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Concise Definitive Review Jonathan E.

Sevransky, MD, MHS, Section Editor

Acute kidney injury in the intensive care unit: An update and


primer for the intensivist
Paula Dennen, MD; Ivor S. Douglas, MD; Robert Anderson, MD

Objective: Acute kidney injury is common in critically ill this review is to address topics important to the practicing
patients and is associated with significant morbidity and mor- intensivist.
tality. Patients across the spectrum of critical illness have Data Synthesis and Findings: Whenever available, preferential
acute kidney injury. This requires clinicians from across dis- consideration was given to randomized controlled trials. In the
ciplines to be familiar with recent advances in definitions, absence of randomized trials, observational and retrospective
diagnosis, prevention, and management of acute kidney injury studies and consensus opinions were included.
in the intensive care unit. The purpose of this concise review, Conclusions: Acute kidney injury in the intensive care unit is a
therefore, is to address, for the non-nephrologist, clinically clinically relevant problem requiring awareness and expertise
relevant topical questions regarding acute kidney injury in the among physicians from a wide variety of fields. Although many
intensive care unit. questions remain controversial and without definitive answers, a
Data Sources: The authors (nephrologists and intensivists) periodic update of this rapidly evolving field provides a framework
performed a directed review of PubMed to evaluate topics for understanding and managing acute kidney injury in the inten-
including the definition, diagnosis, prevention, and treatment sive care unit. (Crit Care Med 2010; 38:261–275)
of acute kidney injury in the intensive care unit. The goal of KEY WORDS: acute kidney injury; intensive care unit

A cute kidney injury (AKI), pre- mortality (5, 6). AKI occurs in approxi- despite adjustment for comorbidities
viously termed acute renal fail- mately 7% of all hospitalized patients (7) and severity of illness.
ure, refers to a sudden decline and in up to 36% to 67% of critically ill Morbidity, a less appreciated conse-
in kidney function causing dis- patients depending on the definition used quence of AKI in the ICU, is associated
turbances in fluid, electrolyte, and acid– (6, 8 –11). Based on ⬎75,000 critically ill with increased cost (18), increased length
base balance because of a loss in small adults, more severe AKI occurs in 4% to of stay (6, 14, 18, 26), and increased risk
solute clearance and decreased glomerular 25% of all ICU admissions (6, 8, 9, 11). of chronic kidney disease (CKD), includ-
filtration rate (GFR). The nomenclature On average, 5% to 6% of ICU patients ing end-stage kidney disease (9, 15, 16,
shift to AKI more accurately represents the with AKI require renal replacement ther- 32–37). The true incidence of CKD after
spectrum of disease from subclinical injury to apy (RRT) (6, 8 –11). AKI is unknown because epidemiologic
complete organ failure. This review focuses Reported mortality in ICU patients studies do not routinely or consistently
on key questions for the intensivist faced with with AKI varies considerably between report rates of renal recovery and those
AKI in the intensive care unit (ICU). studies depending on AKI definition that do use variable definitions (38).
and the patient population studied
Epidemiology of AKI in the ICU (e.g., sepsis, trauma, cardiothoracic Definition of AKI in the ICU
AKI in the ICU is common, increasing surgery, or contrast nephropathy). In More than 35 definitions of AKI cur-
in incidence (1– 4), and is associated with the majority of studies, mortality in- rently exist in the literature (39). The
a substantial increase in morbidity and creases proportionately with increasing Acute Dialysis Quality Initiative convened
severity of AKI (6, 10 –13). In patients in 2002 and proposed the RIFLE classifi-
with severe AKI requiring RRT, mortal- cation (risk, injury, failure, loss, end-
ity is approximately 50% to 70% (9, stage kidney disease) specifically for AKI
From Divisions of Nephrology and Critical Care
Medicine (PD), Division of Pulmonary Sciences and 14 –16). While AKI requiring RRT in the in critically ill patients (Table 1) (40).
Critical Care Medicine (ISD), and Department of Med- ICU is a well-recognized independent Using SCr and urine output, the RIFLE
icine (RA), Denver Health Medical Center and Univer- risk factor for in-hospital mortality criteria define three grades of severity
sity of Colorado, Denver, CO. (17), even small changes in serum cre-
Denver Health Medical Center and University of and two outcome classes. The most se-
Colorado, Denver, CO, are Acute Respiratory Distress atinine (SCr) are associated with in- vere classification met by either criterion
Syndreome network investigation sites (PD and ISD). creased mortality (18 –21). Notably, should be used. Of note, patients with
The authors have not disclosed any potential con- multiple studies of patients with AKI primary kidney diseases such as glomer-
flicts of interest. and sepsis (22–24), mechanical ventila-
For information regarding this article, E-mail: ulonephritis were excluded from this def-
paula.dennen@ucdenver.edu tion (25), major trauma (26, 27), car- inition.
Copyright © 2009 by the Society of Critical Care diopulmonary bypass (17, 28 –30), and More recently the Acute Kidney Injury
Medicine and Lippincott Williams & Wilkins burn injuries (31) have consistently Network (AKIN), an international multi-
DOI: 10.1097/CCM.0b013e3181bfb0b5 demonstrated an increased risk of death disciplinary organization composed of

Crit Care Med 2010 Vol. 38, No. 1 261


Table 1. Classification/staging systems for acute kidney injury

AKIN
RIFLE SCr Criteria UOP Criteria Stage SCr Criteria UOP Criteria

R 1 SCr ⫻ 1.5 ⬍0.5 mL/kg/hr ⫻ 6 hrs 1 1 in SCr ⱖ0.3 mg/dL or 1 ⬍0.5 mL/kg/hr for ⬎8 hrs
ⱖ150% to 200% from
baseline (1.5- to 2-fold)
I 1 SCr ⫻ 2 ⬍0.5 mL/kg/hr ⫻ 12 hrs 2 1 in SCr to ⬎200% to 300% ⬍0.5 mL/kg/hr for ⬎12 hrs
from baseline
(⬎2- to 3-fold)
F 1 SCr ⫻ 3, or SCr ⱖ4 mg/dL ⬍0.5 mL/kg/hr ⫻ 24 hrs 3 1 in SCr to ⬎300% (3-fold) ⬍0.5 mL/kg/hr ⫻ 24 hrs or
with an acute rise of at least or anuria ⫻ 12 hrs from baseline or SCr ⱖ4 anuria ⫻ 12 hrs
0.5 mg/dL mg/dL with an acute rise of
at least 0.5 mg/dL
L Persistent loss of kidney function
for ⬎4 wks
E Persistent loss of kidney function
for ⬎3 months

RIFLE, risk, injury, failure, loss, end-stage kidney disease; AKIN, acute kidney injury network; SCr, serum creatinine; UOP, urine output.
RIFLE criteria adapted from Bellomo et al (40). AKIN criteria adapted from Mehta et al (42).

nephrologists and intensivists, further


modified the RIFLE criteria recognizing
that even very small changes in SCr
(ⱖ0.3 mg/dL) adversely impact clinical
outcome (6, 7, 10, 11, 19, 21, 41). Accord-
ing to AKIN, the most current consensus
diagnostic criteria for AKI is “an abrupt
(within 48 hrs) reduction in kidney func-
tion currently defined as an absolute in-
crease in serum creatinine of more than
or equal to 0.3 mg/dL (ⱖ26.4 ␮mol/L), a
percentage increase in serum creatinine
of ⱖ50% (1.5-fold from baseline), or a
reduction in urine output (documented
oliguria of ⬍0.5 mL/kg/hr for ⬎6 hrs)”
(42). Importantly, the AKIN definition
and classification system incorporates
creatinine, urine output, and time (Table
1). Both the RIFLE and AKIN criteria
were developed to facilitate clinical inves-
tigation and comparison across study
populations. Epidemiologic data compar-
ing the RIFLE and AKIN criteria have Figure 1. Relationship between glomerular filtration rate (GFR) and serum creatinine (SCr). Large
demonstrated concordance in critically ill changes in GFR (e.g., 50% decrease from 120 mL/min to 60 mL/min) are reflected in only small
patients (43, 44). changes in SCr (0.7 mg/dL to 1.2 mg/dL).

Diagnosis of AKI in the ICU


Traditional tools to diagnose AKI distribution, and rate of elimination) are AKI spans the continuum from prere-
(SCr) and determine etiology of AKI variable in the ICU setting (6, 8 –11, 45, nal azotemia to acute tubular necrosis,
(clinical history, physical examination, 46). Medications (e.g., trimethoprim, from functional to structural injury. Ef-
renal ultrasound, fractional excretion of cimetidine) impair creatinine secretion forts to differentiate between these two
sodium [FeNa], fractional excretion of and therefore may cause increases in SCr entities have classically included FeNa
urea, blood urea nitrogen [BUN], and without reflecting a true decrease in and urine microscopy. Urine microscopy
urine microscopy) remain the corner- GFR. Finally, SCr lacks sensitivity and can be helpful in differential diagnosis
stone of diagnostic tools available to the underestimates the degree of kidney dys- (e.g., granular casts and renal tubular
clinician in the ICU. The use of SCr to function in a critically ill patient. In- epithelial cells in acute tubular necrosis,
estimate GFR is limited, however, by the creases in SCr substantially lag behind a cellular casts in glomerular injury, eosi-
lack of steady-state conditions in criti- reduction in GFR (Fig. 1) and thus do not nophiluria in acute interstitial nephritis,
cally ill patients. Determinants of the SCr provide a useful real-time assessment of or atheroembolic AKI). Of clinical note,
(rate of production, apparent volume of GFR. nephrologist review of urine microscopy

262 Crit Care Med 2010 Vol. 38, No. 1


has been demonstrated to be superior to Table 2. Common causes of AKI in the ICU Table 3. Common nephrotoxins that cause acute
clinical laboratory interpretation (47). kidney injury in intensive care unit patients
Five Most Common Causes of AKI in the ICUa
Using a proposed scoring system, micro-
● Sepsis (most common) Exogenous
scopic examination of the urine sediment ● Major surgery ● Medications
is a highly predictive method for differ- ● Low cardiac output —NSAIDS
entiating prerenal azotemia from acute ● Hypovolemia —Antimicrobials
tubular necrosis (48). However, the pres- ● Medications –Aminoglycosides
Other Common Causes of AKI in the ICU –Amphotericin
ence of muddy brown casts and renal ● Hepatorenal syndrome –Penicillinsa
tubular epithelial cells are usually seen ● Trauma –Acyclovirb
relatively late and thus are not sensitive ● Cardiopulmonary bypass —Chemotherapeutic agents
for early detection of AKI (49, 50). FeNa is ● Abdominal compartment syndrome ● Radiocontrast dye
● Rhabdomyolysis ● Ingestions
frequently useful for differentiating “pre-
● Obstruction —Ethylene glycol
renal” (diminished renal perfusion, FeNa Endogenous
⬍1%) from “intra-renal” (ischemia or a
The five most common causes of acute kid- ● Rhabdomyolysis
nephrotoxins, FeNa ⬎2%) (50, 51). Urine ney injury (AKI) in the intensive care unit (ICU) ● Hemolysis (HUS/TTP)
microscopy and FeNa can be valuable based on nearly 30,000 patients (9). ● Tumor lysis syndrome
tools in determining the cause of AKI but
NSAIDS, non-steroidal anti-inflammatory
have no current role in early detection or
drugs; HUS, hemolytic uremic syndrome; TTP,
diagnosis of AKI. Furthermore, “prere- ated with increased morbidity and mor- thrombotic thrombocytopenic purpura.
nal” and “intra-renal” causes of AKI com- tality with elevations in SCr as small as a
Acute interstitial nephritis (AIN); bcrystal
monly coexist in the ICU patient. 0.3 mg/dL (19). Trauma associated AKI is nephropathy.
Prerenal azotemia, in the absence of multi-factorial (e.g., hemorrhagic shock,
validated new diagnostic biomarkers, of- abdominal compartment syndrome,
ten remains a retrospective diagnosis, rhabdomyolysis) and occurs in up to 31% therapy. In contrast to most cases of
made only after response to a volume of adult trauma patients (55). The kid- community-acquired AKI, nearly all cases
challenge. Whereas it is important to ap- neys are early sensors of intra-abdominal of ICU-associated AKI result from more
propriately identify and treat prerenal hypertension and abdominal compart- than a single insult (6, 8 –11, 45, 50, 60,
azotemia, fluid administration is not ment pressures ⱖ12 mm Hg may be as- 61). In the critically ill patient, the first
without consequence in the critically ill sociated with AKI (56). A sustained intra- kidney insult is often not predictable.
patient. A complete assessment of the pa- abdominal pressure ⬎20 mm Hg in Therefore, prevention of AKI in the ICU
tient’s overall volume status is pivotal association with new organ dysfunction often means prevention of a secondary
before aggressive resuscitative efforts to will be associated with AKI in ⬎30% of insult in an “at-risk” patient. For exam-
enhance renal perfusion. This is of par- cases (57, 58). Rhabdomyolysis accounts ple, in a retrospective study of ⬎5000 ICU
ticular importance considering data dem- for 28% of trauma-associated AKI requir- patients, 67% of patients had AKI de-
onstrating adverse effects of volume over- ing dialysis (59). velop, and 45% of AKI occurred after ICU
load in critically ill patients (52, 53). Medications are a common cause of admission (6). It is in these patients that
Because of the limitations of traditional AKI and, according to Uchino et al (9), there is a potential role for prevention.
tools, novel candidate biomarkers of AKI account for nearly 20% of all cases of AKI General principles of “secondary” AKI
(discussed separately) are being actively in the ICU. The mechanism of medication prevention include: (1) recognition of un-
investigated. induced AKI is variable and includes derlying risk factors that predispose pa-
acute interstitial nephritis, direct tubular tients to AKI (e.g., diabetes, chronic kid-
Common Causes of AKI in toxicity (e.g., aminoglycosides), and he- ney disease, age, hypertension, cardiac or
the ICU modynamic perturbations (e.g., nonste- liver dysfunction); and (2) maintenance
roidal anti-inflammatory agents, angio- of renal perfusion, avoidance of hypergly-
The cause of AKI in the ICU is com- tensin-converting enzyme inhibitors). cemia, and avoidance of nephrotoxins in
monly “multi-factorial” and frequently Acute interstitial nephritis is likely an these high-risk patients. Specific clinical
develops from a combination of hypovo- under-recognized etiology of medication- situations in which there is evidence for
lemia, sepsis, medications, and hemody- associated AKI in the ICU because of the preventive strategies (e.g., contrast expo-
namic perturbations (Table 2). It is fre- relative paucity of clinical findings and sure, hepatorenal syndrome [HRS]) are
quently not possible to isolate a single need for high index of suspicion. Table 3 discussed.
cause, thereby further complicating the lists common nephrotoxins encountered Preventing Contrast-Induced Ne-
search for effective interventions in this in the care of critically ill patients. phropathy. The primary strategies for con-
complex disease process. The pathophys- trast-induced nephropathy (CIN) preven-
iology of AKI varies according to the un- Prevention and Management of tion include hydration, N-acetylcysteine
derlying etiology and is beyond the scope AKI in the ICU (NAC), and use of low-volume nonionic
of this article. low-osmolar or iso-osmolar contrast. No
Sepsis is the most common cause of Primary prevention of AKI in the ICU strategy has been effective in completely
AKI in a general ICU, accounting for up is limited to those conditions in which preventing CIN. Risk factors for CIN in-
to 50% of cases (6, 8 –11, 23, 45, 54). AKI the timing of injury is predictable, such clude diabetes, CKD, hypotension, effec-
is common after cardiac surgery, occur- as exposure to radiocontrast dye, cardio- tive or true volume depletion (including
ring in up to 42% of patients without pulmonary bypass, large-volume para- cirrhosis and congestive heart failure),
pre-existing kidney disease, and is associ- centesis in a cirrhotic patient, or chemo- and concurrent use of nephrotoxic med-

Crit Care Med 2010 Vol. 38, No. 1 263


ications. Critically ill patients intuitively trast media resulted in a lower incidence of for CIN prevention is inconsistent across
represent a patient population at high CIN when compared to low-osmolar con- studies. Although two meta-analyses sug-
risk for CIN given frequent hemodynamic trast media. However, Heinrich et al (124), gest that prophylactic theophylline may
instability, multiple organ dysfunction, in the most recent meta-analysis, re- provide some benefit, the studies were
use of nephrotoxic medications, and mul- ported no significant difference between performed in primarily low-risk patients,
tiple underlying comorbidities (e.g., dia- the two unless the low-osmolar contrast and clinically relevant outcomes were not
betes, CKD). However, despite the large media was iohexol, suggesting that all consistently reported (137, 138). There-
number of randomized controlled trials low-osmolar contrast media preparations fore, we cannot currently recommend the
(RCT) published on prevention strategies may not be the same. use of theophylline for prevention of CIN
for CIN, there has been only one RCT Both small observational and prospec- in critically ill patients.
performed specifically in critically ill tive studies have shown an increase in the The majority of these studies were not
adults (111). The true incidence of and risk of CIN with peri-procedural use of performed in critically ill patients and
risk for CIN in critically ill patients is angiotensin-converting enzyme inhibi- therefore provide no definitive guidance
thus unknown. tors (125–127). However, a recent ran- as to how the risk of CIN in the critically
Adequate volume expression is a well- domized prospective trial performed in ill should be ameliorated. Because of the
established measure to decrease the risk stable outpatients did not show any dif- absence of sufficient data in the patient
of CIN, whereas the choice of fluid re- ference in incidence of CIN between pa- population of interest, clinicians must ex-
mains controversial. Trials comparing tients who did or did not discontinue trapolate from the best available evidence
the use of sodium bicarbonate and so- angiotensin-converting enzyme inhibi- from other patient populations. There-
dium chloride for the prevention of CIN tors or angiotensin receptor blockers be- fore, our recommendations include: (1)
have yielded conflicting results. Five fore contrast (128). Angiotensin-convert- avoid use of intravenous contrast in high-
meta-analyses of sodium bicarbonate ing enzyme inhibitors have not been risk patients if alterative imaging tech-
suggest a beneficial role of isotonic so- prospectively studied in the critically ill. niques are available; (2) use preexposure
dium bicarbonate over isotonic saline Therefore, although there is currently in- volume expansion using either bicarbon-
(112–116); however, there is considerable sufficient evidence to support discontin- ate or isotonic saline; (3) although of
heterogeneity and some publication bias uation of these medications in critically questionable benefit, use of NAC is safe,
confounding these findings. The most re- ill adults, further study is warranted inexpensive, and may decrease risk of
cent RCT of bicarbonate vs. normal saline given the widespread use of these agents AKI; (4) avoid concomitant use of neph-
showed no difference in the primary out- in clinical practice. rotoxic medications if possible; and (5)
come of ⱖ25% decrement in GFR within Whereas the use of peri-procedural use low-volume low-osmolar or iso-
4 days (117). Based on currently available hemofiltration in patients undergoing osmolar contrast. Future studies are
evidence, there is a strong suggestion percutaneous coronary intervention was needed to determine the true role of
that sodium bicarbonate may be superior shown, in two studies, to decrease the these preventive measures in critically ill
to isotonic saline to decrease the risk of risk of AKI (5% vs. 50%; p ⫽ .0001) (129, patients.
CIN. 130), this has not been widely adopted Preventing AKI in Hepatic Dysfunc-
NAC is a free radical scavenger shown into clinical practice. In a systematic re- tion. AKI is a common complication of
to decrease the risk of CIN compared to view of extracorporeal therapies for pre- critically ill patients with hepatic failure.
placebo (118). Since 2003, ⬎10 meta- vention of CIN, analysis of the hemodial- Pentoxifylline decreases the incidence of
analyses published on the role of NAC in ysis studies alone (including five RCT), AKI attributable to HRS in acute alco-
CIN have yielded conflicting results likely there was no benefit of hemodialysis and, holic hepatitis (139). Use of intravenous
attributable, in part, to heterogeneity in in fact, there was a trend favoring stan- albumin in patients with cirrhosis and
patient populations. In a recent meta- dard therapy compared to prophylactic spontaneous bacterial peritonitis signifi-
analysis of 41 studies, NAC plus saline hemodialysis (131). A subsequent RCT of cantly reduces both the incidence of AKI
reduced the risk for CIN more effectively prophylactic hemodialysis in 82 patients (33% to 10%) and mortality (41% to
than saline alone (119). A previous meta- with advanced CKD (baseline SCr 4.9 mg/ 22%) (140). Albumin decreases the inci-
analysis in 2007 by Gonzales et al (120) dL) demonstrated improved outcomes dence of AKI after large-volume paracen-
did not support the efficacy of NAC to (shorter length of stay and lower rate of tesis (141), and when used in combina-
prevent or decrease the risk of CIN. Fur- long-term dialysis dependence after hos- tion with splanchnic vasoconstricting
thermore, there are conflicting data as to pital discharge) with prophylactic hemo- agents (e.g., terlipressin) may decrease
whether NAC, itself, may decrease SCr dialysis (132). A critical limitation of all mortality in HRS (142, 143). However,
measurement without affecting GFR of these studies is that the clinical end definitive therapy for AKI as a conse-
(121, 122). point SCr was directly impacted by the quence of HRS remains liver transplan-
Low-volume nonionic low-osmolar or intervention itself (hemofiltration or he- tation in appropriate candidates. Five
iso-osmolar contrast preparations are modialysis). randomized trials of vasoconstricting
clearly associated with a decrease in CIN Fenoldopam and theophylline are two agents (terlipressin or noradrenalin) plus
when compared to high osmolar agents. additional agents that have been consid- albumin in the treatment of HRS all dem-
The data regarding nonionic low-osmolar ered for their potential role in the pre- onstrated improved renal function in
contrast media vs. iso-osmolar contrast vention of CIN. None of the four RCT HRS (144 –148). A mortality benefit was
media (currently only iodixanol) is con- comparing fenoldopam to either saline only demonstrated in responders to ther-
troversial. Two meta-analyses report con- alone (133, 134) or NAC (135, 136) dem- apy (145). Terlipressin is not available in
flicting results (123, 124). McCullough et onstrated any beneficial effect in the pre- the US. In a retrospective study per-
al (123) found that use of iso-osmolar con- vention of CIN. The role of theophylline formed in the US, patients treated with

264 Crit Care Med 2010 Vol. 38, No. 1


vasopressin had significantly higher re- improvement in urine output (66), “re- suscitation with albumin was associated
covery rates and improved survival when nal” dose dopamine does not reduce the with increased mortality in critically ill
compared to octreotide alone (149). Fur- incidence of AKI, the need for RRT, or patients after traumatic brain injury (87).
thermore, findings from three small ob- improve outcomes in AKI (66 –71). Fur- In contrast, there was a trend toward
servational and retrospective studies thermore, “low-dose” dopamine may improved survival in septic shock patients
demonstrate improved outcomes with worsen renal perfusion in critically ill receiving albumin (30.7% in albumin
midodrine and octreotide (HRS reversal adults with AKI (72) and is associated group vs. 35.3% in saline group; p ⫽ .09)
and decreased mortality) (150 –152). with increased myocardial oxygen de- (86). Based on currently available litera-
These findings justify a larger RCT to mand and an increased incidence of atrial ture, there is no evidence of a mortality
appropriately evaluate this treatment fibrillation (73). There is additional con- benefit supporting the preferential use of
modality. cern for extrarenal adverse effects of do- albumin over crystalloids in a heteroge-
Management of AKI in the ICU re- pamine, including negative immuno- nous critically ill patient population (84).
volves around optimizing hemodynamics modulating effects (74). Thus, there is Synthetic colloids (e.g., hydroxyethyl
and renal perfusion, correcting metabolic broad consensus that dopamine is poten- starches, dextrans) are still widely used
derangements, providing adequate nutri- tially harmful and without evidence of despite multiple reported safety concerns
tion, and mitigating progression of in- clinical benefit for either prevention or with regard to renal outcomes (88 –90).
jury. These management considerations treatment of AKI. Therefore, its contin- An increased risk of AKI with the use of
are discussed. ued use for putative “renal protection” hydroxyethyl starches has been demon-
Maintain Renal Perfusion. Optimiza- should be avoided. strated in multiple small studies, and
tion of renal perfusion may require vol- Fenoldopam is a selective dopamine-1 most recently a systematic review of 12
ume resuscitation, inotropic, or vasopres- receptor agonist approved for the treat- randomized trials demonstrated an in-
sor support. Extrapolated primarily from ment of hypertensive crisis (75). Paradox- creased risk of AKI with the use of hy-
animal studies (62, 63), the human kid- ically, the lowest doses of fenoldopam droxyethyl starches among patients with
ney has a compromised ability to auto- (ⱕ1 ␮g/kg per min) are purported to sepsis (91). In contrast, the largest indi-
regulate (maintain constancy of renal increase renal blood flow without sys- vidual retrospective analysis (SOAP study
blood flow and GFR over a wide range of temic effects. Despite encouraging data cohort, 92) explored the effects of hy-
renal perfusion pressures) in AKI. There- from pilot studies, (76 –78) a prospective droxyethyl starches on renal function and
fore, as a priority, prevention or manage- placebo-controlled study of low-dose did not find the use of hydroxyethyl
ment of AKI should include maintenance fenoldopam in sepsis failed to decrease starches to be an independent risk factor
of hemodynamic stability and avoidance mortality or need for RRT despite a for AKI or need for RRT (93). The dose
of volume depletion. A mean arterial smaller increase in SCr (79). Larger stud- and preparation varied between studies.
pressure of ⱖ65 mm Hg is a generally ies to validate the meta-analytic observa- The adverse event profile has been linked,
accepted target; however, the data are tion that fenoldopam both reduces the in part, to the individual preparation,
limited (64, 65) and do not include pa- need for RRT (OR, 0.54; p ⫽ .007) and with the lowest molecular weight offering
tients with established AKI (loss of auto- decreases mortality (OR, 0.64; p ⫽ .01) the best side effect profile.
regulation). The level at which renal (80) are currently ongoing in cardiac sur- The question of fluid management
blood flow becomes dependent on sys- gery patients (clinicaltrials.gov ID: does not end with the choice of fluid;
temic arterial pressure varies signifi- NCT00557219). careful consideration of the amount of
cantly based on age, underlying illness Fluid Choice in AKI. The primary fluid administered is also important. Crit-
(e.g., hypertension), and the acute illness physiologic intention of volume resusci- ical illness is a dynamic process requiring
or condition (AKI, sepsis, and cardiopul- tation is the restoration of circulating frequent assessment of and adjustment to
monary bypass). After volume resuscita- volume to prevent or mitigate organ in- fluid status. In a prospective RCT of pa-
tion, blood flow should be restored to jury. The kidneys normally receive up to tients with acute respiratory distress syn-
within autoregulatory parameters. This 25% of the cardiac output and are exquis- drome, a fluid conservative strategy de-
frequently requires vasopressor or inotro- itely sensitive to hypoperfusion attribut- creased ventilator days and did not
pic support in the setting of septic shock, able to true or relative hypovolemia. For increase the need for RRT (53). Further-
the most common cause of AKI in the this reason, the question of whether a more, an observational study of ⬎3000
ICU. There are currently no RCT compar- particular type of fluid influences devel- patients demonstrated an association be-
ing vasopressor agents; therefore, there is opment of AKI is of pivotal importance. tween positive fluid balance and in-
no evidence that, from a renal protection Whereas crystalloid solutions remain creased mortality in patients with AKI
standpoint, there is a vasopressor agent the preferred treatment in usual care, the (52). However, the question remains
of choice to improve kidney outcomes. debate over whether colloid solutions whether this is simply a marker of sever-
Decreased renal blood flow (attribut- provide any additional benefit remains an ity of illness or true causation; this ob-
able to either hypotension or high renal area of active investigation (81– 85). In a servation warrants further investigation.
vascular resistance, from an imbalance landmark trial evaluating the impact of Avoid Hyperglycemia. Although the
between renal vasoconstriction and vaso- fluid choice on clinical outcomes, the beneficial effects of intensive insulin
dilation) is a common feature in many SAFE study investigators randomized therapy on mortality in critically ill pa-
forms of AKI. Consequently, there has nearly 7000 patients to volume resuscita- tients remains controversial (94 –96), two
been considerable interest in renal vaso- tion with saline or albumin. They dem- large RCT demonstrated a decreased in-
dilators to maintain renal perfusion for onstrated no difference in survival or cidence of AKI and a decreased require-
prevention or treatment of AKI. Whereas need for RRT between the two groups ment for RRT with tight glucose control
dopamine infusion may cause a transient (86). In post hoc subgroup analysis, re- (95, 96). Furthermore, a more detailed

Crit Care Med 2010 Vol. 38, No. 1 265


secondary analysis strongly suggests that pharmacokinetics in critically ill patients tein catabolism and impaired protein syn-
tight blood glucose control may be reno- with and without underlying CKD. thesis.
protective in critically ill patients (97). Diuretics in AKI. Use of diuretics in The impact of CRRT on nutrition in
Two smaller retrospective studies re- the prevention or treatment of AKI has the ICU is two-fold. Because protein ca-
ported similar results (decreased inci- physiologic merit but its use is not sup- tabolism is markedly increased in most
dence of AKI and decreased need for post- ported by prospective clinical study. Di- patients requiring CRRT (165–167), the
operative dialysis) in nondiabetic cardiac uretics can increase urine output but use of CRRT enhances the clinician’s abil-
surgical patients (98) and in patients re- have not been found to have a consistent ity to provide adequate nutrition because
ceiving total parenteral nutrition (99). impact on mortality (153–157). Mehta et of an improved ability to manage volume.
However, in contrast, in the largest and al (157) demonstrated that failure to re- Unfortunately, the recommended
most recent prospective RCT of intensive spond to diuretics was associated with an amount of protein in this population re-
vs. conventional glucose control in increased risk of death and non-recovery mains controversial and recommenda-
⬎6000 critically ill patients, there was no of renal function. Subsequently, in a tions are based solely on expert opinion,
difference in the number of patients re- large, prospective, multinational study, because there are no data available from
quiring RRT (94). The overall incidence Uchino et al (158) did not demonstrate an RCT. Although there are no studies dem-
of AKI, however, was not reported in this increased mortality, thus leaving unre- onstrating a benefit in outcomes (e.g.,
study. It therefore remains unclear if solved the therapeutic role of diuretics in survival or dialysis-free days), consensus
there is a reno-protective role for tight critically ill patients with renal dysfunc- recommendations include nonprotein ca-
glycemic control and, if present, whether tion. Although oliguric AKI has been as- loric intake of 20 to 30 kcal/kg body
any such effect is attributable to the sociated with worse outcomes than nono- weight per day and a protein intake of 1.5
avoidance of glucose toxicity or a benefi- liguric AKI (159), there is no evidence g/kg per day (168). However, several stud-
cial effect of insulin. These findings war- supporting efforts to convert nonoliguric ies have demonstrated a less negative or
rant further study, especially in view of AKI with diuretics. Diuretics have not even positive nitrogen balance in those
the fact that intensive glycemic control been found to shorten the duration of patients receiving up to 2.5 g/kg per day
may be associated with a higher fre- AKI, reduce the need for RRT, or improve while receiving CRRT without evidence of
quency of clinically relevant hypoglyce- overall outcomes (160). Furthermore, a adverse effects (169 –171). An increase in
mia. recently published RCT comparing the nonprotein calories in critically ill pa-
Avoid Nephrotoxins. Nephrotoxic use of furosemide vs. placebo in the re- tients with AKI does not improve nitro-
medications are a contributing factor in covery phase of AKI requiring continuous gen balance (172).
up to 25% of all severe AKI in critically ill renal replacement therapy (CRRT), furo-
patients (8, 9; Table 3). Identification of semide was found to increase urine out- RRT for AKI in the ICU
at-risk patients is pivotal. Aminoglyco- put and sodium excretion but did not
sides, although less commonly used for improve renal recovery (161). In a multi- Despite decades of clinical trials inves-
severe Gram-negative infections than national survey, nephrologists and inten- tigating potential pharmacologic inter-
previously, are associated with significant sivists reported clinical uncertainty about ventions in AKI, current treatment op-
nephrotoxicity. Although once-daily dos- the use of diuretics in AKI, thus justifying tions are primarily limited to RRT.
ing of aminoglycosides has been shown, the need for a definitive RCT (162). Practice patterns vary widely regarding
in some studies, to decrease the inci- Because diuretic use in AKI has not timing of initiation of RRT, dose deliv-
dence of AKI (100, 101), published meta- been shown to decrease mortality, there ered, and choice of modality as evidenced
analyses support comparable efficacy and is no role for diuretics to convert oliguric by international surveys (173–176).
decreased cost but do not consistently AKI to nonoliguric AKI. However, regard- There is no current consensus on the
demonstrate a significant reduction in ing an increased appreciation for the po- indications for RRT for AKI. With a
nephrotoxicity (102–106). Extended in- tential detrimental downstream effects of greater appreciation for and understand-
terval dosing should not be used in pa- volume overload, it may be reasonable to ing of the role of the kidney in distant
tients with CKD. Standard amphotericin try diuretics for control of volume over- organ injury (177), it may be more appro-
B has been associated with AKI in 25% to load. The clinician should, however, be priate to consider renal replacement
30% of patients (107). The lipid formula- careful not to delay initiation of RRT for therapy as renal supportive therapy (178).
tion of amphotericin B is preferred be- volume overload in the critically ill pa- For the purposes of this review, we review
cause of reduced nephrotoxicity of 19% tient with AKI. the most up-to-date evidence available
vs. 34% (108). Caspofungin, a newer an- Nutritional Considerations. Malnutri- addressing timing, dosing, and modality
tifungal agent, is associated with an even tion in hospitalized patients is associated of RRT.
safer renal profile (109). The use of apro- with increased mortality (163). Assess- Timing of Renal Replacement. There
tinin, a serine protease inhibitor used to ment of the nutritional status of critically is little prospective data regarding the
decrease blood loss during cardiac sur- ill patients is limited by the unreliability appropriate timing of initiation of RRT
gery, has been associated with increased of traditional markers of nutritional sta- and that which are available are incon-
risk of AKI and need for dialysis (110). tus in critical illness in general, and AKI clusive. The “absolute” indications for
ICU patients frequently have fluctuat- in particular. Prealbumin is excreted initiation of dialysis (severe hyperkale-
ing renal function and a variable volume mainly by the kidneys and hence may be mia, clinically apparent signs of uremia,
of distribution. Standard estimates of re- falsely elevated in patients with AKI severe acidemia, and volume overload, in-
nal function are poor in critically ill pa- (164). Patients with AKI are hypercata- cluding pulmonary edema complicated
tients. Therefore, medications must be bolic with a negative nitrogen balance by hypoxia or cardiogenic shock) are
carefully dose adjusted because of varied (165), resulting from both increased pro- broadly accepted usual care standards.

266 Crit Care Med 2010 Vol. 38, No. 1


Table 4. Summary of randomized controlled trials of dosing strategies for renal replacement therapy for acute kidney injury in the intensive care unit

Author N Design RRT Modality RRT Doses P/D Survival

Randomized controlled trials with mortalitydifference


Ronco et al (187) 425 Single center CVVH (post-filter dilution) (P) 20 mL/kg/hr 15-day: 41%
(P) 35 mL/kg/hr 57%
(P) 45 mL/kg/hr 58%
Schiffl et al (37) 160 Single center Intermittent HD: daily vs. Daily HD Kt/V(P) 1.19/(D) 0.92 28 day: 72%
alternate day Alternate day HD Kt/V 54%
(P) 1.21/ (D) 0.94
Saudan et al (188) 206 Single center CVVH vs. CVVHDF (D) Mean: 25 mL/kg/hr/87% of prescribed 28-day: 39%
(pre-filter dilution) (D) Mean: 42 mL/kg/hr/83% of prescribed 59%
(includes mean 24 mL/kg/hr
replacement and 18 mL/kg/hr
dialysate
Randomized controlled trials without mortality difference
Bouman et al (184) 106 Two centers CVVH (post-filter dilution): (D) Mean: 48 ml/kg/hr (early) 28-day: 74%
early high-volume vs. (D) Mean: 20 ml/kg/hr (early) 69%
early low-volume vs. late
(D) Mean: 19 ml/kg/hr (late) 75%
low-volume
Tolwani et al (189) 200 Single center CVVHDF (P) 20 mL/kg/hr/(D) 17 mL/kg/hr ICU discharge or
(pre-filter dilution) (P) 35 mL/kg/hr/(D) 29 mL/kg/hr 30 day: 56%
49%

Palevsky et al (190) 1124 Multicenter Intensive vs. less intensive (P) 21 mL/kg/hr or SLED or HD 3⫻/wk 60 day: 44%
RRT (CVVHDF or SLED (D) 22 mL/kg/hr or Kt/V 1.3 3⫻/wk 49%
or HD) (P) 36 mL/kg/hr or SLED or HD 6⫻/wk
(D) 35 mL/kg/hr or Kt/V 1.3 6⫻/wk

P, prescribed; D, delivered; CVVH, continuous veno-venous hemofiltration; HD, hemodialysis; CVVHDF, continuous veno-venous hemodiafiltration;
SLED, slow low-efficiency dialysis.

“Prophylactic” dialysis was introduced in vived, a fact that likely influenced the improved outcomes, specifically de-
the 1960s (179), and the first prospective results of this study. Results from a large creased mortality (37, 187, 188). Ronco et
study was published in 1975 comparing a prospective multi-centered observational al (187) published the first RCT in 2000
BUN trigger of 70 mg/dL vs. nearly 150 study of ⬎1200 patients were internally addressing this question. These investiga-
mg/dL (180). Survival was 64% in the inconsistent and dependent on the defi- tors compared 20, 35, and 45 mL/kg/hr
“early intervention” group as compared nition of “early” or “late” initiation of dosing strategies. There was a high mor-
to 20% in the non-intensive or standard RRT (185). In this study, “late” initiation tality in all groups but a statistically
intervention group (p ⬍ .01). Conven- of RRT was associated with worse out- lower mortality in the two groups with
tional teaching based on this and other comes (higher crude mortality, longer higher dose of ultrafiltration (35 and 45
studies (181, 182) has been to initiate duration of RRT, increased hospital mL/kg/hr) without any difference in com-
RRT before a BUN exceeds 100 mg/dL. length of stay, and greater dialysis depen- plication rates between groups (187). In
Unfortunately, not only is the “ideal” dence) when “late” was defined relative to 2002, Schiffl et al (37) found daily dialysis
BUN not established but also BUN per se date of ICU admission. However, there to be superior to alternate day dialysis in
is an imperfect reference value because it was no difference in crude mortality if the a prospective randomized study. There
is widely influenced by nonrenal factors. timing was defined by serum urea. Fi- were significantly fewer hypotensive epi-
More recently, a review of the data nally, there was a lower crude mortality if sodes in the daily dialysis group (5% vs.
from the PICARD study demonstrated an timing of RRT initiation was defined by 25%). In an intention-to-treat analysis,
increased risk of death associated with SCr at initiation (higher SCr associated mortality was 28% for daily dialysis and
initiation of RRT with a BUN ⬎76 mg/dL with a lower mortality) (185). Unfortu- 46% for alternate-day dialysis (p ⫽ .01)
in comparison to ⬍76 mg/dL (183). An nately, the question of timing remains (37). An important limitation of this
important limitation of this study is that unanswered and controversial (185, 186). study is that the delivered dose was sig-
patients who were conservatively man- There is clearly a need for a large RCT, nificantly less than the prescribed dose;
aged (did not receive RRT) are “invisible” with a clear definition of “early,” to help therefore, the daily dialysis group re-
in this analysis, thereby limiting the va- guide the clinician in determining the ceived only “adequate” therapy as judged
lidity of the findings regarding impact on appropriate timing for initiation of RRT by contemporary standards. It may be
mortality. In the only randomized study for AKI in the ICU. said, therefore, that it was a comparison
of timing of CRRT initiation (n ⫽ 106), Choosing a Renal Replacement Dose. between adequate and inadequate dialy-
there was no effect on mortality (184). Six prospective RCT have been published sis. In 2006, Saudan et al demonstrated
“Early” dialysis was initiated after 6 hrs of addressing the question of dose of RRT in that continuous veno-venous hemodiafil-
oliguria. Of the 36 patients included in critically ill adults (37, 184, 187–190; Ta- tration (CVVHDF); addition of dialysate
the “late” arm of this study, six patients ble 4). Three of these studies suggest that (1–1.5 L/hr) to continuous veno-venous
did not receive RRT, of whom four sur- a higher dose of dialysis translates into hemofiltration (1–2.5 L/hr); improved 28-

Crit Care Med 2010 Vol. 38, No. 1 267


and 90-day survival compared with he- to account for filter clotting, time off the Hybrid therapies include SLED and
mofiltration alone in 206 critically ill machine for interventions, or radio- extended daily dialysis. These modalities
adults; 39% vs. 59%; p ⫽ .03 and 34% vs. graphic studies, etc. For intermittent utilize standard intermittent hemodialy-
59%; p ⫽ .0005, respectively, suggesting RRT, one should target a Kt/V of 1.2 to sis machines but provide a slower solute
that small solute clearance is important 1.4 per treatment for alternate day (three and fluid removal similar to CRRT tech-
(188). times per wk) hemodialysis. Further- nologies. Although there have been no
In contrast, three prospective RCT more, in addition to an appropriate target prospective randomized trials evaluating
have demonstrated no difference in mor- dose, there must be close attention given outcomes, hybrid therapies have been
tality (184, 189, 190; Table 4). Bouman et to the actual delivered dose. In summary, shown to be safe and effective alternatives
al (184), in 2002, showed no difference in one dose does not fit all; RRT dose must to treating AKI in critically ill patients
28-day mortality when comparing early be weight-adjusted. (207, 208).
high-volume hemofiltration, early low- Choosing a Renal Replacement Mo- The question of optimal modality has
volume hemofiltration vs. late low- dality. Continuous RRT modalities more not yet been definitively answered. It is
volume hemofiltration with the median closely approximate normal physiology
important to note that although the data
dose (mL/kg/hr) of 48, 20, and 19, respec- with slow correction of metabolic de-
strongly suggest that there is no differ-
tively. More recently, Tolwani et al (189) rangements and removal of fluid. There-
ence in outcome between intermittent
compared two different doses, 20 mL/ fore, CRRT is commonly thought to be
and continuous modalities, several key
kg/hr and 35 mL/kg/hr, of pre-filter CV- better-tolerated in the critically ill and
VHDF and found no difference in 30-day hemodynamically unstable patient. The patient populations have been excluded.
mortality (44% vs. 51%, p ⫽ .32). Of question of superiority remains given the Namely, hemodynamically unstable pa-
note, the delivered dose in these two absence of clear evidence that these ap- tients, brain-injured patients, and those
groups were 17 mL/kg/hr and 29 mL/kg/ parent physiologic advantages translate with fulminant hepatic failure were ex-
hr, respectively (189). The largest and only into a decrease in ICU or hospital mor- cluded and are widely believed to require
multi-centered trial designed to address the tality (191–196). continuous modalities. Furthermore, a
question of dose of RRT in critically ill Since 2000 there have been seven pro- critical limitation of all of the studies is
adults is the acute tubular necrosis study spective RCT designed to address the im- the absence of a standardized dose (both
published in 2008 (190). This was a two- portant clinical question regarding opti- within and between modalities) (202).
arm study comparing intensive to standard mal RRT modality (192, 193, 195, 197– RRT, like other medical treatments, must
RRT. The intensive therapy group under- 200); of these, only three were multi- be considered in terms of dose adequacy
went daily dialysis, CVVHDF, or sustained centered studies (193, 198, 200). Of note, to appropriately draw conclusions regard-
low-efficiency dialysis (SLED) at a dose of many of these trials, although published ing clinical outcomes. Large randomized
35 mL/kg/hr, whereas the standard ther- after 2000, enrolled patients in the 1990s. trials may be necessary to identify other
apy group had alternate day dialysis In six of the trials, mortality was the potential subsets of patients who might
(three times per wk), CVVHDF, or SLED primary outcome. There have been sev- benefit from continuous modalities.
at 20 mL/kg/hr. Notably, patients were eral meta-analyses and systematic re- Anticoagulation is frequently required
able to move from intermittent to con- views comparing outcomes of intermit- to prevent clotting in extracorporeal cir-
tinuous modalities based on hemody- tent vs. continuous renal replacement cuits. There are no large RCT available to
namic stability but they stayed within modalities with conflicting results (191, guide the choice of anticoagulation: hep-
their assigned intensive or standard treat- 201–204). A recent meta-analysis (nine arin (unfractionated or low-molecular-
ment therapy groups. There was no dif- randomized trials) comparing intermit- weight heparin) or citrate-based proto-
ference in the primary outcome, death tent to continuous renal replacement cols. Bleeding complications remain the
from any cause (190). The RENAL study, therapy (intermittent RRT vs. CRRT) in primary concern with anticoagulation.
comparing CVVHDF 25 mL/kg/hr to 40 AKI demonstrated no difference in mor- Three small RCT, however, have demon-
mL/kg/hr, has completed enrollment but tality or renal recovery (defined as inde-
strated both similar or prolonged filter
results have not yet been published. pendence from RRT) (202). Of note, mor-
life and less bleeding and transfusion
An important factor in considering the tality was the primary outcome in eight
with citrate protocols when compared to
results of the currently available data are of the nine included trials. Mortality,
use of heparins (209 –211). In a recent
the difference between study populations, however, may not be the only clinically
use of solely convective or combination significant outcome. Two studies have larger, randomized, non-blinded trial com-
convective and diffusive modalities, and shown that CRRT is associated with bet- paring citrate to nadroparin, circuit sur-
the potential gap between prescribed and ter long-term kidney recovery when com- vival was similar in both groups, but the
delivered doses. Findings from these neg- pared to intermittent RRT (205, 206). In citrate group had a lower mortality rate
ative trials should not be interpreted to contrast, four RCT that included renal (212). Currently available data support the
mean that dose is not important. On the recovery as a primary outcome showed use of citrate for anticoagulation; however,
contrary, it is likely that dose is impor- no difference in need for chronic RRT this requires local expertise.
tant and, above a minimal dose, further (193, 195, 198, 200). In the absence of In summary, whereas RRT remains
escalation may not provide additional definitive data in support of a particular the cornerstone of treatment of AKI in
benefit. Based on currently available data, modality (191, 201), the choice of RRT the ICU, many key questions remain con-
it is our recommendation that to ensure modality is currently influenced by mul- troversial. This is a rapidly evolving field
an actual delivered dose of 20 mL/kg/hr tiple factors, including individual site and requires early consultation for appro-
for continuous modalities one must pre- availability, expertise, resources, cost, priate expertise in the management of
scribe a higher dose (e.g., 25 mL/kg/hr) and likely clinician bias. RRT for the critically ill patient with AKI.

268 Crit Care Med 2010 Vol. 38, No. 1


On the Horizon 234). Urinary excretion of enzymes (alka- was compared to CRRT alone, are prom-
line phosphatase, gamma glutamyl ising with respect to both safety and effi-
The identification of novel candidate transaminase, N-acetyl-beta-d-glu- cacy. There was a non-statistically signif-
biomarkers of early AKI provides hope for cosamine) (235), transporters (sodium- icant decrease in mortality at 28 days and
the success of future clinical early inter- hydrogen exchanger isoform 3) (236), cy- a statistically significant difference at 180
vention trials. Advances in treatment of tokines (IL-6, IL-8, and IL-18), and days (secondary outcome) (250).
AKI have been limited by the inability to protein-like substances (fetuin A) (237) Hemofiltration for Sepsis. Payen et al
diagnose AKI early. Previously failed in- are presumably “shed” into the urine (251) recently published the findings
terventions may portend different out- with AKI; therefore, they may have a role from the largest RCT of hemofiltration
comes if implemented earlier in the in the early identification of AKI (232, for severe sepsis and septic shock. At in-
course of AKI. Novel pharmacologic 233). terim analysis, standard CVVH was found
agents on the horizon include erythro- In addition to emerging biomarkers, to be deleterious, with increased organ
poietic agents and natriuretic peptides. promising real-time imaging for use in failures in the CVVH group compared to
Novel interventions include the use of early detection of AKI is on the horizon standard therapy. The study was stopped
stem cell therapy, renal tubule assist de- (238, 239). Ongoing discovery using uri- at interim analysis and consequently en-
vice, and high-flux hemofiltration for nary proteomic analyses or analysis of rollment was insufficient to detect a dif-
sepsis. genetic polymorphisms may identify sus- ference in mortality with sufficient
Candidate Biomarkers. Biomarkers of ceptibility to AKI (240 –244). Overall, bi- power. These findings contrast with those
AKI in the ICU have three primary poten- omarkers in AKI, although rapidly evolv- of Honore et al (252) in 2000, suggesting
tial roles: early detection of AKI, differen- ing, are a field still in its relative infancy. a beneficial role for hemofiltration in re-
tial diagnosis (e.g., hepatorenal syndrome Their role in the diagnosis and manage- fractory septic shock. An important dif-
vs. acute tubular necrosis), and prognosis ment of AKI in the ICU, although prom- ference between these two studies was
(e.g., need for RRT or mortality). The ising, remains unproven. Furthermore, the delivered dose. In the first study, the
ideal biomarker for AKI would be sensi- judging novel biomarkers against an im- dose, on average, was approximately 2
tive, specific, inexpensive, available non- perfect “gold-standard” biomarker (SCr) L/hr, whereas in the second study the
invasively as a point-of-care test, and pro- may have its limitations. dose was, on average, 8.7 L/hr for 4 hrs.
vide a real-time assessment of GFR. A Erythropoietic Agents. The endothe- Stem Cells and the Kidney. Progenitor
panel of biomarkers or kidney function lium plays a central role in the initiation cell therapies represent an exciting future
tests may be needed to address the com- and maintenance phases of AKI. Animal opportunity for treatment of AKI in the
plexity and heterogeneity of AKI in the models demonstrate a renal-protective ef- critically ill. Phase 1 trials of mesenchymal
ICU (213). Early identification of AKI fect of erythropoietin on endotoxin- stem cells for treatment of patients at high
with rapid and reproducible biomarkers related kidney injury (245). Decreased se- risk for cardiac surgery-associated AKI are
is a critical first step toward improving verity of AKI is proposed to occur underway. A phase 2 RCT will be conducted
outcomes in AKI. through tubular regeneration from the if safety is demonstrated in phase 1 (clini-
According to several studies in criti- direct effects of erythropoietin on tubular caltrials.gov ID: NCT00733876).
cally ill patients, serum cystatin C is bet- epithelial cells (246). These findings sup-
ter than SCr for early detection of AKI port the ongoing trials exploring the role CONCLUSIONS
(214, 215) and as a more sensitive marker of erythropoietic agents in the prevention
of small changes in GFR (216 –218). or early intervention for AKI using early Many unanswered questions remain
However, in one smaller study there was biomarkers (personal communication with respect to early identification, pre-
no correlation between cystatin C and and clinicaltrials.gov NCT00476619). vention, optimal timing, dose, and mo-
SCr (219). In a recent study, urinary cys- Atrial Natriuretic Peptide. Recombi- dality of RRT for AKI in the ICU. With
tatin C but not plasma cystatin C was nant human atrial natriuretic peptide de- respect to AKI in the ICU, the fundamen-
superior to conventional plasma markers creased the need for dialysis (21% vs. tal principal that guides all medical ther-
in the early identification of AKI after 47%) and improved dialysis-free survival apy— do no harm—is especially perti-
cardiac surgery (220). Whereas rapid au- at 21 days (57% vs. 28%) in a RCT of 61 nent. AKI in the ICU most commonly
tomated assays for cystatin C are cur- complicated post-cardiopulmonary by- results from multiple insults. Therefore,
rently available, more information on the pass patients without preexisting CKD appropriate and early identification of pa-
use of cystatin C in the ICU setting and in (247). Previously, however, in two multi- tients at risk for AKI provides an oppor-
specific patient populations (e.g., post- centered, prospective, randomized trials tunity to prevent subsequent renal in-
cardiothoracic surgery, sepsis, and in patients with acute tubular necrosis sults and ultimately impact overall ICU
trauma) is necessary before implementa- (248) or late oliguric AKI (249), atrial morbidity and mortality. Strategies to
tion in clinical practice. natriuretic peptide had no effect on need prevent AKI in these patients are of piv-
Several studies support neutrophil ge- for dialysis or overall mortality. Further otal importance. Key components of op-
latinase-associated lipocalin (221–227), trials are needed before the use of atrial timal prevention and management of the
kidney injury molecule-1 (228, 229), and natriuretic peptide can be recommended critically ill patient with AKI include
interleukin (IL)-18 (222, 230, 231) as for routine clinical use in cardiac surgery maintenance of renal perfusion and
promising candidate biomarkers for the patients. avoidance of nephrotoxins. Whereas
early detection of AKI. Point-of-care tests Renal Tubule Assist Device. Results management of AKI remains limited pri-
for urinary IL-18 and neutrophil gelati- from a recent RCT of the renal tubule marily to supportive care, there are many
nase-associated lipocalin will likely be assist device, in which the renal tubule potential therapies and interventions on
available for clinical use soon (213, 231– assist device added to conventional CRRT the horizon.

Crit Care Med 2010 Vol. 38, No. 1 269


Although it is widely accepted that tensive care unit: The PICARD experience. Septic acute kidney injury in critically ill
early intervention therapies have been Kidney international 2004; 66:1613–1621 patients: Clinical characteristics and out-
limited by the lack of tools for early de- 9. Uchino S, Kellum JA, Bellomo R, et al: comes. Clin J Am Soc Nephrol 2007;
tection, there are several promising can- Acute renal failure in critically ill patients: 2:431– 439
A multinational, multicenter study. Jama 24. Bernieh B, Al Hakim M, Boobes Y, et al:
didate biomarkers in the pipeline. Fur-
2005; 294:813– 818 Outcome and predictive factors of acute re-
thermore, through the establishment of 10. Uchino S, Bellomo R, Goldsmith D, et al: An nal failure in the intensive care unit. Trans-
AKIN, an international and interdiscipli- assessment of the RIFLE criteria for acute plant Proc 2004; 36:1784 –1787
nary collaborative network with the over- renal failure in hospitalized patients. Criti- 25. Vincent JL, de Mendonca A, Cantraine F, et
arching objective to address AKI in the cal care medicine 2006; 34:1913–1917 al: Use of the SOFA score to assess the
ICU, there has been tremendous progress 11. Ostermann M, Chang RW: Acute kidney in- incidence of organ dysfunction/failure in in-
in establishing a uniform definition jury in the intensive care unit according to tensive care units: Results of a multicenter,
(AKIN criteria) that is valuable for classi- RIFLE. Crit Care Med 2007; 35:1837–1843; prospective study. Working group on “sep-
fication, clinical research study design, quiz 1852 sis-related problems” of the European Soci-
and prognosis. 12. Lin CY, Chen YC, Tsai FC, et al: RIFLE ety of Intensive Care Medicine. Crit Care
classification is predictive of short-term Med 1998; 26:1793–1800
A greater appreciation for the role of
prognosis in critically ill patients with acute 26. Harbrecht BG, Rosengart MR, Zenati MS, et
AKI in the ICU as an active contributor to renal failure supported by extracorporeal al: Defining the contribution of renal dys-
morbidity and mortality is essential to membrane oxygenation. Nephrol Dial function to outcome after traumatic injury.
furthering our knowledge and under- Transplant 2006; 21:2867–2873 Am Surg 2007; 73:836 – 840
standing of the influence of AKI in the 13. Lopes JA, Jorge S, Resina C, et al: Prognos- 27. Radovic M, Ostric V, Djukanovic L: Validity
critically ill patient. Early detection will tic utility of RIFLE for acute renal failure in of prediction scores in acute renal failure
facilitate early intervention. Early inter- patients with sepsis. Crit Care 2007; 11:408 due to polytrauma. Ren Fail 1996; 18:
vention designed to target the deleterious 14. Metnitz PG, Krenn CG, Steltzer H, et al: 615– 620
systemic effects of AKI will likely improve Effect of acute renal failure requiring renal 28. Kuitunen A, Vento A, Suojaranta-Ylinen R,
overall morbidity and mortality. For now, replacement therapy on outcome in criti- et al: Acute renal failure after cardiac sur-
cally ill patients. Crit Care Med 2002; 30: gery: evaluation of the RIFLE classification.
recognition of risk factors, excellent sup-
2051–2058 Ann Thorac Surg 2006; 81:542–546
portive care, and avoidance of clinical
15. Liano F, Felipe C, Tenorio MT, et al: Long- 29. Thakar CV, Worley S, Arrigain S, et al: In-
conditions known to cause or worsen AKI term outcome of acute tubular necrosis: A fluence of renal dysfunction on mortality
remain the cornerstone of management contribution to its natural history. Kidney- after cardiac surgery: Modifying effect of
of AKI in the ICU. Int 2007; 71:679 – 686 preoperative renal function. Kidney inter-
16. Bagshaw SM, Laupland KB, Doig CJ, et al: national 2005; 67:1112–1119
REFERENCES Prognosis for long-term survival and renal 30. Bove T, Calabro MG, Landoni G, et al: The
recovery in critically ill patients with severe incidence and risk of acute renal failure
1. Bagshaw SM, George C, Bellomo R: acute renal failure: A population-based after cardiac surgery. J Cardiothorac Vasc
Changes in the incidence and outcome for study. Crit Care 2005; 9:R700 –R709 Anesth 2004; 18:442– 445
early acute kidney injury in a cohort of 17. Chertow GM, Levy EM, Hammermeister 31. Holm C, Horbrand F, von Donnersmarck
Australian intensive care units. Crit Care KE, et al: Independent association between GH, et al: Acute renal failure in severely
2007; 11:R68 acute renal failure and mortality following burned patients. Burns 1999; 25:171–178
2. Collins AJ, Foley R, Herzog C, et al: Ex- cardiac surgery. Am J Med 1998; 104: 32. Morgera S, Kraft AK, Siebert G, et al: Long-
cerpts from the United States Renal Data 343–348 term outcomes in acute renal failure pa-
System 2007 annual data report. Am J Kid- 18. Chertow GM, Burdick E, Honour M, et al: tients treated with continuous renal re-
ney Dis 2008; 51:S1–S320 Acute kidney injury, mortality, length of placement therapies. Am J Kidney Dis 2002;
3. Waikar SS, Wald R, Chertow GM, et al: stay, and costs in hospitalized patients. 40:275–279
Validity of International Classification of J Am Soc Nephrol 2005; 16:3365–3370 33. Prescott GJ, Metcalfe W, Baharani J, et al: A
Diseases, Ninth Revision, Clinical Modifica- 19. Lassnigg A, Schmidlin D, Mouhieddine M, prospective national study of acute renal
tion Codes for Acute Renal Failure. J Am et al: Minimal changes of serum creatinine failure treated with RRT: Incidence, aetiol-
Soc Nephrol 2006; 17:1688 –1694 predict prognosis in patients after cardio- ogy and outcomes. Nephrol Dial Transplant
4. Xue JL, Daniels F, Star RA, et al: Incidence thoracic surgery: A prospective cohort 2007; 22:2513–2519
and mortality of acute renal failure in Medi- study. J Am Soc Nephrol 2004; 15: 34. Leacche M, Rawn JD, Mihaljevic T, et al:
care beneficiaries, 1992 to 2001. J Am Soc 1597–1605 Outcomes in patients with normal serum
Nephrol 2006; 17:1135–1142 20. Waikar SS, Liu KD, Chertow GM: The inci- creatinine and with artificial renal support
5. Chertow GM, Soroko SH, Paganini EP, et al: dence and prognostic significance of acute for acute renal failure developing after cor-
Mortality after acute renal failure: Models kidney injury. Curr Opin Nephrol Hyper- onary artery bypass grafting. Am J Cardiol
for prognostic stratification and risk adjust- tens 2007; 16:227–236 2004; 93:353–356
ment. Kidney international 2006; 70: 21. Coca SG, Peixoto AJ, Garg AX, et al: The 35. Korkeila M, Ruokonen E, Takala J: Costs of
1120 –1126 prognostic importance of a small acute dec- care, long-term prognosis and quality of life
6. Hoste EA, Clermont G, Kersten A, et al: rement in kidney function in hospitalized in patients requiring renal replacement
RIFLE criteria for acute kidney injury are patients: a systematic review and meta- therapy during intensive care. Intensive
associated with hospital mortality in criti- analysis. Am J Kidney Dis 2007; 50:712–720 Care Med 2000; 26:1824 –1831
cally ill patients: A cohort analysis. Crit 22. Yegenaga I, Hoste E, Van Biesen W, et al: 36. Basile DP: Novel approaches in the investi-
Care 2006; 10:R73 Clinical characteristics of patients develop- gation of acute kidney injury. J Am Soc
7. Nash K, Hafeez A, Hou S: Hospital-acquired ing ARF due to sepsis/systemic inflamma- Nephrol 2007; 18:7–9
renal insufficiency. Am J Kidney Dis 2002; tory response syndrome: Results of a pro- 37. Schiffl H, Lang SM, Fischer R: Daily hemo-
39:930 –936 spective study. Am J Kidney Dis 2004; 43: dialysis and the outcome of acute renal fail-
8. Mehta RL, Pascual MT, Soroko S, et al: 817– 824 ure. N Engl J Med 2002; 346:305–310
Spectrum of acute renal failure in the in- 23. Bagshaw SM, Uchino S, Bellomo R, et al: 38. Macedo E, Bouchard J, Mehta RL: Renal

270 Crit Care Med 2010 Vol. 38, No. 1


recovery following acute kidney injury. outcome in patients with acute renal fail- 68. Marik PE: Low-dose dopamine: A systematic
Curr Opin Crit Care 2008; 14:660 – 665 ure. Crit Care 2008; 12:R74 review. Intensive Care Med 2002; 28:
39. Mehta RL, Chertow GM: Acute renal failure 53. Wiedemann HP, Wheeler AP, Bernard GR, 877– 883
definitions and classification: Time for et al: Comparison of two fluid-management 69. Holmes CL, Walley KR: Bad medicine: Low-
change? J Am Soc Nephrol 2003; 14: strategies in acute lung injury. N Engl dose dopamine in the ICU. Chest 2003; 123:
2178 –2187 J Med 2006; 354:2564 –2575 1266 –1275
40. Bellomo R, Ronco C, Kellum JA, et al: Acute 54. Ali T, Khan I, Simpson W, et al: Incidence 70. Dunning J, Khasati N, Barnard J: Low dose
renal failure— definition, outcome mea- and outcomes in acute kidney injury: A (renal dose) dopamine in the critically ill
sures, animal models, fluid therapy and in- comprehensive population-based study. patient. Interact Cardiovasc Thorac Surg
formation technology needs: The Second J Am Soc Nephrol 2007; 18:1292–1298 2004; 3:114 –117
International Consensus Conference of the 55. Vivino G, Antonelli M, Moro ML, et al: Risk 71. Bellomo R, Chapman M, Finfer S, et al: Low-
Acute Dialysis Quality Initiative (ADQI) factors for acute renal failure in trauma dose dopamine in patients with early renal
Group. Crit Care 2004; 8:R204 –R212 patients. Intensive Care Med 1998; 24: dysfunction: A placebo-controlled randomised
41. Dasta JF, Kane-Gill SL, Durtschi AJ, et al: 808 – 814 trial. Australian and New Zealand Intensive
Costs and outcomes of acute kidney injury 56. De laet I, Malbrain ML, Jadoul JL, et al: Care Society (ANZICS) Clinical Trials Group.
(AKI) following cardiac surgery. Nephrol Renal implications of increased intra- Lancet 2000; 356:2139 –2143
Dial Transplant 2008 abdominal pressure: are the kidneys the ca- 72. Lauschke A, Teichgraber UK, Frei U, et al:
42. Mehta RL, Kellum JA, Shah SV, et al: Acute nary for abdominal hypertension? Acta Clin ‘Low-dose’ dopamine worsens renal perfu-
Kidney Injury Network: Report of an initia- Belg Suppl 2007:119 –130 sion in patients with acute renal failure.
tive to improve outcomes in acute kidney 57. Sugrue M, Jones F, Deane SA, et al: Intra- Kidney Int 2006; 69:1669 –1674
injury. Crit Care 2007; 11:R31 abdominal hypertension is an independent 73. Argalious M, Motta P, Khandwala F, et al:
43. Bagshaw SM, George C, Bellomo R: A com- cause of postoperative renal impairment. “Renal dose” dopamine is associated with
parison of the RIFLE and AKIN criteria for Arch Surg 1999; 134:1082–1085 the risk of new-onset atrial fibrillation after
acute kidney injury in critically ill patients. 58. Cheatham ML, Malbrain ML, Kirkpatrick A, cardiac surgery. Crit Care Med 2005; 33:
Nephrol Dial Transplant 2008; 23: et al: Results from the International Con- 1327–1332
1569 –1574 ference of Experts on Intra-abdominal Hy- 74. Devins SS, Miller A, Herndon BL, et al:
44. Lopes JA, Fernandes P, Jorge S, et al: Acute pertension and Abdominal Compartment Effects of dopamine on T-lymphocyte pro-
kidney injury in intensive care unit pa- Syndrome. II. Recommendations. Intensive liferative responses and serum prolactin
Care Med 2007; 33:951–962 concentrations in critically ill patients. Crit
tients: A comparison between the RIFLE
59. Sharp LS, Rozycki GS, Feliciano DV: Rhab- Care Med 1992; 20:1644 –1649
and the Acute Kidney Injury Network clas-
domyolysis and secondary renal failure in 75. Murphy MB, Murray C, Shorten GD:
sifications. Crit Care 2008; 12:R110
critically ill surgical patients. Am J Surg Fenoldopam: A selective peripheral dopam-
45. Guerin C, Girard R, Selli JM, et al: Initial
2004; 188:801– 806 ine-receptor agonist for the treatment of
versus delayed acute renal failure in the
60. Obialo CI, Okonofua EC, Tayade AS, et al: severe hypertension. N Engl J Med 2001;
intensive care unit. A multicenter prospec-
Epidemiology of de novo acute renal failure 345:1548 –1557
tive epidemiological study. Rhone-Alpes
in hospitalized African Americans: Compar- 76. Samuels J, Finkel K, Gubert M, et al: Effect
Area Study Group on Acute Renal Failure.
ing community-acquired vs hospital-ac- of fenoldopam mesylate in critically ill pa-
Am J Respir Crit Care Med 2000; 161:
quired disease. Arch Intern Med 2000; 160: tients at risk for acute renal failure is dose
872– 879
1309 –1313 dependent. Ren Fail 2005; 27:101–105
46. Moran SM, Myers BD: Course of acute renal
61. Wang Y, Cui Z, Fan M: Hospital-acquired 77. Brienza N, Malcangi V, Dalfino L, et al: A
failure studied by a model of creatinine ki-
and community-acquired acute renal fail- comparison between fenoldopam and low-
netics. Kidney international 1985; 27:
ure in hospitalized Chinese: A ten-year re- dose dopamine in early renal dysfunction of
928 –937 view. Ren Fail 2007; 29:163–168 critically ill patients. Crit Care Med 2006;
47. Tsai JJ, Yeun JY, Kumar VA, et al: Compar- 62. Kelleher SP, Robinette JB, Conger JD: Sym- 34:707–714
ison and interpretation of urinalysis per- pathetic nervous system in the loss of au- 78. Tumlin JA, Finkel KW, Murray PT, et al:
formed by a nephrologist versus a hospital- toregulation in acute renal failure. Am J Fenoldopam mesylate in early acute tubular
based clinical laboratory. Am J Kidney Dis Physiol 1984; 246:F379 –F386 necrosis: A randomized, double-blind, pla-
2005; 46:820 – 829 63. Schlichtig R, Kramer DJ, Boston JR, et al: cebo-controlled clinical trial. Am J Kidney
48. Perazella MA, Coca SG, Kanbay M, et al: Renal O2 consumption during progressive Dis 2005; 46:26 –34
Diagnostic value of urine microscopy for hemorrhage. J Appl Physiol 1991; 70: 79. Morelli A, Ricci Z, Bellomo R, et al: Prophy-
differential diagnosis of acute kidney injury 1957–1962 lactic fenoldopam for renal protection in
in hospitalized patients. Clin J Am Soc 64. Bourgoin A, Leone M, Delmas A, et al: In- sepsis: A randomized, double-blind, place-
Nephrol 2008; 3:1615–1619 creasing mean arterial pressure in patients bo-controlled pilot trial. Crit Care Med
49. da Silva Magro MC, de Fatima Fernandes with septic shock: Effects on oxygen vari- 2005; 33:2451–2456
Vattimo M: Does urinalysis predict acute ables and renal function. Crit Care Med 80. Landoni G, Biondi-Zoccai GG, Tumlin JA, et
renal failure after heart surgery? Ren Fail 2005; 33:780 –786 al: Beneficial impact of fenoldopam in criti-
2004; 26:385–392 65. LeDoux D, Astiz ME, Carpati CM, et al: cally ill patients with or at risk for acute renal
50. Lee VWS, Harris DCH, Anderson RJ, et al: Effects of perfusion pressure on tissue per- failure: a meta-analysis of randomized clinical
Acute Renal Failure. In: Diseases of the Kid- fusion in septic shock. Crit Care Med 2000; trials. Am J Kidney Dis 2007; 49:56 – 68
ney & Urinary Tract. 8th ed. Schrier RW 28:2729 –2732 81. Schierhout G, Roberts I: Fluid resuscitation
(Ed). Philadelphia, Wolters Kluwer Health/ 66. Friedrich JO, Adhikari N, Herridge MS, et with colloid or crystalloid solutions in crit-
Lippincott Williams & Wilkins, 2007 al: Meta-analysis: Low-dose dopamine in- ically ill patients: A systematic review of
51. Miller TR, Anderson RJ, Linas SL, et al: creases urine output but does not prevent randomised trials. BMJ 1998; 316:961–964
Urinary diagnostic indices in acute renal renal dysfunction or death. Ann Intern Med 82. Alderson P, Schierhout G, Roberts I, et al:
failure: a prospective study. Ann Intern Med 2005; 142:510 –524 Colloids versus crystalloids for fluid resus-
1978; 89:47–50 67. Kellum JA, M Decker J: Use of dopamine in citation in critically ill patients. Cochrane
52. Payen D, de Pont AC, Sakr Y, et al: A posi- acute renal failure: A meta-analysis. Crit Database Syst Rev 2000:CD000567
tive fluid balance is associated with a worse Care Med 2001; 29:1526 –1531 83. Alderson P, Bunn F, Lefebvre C, et al: Hu-

Crit Care Med 2010 Vol. 38, No. 1 271


man albumin solution for resuscitation and Hyperglycemia is associated with adverse 114. Hogan SE, L’Allier P, Chetcuti S, et al:
volume expansion in critically ill patients. outcomes in patients receiving total paren- Current role of sodium bicarbonate-based
Cochrane Database Syst Rev 2002: teral nutrition. Diabetes Care 2005; 28: preprocedural hydration for the prevention
CD001208 2367–2371 of contrast-induced acute kidney injury: A
84. Alderson P, Bunn F, Lefebvre C, et al: Hu- 100. Rybak MJ, Abate BJ, Kang SL, et al: Pro- meta-analysis. Am Heart J 2008; 156:
man albumin solution for resuscitation and spective evaluation of the effect of an ami- 414 – 421
volume expansion in critically ill patients. noglycoside dosing regimen on rates of ob- 115. Meier P, Ko DT, Tamura A, et al: Sodium
Cochrane Database Syst Rev 2004: served nephrotoxicity and ototoxicity. bicarbonate-based hydration prevents con-
CD001208 Antimicrob Agents Chemother 1999; 43: trast-induced nephropathy: A meta-analy-
85. Choi PT, Yip G, Quinonez LG, et al: Crys- 1549 –1555 sis. BMC Med 2009; 7:23
talloids vs. colloids in fluid resuscitation: A 101. Prins JM, Buller HR, Kuijper EJ, et al: Once 116. Navaneethan SD, Singh S, Appasamy S, et
systematic review. Critical care medicine versus thrice daily gentamicin in patients al: Sodium bicarbonate therapy for preven-
1999; 27:200 –210 with serious infections. Lancet 1993; 341: tion of contrast-induced nephropathy: A
86. Finfer S, Bellomo R, Boyce N, et al: A com- 335–339 systematic review and meta-analysis. Am J
parison of albumin and saline for fluid re- 102. Hatala R, Dinh T, Cook DJ: Once-daily ami- Kidney Dis 2009; 53:617– 627
suscitation in the intensive care unit. noglycoside dosing in immunocompetent 117. Brar SS, Shen AY, Jorgensen MB, et al:
N Engl J Med 2004; 350:2247–2256 adults: a meta-analysis. Ann Intern Med Sodium bicarbonate vs sodium chloride for
87. Myburgh J, Cooper DJ, Finfer S, et al: Saline 1996; 124:717–725 the prevention of contrast medium-induced
or albumin for fluid resuscitation in pa- 103. Barza M, Ioannidis JP, Cappelleri JC, et al: nephropathy in patients undergoing coro-
tients with traumatic brain injury. N Engl Single or multiple daily doses of aminogly- nary angiography: A randomized trial. JAMA
J Med 2007; 357:874 – 884 cosides: a meta-analysis. BMJ 1996; 312: 2008; 300:1038 –1046
88. Schortgen F, Lacherade JC, Bruneel F, et al. 338 –345 118. Tepel M, van der Giet M, Schwarzfeld C, et
Effects of hydroxyethylstarch and gelatin on 104. Munckhof WJ, Grayson ML, Turnidge JD: A al: Prevention of radiographic-contrast-
renal function in severe sepsis: A multicen- meta-analysis of studies on the safety and agent-induced reductions in renal function
tre randomised study. Lancet 2001; 357: efficacy of aminoglycosides given either by acetylcysteine. N Engl J Med 2000; 343:
911–916 once daily or as divided doses. J Antimicrob 180 –184
89. Brunkhorst FM, Engel C, Bloos F, et al: Chemother 1996; 37:645– 663 119. Kelly AM, Dwamena B, Cronin P, et al:
Intensive insulin therapy and pentastarch 105. Galloe AM, Graudal N, Christensen HR, et Meta-analysis: Effectiveness of drugs for
resuscitation in severe sepsis. N Engl J Med al: Aminoglycosides: Single or multiple preventing contrast-induced nephropathy.
2008; 358:125–139 daily dosing? A meta-analysis on efficacy Ann Intern Med 2008; 148:284 –294
90. Cittanova ML, Leblanc I, Legendre C, et al: and safety. Eur J Clin Pharmacol 1995; 48: 120. Gonzales DA, Norsworthy KJ, Kern SJ, et al:
Effect of hydroxyethylstarch in brain-dead 39 – 43 A meta-analysis of N-acetylcysteine in con-
kidney donors on renal function in kidney- 106. Ferriols-Lisart R, Alos-Alminana M: Effec- trast-induced nephrotoxicity: Unsupervised
transplant recipients. Lancet 1996; 348: tiveness and safety of once-daily aminogly- clustering to resolve heterogeneity. BMC
1620 –1622 cosides: A meta-analysis. Am J Health Syst Med 2007; 5:32
91. Wiedermann CJ: Systematic review of ran- Pharm 1996; 53:1141–1150 121. Hoffmann U, Fischereder M, Kruger B, et al:
domized clinical trials on the use of hy- 107. Harbarth S, Pestotnik SL, Lloyd JF, et al: The value of N-acetylcysteine in the preven-
droxyethyl starch for fluid management in The epidemiology of nephrotoxicity associ- tion of radiocontrast agent-induced ne-
sepsis. BMC Emerg Med 2008; 8:1 ated with conventional amphotericin B phropathy seems questionable. J Am Soc
92. Vincent JL, Sakr Y, Sprung CL, et al: Sepsis therapy. Am J Med 2001; 111:528 –534 Nephrol 2004; 15:407– 410
in European intensive care units: Results of 108. Walsh TJ, Finberg RW, Arndt C, et al: Lipo- 122. Haase M, Haase-Fielitz A, Ratnaike S, et al:
the SOAP study. Crit Care Med 2006; 34: somal amphotericin B for empirical therapy N-Acetylcysteine does not artifactually
344 –353 in patients with persistent fever and neu- lower plasma creatinine concentration.
93. Sakr Y, Payen D, Reinhart K, et al: Effects of tropenia. National Institute of Allergy and Nephrol Dial Transplant 2008
hydroxyethyl starch administration on re- Infectious Diseases Mycoses Study Group. 123. McCullough PA, Bertrand ME, Brinker JA,
nal function in critically ill patients. Br J N Engl J Med 1999; 340:764 –771 et al: A meta-analysis of the renal safety of
Anaesth 2007; 98:216 –224 109. Wingard JR, Wood CA, Sullivan E, et al: isosmolar iodixanol compared with low-
94. Finfer S, Chittock DR, Su SY, et al: Inten- Caspofungin versus amphotericin B for can- osmolar contrast media. J Am Coll Cardiol
sive versus conventional glucose control in didemia: A pharmacoeconomic analysis. 2006; 48:692– 699
critically ill patients. N Engl J Med 2009; Clin Ther 2005; 27:960 –969 124. Heinrich MC, Haberle L, Muller V, et al:
360:1283–1297 110. Mangano DT, Tudor IC, Dietzel C: The risk Nephrotoxicity of iso-osmolar iodixanol com-
95. Van den Berghe G, Wilmer A, Hermans G, et associated with aprotinin in cardiac sur- pared with nonionic low-osmolar contrast
al: Intensive insulin therapy in the medical gery. N Engl J Med 2006; 354:353–365 media: Meta-analysis of randomized con-
ICU. N Engl J Med 2006; 354:449 – 461 111. Huber W, Eckel F, Hennig M, et al: Prophy- trolled trials. Radiology 2009; 250:68 – 86
96. van den Berghe G, Wouters P, Weekers F, et laxis of contrast material-induced nephrop- 125. Holscher B, Heitmeyer C, Fobker M, et al:
al: Intensive insulin therapy in the critically athy in patients in intensive care: Acetylcys- Predictors for contrast media-induced ne-
ill patients. N Engl J Med 2001; 345: teine, theophylline, or both? A randomized phropathy and long-term survival: prospec-
1359 –1367 study. Radiology 2006; 239:793– 804 tively assessed data from the randomized
97. Schetz M, Vanhorebeek I, Wouters PJ, et al: 112. Joannidis M, Schmid M, Wiedermann CJ: controlled Dialysis-Versus-Diuresis (DVD)
Tight blood glucose control is renoprotec- Prevention of contrast media-induced ne- trial. Can J Cardiol 2008; 24:845– 850
tive in critically ill patients. J Am Soc Neph- phropathy by isotonic sodium bicarbonate: 126. Cirit M, Toprak O, Yesil M, et al: Angioten-
rol 2008; 19:571–578 A meta-analysis. Wien Klin Wochenschr sin-converting enzyme inhibitors as a risk
98. Lecomte P, Van Vlem B, Coddens J, et al: 2008; 120:742–748 factor for contrast-induced nephropathy.
Tight perioperative glucose control is asso- 113. Ho KM, Morgan DJ: Use of isotonic sodium Nephron Clin Pract 2006; 104:c20 – c27
ciated with a reduction in renal impairment bicarbonate to prevent radiocontrast ne- 127. Onuigbo MA, Onuigbo NT: Does renin-
and renal failure in non-diabetic cardiac phropathy in patients with mild pre- angiotensin aldosterone system blockade
surgical patients. Crit Care 2008; 12:R154 existing renal impairment: A meta-analysis. exacerbate contrast-induced nephropathy
99. Cheung NW, Napier B, Zaccaria C, et al: Anaesth Intensive Care 2008; 36:646 – 653 in patients with chronic kidney disease? A

272 Crit Care Med 2010 Vol. 38, No. 1


prospective 50-month Mayo Clinic study. comparative study of therapeutic paracen- 155. Ho KM, Sheridan DJ: Meta-analysis of
Ren Fail 2008; 30:67–72 tesis with and without intravenous albumin frusemide to prevent or treat acute renal
128. Rosenstock JL, Bruno R, Kim JK, et al: The in cirrhosis. Gastroenterology 1988; 94: failure. BMJ 2006; 333:420
effect of withdrawal of ACE inhibitors or 1493–1502 156. Bagshaw SM, Delaney A, Haase M, et al:
angiotensin receptor blockers prior to cor- 142. Gluud LL, Kjaer MS, Christensen E: Terlip- Loop diuretics in the management of acute
onary angiography on the incidence of con- ressin for hepatorenal syndrome. Cochrane renal failure: A systematic review and meta-
trast-induced nephropathy. Int Urol Neph- Database Syst Rev 2006:CD005162 analysis. Crit Care Resusc 2007; 9:60 – 68
rol 2008; 40:749 –755 143. Ortega R, Gines P, Uriz J, et al: Terlipressin 157. Mehta RL, Pascual MT, Soroko S, et al:
129. Marenzi G, Marana I, Lauri G, et al: The therapy with and without albumin for pa- Diuretics, mortality, and nonrecovery of re-
prevention of radiocontrast-agent-induced tients with hepatorenal syndrome: Results nal function in acute renal failure. JAMA
nephropathy by hemofiltration. N Engl of a prospective, nonrandomized study. 2002; 288:2547–2553
J Med 2003; 349:1333–1340 Hepatology 2002; 36:941–948 158. Uchino S, Doig GS, Bellomo R, et al: Di-
130. Marenzi G, Lauri G, Campodonico J, et al: 144. Solanki P, Chawla A, Garg R, et al: Benefi- uretics and mortality in acute renal failure.
Comparison of two hemofiltration protocols cial effects of terlipressin in hepatorenal Crit Care Med 2004; 32:1669 –1677
for prevention of contrast-induced ne- syndrome: A prospective, randomized pla- 159. Chertow GM, Lazarus JM, Paganini EP, et
phropathy in high-risk patients. Am J Med cebo-controlled clinical trial. J Gastroen- al: Predictors of mortality and the provision
2006; 119:155–162 terol Hepatol 2003; 18:152–156 of dialysis in patients with acute tubular
131. Cruz DN, Perazella MA, Bellomo R, et al: 145. Sanyal AJ, Boyer T, Garcia-Tsao G, et al: A necrosis. The Auriculin Anaritide Acute Re-
Extracorporeal blood purification therapies randomized, prospective, double-blind, pla- nal Failure Study Group. J Am Soc Nephrol
for prevention of radiocontrast-induced ne- cebo-controlled trial of terlipressin for type 1998; 9:692– 698
phropathy: A systematic review. Am J Kid- 1 hepatorenal syndrome. Gastroenterology 160. Venkataram R, Kellum JA: The role of di-
ney Dis 2006; 48:361–371 2008; 134:1360 –1368 uretic agents in the management of acute
132. Lee PT, Chou KJ, Liu CP, et al: Renal pro- 146. Martin-Llahi M, Pepin MN, Guevara M, et al: renal failure. Contrib Nephrol 2001:
tection for coronary angiography in ad- Terlipressin and albumin vs albumin in patients 158 –170
vanced renal failure patients by prophylac- with cirrhosis and hepatorenal syndrome: A ran- 161. van der Voort PH, Boerma EC, Koopmans
tic hemodialysis. A randomized controlled domized study. Gastroenterology 2008; 134: M, et al: Furosemide does not improve renal
trial. J Am Coll Cardiol 2007; 50:1015–1020 1352–1359 recovery after hemofiltration for acute renal
133. Tumlin JA, Wang A, Murray PT, et al: 147. Alessandria C, Ottobrelli A, Debernardi- failure in critically ill patients: A double
Fenoldopam mesylate blocks reductions in Venon W, et al: Noradrenalin vs terlipressin blind randomized controlled trial. Critical
renal plasma flow after radiocontrast dye in patients with hepatorenal syndrome: A care medicine 2009; 37:533–538
infusion: A pilot trial in the prevention of prospective, randomized, unblinded, pilot 162. Bagshaw SM, Delaney A, Jones D, et al:
contrast nephropathy. Am Heart J 2002; study. J Hepatol 2007; 47:499 –505 Diuretics in the management of acute kid-
143:894 –903 148. Sharma P, Kumar A, Shrama BC, et al. An ney injury: A multinational survey. Contrib
134. Stone GW, McCullough PA, Tumlin JA, et open label, pilot, randomized controlled Nephrol 2007; 156:236 –249
al: Fenoldopam mesylate for the prevention trial of noradrenaline versus terlipressin in 163. McWhirter JP, Pennington CR: Incidence
of contrast-induced nephropathy: A ran- the treatment of type 1 hepatorenal syn- and recognition of malnutrition in hospital.
domized controlled trial. JAMA 2003; 290: drome and predictors of response. Am J BMJ 1994; 308:945–948
2284 –2291 Gastroenterol 2008; 103:1689 –1697 164. Goldstein-Fuchs D: Assessment of nutri-
135. Allaqaband S, Tumuluri R, Malik AM, et al: 149. Kiser TH, Fish DN, Obritsch MD, et al: tional status in renal diseases. In: Handbook
Prospective randomized study of N-acetyl- Vasopressin, not octreotide, may be benefi- of Nutrition and Kidney. Mitch WE, Klahr S
cysteine, fenoldopam, and saline for preven- cial in the treatment of hepatorenal syn- (Eds). Philadelphia: Lippincott Williams &
tion of radiocontrast-induced nephropathy. drome: A retrospective study. Nephrol Dial Wilkins, 2002, pp. 42–92
Catheter Cardiovasc Interv 2002; 57: Transplant 2005; 20:1813–1820 165. Druml W: Nutritional management of acute
279 –283 150. Angeli P, Volpin R, Gerunda G, et al: Rever- renal failure. J Ren Nutr 2005; 15:63–70
136. Briguori C, Colombo A, Airoldi F, et al: sal of type 1 hepatorenal syndrome with the 166. Frankenfield DC, Reynolds HN: Nutri-
N-Acetylcysteine versus fenoldopam mesy- administration of midodrine and octreotide. tional effect of continuous hemodiafiltra-
late to prevent contrast agent-associated Hepatology 1999; 29:1690 –1697 tion. Nutrition 1995; 11:388 –393
nephrotoxicity. J Am Coll Cardiol 2004; 44: 151. Esrailian E, Pantangco ER, Kyulo NL, et al: 167. Wooley JA, Btaiche IF, Good KL: Metabolic
762–765 Octreotide/Midodrine therapy significantly and nutritional aspects of acute renal fail-
137. Bagshaw SM, Ghali WA: Theophylline for improves renal function and 30-day survival ure in critically ill patients requiring con-
prevention of contrast-induced nephropa- in patients with type 1 hepatorenal syn- tinuous renal replacement therapy. Nutr
thy: A systematic review and meta-analysis. drome. Dig Dis Sci 2007; 52:742–748 Clin Pract 2005; 20:176 –191
Arch Intern Med 2005; 165:1087–1093 152. Skagen C, Einstein M, Lucey MR, et al: 168. Cano N, Fiaccadori E, Tesinsky P, et al:
138. Ix JH, McCulloch CE, Chertow GM: The- Combination treatment with octreotide, ESPEN Guidelines on Enteral Nutrition:
ophylline for the prevention of radiocon- midodrine, and albumin improves survival Adult renal failure. Clin Nutr 2006; 25:
trast nephropathy: A meta-analysis. Nephrol in patients with type 1 and type 2 hepato- 295–310
Dial Transplant 2004; 19:2747–2753 renal syndrome. J Clin Gastroenterol 2009; 169. Macias WL, Alaka KJ, Murphy MH, et al:
139. Akriviadis E, Botla R, Briggs W, et al: Pentoxi- 43:680 – 685 Impact of the nutritional regimen on pro-
fylline improves short-term survival in severe 153. Cantarovich F, Rangoonwala B, Lorenz H, tein catabolism and nitrogen balance in pa-
acute alcoholic hepatitis: A double-blind, pla- et al: High-dose furosemide for established tients with acute renal failure. JPEN J Par-
cebo-controlled trial. Gastroenterology 2000; ARF: A prospective, randomized, double- enter Enteral Nutr 1996; 20:56 – 62
119:1637–1648 blind, placebo-controlled, multicenter trial. 170. Bellomo R, Tan HK, Bhonagiri S, et al: High
140. Sort P, Navasa M, Arroyo V, et al: Effect of Am J Kidney Dis 2004; 44:402– 409 protein intake during continuous hemodi-
intravenous albumin on renal impairment 154. Sampath S, Moran JL, Graham PL, et al: afiltration: Impact on amino acids and ni-
and mortality in patients with cirrhosis and The efficacy of loop diuretics in acute renal trogen balance. Int J Artif Organs 2002;
spontaneous bacterial peritonitis. N Engl failure: Assessment using Bayesian evidence 25:261–268
J Med 1999; 341:403– 409 synthesis techniques. Crit Care Med 2007; 171. Scheinkestel CD, Kar L, Marshall K, et al:
141. Gines P, Tito L, Arroyo V, et al: Randomized 35:2516 –2524 Prospective randomized trial to assess ca-

Crit Care Med 2010 Vol. 38, No. 1 273


loric and protein needs of critically Ill, an- 187. Ronco C, Bellomo R, Homel P, et al: Effects Results of a randomized clinical trial. Neph-
uric, ventilated patients requiring continu- of different doses in continuous veno- rol Dial Transplant 2009; 24:512–518
ous renal replacement therapy. Nutrition venous haemofiltration on outcomes of 201. Kellum JA, Angus DC, Johnson JP, et al:
2003; 19:909 –916 acute renal failure: A prospective random- Continuous versus intermittent renal re-
172. Fiaccadori E, Maggiore U, Rotelli C, et al: ised trial. Lancet 2000; 356:26 –30 placement therapy: A meta-analysis. Inten-
Effects of different energy intakes on nitro- 188. Saudan P, Niederberger M, De Seigneux S, sive Care Med 2002; 28:29 –37
gen balance in patients with acute renal et al: Adding a dialysis dose to continuous 202. Bagshaw SM, Berthiaume LR, Delaney A, et
failure: A pilot study. Nephrol Dial Trans- hemofiltration increases survival in patients al: Continuous versus intermittent renal re-
plant 2005; 20:1976 –1980 with acute renal failure. Kidney Int 2006; placement therapy for critically ill patients
173. Ricci Z, Picardo S, Ronco C: Results from 70:1312–1317 with acute kidney injury: A meta-analysis.
international questionnaires. Contrib 189. Tolwani AJ, Campbell RC, Stofan BS, et al: Critical care medicine 2008; 36:610 – 617
Nephrol 2007; 156:297–303 Standard versus high-dose CVVHDF for 203. Ghahramani N, Shadrou S, Hollenbeak C: A
174. Ricci Z, Ronco C, D’Amico G, et al: Practice ICU-related acute renal failure. J Am Soc systematic review of continuous renal re-
patterns in the management of acute renal Nephrol 2008; 19:1233–1238 placement therapy and intermittent haemo-
failure in the critically ill patient: An inter- 190. Palevsky PM, Zhang JH, O’Connor TZ, et al: dialysis in management of patients with
national survey. Nephrol Dial Transplant Intensity of renal support in critically ill acute renal failure. Nephrology (Carlton)
2006; 21:690 – 696 patients with acute kidney injury. N Engl 2008; 13:570 –578
175. Ronco C, Ricci Z, Bellomo R: Current J Med 2008; 359:7–20 204. Pannu N, Klarenbach S, Wiebe N, et al:
worldwide practice of dialysis dose prescrip- 191. Tonelli M, Manns B, Feller-Kopman D: Renal replacement therapy in patients with
tion in acute renal failure. Current opinion Acute renal failure in the intensive care acute renal failure: A systematic review.
in critical care 2006; 12:551–556 unit: A systematic review of the impact of JAMA 2008; 299:793– 805
176. RENAL Study Investigators: Renal replace- dialytic modality on mortality and renal re- 205. Uchino S, Bellomo R, Kellum JA, et al: Patient
ment therapy for acute kidney injury in covery. Am J Kidney Dis 2002; 40:875– 885 and kidney survival by dialysis modality in
Australian and New Zealand intensive care 192. Uehlinger DE, Jakob SM, Ferrari P, et al: critically ill patients with acute kidney injury.
units: A practice survey. Crit Care Resusc Comparison of continuous and intermittent Int J Artif Organs 2007; 30:281–292
2008; 10:225–230 renal replacement therapy for acute renal 206. Bell M, Granath F, Schon S, et al: Continuous
177. Hoke TS, Douglas IS, Klein CL, et al: Acute failure. Nephrol Dial Transplant 2005; 20: renal replacement therapy is associated with
renal failure after bilateral nephrectomy is 1630 –1637 less chronic renal failure than intermittent
associated with cytokine-mediated pulmonary haemodialysis after acute renal failure. Inten-
193. Vinsonneau C, Camus C, Combes A, et al:
injury. J Am Soc Nephrol 2007; 18:155–164 sive Care Med 2007; 33:773–780
Continuous venovenous haemodiafiltration
178. Mehta RL: Indications for dialysis in the 207. Kumar VA, Yeun JY, Depner TA, et al: Ex-
versus intermittent haemodialysis for acute
ICU: Renal replacement vs. renal support. tended daily dialysis vs. continuous hemo-
renal failure in patients with multiple-organ
Blood Purif 2001; 19:227–232 dialysis for ICU patients with acute renal
dysfunction syndrome: A multicentre ran-
179. Teschan PE, Baxter CR, O’Brien TF, et al: failure: A two-year single center report. Int
domised trial. Lancet 2006; 368:379 –385
Prophylactic hemodialysis in the treatment J Artif Organs 2004; 27:371–379
194. Bagshaw SM, Bellomo R: Fluid resuscita-
of acute renal failure. Ann Intern Med 1960; 208. Kielstein JT, Kretschmer U, Ernst T, et al:
tion and the septic kidney. Curr Opin Crit
53:992–1016 Efficacy and cardiovascular tolerability of
Care 2006; 12:527–530
180. Conger JD: A controlled evaluation of pro- extended dialysis in critically ill patients: A
195. Augustine JJ, Sandy D, Seifert TH, et al: A
phylactic dialysis in post-traumatic acute randomized controlled study. Am J Kidney
randomized controlled trial comparing in-
renal failure. J Trauma 1975; 15:1056 –1063 Dis 2004; 43:342–349
termittent with continuous dialysis in pa-
181. Gillum DM, Dixon BS, Yanover MJ, et al: 209. Monchi M, Berghmans D, Ledoux D, et al:
tients with ARF. Am J Kidney Dis 2004;
The role of intensive dialysis in acute renal Citrate vs. heparin for anticoagulation in
failure. Clin Nephrol 1986; 25:249 –255 44:1000 –1007 continuous venovenous hemofiltration: A
182. Gettings LG, Reynolds HN, Scalea T: Out- 196. Rabindranath K, Adams J, Macleod AM, et prospective randomized study. Intensive
come in post-traumatic acute renal failure al: Intermittent versus continuous renal re- Care Med 2004; 30:260 –265
when continuous renal replacement ther- placement therapy for acute renal failure in 210. Kutsogiannis DJ, Gibney RT, Stollery D, et
apy is applied early vs. late. Intensive Care adults. Cochrane Database Syst Rev 2007: al: Regional citrate versus systemic heparin
Med 1999; 25:805– 813 CD003773 anticoagulation for continuous renal re-
183. Liu KD, Himmelfarb J, Paganini E, et al: 197. John S, Griesbach D, Baumgartel M, et al: placement in critically ill patients. Kidney
Timing of initiation of dialysis in critically Effects of continuous haemofiltration vs in- Int 2005; 67:2361–2367
ill patients with acute kidney injury. Clin termittent haemodialysis on systemic hae- 211. Betjes MG, van Oosterom D, van Agteren M,
J Am Soc Nephrol 2006; 1:915–919 modynamics and splanchnic regional perfu- et al: Regional citrate versus heparin anti-
184. Bouman CS, Oudemans-Van Straaten HM, sion in septic shock patients: A prospective, coagulation during venovenous hemofiltra-
Tijssen JG, et al: Effects of early high- randomized clinical trial. Nephrol Dial tion in patients at low risk for bleeding:
volume continuous venovenous hemofiltra- Transplant 2001; 16:320 –327 Similar hemofilter survival but significantly
tion on survival and recovery of renal func- 198. Mehta RL, McDonald B, Gabbai FB, et al: A less bleeding. J Nephrol 2007; 20:602– 608
tion in intensive care patients with acute randomized clinical trial of continuous ver- 212. Oudemans-van Straaten HM, Bosman RJ,
renal failure: A prospective, randomized sus intermittent dialysis for acute renal fail- Koopmans M, et al: Citrate anticoagulation
trial. Crit Care Med 2002; 30:2205–2211 ure. Kidney Int 2001; 60:1154 –1163 for continuous venovenous hemofiltration.
185. Bagshaw SM, Uchino S, Bellomo R, et al: 199. Gasparovic V, Filipovic-Grcic I, Merkler M, et Crit Care Med 2009; 37:545–552
Timing of renal replacement therapy and al: Continuous renal replacement therapy 213. Dennen P, Parikh CR: Biomarkers of acute
clinical outcomes in critically ill patients (CRRT) or intermittent hemodialysis kidney injury: Can we replace serum creat-
with severe acute kidney injury. J Crit Care (IHD)–what is the procedure of choice in crit- inine? Clin Nephrol 2007; 68:269 –278
2009; 24:129 –140 ically ill patients? Ren Fail 2003; 25:855– 862 214. Ahlstrom A, Tallgren M, Peltonen S, et al:
186. Bouman CS, Oudemans-van Straaten HM: 200. Lins RL, Elseviers MM, Van der Niepen P, et Evolution and predictive power of serum
Timing of renal replacement therapy in al: Intermittent versus continuous renal re- cystatin C in acute renal failure. Clin Neph-
critically ill patients with acute kidney in- placement therapy for acute kidney injury rol 2004; 62:344 –350
jury. Curr Opin Crit Care 2007; 13:656 – 661 patients admitted to the intensive care unit: 215. Herget-Rosenthal S, Marggraf G, Husing J,

274 Crit Care Med 2010 Vol. 38, No. 1


et al: Early detection of acute renal failure gency department measurement of urinary to which genotype information may add to
by serum cystatin C. Kidney international neutrophil gelatinase-associated lipocalin the prediction of disturbed perinatal adap-
2004; 66:1115–1122 for diagnosing acute kidney injury. Ann In- tation: none, minor, or major? Pediatr Res
216. Le Bricon T, Leblanc I, Benlakehal M, et al: tern Med 2008; 148:810 – 819 2007; 62:610 – 614
Evaluation of renal function in intensive 228. Han WK, Bailly V, Abichandani R, et al: 241. Haase-Fielitz A, Haase M, Bellomo R, et al:
care: plasma cystatin C vs. creatinine and Kidney Injury Molecule-1 (KIM-1): A novel Genetic polymorphisms in sepsis- and cardio-
derived glomerular filtration rate estimates. biomarker for human renal proximal tubule pulmonary bypass-associated acute kidney in-
Clin Chem Lab Med 2005; 43:953–957 injury. Kidney Int 2002; 62:237–244 jury. Contrib Nephrol 2007; 156:75–91
217. Delanaye P, Lambermont B, Chapelle JP, et al: 229. Han WK, Waikar SS, Johnson A, et al: Uri- 242. Jaber BL, Pereira BJ, Bonventre JV, et al:
Plasmatic cystatin C for the estimation of nary biomarkers in the early diagnosis of Polymorphism of host response genes: Im-
glomerular filtration rate in intensive care acute kidney injury. Kidney Int 2008; 73: plications in the pathogenesis and treat-
units. Intensive Care Med 2004; 30:980 –983 863– 869 ment of acute renal failure. Kidney Int
218. Villa P, Jimenez M, Soriano MC, et al: Se- 230. Parikh CR, Jani A, Melnikov VY, et al: Uri- 2005; 67:14 –33
rum cystatin C concentration as a marker of nary interleukin-18 is a marker of human 243. Liangos O, Balakrishnan VS, Pereira BJ, et
acute renal dysfunction in critically ill pa- acute tubular necrosis. Am J Kidney Dis al: Cytokine single nucleotide polymor-
tients. Crit Care 2005; 9:R139 –R143 2004; 43:405– 414 phism. Role in acute renal failure. Contrib
219. Mazul-Sunko B, Zarkovic N, Vrkic N, et al: 231. Parikh CR, Abraham E, Ancukiewicz M, et Nephrol 2004; 144:63–75
Proatrial natriuretic peptide (1–98), but not al: Urine IL-18 is an early diagnostic marker 244. Nguyen MT, Ross GF, Dent CL, et al: Early
cystatin C, is predictive for occurrence of for acute kidney injury and predicts mortal- prediction of acute renal injury using urinary
acute renal insufficiency in critically ill septic ity in the intensive care unit. J Am Soc proteomics. Am J Nephrol 2005; 25:318 –326
patients. Nephron Clin Pract 2004; 97: Nephrol 2005; 16:3046 –3052 245. Mitra A, Bansal S, Wang W, et al: Erythro-
c103– c107 232. Trof RJ, Di Maggio F, Leemreis J, et al: poietin ameliorates renal dysfunction dur-
220. Koyner JL, Bennett MR, Worcester EM, et Biomarkers of acute renal injury and renal ing endotoxaemia. Nephrol Dial Transplant
al: Urinary cystatin C as an early biomarker failure. Shock 2006; 26:245–253
2007; 22:2349 –2353
of acute kidney injury following adult car- 233. Waikar SS, Bonventre JV: Biomarkers for
246. Sharples EJ, Yaqoob MM: Erythropoietin in
diothoracic surgery. Kidney Int 2008; 74: the diagnosis of acute kidney injury. Curr
experimental acute renal failure. Nephron
1059 –1069 Opin Nephrol Hypertens 2007; 16:557–564
Exp Nephrol 2006; 104:e83– e88
221. Mishra J, Dent C, Tarabishi R, et al: Neu- 234. Bonventre JV: Diagnosis of acute kidney
247. Sward K, Valsson F, Odencrants P, et al:
trophil gelatinase-associated lipocalin injury: from classic parameters to new bi-
Recombinant human atrial natriuretic pep-
(NGAL) as a biomarker for acute renal in- omarkers. Contrib Nephrol 2007; 156:
tide in ischemic acute renal failure: A ran-
jury after cardiac surgery. Lancet 2005; 213–219
domized placebo-controlled trial. Crit Care
365:1231–1238 235. Westhuyzen J, Endre ZH, Reece G, et al:
Med 2004; 32:1310 –1315
222. Parikh CR, Mishra J, Thiessen-Philbrook H, Measurement of tubular enzymuria facili-
248. Allgren RL, Marbury TC, Rahman SN, et al:
et al: Urinary IL-18 is an early predictive tates early detection of acute renal impair-
Anaritide in acute tubular necrosis. Auricu-
biomarker of acute kidney injury after car- ment in the intensive care unit. Nephrol
diac surgery. Kidney Int 2006; 70:199 –203 Dial Transplant 2003; 18:543–551 lin Anaritide Acute Renal Failure Study
223. Wagener G, Jan M, Kim M, et al: Association 236. du Cheyron D, Daubin C, Poggioli J, et al: Group. N Engl J Med 1997; 336:828 – 834
between increases in urinary neutrophil Urinary measurement of Na⫹/H⫹ ex- 249. Lewis J, Salem MM, Chertow GM, et al: Atrial
gelatinase-associated lipocalin and acute changer isoform 3 (NHE3) protein as new natriuretic factor in oliguric acute renal fail-
renal dysfunction after adult cardiac sur- marker of tubule injury in critically ill pa- ure. Anaritide Acute Renal Failure Study
gery. Anesthesiology 2006; 105:485– 491 tients with ARF. Am J Kidney Dis 2003; Group. Am J Kidney Dis 2000; 36:767–774
224. Mishra J, Ma Q, Kelly C, et al: Kidney NGAL 42:497–506 250. Tumlin J, Wali R, Williams W, et al: Efficacy
is a novel early marker of acute injury fol- 237. Zhou H, Pisitkun T, Aponte A, et al: Exoso- and safety of renal tubule cell therapy for
lowing transplantation. Pediatr Nephrol mal Fetuin-A identified by proteomics: a acute renal failure. J Am Soc Nephrol 2008;
2006; 21:856 – 863 novel urinary biomarker for detecting acute 19:1034 –1040
225. Parikh CR, Jani A, Mishra J, et al: Urine kidney injury. Kidney Int 2006; 70: 251. Payen D, Mateo J, Cavaillon JM, et al: Im-
NGAL and IL-18 are predictive biomarkers 1847–1857 pact of continuous venovenous hemofiltra-
for delayed graft function following kidney 238. Yu W, Sandoval RM, Molitoris BA: Rapid tion on organ failure during the early phase
transplantation. Am J Transplant 2006; determination of renal filtration function of severe sepsis: A randomized controlled
6:1639 –1645 using an optical ratiometric imaging ap- trial. Crit Care Med 2009; 37:803– 810
226. Zappitelli M, Washburn KK, Arikan AA, et proach. Am J Physiol Renal Physiol 2007; 252. Honore PM, Jamez J, Wauthier M, et al:
al: Urine neutrophil gelatinase-associated 292:F1873–R1880 Prospective evaluation of short-term, high-
lipocalin is an early marker of acute kidney 239. Rabito CA, Panico F, Rubin R, et al: Nonin- volume isovolemic hemofiltration on the
injury in critically ill children: A prospec- vasive, real-time monitoring of renal func- hemodynamic course and outcome in pa-
tive cohort study. Crit Care 2007; 11:R84 tion during critical care. J Am Soc Nephrol tients with intractable circulatory failure
227. Nickolas TL, O’Rourke MJ, Yang J, et al: 1994; 4:1421–1428 resulting from septic shock. Crit Care Med
Sensitivity and specificity of a single emer- 240. Treszl A, Kaposi A, Hajdu J, et al: The extent 2000; 28:3581–3587

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