7/6/2017 AcuteKidneyInjury:PracticeEssentials,Background,Pathophysiology

AcuteKidneyInjury
Updated:Jan13,2017
Author:BiruhTWorkeneh,MD,PhD,FASNChiefEditor:VecihiBatuman,MD,FASNmore...

OVERVIEW

Background
Acutekidneyinjury(AKI)oracuterenalfailure(ARF),asitwaspreviouslytermedisdefinedas
anabruptorrapiddeclineinrenalfiltrationfunction.Thisconditionisusuallymarkedbyarisein
serumcreatinineconcentrationorbyazotemia(ariseinbloodureanitrogen[BUN]concentration).
[1] However,immediatelyafterakidneyinjury,BUNorcreatininelevelsmaybenormal,andthe
onlysignofakidneyinjurymaybedecreasedurineproduction.(SeeHistory.)

Ariseinthecreatininelevelcanresultfrommedications(eg,cimetidine,trimethoprim)thatinhibit
thekidneystubularsecretion,whileariseintheBUNlevelcanalsooccurwithoutrenalinjury,
resultinginsteadfromsuchsourcesasgastrointestinal(GI)ormucosalbleeding,steroiduse,or
proteinloading.Therefore,acarefulinventorymustbetakenbeforeconcludingthatakidneyinjury
ispresent.(SeeEtiologyandHistory.)

SeeChronicKidneyDiseaseandAcuteTubularNecrosisforcompleteinformationonthesetopics.
Forinformationonpediatriccases,seeChronicKidneyDiseaseinChildren.

CategoriesofAKI
AKImaybeclassifiedinto3generalcategories,asfollows:

PrerenalAsanadaptiveresponsetoseverevolumedepletionandhypotension,with
structurallyintactnephrons
IntrinsicInresponsetocytotoxic,ischemic,orinflammatoryinsultstothekidney,with
structuralandfunctionaldamage
PostrenalFromobstructiontothepassageofurine

Whilethisclassificationisusefulinestablishingadifferentialdiagnosis,manypathophysiologic
featuresaresharedamongthedifferentcategories.(SeeEtiology.)

OliguricandnonoliguricpatientswithAKI

PatientswhodevelopAKIcanbeoliguricornonoliguric,canhavearapidorslowriseincreatinine
levels,andmayhavequalitativedifferencesinurinesoluteconcentrationsandcellularcontent.
(Approximately5060%ofallcausesofAKIarenonoliguric.)Thislackofauniformclinical
presentationreflectsthevariablenatureoftheinjury.

ClassifyingAKIasoliguricornonoliguriconthebasisofdailyurineexcretionhasprognosticvalue.
Oliguriaisdefinedasadailyurinevolumeoflessthan400mLandhasaworseprognosis.

Anuriaisdefinedasaurineoutputoflessthan100mL/dayand,ifabruptinonset,suggests
bilateralobstructionorcatastrophicinjurytobothkidneys.

Stratificationofrenalinjuryalongtheselineshelpsindiagnosisanddecisionmaking(eg,timingof
dialysis)andcanbeanimportantcriterionforpatientresponsetotherapy.
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RIFLEclassificationsystem

In2004,theAcuteDialysisQualityInitiativeworkgroupsetforthadefinitionandclassification
systemforacuterenalfailure,describedbytheacronymRIFLE(Riskofrenaldysfunction,Injuryto
thekidney,FailureorLossofkidneyfunction,andEndstagekidneydisease).[2]Investigators
havesinceappliedtheRIFLEsystemtotheclinicalevaluationofAKI,althoughitwasnotoriginally
intendedforthatpurpose.AKIresearchincreasinglyusesRIFLE.SeeTable1,below.

Table1.RIFLEClassificationSystemforAcuteKidneyInjury(OpenTableinanewwindow)

Urine
Stage GFR** Output Probability
Criteria Criteria

SCreat
increased
1.5

High
or UO< sensitivity
Risk 0.5 (Risk
mL/kg/h >Injury
6h >Failure)
GFR
decreased
>25%

SCreat
increased
2

or
UO<0.5
Injury mL/kg/h
12h
GFR
decreased
>50%

Failure SCreat UO<0.3

increased mL/kg/h
3 24h

or (oliguria)

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GFR or
decreased
75%

anuria
12h
or

SCreat4
mg/dL
acuterise
0.5
mg/dL

Persistent
acute
renal
failure:
High
Loss complete
specificity
lossof
kidney
function
>4wk

Complete
lossof
ESKD* kidney
function
>3mo

*ESKDendstagekidneydisease**GFR
glomerularfiltrationrateSCreatserum
creatinineUOurineoutput

Note:PatientscanbeclassifiedbyGFRcriteria
and/orUOcriteria.Thecriteriathatsupportthemost
severeclassificationshouldbeused.The
superimpositionofacuteonchronicfailureis
indicatedwiththedesignationRIFLEFCfailureis
presentinsuchcaseseveniftheincreaseinSCreat
islessthan3fold,providedthatthenewSCreatis
greaterthan4.0mg/dL(350mol/L)andresults
fromanacuteincreaseofatleast0.5mg/dL(44
mol/L).

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WhenthefailureclassificationisachievedbyUOcriteria,thedesignationofRIFLEFOisusedto
denoteoliguria.

Theinitialstage,risk,hashighsensitivitymorepatientswillbeclassifiedinthismildcategory,
includingsomewhodonotactuallyhaverenalfailure.Progressionthroughtheincreasinglysevere
stagesofRIFLEismarkedbydecreasingsensitivityandincreasingspecificity.

AcuteKidneyInjuryNetworkclassificationsystem

TheAcuteKidneyInjuryNetwork(AKIN)hasdevelopedspecificcriteriaforthediagnosisofAKI.
TheAKINdefinesAKIasabrupt(within48hours)reductionofkidneyfunction,manifestedbyany1
ofthefollowing[3]:

Anabsoluteincreaseinserumcreatinineof0.3mg/dLorgreater(26.4mol/L)
Apercentageincreaseinserumcreatinineof50%orgreater(1.5foldfrombaseline)
Areductioninurineoutput,definedaslessthan0.5mL/kg/hformorethan6hours

AKINhasproposedastagingsystemforAKIthatismodifiedfromRIFLE.Inthissystem,either
serumcreatinineorurineoutputcriteriacanbeusedtodeterminestage.SeeTable2,below.

Table2.AcuteKidneyInjuryNetworkClassification/StagingSystemforAKI[3](OpenTableina
newwindow)

Urine
Stage SerumCreatinineCriteria Output
Criteria

Increaseof0.3mg/dL(26.4 <0.5
1 mol/L)or1.5to2foldincrease mL/kg/h
frombaseline for>6h

<0.5
>2foldto3foldincreasefrom
2 mL/kg/h
baseline
for>12h

<0.3
>3foldincreasefrombaseline,or
mL/kg/h
increaseof4.0mg/dL(35.4
3* for24h
mol/L)withanacuteincreaseof
oranuria
atleast0.5mg/dL(44mol/L)
for12h

*Patientswhoreceiverenalreplacement
therapy(RRT)areconsideredtohavemet
thecriteriaforstage3irrespectiveofthe
stagetheyareinatthetimeofRRT.

Cardiovascularcomplications

Cardiovascularcomplications(eg,heartfailure,myocardialinfarction,arrhythmias,cardiacarrest)
havebeenobservedinasmanyas35%ofpatientswithAKI.Fluidoverloadsecondarytooliguric
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AKIisaparticularriskforelderlypatientswithlimitedcardiacreserve.Incardiacpatientswho
experienceAKIeitherinthesettingofacutedecompensatedheartfailureorcardiacsurgery,AKIis
associatedwithworsemorbidityandmortality.[4]

PericarditisisarelativelyrarecomplicationofAKI.WhenpericarditiscomplicatesAKI,consider
additionaldiagnoses,suchassystemiclupuserythematosus(SLE)andhepatorenalsyndrome.

AKIalsocanbeacomplicationofcardiacdiseases,suchasendocarditis,decompensatedheart
failure,oratrialfibrillationwithemboli.CardiacarrestinapatientwithAKIalwaysshouldarouse
suspicionofhyperkalemia.Manyauthorsrecommendatrialofintravenouscalciumchloride(or
gluconate)inallpatientswithAKIwhoexperiencecardiacarrest.

Pulmonarycomplications
Pulmonarycomplicationshavebeenreportedinapproximately54%ofpatientswithAKIandare
thesinglemostsignificantriskfactorfordeathinpatientswithAKI.Inaddition,diseasesexistthat
commonlypresentwithsimultaneouspulmonaryandrenalinvolvement,includingthefollowing:

Goodpasturesyndrome
Granulomatosiswithpolyangiitis(Wegenergranulomatosis)
Polyarteritisnodosa
Cryoglobulinemia
Sarcoidosis

Hypoxiacommonlyoccursduringhemodialysisandcanbeparticularlysignificantinthepatient
withpulmonarydisease.Thisdialysisrelatedhypoxiaisthoughttooccursecondarytowhiteblood
cell(WBC)lungsequestrationandalveolarhypoventilation.

GIcomplications

Nausea,vomiting,andanorexiaarefrequentcomplicationsofAKIandrepresentoneofthe
cardinalsignsofuremia.GIbleedingoccursinapproximatelyonethirdofpatientswithAKI.Most
episodesaremild,butGIbleedingaccountsfor38%ofdeathsinpatientswithAKI.

Pancreatitis

MildhyperamylasemiacommonlyisseeninAKI(23timescontrols).Elevationofbaselineamylase
concentrationscancomplicatediagnosisofpancreatitisinpatientswithAKI.Measurementof
lipase,whichcommonlyisnotelevatedinAKI,oftenisnecessarytomakethediagnosisof
pancreatitis.PancreatitishasbeenreportedasaconcurrentillnesswithAKIinpatientswith
atheroemboli,vasculitis,andsepsisfromascendingcholangitis.

Jaundice

JaundicehasbeenreportedtocomplicateAKIinapproximately43%ofcases.Etiologiesof
jaundicewithAKIincludehepaticcongestion,bloodtransfusions,andsepsis.

Hepatitis

HepatitisoccurringconcurrentlywithAKIshouldpromptconsiderationofthefollowingdisordersin
thedifferentialdiagnosis:

Commonbileductobstruction
FulminanthepatitisB
Leptospirosis
Acetaminophentoxicity
Amanitaphalloidespoisoning

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Infectiouscomplications

InfectionscommonlycomplicatethecourseofAKIandhavebeenreportedtooccurinasmanyas
33%ofpatientswithAKI.Themostcommonsitesofinfectionarethepulmonaryandurinarytracts.
InfectionsaretheleadingcauseofmorbidityanddeathinpatientswithAKI.Variousstudieshave
reportedmortalityratesof1172%ininfectionscomplicatingAKI.

Neurologiccomplications

NeurologicsignsofuremiaareacommoncomplicationofAKIandhavebeenreportedin
approximately38%ofpatientswithAKI.Neurologicsequelaeincludelethargy,somnolence,
reversalofthesleepwakecycle,andcognitiveormemorydeficits.Focalneurologicdeficitsare
rarelycausedsolelybyuremia.

Thepathophysiologyofneurologicsymptomsisstillunknown,butthesesymptomsdonotcorrelate
welltolevelsofBUNorcreatinine.

Anumberofdiseasesexpressthemselveswithconcurrentneurologicandrenalmanifestations,
includingthefollowing:

SLE
Thromboticthrombocytopenicpurpura(TTP)
Hemolyticuremicsyndrome(HUS)
Endocarditis
Malignanthypertension

AlsoseeManagementofAcuteComplicationsofAcuteRenalFailure.

Patienteducation

Educatingpatientsaboutthenephrotoxicpotentialofcommontherapeuticagentsisalwayshelpful.
Nonsteroidalantiinflammatorydrugs(NSAIDs)provideagoodexamplemostpatientsare
unawareoftheirnephrotoxicity,andtheiruniversalavailabilitymakesthemaconstantconcern.

Forpatienteducationinformation,seetheDiabetesCenter,aswellasAcuteKidneyFailure.

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