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ARF was available. Kellum et al12

reported that more than 35 differ-

ent definitions of acute renal failure

were used in clinical practice. A need

for clear definitions of renal injury

and renal failure has led to the request

for measurable criteria. A consensus

on the need for a definition and a

classification system to enable more

accurate diagnosis of kidney injury

was reached by the Acute Dialysis

Quality Initiative group.6,11 AKI

refers to a sudden decline in kidney

function that causes disturbances in

fluid, electrolyte, and acid-base bal-

ances because of a loss in clearanceof small solutes and a decreased

glomerular filtration rate (GFR).13

Therefore, the term AKI has replaced

the term ARF, with the understand-

ing that AKI has a broad spectrum

and encompasses the entire syn-

drome in all patients, not just

patients who require renal replace-

ment therapy but also patients with

minor changes in renal function.

14

In this article, I review AKI,

including causes, detection with

conventional and new markers,

impact on outcome in critically ill

patients, and prevention.

AKI ClassificationClassification criteria for AKI

include assessment of 3 grades of

risk factor for nonrenal complica-

tions.3 Factors that may influence

the high mortality rates includethe increasing age of the popula-

tion of patients and the existence

of comorbid conditions (eg, dia-

betes, heart disease, preexisting

renal disease, preexisting vascular

disease, and respiratory failure).3

Additional evidence4-7 indicates

that even milder forms of acute

kidney injury (AKI), not just ARF

requiring renal replacement ther-apy, are associated with excess mor-

tality. Numerous studies8-11 have

shown that ARF in patients in the

intensive care unit (ICU) is associ-

ated with high short- and long-term

case fatality rates, dialysis depend-

ence, and reduced quality of life.

Until recently, no uniform stan-

dard for diagnosing and classifying

T

he development of acute

renal failure (ARF) con-

tinues to be a problemthat markedly affects

outcome in critically ill

patients. Despite advances in treat-

ment, development of ARF contin-

ues to be associated with high

mortality rates, ranging from 40%

to 90%.1,2 In addition, ARF is a major

2011 American Association of Critical-

Care Nurses doi: 10.4037/ccn2011946

This article has been designated for CE credit.A closed-book, multiple-choice examinationfollows this article, which tests your knowledgeof the following objectives:

1. Defineand discussacutekidneyinjury(AKI)2. Compare and contrast renal biomarkers

for early detection of AKI3. Understand the RIFLE classification system4. Discuss prevention and treatment strate-

gies for AKI

CEContinuing Education

Until recently, no uniform standard existed for diagnosing and classifying acute

renal failure. To clarify diagnosis, the Acute Dialysis Quality Initiative group stated

its consensus on the need for a clear definition and classification system of renal

dysfunction with measurable criteria. Today the term acute kidney injuryhas replaced

the termacute renal failure, with an understanding that such injury is a common

clinical problem in critically ill patients and typically is predictive of an increase inmorbidity and mortality. A classification system, known as RIFLE (risk of injury,

injury, failure, loss of function, and end-stage renal failure), includes specific goals for

preventing acute kidney injury: adequate hydration, maintenance of renal perfusion,

limiting exposure to nephrotoxins, drug protective strategies, and the use of renal

replacement therapies that reduce renal injury. (Critical Care Nurse. 2011;31[1]:37-50)

www.ccnonline.org CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 37

Acute Kidney Injury: Not JustAcute Renal Failure Anymore?

Susan Dirkes,RN, MSA, CCRN

Feature
http://ccn.aacnjournals.org/http://ccn.aacnjournals.org/

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severity: risk of acute renal failure,

injury to the kidney, and failure ofrenal function. The 2 outcome clas-

sifications are loss of kidney func-

tion and end-stage renal disease.

This 5-point system (risk of injury,

injury, failure, loss of function, and

end-stage renal failure) is known as

the RIFLE classification system6,12,15

(Table 1). In several investiga-

tions2,7,8,14,16-19 on use of the RIFLE

system in different populations ofpatients, RIFLE criteria correlated

with outcome (see Figure). Conse-

quently, the RIFLE classification is

being used to identify kidney injury

and improve patients outcome.

Conventional Markersfor AKI

The loss of kidney excretory

function can be manifested by the

accumulation of end products of

metabolism. The detection of changes

in these end products, or what arecurrently the conventional renal

markers (Table 2), is the impetus

for the diagnosis of AKI. Markers

commonly used now are measure-

ment of serum levels of creatinine

and urea nitrogen, fractional excre-

tion of sodium to assess GFR, and

changes in urine output.20 Changes

in these markers have been used to

assess renal function for decades,but each marker has limitations.21

Because AKI has such a poor prog-

nosis and increases risk for death in

critically ill patients, tests of kidney

function that allow early diagnosis

of kidney injury are desirable. In

addition, the time required for abnor-

mal accumulation of the markers to

become detectable in the serum can

cause a delay in the diagnosis and,

potentially, the treatment of AKI.22

Creatinine

Creatinine is released from theplasma at a relatively constant rate,

is freely filtered at the glomerulus,

and is not reabsorbed or metabo-

lized by the kidneys. Measurement

of the serum level of creatinine is

the most widely used method of

assessing renal function.23 The his-

torical belief was that when the cre-

atinine level becomes greater than

the normal reference range of 0.5 to1.0 mg/dL (to convert to micro-

moles per liter, multiply by 88.4),

the GFR decreases.21 Thus, changes

in the serum level of creatinine in

an ideal situation should be directly

proportional to changes in GFR.

Unfortunately, critically ill patients

do not represent an ideal situation.

The serum level of creatinine may

be a poor reflection of kidney func-

tion because the patients are not ina steady state and an increase in the

creatinine level lags behind renal

injury by as much as 12 hours to 2

days.22 Use of creatinine as a marker

for renal function has additional

limitations. Patients age, sex, dietary

intake, and muscle mass all influence

the baseline level of creatinine, as

Susan Dirkes is an educator in the progressive care unit, University of Michigan HealthSystem, Ann Arbor, Michigan.

Author

Corresponding author: Susan Dirkes,RN, MSA, CCRN,University of Michigan Health System, 6326 Sterling Dr,Newport, MI 48166 (e-mail: [email protected]).

To purchase electronic or print reprints, contact The InnoVision Group, 101 Columbia, Aliso Viejo, CA 92656.Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, [email protected].

Table 1 RIFLE classification system for acute kidney injury

RIFLE category

Grades of severity

Risk

Injury

Failure

Outcomes

Loss

End-stage kidney disease

Urine output

75% or serum creatinine level >4 mg/dL

Complete loss of renal function for >4 weeks

Need for renal replacement therapy for >3 months

Criteria

38 CriticalCareNurse Vol 31, No. 1, FEBRUARY 2011 www.ccnonline.org

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do some disease states and drugs

(eg, cimetidine).23 Sex and age are

influences because men typicallyhave greater muscle mass than women

do. As a person becomes older, a

decrease in muscle mass occurs. Such

a decrease also occurs in patients

taking corticosteroids.24 Excess intake

of cooked meat also can elevate the

creatinine level in the absence of

renal failure. Cimetidine is known

to enhance creatinine clearance,

thereby changing the amount of cre-

atinine that is secreted.25 Measure-

ment of serum creatinine levels does

not depict real-time changes in GFR

that occur with acute reduction in

kidney function.21

Urea

Urea is another commonly used

marker for the diagnosis of renal

failure. Urea is a by-product of pro-

tein metabolism and is used as a

marker in AKI for retention andelimination of uremic solutes.23 Like

creatinine, urea is not produced at a

constant rate, and the rate can be

influenced by extrarenal factors.

Urea production can be increased

by diet, critical illness, burns, trauma,

gastrointestinal bleeding, and sepsis

and can be influenced by drugs, such

as corticosteroids.20 Thus, patients

being treated with steroids, such as

transplant recipients, may have

increases in the serum concentration

of urea without increases in serum

level of creatinine. Also, critically ill

patients who receive corticosteroids

have an increase in protein catabo-

lism associated with the medications

and the overall hypercatabolism of

their illness.20 Patients such as those

with chronic liver disease may have

normal values of urea because of

decreased urea production and pro-

tein restriction and normal levels of

serum creatinine despite markedly

reduced GFR.21 In patients with

decreased circulating blood volumedue to volume depletion or low car-

diac output, resorption of urea

increases because of the relation-

ship between urea levels and water

conservation mechanisms.26 There-

fore, urea, like creatinine, can be

influenced by multiple factors and

does not represent real-time changes

in GFR because the accumulation

of urea requires, at a minimum,

several hours or longer.23

Fractional Excretion of Sodium

Fractional excretion of sodium

has also been used as a marker for

renal function. Its use is based on

the principle that filtered sodium is

reabsorbed into the renal tubules

from glomerular filtrate in prerenal

azotemia, in which tubular func-

tion remains intact.27

In prerenalazotemia, fractional excretion of

sodium in urine is less than 1%.28

Fractional excretion is often greater

than 1% in patients receiving

diuretics and can be less than 1%

in conditions such as sepsis, rhab-

domyolysis, and exposure to radio-

logical contrast media.29,30 In

summary, in the clinical setting,

fractional excretion of sodium is

not an accurate indicator of renal

injury, and the level is influenced

by numerous conditions that reflect

injury of the renal parenchyma.31

Novel Biomarkers for AKIStudies32-34 in which variables

such as levels of urea and creatinine

and urine output have been used as

Figure Mortality by RIFLE class.

90

80

70

60

50

40

30

20

10

0

Hoste andKellum8

Uchino et al17 Ostermannand Chang2

Abosaif et al16 Maccarielloet al18

Mortality,

%

Risk Injury Failure


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indicators of kidney function or

injury have not provided interven-

tions that decrease the need for

dialysis or reduce mortality. At the

same time, the inability to diagnose

AKI quickly and accurately places

an enormous financial burden on

society: AKI-associated medical

expenses are estimated to be $8

billion annually in the United

States.33,35,36 Therefore, the use of

biomarkers that could be used to

detect early renal injury may affecttimely diagnosis and, possibly, out-

comes in AKI.

Desirable characteristics of bio-

markers for detection of AKI are

ease of use and noninvasiveness;

usability at the bedside or in a con-

ventional clinical laboratory with

samples such as blood or urine;

reliance on a rapid, reliable, and

standard test; and a high sensitivity

to facilitate early detection.37 These

biomarkers should be highly specific

for AKI. Biomarkers may be able to

(1) indicate the location of the injury,

the duration of kidney failure, causes

of renal injury, and the duration and

need for renal replacement therapy

and (2) be used to monitor the

response to interventions.37,38

Some of the newer biomarkers

are interleukin 18 (IL-18) neutrophil

gelatinase-associated lipocalin

(NGAL), and kidney injury mole-

cule-1 (KIM-1). These markers were

discovered initially in studies on the

pathophysiology of AKI in animal

models.38-40 Use of these biomarkers

for AKI may enable earlier detection

of renal injury and aid in identifying

the time of occurrence of the initial

injury, the nature of the injury, and

the duration of AKI. Use of thesebiomarkers may also provide a win-

dow of opportunity for interventions

that may be of more benefit if pro-

vided early enough in the course of

the disease. The markers also may

be useful in predicting the overall

prognosis and any potential dialysis

requirements. Currently, they have

only been tested in small studies

and in limited clinical situations.

Interleukin 18

IL-18 is a proinflammatory

cytokine produced in the proximal

tubule after AKI. The intracellular

protease capsase-1 converts the

cytokines interleukin 1b and IL-18

to their active forms. IL-18 then

exits the cell and enters the urine.

Urinary levels of IL-18 have been

shown to increase in ischemic AKI.37,41

Parikh et al42 found that IL-18 was an

early marker for AKI in patients

with acute respiratory distress syn-

drome. Urinary IL-18 levels greater

than 100 pg/mg were predictive of

the development of AKI 24 hours

before the level of creatinine increased.

The level of urinary IL-18 on the day

of initiation of mechanical ventila-

tion was also predictive of mortality

in patients with acute respiratorydistress syndrome, independent of

the severity of illness, urine level of

creatinine, and urine output.

Neutrophil Gelatinin-Associated

Lipocalin

NGAL is normally present at

low levels in several human tissues,

including the kidneys, lungs, stom-

ach, and colon.37NGAL expression

is markedly elevated in injured

epithelium, which occurs in acute

bacterial infections, asthma, and

pulmonary disease.39,43-45NGAL was

detected more often than conven-

tional markers of AKI in the kidneys

after ischemic or nephrotoxic injury

in animals models and was easily

detected in urine and blood.44,45

Table 2 Conventional markers for acute kidney injury

Marker

Urea

Creatinine

Fractionalexcretionof sodium

Normal value

8-20 mg/dL

0.7-1.5 mg/dL

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continue hydration should be care-

fully considered according to the

patients weight, blood pressure,

central venous pressure, and the

use of any vasoactive drugs.

Maintaining Renal PerfusionPressure

Maintenance of fluid volume

on the basis of mean arterial pres-

sure is standard practice in the

ICU. Sepsis, trauma, major surgery,

and the use of certain drugs can

cause systemic hypotension.62

Expansion and maintenance of

fluid volume should be tailored to

the achievement of targets such as

cardiac output, central venous

pressure, and urine output. Early

goal-directed therapy with volume

expansion for rapid fluid replace-

ment is now a cornerstone in the

management of sepsis.63 The result

of this therapy is a vigorous replace-

ment of fluid volume in the vascular

space. In patients with hypotension

and capillary leak, this increased

fluid volume can lead to abdominalorgan edema and pulmonary com-

plications.64 Edema of solid organs

and the visceral wall causes an

increase in intraperitoneal pres-

sure. This pressure can compress

abdominal organs and cause organ

and tissue ischemia. As abdominal

ischemia progresses, ascities occurs,

leading to a loss of fluids, elec-

trolytes, and proteins through leaky

capillaries and a loss of membrane

integrity.65 The result is increased

intra-abdominal pressure (IAP),

which is associated with abnormal-

ities in many organ systems. The

overall increase in IAP causes com-

pression of renal veins, and inade-

quate cardiac output diminishes

renal blood flow.66

Abdominal Compartment

Syndrome

According to the World Society

of Abdominal Compartment Syn-

drome,67 normal IAP in healthy per-

sons is less than 5 to 7 mm Hg. The

upper limit of nonpathological IAPis 12 mm Hg, and sustained increased

pressure greater than 12 mm Hg is

defined as intra-abdominal hyper-

tension.68 Similar to the situation in

cerebral perfusion pressure, a rela-

tionship exists between mean arte-

rial pressure and IAP that is related

to abdominal perfusion pressure.69

Increased IAP compromises venous

return, cardiac output, and systemic

oxygen delivery. As IAP increases,oliguria and renal injury occur

despite continued fluid replace-

ment.70 Unfortunately, once intra-

abdominal hypertension has

occurred, relieving this pressure (ie,

abdominal compartment syndrome)

does not stop the renal injury. The

goal is to detect the onset of renal

injury by using new biomarkers.38

Currently, relief of abdominal com-partment syndrome by laparotomy

is the standard of care to prevent

further renal injury.66 The primary

strategy to prevent AKI is to mini-

mize the risk of kidney injury by

monitoring IAP before the onset of

abdominal compartment syndrome.

Exposure to Nephrotoxins

Critically ill patients are often

exposed to nephrotoxic materials,

including, but not limited to, amino-

glycosides, amphotericin B, and

radiological contrast agents. In the

ICU, nephrotoxic effects, either

alone or more commonly associated

with ischemia, have been a factor in

the development of AKI in almost

one-half of the cases.71,72 Because the

kidneys are responsible for the

excretion of many drugs, the most

common mechanism of nephrotoxic

injury is the toxic effect on the renal

tubules, causing cellular injury and

death or inflammation.73

Aminoglycosides.Aminoglyco-sides are used often in critical care

and are a contributing factor in 19%

to 25% of cases of severe renal fail-

ure.7 Aminoglycosides are elimi-

nated by glomerular filtration, but

a fraction of the dose given is reab-

sorbed in the proximal tubule.74,75

After glomerular filtration, part of

the aminoglycoside is transported

to the intracellular compartment.

Intracellular accumulation of the

aminoglycoside is thought to inter-

fere with cellular function, eventu-

ally leading to cell death and a

decreased GFR.76

Nephrotoxic effects due to

aminoglycosides are common in

high-risk patients such as the eld-

erly; renal dysfunction develops in

15% of elderly patients treated with

these drugs.77

Once the nephrotoxiceffects develop, the impaired renal

function prevents the kidneys from

excreting the dose of aminoglyco-

side within the dosing interval. Cur-

rently, the only clinical approach

used to prevent the nephrotoxic

effects is decreasing the dosage

schedule to prevent further damage

of the kidneys.78 In a meta-analysis79

of multiple and single daily dosing

of aminoglycosides, the overall rate

of nephrotoxic effects was 5.5% for a

single daily dose and 7.7% for multi-

ple daily doses. In other studies,78,80,81

once-daily dosing and multiple daily

doses had similar efficacy in treating

infections, but a trend favoring once-

daily dosing in reducing nephro-

toxic effects was noted. Current


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recommendations are to consider

alternative antimicrobial agents in

patients such as elderly persons who

are at high risk for nephrotoxic

effects due to aminoglycosides.73

Amphotericin B.Amphotericin B

is an extremely nephrotoxic drug.82

AKI associated with conventional

use of amphotericin B occurs in 25%

to 30% of patients treated with the

drug, and the risk increases with

cumulative doses.83 Amphotericin B

directly binds to the tubular epithe-

lial cells in the collecting duct, caus-

ing altered cell permeability, which

in turn causes sodium, potassium,

and magnesium wasting. The med-

ication then directly causes vasocon-

striction of the intrarenal arteries

and arterioles.84-86 Renal function

can improve when treatment with

the drug is discontinued; other strate-

gies to reduce the nephrotoxic

effects of amphotericin B include

sodium loading87 and longer infu-

sion times, up to 24 hours.82 In a

comparison82 of patients given a

rapid infusion (over 4 hours) ofamphotericin B and patients given a

24-hour infusion, patients in the

rapid infusion group had significantly

more nephrotoxic effects. Although

this study82 and other studies83,84,87

showed a reduction in nephrotoxic

effects when the drug was given by

continuous infusion, all the studies

had small sample sizes and were

done in low-risk patients. New drugs

have been approved for treatment

of fungal infections, but because of

its low cost and broad spectrum of

activity, amphotericin B is still

widely used.73

Vancomycin.Vancomycin is com-

monly used in the ICU for methicillin-

resistantStaphylococcus aureusand

gram-positive bacterial infections.88

It is widely used in conjunction

with other aminoglycosides, and

the reported frequency of ARF in

patients treated with vancomycin

plus an aminoglycoside is 20% to

30%.89 Vancomycin is excreted by

glomerular filtration; 80% to 90% iseliminated in an unaltered form.

The mechanism of the nephrotoxic

effects is unknown, but risk factors

include age, use of other nephro-

toxic agents, duration of therapy,

and drug levels achieved.90,91 Stan-

dards of care to prevent the risk of

nephrotoxic effects due to van-

comycin include monitoring of

trough levels of the drug and atten-

tion to dosing frequency.

Radiological Contrast Media.

The multiple types of radiological

imaging for critically ill patients

often involve use of contrast agents.

At the same time, critically ill patients

are likely to have compromised

renal function and are often elderly.92

Contrast mediuminduced nephropa-

thy (CIN) is a serious complication;

it is associated with increases inhospital length of stay, requirement

for dialysis, and risk for death.15,93

CIN is defined as an increase in

serum creatinine that occurs within

the first 24 hours after exposure to

contrast medium and peaks within

3 days after the exposure.94 In a large

study,14 the risk of death in patients

with CIN was 34% compared with

7% in matched controls. Specific

risk factors for CIN in hospitalized

patients include diabetes mellitus,95

heart failure, volume depletion,96

nephrotoxic drugs, and unstable

hemodynamic status.97,98 When radi-

ological contrast material is used,

the type and volume of the material

administered may influence the risk

for nephrotoxic effects.99

Once administered, iodinated

contrast material collects and

dwells in the urinary space of the

glomerulus and renal tubules,

where it has a direct cytotoxic effect

on the renal tubular cells.100 Some

research99

indicates the risk for CINis less when low-osmolality agents

are used, although use of low-

osmolality agents did not influence

the development of AKI or the need

for dialysis. Other studies have had

conflicting results. Strategies to

reduce the incidence of CIN include

volume expansion with isotonic

crystalloid,101 hemofiltration,102,103

and use ofN-acetylcysteine.104

Pharmacological Strategiesto Prevent AKI

Table 3 lists pharmacological

strategies for prevention of AKI.

Loop Diuretics

Oliguria develops in many ICU

patients. Therapeutic options for

these patients include ruling out

urinary tract obstruction, restora-tion and maintenance of fluid bal-

ance, and restoration of urine flow.120

Loop diuretics have long been used

to treat ICU patients with AKI. These

agents act in the kidney in the loop

of Henle to prevent the reabsorp-

tion of water.55 Loop diuretics aid

in the management of fluid volume

overload by augmenting diuresis

and help maintain homeostasis.120

In a multinational study,121

furosemide was by far the most

common diuretic used, but most

clinicians did not actually think use

of this diuretic would lead to

improved clinical outcomes.

Although use of furosemide in ani-

mal models of AKI has shown it can

reduce injury and improve renal


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hemodynamics, these results were

not universal.105,121-124 In contrast, in

vitro studies125 with peripheral blood

mononuclear cells stimulated with

lipopolysaccharide have shown that

high concentrations of furosemide

have cytotoxic and immunosupressive

effects. Other evidence106 indicates that

furosemide does not improve out-

come in AKI. Therefore, an accu-rate assessment of each patient and

the patients clinical feature should

guide the use of loop diuretics.

Dopamine

Dopamine increases renal blood

flow by splanchnic vasodilatation,

increasing cardiac output and

improving perfusion pressure.107

Several investigators108-110 have eval-

uated the role of dopamine in pre-

venting the deterioration of renal

function in ICU patients. The

results indicated that the drug did

not prevent the onset of ARF or the

need for dialysis or improve mortal-

ity,108,109 and Bellomo et al110 con-

cluded that dopamine has no role

in the prevention of AKI.

Natriuretic Peptides

Low-dose human recombinant

natriuretic peptides have been

evaluated for prevention of AKI in

cardiac surgery patients.115,116,126 The

studies had small sample sizes and

did not show any benefit of use of

the peptides. However, in the study

by Swrd et al,116 compared with

continuous infusion of a placebo,

continuous infusion of low-dose

human recombinant natriuretic pep-

tide was associated with a decrease

in use of dialysis and an improve-

ment in dialysis-free survival.

N-Acetylcysteine

N-acetylcysteine is an antioxi-dant.117 In several studies with

small sample sizes, treatment with

this antioxidant decreased CIN.118,127

N-acetylcysteine has a low cost,

and may prevent CIN in patients at

high risk for this nephropathy.1

N-acetylcysteine has also been used

in conjunction with fenoldopam, a

selective stimulator of the D1

Table 3 Pharmacological strategies for acute kidney injuries

Method

Loop diureticsa

Dopamineb

Fenoldopamc

Natriureticpeptidesd

N-acetylcysteinee

Summary

Adverse effects include risk of temporary deafness and tinnitus with use of highdoses

No data indicate that loop diuretics decrease need for renal replacement or numberof dialysis sessions

Use may be associated with increased risk of death or nonrecovery of renal functionIn studies on the role of dopamine in the prevention of deterioration of renal func-

tion in intensive care units, dopamine did not prevent onset of acute renal failure,need for dialysis, or mortality

Use decreases incidence of acute renal failure in intensive care patientsUse significantly reduces the risk for acute kidney injury, need for renal replacement

therapy, and in-hospital death in intensive care patients and patients undergoingmajor surgery

Currently, used alone, fenoldopam has no role in the prevention of contrast-induced nephropathy

Oliguric patients (urine ouptut

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dopamine receptor that increases

renal blood flow. The effects of

N-acetylcysteine plus fenoldopam

on morbidity and mortality, treat-

ment, and length of hospital stay

have been studied in cardiac surgical

patients with moderate to severepreoperative renal dysfunction.118,127

Barr and Kolodner128 found that use

of the 2 medications together had

some renal-protective effects in the

immediate postoperative period for

patients with moderate to severe

renal dysfunction but had no signifi-

cant effect on length of stay, use of

dialysis, or mortality.

Renal ReplacementTherapies for AKI

Historically, the treatment of

ARF has been supportive care. The

most commonly used renal replace-

ment therapy has been intermittent

hemodialysis (IHD), for both patients

with chronic renal failure and criti-

cally ill patients.129 Conventional

indications for renal replacement

therapy in AKI include fluid volumeexcess, hyperkalemia, metabolic aci-

dosis, and uremia. This therapy also

can be used for drug overdose.130

The focus of dialysis is removal of

excess water and wastes via a dialy-

sis machine and a dialyzer. IHD is

intended to be used for short periods,

typically 3 to 4 hours, to aggres-

sively change fluid volume and

remove wastes.131 A well-known con-

sequence of this therapy is unstable

hemodynamic status.132,133 IHD may

be more suited to patients who are

not critically ill, because less ill

patients typically have a more stable

hemodynamic status and may toler-

ate sudden shifts in water volume

and electrolyte levels.134

Research has shown that the

rapid changes in fluid status andplasma osmolality associated with

IHD may cause renal ischemia and

delay renal recovery even after tran-

sient periods of hypotension.135

Episodes of renal hypoperfusion

causing ischemia limit not only

blood flow to the kidney but also

the delivery of oxygen. Compared

with cells in other organs, the tubu-

lar cells also depend on large amounts

of oxygen.136 Small changes in oxy-

gen delivery may exacerbate tissue

hypoxia. When renal hypoperfusion

occurs, the return of blood flow

causes a series of events, including

cytokine synthesis, altered cell

adhesion, leukocyte migration, and

leukocyte-mediated cell damage,

causing physical blockage of renal

microcirculation.137,138 With more

severe injury, tubular cells die, caus-ing the loss of tubular integrity and

loss of renal function.139

Because of the renal abnormali-

ties associated with IHD, the stan-

dard of care for patients who have

this treatment may not be applica-

ble to critical care patients, who dif-

fer in the nature of their illness,

their catabolic state, the presence

of systemic inflammatory syndrome

with or without sepsis, and the

presence of other organ failure.140

Therefore, other types of renal

replacement therapies have been

used in critically ill patients; the

goals are to prevent further renal

injury and preserve renal function.

Continuous renal replacement

therapy (CRRT) is currently used in

critically ill patients because of its

many advantages compared with

IHD: no abrupt variations in fluid

removal or osmolality, good clear-

ance of solutes, and better hemody-

namic tolerance.141 Similar to IHD,

CRRT requires an extracorporealcircuit, but the dialysis is continu-

ous, 24 hours a day for several days.

Compared with IHD, CRRT removes

plasma water and wastes more slowly

but still provides effective clearance

of water and wastes.134 Removing

water at a slower rate helps prevent

hemodynamic complications.

Despite the apparent advan-

tages of CRRT versus IHD, no defin-

itive studies comparing morbidity

associated with the 2 methods have

been done.141-144 Only a few stud-

ies145,146 have shown improved return

of renal function with CRRT. In the

Beginning and Ending Supportive

Therapy for the Kidney study,147

investigators examined the effect

of treatment choice on survival and

renal recovery. Their results suggest

that among survivors, IHD mayincrease dialysis dependence in

AKI more than CRRT does. In a

study to determine which method

was better, Vinsonneau et al148

found no difference in mortality,

ICU or hospital length of stay, or

rate and time to renal recovery.

In a recent study149 of intensive

versus less intensive treatment

strategies in IHD and CRRT, inves-

tigators compared standard dialysis

3 times per week with intensive

dialysis 6 times per week, and

CRRT at a standard effluent flow of

20 mL/kg per hour versus 35

mL/kg per hour. The rate of death

from any cause by day 60 was 53.6%

with intensive therapy and 51.5%

with less-intensive therapy. The 2

To learn more about acute kidney failure,read Residual Urine Output and Postopera-tive Mortality in Maintenance HemodialysisPatients, by Lin et al in theAmerican Jour-nal of Critical Care,2009;18:446-455. Avail-able atwww.ajcconline.org.


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groups did not differ significantly in

the duration of renal replacement

therapy or the rate of recovery of

kidney function or nonrenal organ

failure. Hypotension during inter-

mittent dialysis occurred in more

patients randomly assigned toreceive intensive therapy, although

the frequency of hemodialysis ses-

sions complicated by hypotension

was similar in the 2 groups.

SummaryAKI is a serious and common

clinical problem in the ICU; even

mild forms of AKI are associated with

high mortality rates. The term AKI

has replaced ARF, with the under-

standing that the spectrum of AKI is

broad and includes different degrees

of severity. A new classification sys-

tem, known as the RIFLE system,

can be used to identify kidney injury

and outcome. New biomarkers are

being studied to replace conventional

markers such as urea and creatinine,

but although the markers appear to

hold promise in identifying kidneyinjury, they still are not commonly

available and require more study.

Methods to prevent AKI include

maintenance of fluid volume, renal

perfusion pressure, avoidance of

nephrotoxic agents, and treatment

of AKI by dialysis methods after care-

ful assessment of the patient and the

clinical picture. Use of a variety of

methods to prevent AKI, including

renal replacement therapies, may

improve the outcome from AKI.CCN

Financial DisclosuresNone reported

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