95%.68 Burn surgeons should be aware of all these phys-
iologic responses when working towards correcting the
preload and re-establishing renal blood flow.
Denatured proteins
Muscle breakdown and the release of denatured pro-
teins are implicated in the development of AKI. Rhab-
domyolysis in particular contributes to AKI following se-
vere burns,69 caused by direct thermal injury, compartment
syndrome, or severe electrical injury. The release of myo-
globin and free hemoglobin results in the blockage of re-
nal tubules, constriction of afferent arterioles, and the gen-
eration of oxygen free radicals. Myoglobinuria occurs
70
when serum myoglobin is greater than 1,500-3,000 ng/ml
and is typically associated with elevated levels of creatine
kinase (CK). AKI has been shown to be associated with
CK levels in excess of 5,000 U/L. Fortunately the inci-
dence of denatured proteins causing AKI is low, and the
overall prognosis is favorable when appropriate therapy,
in the form of hydration with isotonic crystalloids, is ini-
tiated in a timely fashion.71
Sepsis
Sepsis and septic shock are the most common causes
of death in the ICU and are observed in up to 87% of burn
patients suffering AKI.72,73 The extent of sepsis is directly
related to the incidence of AKI.74,75 The etiology of AKI in
sepsis is multifactorial. It can be thought to occur as a re-
sult of three pathological processes that result from alter-
ations in the homeostatic balance, between production and
inactivation, of inflammatory meditators: direct endothelial
damage, vasoparalysis, and a procoagulant state. Va-
soparalysis results in a state of severe hypotension and de-
creased tissue perfusion. This is followed by activation of
the neurohumoral axis and an increase in plasma levels of
catecholamines, vasopressin, and angiotensin-II in an effort
to increase in cardiac output and restore normal tissue per-
fusion. However, this also results in direct renal arteriolar
61
vasoconstriction, which may cause a pre-renal state com-
promising renal perfusion. This is further compounded by
the release of vasoconstrictive agents (TNF, endothelin).76,77
With respect to the pro-coagulant state, sepsis is known to
upregulate the expression of complement and to enhance
the fibrinolytic cascade.78-80 This may lead to disseminated
intravascular coagulation and subsequent direct injury to
glomeruli by microthrombi.81 Acute tubular necrosis ensues

secondary to the induced ischemic injury.
Diagnosis
Diagnosing AKI in burn patients requires a compre-
hensive understanding of the changes underlying the phys-
iology of burn patients throughout their course of treat-
ment. Renal injury may occur despite normal renal pa-
rameters (urine output, biochemical markers, etc.) and burn
surgeons must therefore constantly monitor their patients’
global physiologic picture in an effort to anticipate any sign
pointing to early renal injury. A stepwise approach to the
diagnosis and treatment of AKI should be implemented.
Urine output
A decrease in urine output is probably the first and
most obvious sign of renal dysfunction. This parameter has
a high specificity but a low sensitivity.82
The majority of burn physicians do not give much di-
agnostic value to urine output alone in assessing renal func-
tion as severe renal insult can occur without alterations in
urine output. This is because urine output is not a direct
reflection of GFR but rather of the difference between GFR
and tubular reabsorption. Only in the instance of anuria (<
50 cc/d) is urine output alone diagnostic.83 Pre-renal fail-
ure is the most common cause of anuria (excluding a post-
renal obstruction). The incidence of other conditions as-
sociated with anuria (acute cortical necrosis, bilateral ar-
terial occlusion, and rapidly progressive acute glomeru-
lonephritis) is low, and their diagnosis can usually be made
from other clinical signs.
Urine microscopy and chemistry
Although a decrease in urine output may be indicative
of an underlying renal dysfunction, it does not specify eti-
ology. This can be established by microscopic and bio-
chemical analysis of the urine, which can be used to sup-
port the diagnosis of AKI and guide treatment options. A
combination of normal urinary sediment and hyaline casts
and an oliguric/anuric state suggests a pre-renal cause. The
presence of epithelial casts with tubular epithelial cells is
pathognomonic for acute tubular necrosis.84 Pigmented casts
on microscopy point to myoglobinuria (most likely due to
rhabdomyolsis). It is worth noting that urinary electrolytes
also carry a diagnostic potential and should be obtained
when microscopy is not diagnostic. Urine electrolytes are
also beneficial in differentiating between the pre-renal and
renal forms of AKI. For this purpose, the fractional ex-
cretion of sodium (FENa) is calculated and interpreted.
The underlying concept is that a pre-renal state in the pres-
ence of a normally functioning nephron causes increased
absorption of sodium. FENa= (urine sodium X plasma cre-
atinine)/(plasma sodium X urinary creatinine). A value <
1% is associated with pre-renal injury while a value > 1%
Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013
suggests intrinsic renal injury.85 There are, however, cer-
tain instances when renal absorption of sodium is impaired,
and hence FENa would not be a reliable discriminating
test between pre-renal azotemia and renal injury.
Numerous reports of low FENa (< 1%) have appeared
in various clinical settings of oliguric and nonoliguric states
such as acute tubular necrosis, urinary tract obstruction,
acute glomerulonephritis, hepatorenal syndrome, renal al-
lograft rejection, sepsis, and drug-related alterations in re-
nal hemodynamics. In this situation, one particular uri-
86
nary index cannot be used to differentiate between pre-re-
nal azotemia and acute renal failure. An additional modal-
ity, such as urea excretion, may be appropriate. Recently,
it was suggested that fractional excretion of urea (FEUrea
< 35) may have more specificity and sensitivity than FE-
Na in discriminating between pre-renal and renal azotemia.87
Plasma creatinine
A true biomarker for AKI is needed; a signature mol-
ecule (found in blood or urine) that signals the presence
of early renal injury, detects the nephron segment most-
ly affected, identifies the best drug or fluids therapy, meas-
ures the progress of renal function, and can be rapidly
and easily measured.88 At present, however, such an ide-
al biomarker does not exist and creatinine-based estimat-
ed GFR (eGFRcreatinine) is considered the key measure of
kidney function in clinical practice. Creatinine is freely
filtered across the kidney and is neither reabsorbed nor
metabolized. The Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) creatinine equation was used to
estimate eGFRcreatinine as follows:
• eGFRcreatinine = 141 × (minimum of standardized
serum creatinine mg/dl /κ or 1)α × (maximum of
standardized serum creatinine mg/dl /κ or 1)−1.209 ×
0.993age × (1.018 if female) × (1.159 if black),
• where κ is 0.7 if female and 0.9 if male and α is
−0.329 if female and −0.411 if male.89
It should be noted that creatinine clearance often over-
estimates the true GFR by 10-20%;90 this is because the
renal tubules secrete a small quantity of creatinine in the
urine which adds to the amount filtered by the glomeruli.
Furthermore, several non-GFR determinants of creatinine
(e.g., muscle mass and diet) bias GFR estimates and re-
sult in misclassification. The illness itself, due to the re-
sulting non steady physiologic state and muscle wasting,
seems to considerably bias the use of serum creatinine as
a marker for GFR82,91 since plasma creatinine concentra-
tion depends on its clearance by the kidney but also varies
according to its total production and volume of distribu-
tion within the body. In critically ill patients, changes in
serum creatinine typically lag behind the timing of renal
injury and recovery;82 and it is therefore more appropriate
to consider variations in serum creatinine over change in
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Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013
time. Moran and Myers demonstrated this concept in a
computerized model of creatinine kinetics in patients with
post-ischemic acute renal failure. They showed that the
92
relationship between creatinine clearance and plasma cre-
atinine concentration was not always inversely proportional
and that it dissociated in conditions of acute renal failure
and recovery. In other words, a rising serum creatinine is
not always a reliable indicator of deteriorating kidney func-
tion; conversely, a decreasing serum creatinine does not
always reflect an improving GFR. What appeared to be
of prognostic value was the number of days plasma cre-
atinine continued to rise following the initial ischemic in-
jury. Day 4 post-injury seems to be a point of no return;
that is, a continued increase in serum creatinine beyond
day 4 indicates that renal recovery has not begun and a
severe protracted course of renal failure is likely to fol-
low. Although this study was not conducted in the burn
population, it parallels key points in the ischemic patho-
physiology of renal failure, in particular early renal fail-
ure.
Physicians caring for burn patients should understand
the limitations of any biologic molecule estimating GFR
during renal injury. Serum creatinine is currently regard-
ed as the “gold standard”, but this is not an “ideal mark-
er”. GFR estimations based on creatinine clearance should
be calculated over short time intervals with the serum cre-
atinine value reflecting the central tendency of the values
obtained at the beginning and end of the collection inter-
val. The search for the ideal biomarker or combination of
markers to predict kidney function is an area of substan-
tial interest. Cystatin C for example, an alternate marker
of kidney function, was shown to estimate GFR as accu-
rately as serum creatinine in a large sample of chronic
kidney disease patients.93 Additional data also suggested
that eGFR by Cystatin C (eGFRcystatin) had a stronger as-
sociation with mortality and cardiovascular disease than
eGFRcreatinine.94-101
Treatment of acute renal failure
As outlined above, several studies have shown that
AKI is associated with an increase in morbidity and mor-
tality in critically ill and hospitalized patients.1,6,86 Few ther-
apeutic interventions, however, have been successful in
treating or preventing AKI, possibly owing to delayed di-
agnosis. Patients at risk for AKI, or those with AKI, re-
quire careful attention to hemodynamic and general phys-
iologic status. The key to adequate AKI treatment is ear-
ly diagnosis and rapid termination of the underlying insult
while preserving renal function and preventing iatrogenic
injury. When conservative measures fail, RRT is required.
This section will re-examine measures for the prevention
of AKI, and will outline current evidence regarding the
use of RRT initiation.
20
Early AKI
Early AKI may be caused by hypovolemia, leading to
a decrease in renal perfusion and resultant renal injury. Sev-
eral studies have advocated early fluid administration to
prevent or minimize the effects of AKI. In severe sep-
4,102
sis and septic shock, the administration of intravenous flu-
ids and vasopressors in the first hours of an acute critical
illness have been considered to be among the most impor-
tant interventions toward improved outcomes.103 Several for-
mulas have been suggested for optimizing resuscitation -
which one to follow is not crucial. The key is to recognize
that these formulas estimate the fluid requirements over a
period of time. The true immediate amount depends di-
rectly on the patient’s general physiologic status and the
extent of injury. As with any type of traumatic human in-
sult, indicators of regional and global body perfusion should
be continuously monitored and used to assess the adequa-
cy of resuscitation. When the assessment of renal perfusion
becomes challenging, invasive modalities for monitoring
central pressures and global related volume variables (such
as global end diastolic volume, extra vascular lung water
volume, intrathoracic blood volume) may be of use. In-
104
terestingly, Schiller et al. compared the resuscitation of burn
patients to the use of invasive hemodynamic monitoring
and a hyperdynamic resuscitation protocol to that of a con-
trol group for which resuscitation was guided by tradition-
al end points such as blood pressure, heart rate, and urine
output. Patients treated with hyperdynamic resuscitation
showed improved microcirculatory flow, tissue perfusion
and tissue oxygenation and appeared to have less renal and
hepatic dysfunction with a significant reduction in the mor-
tality rate. A statistically significant difference in early he-
modynamic response was noted between survivors and non-
survivors. The association between improved survival and
105
an early self-generated hyperdynamic response has been
previously demonstrated. Whether the use of invasive mon-
itors can actually improve outcome has not been proven
conclusively and the use of invasive monitoring carries in-
herent risks, especially in an immunocompromised host,
such as a burn patient.68,106 Lastly, it is worth reiterating that,
while striving to restore an effective circulatory volume,
physicians should keep in mind the possibility of early my-
ocardial dysfunction as a cause of decreased renal perfu-
sion and early AKI.
Late AKI
Late AKI is viewed as being multifactorial and is of-
ten associated with sepsis and multi-organ dysfunction
(MODS). The most effective therapy is prevention and ear-
ly recognition of the septic state.107 Early sepsis can be sus-
pected on the basis of feeding intolerance, insulin resistance,
elevation of acute phase reactants, and many other markers.
Source control, identification of the offending organism or
organisms, and early directed-goal therapy (EGDT) should

be initiated.103 The role of infectious surveillance in the burn
patient for a targeted control of offending microbes and pre-
vention of systemic dissemination cannot be overstated.
RRT overview
As a result of major advances in burn resuscitation
and the management of sepsis, renal failure requiring
108
RRT is becoming a relatively rare event.109 The reported
incidence varies between 1 and 3%; however, the overall
mortality associated with renal failure requiring RRT can
be as high as 80%.17,73,110,111
Optimal timing
The issue of when to initiate RRT in patients with
AKI has been debated nearly as long as hemodialysis has
been part of the armamentarium of clinical medicine.12 Al-
though numerous studies over more than a half century
have attempted to resolve the issue of optimal timing, the
level of evidence guiding current practice remains weak,
derived primarily from retrospective and observational co-
hort studies and small underpowered prospective trials. Suf-
fice it to say that the standard indications for dialysis (vol-
ume overload; severe hyperkalemia and metabolic acido-
sis; overt uremic symptoms) are less relevant in the ther-
mally injured patient. A recent consensus advocated the
initiation of RRT in critically ill patients with AKI before
the development of extreme metabolic derangements and
life-threatening events. Additionally, preliminary evidence
14
suggests that a more aggressive approach to RRT in burn
patients may be beneficial.112,113
Modality of RRT
Peritoneal dialysis (PD) has long been used as a form
of RRT in AKI.114 In a burn management setting, this form
is limited by clearance rates and the need for catheter in-
sertion through the abdominal wall. In the past two decades,
other RRT modalities were examined in the ICU setting,
namely intermittent hemodialysis (IHD), continuous and
prolonged intermittent RRT (CRRT and PIRRT), and sus-
tained low-efficiency dialysis. There is no evidence that
any single modality of RRT is associated with improved
survival or recovery of kidney function, although slower
modalities (e.g., CRRT, PIRRT) may be better tolerated
in hemodynamically unstable patients and permit achieve-
ment of a more negative fluid balance.115 An additional po-
tential benefit of continuous hemofiltration is the clearance
of pro-inflammatory mediators and therefore the theoreti-
cal reduction in the development of multi-organ dysfunc-
tion.116 Conversely, studies have shown that the cytokine
clearances attainable with even high-volume continuous
filtration are trivial in comparison to endogenous produc-
tion, and cytokine removal is nonselective and results in
removal of both pro-inflammatory and anti-inflammatory
mediators.117 In any case, although preliminary (non-
Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013
prospective) studies with CRRT in the burn patient demon-
strated improved survival,112,113 future prospective random-
ized studies are required.
Intensity of RRT
It has been suggested that prevention of severe metabolic
derangements by earlier initiation of RRT in the critically
burned patient may be beneficial. Likewise, prevention or
correction of severe metabolic derangements with more in-
tensive RRT has also been suggested. There is no solid ev-
idence, however, that augmented doses of RRT in critically
ill patients with AKI are associated with improved outcomes,
and most studies examining the impact of more intensive
RRT quantified the intensity of therapy based on the clear-
ance of urea (a low molecular-weight solute), ignoring the
clearance of higher-molecular-weight solutes and, even more
importantly, the management of extracellular volume.
12,118-121.
Conclusion
Significant advances in the management of burn pa-
tients have been made over the past four decades. Increas-
ing evidence points to the need for early aggressive fluid
repletion (probably with isotonic crystalloids rather than
colloids) for expansion of intravascular volume. Urine out-
put is still considered a good indicator for adequate resus-
citation. Persistent low urine output invariably indicates in-
adequate resuscitation but an adequate urine output does
not necessarily mean that the burn patient is not develop-
ing acute non-oliguric renal failure either due to insuffi-
cient resuscitation or to massive release of inflammatory
mediators. Moreover, relying on urine output alone could
be misleading, resulting in over-resuscitation and fluid
creep. Consideration of urine output together with other re-
suscitation parameters should thus be the standard of care.
In instances where it is necessary to decrease overall
fluid requirements, the addition of albumin appears justi-
fied. This is best coupled with early burn wound excision
(first 72 h) and burn wound closure. While this approach
appears to reduce the incidence of early AKI, this disor-
der may still occur at a later stage following prolonged or
delayed initial resuscitation and following sepsis. At this
stage, once AKI occurs and hemodynamics are stabilized,
the relevance of a restrictive fluid balance and the use of
diuretics or RRT to prevent or treat fluid overload and im-
prove outcomes in this population, without worsening kid-
ney function, need to be confirmed with RCTs. Neverthe-
less, physicians should monitor the complex physiologic
state of the burn patient constantly in order to anticipate
any condition that may injure the kidneys. This will en-
sure prompt initiation of appropriate treatment and possi-
bly prevent the development of acute kidney injury. In an
era where no pharmacologic agent exists to treat this con-
dition, prevention remains the best (and only) remedy.
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Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013

RÉSUMÉ. Les lésions rénales aiguës (LRA) sont rares, mais elles constituent une complication majeure des brûlures qui mène
souvent à la mortalité. Ces lésions sont provoquées par une interaction complexe de divers changements cellulaires et neuro-
humoraux qui affectent les patients brûlés. Les directives pour le traitement de ces patients ne sont pas encore bien définies et, par
conséquent, la prévention et le diagnostic précoce sont essentiels pour éviter le pronostic défavorable des LRA. Cela nécessite une
compréhension complète des changements physiologiques présents dans ces patients et une interprétation judicieuse de leurs conti-
nuelles altérations homéostatiques. Les Auteurs se sont proposé de présenter les principales caractéristiques de la physiologie du
patient brûlé qui contribuent à ce type de lésion. Apres avoir discuté les stratégies pour identifier ces lésions en phase précoce, ils
concluent avec une description des différentes modalités de traitement.

Mots-clés: brûlures et insuffisance rénale, brûlures et dysfonction rénale, brûlures et dialyse, classification des lésions rénales, trai-
tement de l’insuffisance rénale

BIBLIOGRAPHY Care (London, England), 8: R204-12, 2004.

1. Uchino S: The epidemiology of acute renal failure in the world.
Current opinion in critical care, 12: 538-43, 2006.
2. Chertow GM, Christiansen CL, Cleary PD et al.: Prognostic strat-
ification in critically ill patients with acute renal failure requir-
ing dialysis. Archives Internal Medicine, 155: 1505-11, 1995.
3. Liaño F, Junco E, Pascual J et al.: The spectrum of acute renal
failure in the intensive care unit compared with that seen in oth-
er settings. The Madrid Acute Renal Failure Study Group. Kid-
ney International Supplement, 66: S16-24, 1998.
4. Star RA: Treatment of acute renal failure. Kidney International,
54: 1817-31, 1998.
5. Belba M, Belba G: Acute renal failure in severe burns: Conclu-
sion after analysis of deaths during 1998. Ann Burns Fire Dis-
asters, 13: 77-80, 2000.
6. Chertow GM, Burdick E, Honour M et al.: Acute kidney injury,
mortality, length of stay, and costs in hospitalized patients. J
American Society Nephrology, 16: 3365-70, 2005.
7. Coca SG, Yusuf B, Shlipak MG et al.: Long-term risk of mor-
tality and other adverse outcomes after acute kidney injury: A
systematic review and meta-analysis. American J Kidney Dis-
eases, 53: 961-73, 2009.
8. Kim G-H, Oh KH, Yoon JW et al.: Impact of burn size and ini-
tial serum albumin level on acute renal failure occurring in ma-
jor burn. American J Nephrology, 23: 55-60, 2003.
9. Curiel-Balsera E, Prieto-Palomino MA, Fernández-Jiménez S et
al.: Epidemiology, initial management and analysis of morbidi-
ty/mortality of severe burn patient. Medicina intensiva / Sociedad
Española de Medicina Intensiva y Unidades Coronarias, 30: 363-
9, 2006.
10. Lopes JA, Jorge S, Neves FC et al.: An assessment of the RI-
FLE criteria for acute renal failure in severely burned patients.
Nephrology, dialysis, transplantation. Official Publication of the
European Dialysis and Transplant Association - European Renal
Association, 22: 285, 2007.
11. Palmieri T, Lavrentieva A, Greenhalgh DG: Acute kidney injury
in critically ill burn patients. Risk factors, progression and im-
pact on mortality. Burns, 36: 205-11, 2010.
12. Palevsky PM: Renal replacement therapy in acute kidney injury.
Advances in Chronic Kidney Disease, 20: 76-84, 2013.
13. Bellomo R, Ronco C, Kellum JA et al.: Acute renal failure - def-
inition, outcome measures, animal models, fluid therapy and in-
formation technology needs. Second International Consensus Con-
ference of the Acute Dialysis Quality Initiative Group. Critical
14. Brochard L, Abroug F, Brenner M et al.: An official ATS/ERS/ES-
ICM/SCCM/SRLF statement: Prevention and management of
acute renal failure in the ICU patient. International Consensus
Conference in Intensive Care Medicine. American J Respiratory
and Critical Care Medicine, 181: 1128-55, 2010.
15. Bagshaw SM, George C, Bellomo R: A comparison of the RI-
FLE and AKIN criteria for acute kidney injury in critically ill
patients. Nephrology, dialysis, transplantation: Official Publica-
tion of the European Dialysis and Transplant Association - Eu-
ropean Renal Association, 23: 1569-74, 2008.
16. Mosier MJ, Pham TN, Klein MB et al.: Early acute kidney in-
jury predicts progressive renal dysfunction and higher mortality
in severely burned adults. J Burn Care Research, 31: 83-92, 2010.
17. Davies DM, Pusey CD, Rainford DJ et al.: Acute renal failure in
burns. Scandinavian J Plastic and Reconstructive Surgery, 13:
189-92, 1979.
18. Planas M, Wachtel T, Frank H et al.: Characterization of acute
renal failure in the burned patient. Archives Internal Medicine,
142: 2087-91, 1982.
19. Schiavon M, Di Landro D, Baldo M et al.: A study of renal dam-
age in seriously burned patients. Burns, 14: 107-12, 1988.
20. Haberal M, Ozdemir A, Bayraktar U et al.: Gastrointestinal and
renal complications in burned patients. Ann Burns Fire Disasters,
6: 26-28, 1993.
21. Borgognone A, Gherardini G: Disseminated intravascular coagu-
lation as the underlying cause of multiple organ failure in burned
patients: Preliminary observations. Ann Burns Fire Disasters, 4:
13-15, 1991.
22. Bouchard J, Soroko SB, Chertow GM et al.: Fluid accumulation,
survival and recovery of kidney function in critically ill patients
with acute kidney injury. Kidney International, 76: 422-7, 2009.
23. Heung M, Wolfgram DF, Kommareddi M et al.: Fluid overload
at initiation of renal replacement therapy is associated with lack
of renal recovery in patients with acute kidney injury. Nephrol-
ogy, dialysis, transplantation: Official Publication of the Euro-
pean Dialysis and Transplant Association - European Renal As-
sociation, 27: 956-61, 2012.
24. Payen D, De Pont AC, Sakr Y et al.: A positive fluid balance is
associated with a worse outcome in patients with acute renal fail-
ure. Critical Care (London, England), 12: R74, 2008.
25. Cartotto R, Choi J, Gomez M et al.: A prospective study on the
implications of a base deficit during fluid resuscitation. J Burn
Care Rehabil, 24: 75-84, 2003.
26. Cochran A, Edelman LS, Saffle JR et al.: The relationship of

22

serum lactate and base deficit in burn patients to mortality. J Burn
Care & Research, 28: 231-40, 2007.
27. Jeng JC, Lee K, Jablonski K et al.: Serum lactate and base deficit
suggest inadequate resuscitation of patients with burn injuries:
Application of a point-of-care laboratory instrument. J Burn Care
Rehabil, 18: 402-5, 1997.
28. Kaups KL, Davis JW, Dominic WJ: Base deficit as an indicator
or resuscitation needs in patients with burn injuries. J Burn Care
Rehabil, 19: 346-8, 1998.
29. Wolf SE, Rose JK, Desai MH et al.: Mortality determinants in
massive pediatric burns. An analysis of 103 children with > or =
80% TBSA burns > or = 70% full-thickness). Annals Surgery,
225: 554-69, 1997.
30. Davis JW: The relationship of base deficit to lactate in porcine
hemorrhagic shock and resuscitation. J Trauma, 36: 168-72, 1994.
31. Braquet M, Carsin H, Guilbaud J et al.: Plasma atrial natriuretic
peptide in severe thermal injury. Lancet, 2: 456, 1986.
32. Nguyen NL, Gun RT, Sparnon AL et al.: The importance of ini-
tial management: A case series of childhood burns in Vietnam.
Burns, 28: 167-72, 2002.
33. Jeschke MG, Barrow RE, Wolf SE et al.: Mortality in burned
children with acute renal failure. Arch Surg (Chicago, Ill: 1960),
133: 752-6, 1998.
34. Ioannovich J, Alexakis D, Parker J et al.: Parkland formula as a
guide for resuscitation. Ann Burns Fire Disasters, 2: 29-33, 1989.
35. Davis JW, Shackford SR, Mackersie RC et al.: Base deficit as a
guide to volume resuscitation. J Trauma, 28: 1464-7, 1988.
36. Navar PD, Saffle JR, Warden GD: Effect of inhalation injury on
fluid resuscitation requirements after thermal injury. American J
Surgery, 150: 716-20, 1985.
37. Klein MB, Silver G, Gamelli RL et al.: Inflammation and the
host response to injury: An overview of the multicenter study of
the genomic and proteomic response to burn injury. J Burn Care
& Research, 27: 448-51, 2006.
38. Finnerty CC, Jeschke MG, Herndon DN et al.: Temporal cytokine
profiles in severely burned patients: A comparison of adults and
children. Molecular Medicine (Cambridge, Mass), 14: 553-60,
2008.
39. Saffle JIL: The phenomenon of “fluid creep” in acute burn re-
suscitation. J Burn Care & Research, 28: 382-95, 2007.
40. Cancio LC, Chávez S, Alvarado-Ortega M et al.: Predicting in-
creased fluid requirements during the resuscitation of thermally
injured patients. J Trauma, 56: 404-14, 2004.
41. Klein MB, Hayden D, Elson C et al.: The association between
fluid administration and outcome following major burn: A mul-
ticenter study. Ann Surgery, 245: 622-8, 2007.
42. Hobson KG, Young KM, Ciraulo A et al.: Release of abdominal
compartment syndrome improves survival in patients with burn
injury. J Trauma, 53: 1129-34, 2002.
43. Harman PK, Kron IL, McLachlan HD et al.: Elevated intra-ab-
dominal pressure and renal function. Ann Surgery, 196: 594-7,
1982.
44. Kashtan J, Green JF, Parsons EQ et al.: Hemodynamic effect of
increased abdominal pressure. J Surgical Research, 30: 249-55,
1981.
45. Richardson JD, Trinkle JK: Hemodynamic and respiratory alter-
ations with increased intra-abdominal pressure. J Surgical Re-
search, 20: 401-4, 1976.
46. Malbrain MLNG, Chiumello D, Pelosi P et al.: Incidence and
Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013
prognosis of intra-abdominal hypertension in a mixed population
of critically ill patients: A multiple-center epidemiological study.
Critical Care Medicine, 33: 315-22, 2005.
47. Greenhalgh DG, Warden GD: The importance of intra-abdomi-
nal pressure measurements in burned children. J Trauma, 36: 685-
90, 1994.
48. Ivy ME, Atweh NA, Palmer J et al.: Intra-abdominal hyperten-
sion and abdominal compartment syndrome in burn patients. J
Trauma, 49: 387-91, 2000.
49. O’Mara MS, Slater H, Goldfarb IW et al.: A prospective, ran-
domized evaluation of intra-abdominal pressures with crystalloid
and colloid resuscitation in burn patients. J Trauma, 58: 1011-8,
2005.
50. Elgjo GI, Poli de Figueiredo LF, Schenarts PJ et al.: Hypertonic
saline dextran produces early (8-12 hrs) fluid sparing in burn re-
suscitation: A 24-hr prospective, double-blind study in sheep. Crit-
ical Care Medicine, 28: 163-71, 2000.
51. Griswold JA, Anglin BL, Love RT et al.: Hypertonic saline re-
suscitation: Efficacy in a community-based burn unit. Southern
Medical Journal, 84: 692-6, 1991.
52. Guha SC, Kinsky MP, Button B et al.: Burn resuscitation: Crys-
talloid versus colloid versus hypertonic saline hyperoncotic col-
loid in sheep. Critical Care Medicine, 24: 1849-57, 1996.
53. Kramer GC, Gunther RA, Nerlich ML et al.: Effect of dextran-
70 on increased microvascular fluid and protein flux after ther-
mal injury. Circulatory Shock, 9: 529-41, 1982.
54. Milner SM, Kinsky MP, Guha SC et al.: A comparison of two
different 2400 mOsm solutions for resuscitation of major burns.
J Burn Care Rehabil, 18: 109-15, 1997.
55. Arlati S, Storti E, Pradella V et al.: Decreased fluid volume to
reduce organ damage: A new approach to burn shock resuscita-
tion? A preliminary study. Resuscitation, 72: 371-8, 2007.
56. Abu-Sittah GS, Sarhane KA, Dibo SA et al.: Cardiovascular dys-
function in burns: Review of the literature. Ann Burns Fire Dis-
asters, 25: 26-37, 2012.
57. Jeschke MG, Chinkes DL, Finnerty CC et al.: Pathophysiologic
response to severe burn injury. Ann Surgery, 248: 387-401, 2008.
58. Blalock A: Experimental shock. VIII. The importance of the lo-
cal loss of fluid in the production of the low blood pressure af-
ter burns. Arch Surg, 22: 610-7, 1931.
59. Becker RA, Vaughan GM, Goodwin CW et al.: Plasma norepi-
nephrine, epinephrine, and thyroid hormone interactions in se-
verely burned patients. Arch Surg (Chicago, Ill: 1960), 115: 439-
43, 1980.
60. Crum R, Bobrow B, Shackford S et al.: The neurohumoral re-
sponse to burn injury in patients resuscitated with hypertonic
saline. J Trauma, 28: 1181-7, 1988.
61. Dolecek R, Adámková M, Sotorníková T et al.: Endocrine re-
sponse after burn. Scandinavian J Plast Reconstr Surgery, 13: 9-
16, 1979.
62. Kelly RA, Smith TW: Cytokines and cardiac contractile function.
Circulation, 95: 778-81, 1997.
63. Nora R, Abrams JS, Tait NS et al.: Myocardial toxic effects dur-
ing recombinant interleukin-2 therapy. J National Cancer Insti-
tute, 81: 59-63, 1989.
64. Baxter CR: Fluid volume and electrolyte changes of the early
postburn period. Clinics in Plastic Surgery, 1: 693-703, 1974.
65. Bond RF, Roberts DE, Manning ES: Effects of anesthetics on
myocardial contractility and total body O2 consumption during
23
Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013
hemorrhage. Archives Internationales Pharmacodynamie et
Thérapie, 204: 228-41, 1973.
66. Cioffi WG, DeMeules JE, Gamelli RL: The effects of burn in-
jury and fluid resuscitation on cardiac function in vitro. J Trau-
ma, 26: 638-42, 1986.
67. Gilmore JP: Cardiovascular changes of the burned dog following
the infusion of intravenous solutions. American J Physiology, 190:
513-6, 1957.
68. Munster AM, Di Vincenti FC, Foley FD et al.: Cardiac infections
in burns. American J Surgery, 122: 524-7, 1971.
69. Lazarus D, Hudson DA: Fatal rhabdomyolysis in a flame burn
patient. Burns, 23: 446-50, 1997.
70. Sharp LS, Rozycki GS, Feliciano DV: Rhabdomyolysis and sec-
ondary renal failure in critically ill surgical patients. American J
Surgery, 188: 801-6, 2004.
71. Rosen CL, Adler JN, Rabban JT et al.: Early predictors of myo-
globinuria and acute renal failure following electrical injury. J
Emergency Medicine, 17: 783-9, 1999.
72. Steinvall I, Bak Z, Sjoberg F: Acute kidney injury is common,
parallels organ dysfunction or failure, and carries appreciable mor-
tality in patients with major burns: A prospective exploratory co-
hort study. Critical Care (London, England), 12: R124, 2008.
73. Coca SG, Bauling P, Schifftner T et al.: Contribution of acute
kidney injury toward morbidity and mortality in burns: A con-
temporary analysis. American J Kidney Diseases, 49: 517-23,
2007.
74. Rangel-Frausto MS, Pittet D, Costigan M et al.: The natural his-
tory of the systemic inflammatory response syndrome (SIRS). A
prospective study. JAMA, 273: 117-23, 1995.
75. Riedemann NC, Guo R-F, Ward PA: The enigma of sepsis. J
Clinical Investigation, 112: 460-7, 2003.
76. Hohlfeld T, Klemm P, Thiemermann C et al.: The contribution
of tumour necrosis factor-alpha and endothelin-1 to the increase
of coronary resistance in hearts from rats treated with endotox-
in. British J Pharmacology, 116: 3309-15, 1995.
77. Schrier RW, Wang W: Acute renal failure and sepsis. New Eng-
land J Medicine, 351: 159-69, 2004.
78. Czermak BJ, Sarma V, Pierson CL et al.: Protective effects of
C5a blockade in sepsis. Nature Medicine, 5: 788-92, 1999.
79. Huber-Lang MS, Riedeman NC, Sarma JV et al.: Protection of
innate immunity by C5aR antagonist in septic mice. Federation
American Societies Experimental Biology, 16: 1567-74, 2002.
80. Riedemann NC, Guo R-F, Neff TA et al.: Increased C5a recep-
tor expression in sepsis. J Clinical Investigation, 110: 101-8, 2002.
81. Reinhart K, Bayer O, Brunkhorst F et al.: Markers of endothe-
lial damage in organ dysfunction and sepsis. Critical Care Med-
icine, 30: S302-12, 2002.
82. Lameire N, Hoste E: Reflections on the definition, classification,
and diagnostic evaluation of acute renal failure. Current Opinion
in Critical Care, 10: 468-75, 2004.
83. Miller PD, Krebs RA, Neal BJ et al.: Polyuric prerenal failure.
Archives Internal Medicine, 140: 907-9, 1980.
84. Anderson RJ, Barry DW: Clinical and laboratory diagnosis of
acute renal failure. Best Practice & Research Clinical Anaesthe-
siology, 18: 1-20, 2004.
85. Steiner RW: Interpreting the fractional excretion of sodium. Amer-
ican J Medicine, 77: 699-702, 1984.
86. Zarich S, Fang LS, Diamond JR: Fractional excretion of sodium.
Exceptions to its diagnostic value. Archives Internal Medicine,
24
145: 108-12, 1985.
87. Carvounis CP, Nisar S, Guro-Razuman S: Significance of the
fractional excretion of urea in the differential diagnosis of acute
renal failure. Kidney International, 62: 2223-9, 2002.
88. Han WK, Bonventre JV: Biologic markers for the early detection
of acute kidney injury. Current Opinion in Critical Care, 10: 476-
82, 2004.
89. Levey AS, Stevens LA, Schmid CH et al.: A new equation to es-
timate glomerular filtration rate. Ann Internal Medicine, 150: 604-
12, 2009.
90. Doolan PD, Alpen EL, Theil GB: A clinical appraisal of the plas-
ma concentration and endogenous clearance of creatinine. Amer-
ican J Medicine, 32: 65-79, 1962.
91. Clark WR, Mueller BA, Kraus MA et al.: Quantification of cre-
atinine kinetic parameters in patients with acute renal failure. Kid-
ney International, 54: 554-60, 1998.
92. Moran SM, Myers BD: Course of acute renal failure studied by
a model of creatinine kinetics. Kidney International, 27: 928-37,
1985.
93. Stevens LA, Coresh J, Schmid CH et al.: Estimating GFR using
serum cystatin C alone and in combination with serum creatinine:
A pooled analysis of 3,418 individuals with CKD. American J
Kidney Diseases, 51: 395-406, 2008.
94. O’Hare AM, Newman AB, Katz R et al.: Cystatin C and inci-
dent peripheral arterial disease events in the elderly: Results from
the Cardiovascular Health Study. Archives Internal Medicine, 165:
2666-70, 2005.
95. Peralta CA, Shlipak MG, Fan D et al.: Risks for end-stage renal
disease, cardiovascular events, and death in Hispanic versus non-
Hispanic white adults with chronic kidney disease. J American
Society Nephrology, 17: 2892-9, 2006.
96. Sarnak MJ, Katz R, Stehman-Breen CO et al.: Cystatin C con-
centration as a risk factor for heart failure in older adults. Ann
Internal Medicine, 142: 497-505, 2005.
97. Seliger SL, Longstreth WT, Katz R et al.: Cystatin C and sub-
clinical brain infarction. J American Society Nephrology, 16:
3721-7, 2005.
98. Shlipak MG, Fried LF, Cushman M et al.: Cardiovascular mor-
tality risk in chronic kidney disease: Comparison of traditional
and novel risk factors. J American Medical Association, 293:
1737-45, 2005.
99. Shlipak MG, Katz R, Fried LF et al.: Cystatin-C and mortality
in elderly persons with heart failure. J American College Cardi-
ology, 45: 268-71, 2005.
100. Shlipak MG, Sarnak MJ, Katz R et al.: Cystatin C and the risk
of death and cardiovascular events among elderly persons. New
England J Medicine, 352: 2049-60, 2005.
101. Shlipak MG, Wassel-Fyr CL, Chertow GM et al.: Cystatin C and
mortality risk in the elderly: The health, aging, and body com-
position study. J American Society Nephrology, 17: 254-61, 2006.
102. Kellum JA, Levin N, Bouman C et al.: Developing a consensus
classification system for acute renal failure. Current Opinion in
Critical Care, 8: 509-14, 2002.
103. Rivers E, Nguyen B, Havstad S et al.: Early goal-directed ther-
apy in the treatment of severe sepsis and septic shock. New Eng-
land J Medicine, 345: 1368-77, 2001.
104. Poeze M, Solberg BCJ, Greve JWM et al.: Monitoring global vol-
ume-related hemodynamic or regional variables after initial re-
suscitation: What is a better predictor of outcome in critically ill

septic patients? Critical Care Medicine, 33: 2494-500, 2005.
105. Schiller WR, Bay RC, Mclachlan JG et al.: Survival in major
burn injuries is predicted by early response. J Surgery, 170: 696-
700, 1995.
106. Ehrie M, Morgan AP, Moore FD et al.: Endocarditis with the in-
dwelling balloon-tipped pulmonary artery catheter in burn pa-
tients. J Trauma, 18: 664-6, 1978.
107. Manni C: Prevention and therapy of acute renal failure in se-
verely burned patients. Ann Burns Fire Disasters, 1: 103-6, 1988.
108. Dellinger RP, Carlet JM, Masur H et al.: Surviving Sepsis Cam-
paign guidelines for management of severe sepsis and septic shock.
Critical Care Medicine, 32: 858-73, 2004.
109. Leblanc M, Thibeault Y, Quérin S: Continuous haemofiltration
and haemodiafiltration for acute renal failure in severely burned
patients. Burns, 23: 160-5, 1997.
110. Cameron JS, Miller-Jones CM: Renal function and renal failure
in badly burned children. British J Surgery, 54: 132-41, 1967.
111. Brusselaers N, Monstrey S, Colpaert K et al.: Outcome of acute kid-
ney injury in severe burns: A systematic review and meta-analysis.
Intensive Care Medicine, 36: 915-25, 2010.
112. Chung KK, Juncos LA, Wolf SE et al.: Continuous renal re-
placement therapy improves survival in severely burned military
casualties with acute kidney injury. J Trauma, 64: S179-87, 2008.
113. Chung KK, Lundy JB, Matson JR et al.: Continuous venovenous
hemofiltration in severely burned patients with acute kidney in-
jury: A cohort study. Critical Care (London, England), 13: R62,
2009.
114. Pomeranz A, Reichenberg Y, Schurr D et al.: Acute renal failure
in a burn patient: The advantages of continuous peritoneal dial-
ysis. Burns, 11: 367-70 1985.
Annals of Burns and Fire Disasters - vol. XXVI - n. 1 - March 2013
115. Bagshaw SM, Berthiaume LR, Delaney A et al.: Continuous ver-
sus intermittent renal replacement therapy for critically ill patients
with acute kidney injury: A meta-analysis. Critical Care Medi-
cine, 36: 610-7, 2008.
116. Vincent JL, Tielemans C: Continuous hemofiltration in severe
sepsis: Is it beneficial? J Critical Care, 10: 27-32, 1995.
117. Sieberth HG, Kierdorf HP: Is cytokine removal by continuous he-
mofiltration feasible? Kidney International Supplement, S79-83,
1999.
118. Faulhaber-Walter R, Hafer C, Jahr N et al.: The Hannover Dial-
ysis Outcome study: Comparison of standard versus intensified
extended dialysis for treatment of patients with acute kidney in-
jury in the intensive care unit. Nephrology, Dialysis, Transplan-
tation, 24: 2179-86, 2009.
119. Tolwani AJ, Campbell RC, Stofan BS et al.: Standard versus
high-dose CVVHDF for ICU-related acute renal failure. J Amer-
ican Society Nephrology, 19: 1233-8, 2008.
120. Bellomo R, Cass A, Cole L et al.: Intensity of continuous renal
replacement therapy in critically ill patients. New England J Med-
icine, 361: 1627-38, 2009.
121. Abichandani R, Pereira BJ: Effects of different doses in contin-
uous veno-venous haemofiltration on outcomes of acute renal fail-
ure: A prospective randomised trial, by Ronco C, Bellomo R,
Homel P, Brendolan A, Dan M, Piccinni P, and La Greca G.
Lancet, 355: 26-30, 2000. Seminars in dialysis, 14: 233-4, 2001.
This paper was accepted on 31 January 2013.
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