Andersons pediatric cardiology 2096

Study(Subjects)

Period

Outcomes

Mammen10(n=126)

1year

Morgan8(n=127)

2years

Cooper46(n=51)

5–7years

Madsen47(n=382)

5–15years

Greenberg-TRIBE
Consortium48(n=131)

5years

Microalbuminuria/proteinuria(10%)
GFR60–90mL/min/1.73m2(38%)
GFR>150mL/min/1.73m2(9%)
Mortality(10%AKIvs.4.3%noAKI)

Increasedhospitalizations(stage3AKI)
DecreasedheightSDS(stage3AKI)
NodifferenceinstandardCKDassessments(AKIvs.no
AKI)
Increasedurinarydamagebiomarkerconcentrationsin
patientswithAKIvs.noAKI
IncreasedCKDprevalenceAKIvs.noAKI(5-yearHR3.8(95%
CI1.4–10.4)
Hypertension(10%)
Microalbuminuria(8%)
GFR<90mL/min/1.73m2(13%)
NodifferenceinCKDprevalenceinAKIvs.non-AKI

AKI,Acutekidneyinjury;CI,confidenceinterval;CKD,chronickidneydisease;GFR,glomerular
filtrationrate;HR,hazardratio;SDS,standarddeviationscore.

TranslationalResearchandFuture
Interventions:NovelAKIBiomarkers
Theclinicalexperiencedescribedabovedemonstratesthatcurrentkidney
functionassessmentbyserumcreatinineandurineoutputassociatestronglywith
pooroutcomes.Thus,anextensiveresearchefforthasbeenexpendedoverthe
past2decadestoidentifynovelkidneybiomarkersthatheraldstructuralkidney
damagepriortothefunctionalchangesobservedbycreatinineorurineoutput
(Table78.9).52Manyofthesebiomarkershavebeeninitiallyassessedinthe
pediatriccardiacsurgerypopulation;sincethetimingofAKIisknown,urinecan
beobtainedfrequentlyintheintraoperativeandpostoperativeperiod,andthis
populationdoesnothavemanycomorbidities.Adetailedreviewofthe
performanceofthesebiomarkersisbeyondthescopeofthischapter.Ingeneral,
theirconcentrationsarerelativelyincreasedinpatientswhodevelopAKI
anywherebetween2and12hoursafterbypassinitiation,or24to36hours

beforepatientsdevelopAKI,asmeasuredbyserumcreatinine(Fig.78.2).53–56
Theconceptofcombiningfunctionalandstructuralbiomarkersfortheprediction
ofAKIdevelopmentandduration,wheretheelevationofcreatininewithoutan
increaseinadamagemarkerpredictsashortdurationbutwheretheopposite
combinationpredictsalongAKIduration,hasbeenvalidatedinthepediatric
cardiacsurgerypopulation.57Finally,aprospectiverandomizedstudytoassess


theabilityofintraoperativefenoldopamtopreventAKIutilizedbothurinary
neutrophilgelatinase-associatedlipocalin(NGAL)andcystatinCasoutcome
variables.58Thisstudyshowedthatfenoldopampreventedincreasedinurinary
NGALandcystatinCaftercardiacsurgeryinchildren,highlightingthis
potentialuseofdamagemarkersinoutcomesstudies.59
Table78.9
CharacteristicsofNovelAcuteKidneyInjuryBiomarkersStudiedinPediatricCardiacSurgery
Patients
Biomarker
NGAL53,55,56

IL-1853

KIM-153,55

L-FABP53,55
TIMP-2*IGFBP-756

Characteristics
25-kDprotein
Upregulatedinthickascendinglimbandcollectingductafterischemicinjury
Ironbindingprotein

Bacteriostatic
22-kDprotein
Proinflammatorycytokine
Increasedafterischemia-reperfusioninjury
PromotesinflammatoryprocessesthatextendAKI
38.7-kDtransmembraneprotein
Upregulatedinproximaltubuleafterischemicinjury
Promotesphagocytosisofapoptoticbodiesandnecroticdebris
14-kDprotein
Expressioninrenalcortexincreaseinducedbyhypoxiaseverityandduration
InduceG1cellcyclearrestafterrenalinsulttopreventensuingcelldeath
Upregulatesp21andp53

AKI,Acutekidneyinjury;IGFBP-7,insulin-likegrowthfactorbindingprotein-7;IL-18,interleukin18;KIM-1,kidneyinjurymolecule-1;kD,kiloDalton;L-FABP,liver-typefattyacidbindingprotein;
NGAL,neutrophilgelatinase-associatedlipocalin;TIMP-2,tissueinhibitormetalloproteinase-2.


FIG.78.2 Temporalrelationshipofnovelacutekidneyinjurybiomarkersin
thepediatricpostcardiacsurgerypopulation.pNGAL,Plasmaneutrophil
gelatinase-associatedlipocalin;uIL-18,urinaryinterleukin-18;uKIM-1,
urinarykidneyinjurymolecule-1;uL-FABP,urinaryliver-typefattyacid
bindingprotein;uNGAL,urinaryneutrophilgelatinase-associatedlipocalin.
(FromAlgeJL,ArthurJM.BiomarkersofAKI:areviewofmechanistic
relevanceandpotentialtherapeuticimplications.ClinJAmSocNephrol.
2015;10[1]:147–155.)

HeartFailure(SeeAlsoChapter64)
Acutedecompensatedheartfailure(ADHF)isstronglyassociatedwithAKI,and
thissyndromehasbeenstudiedextensivelyintheadultheartfailure
population.60However,thereareonlylimiteddatainchildrenasADHFisa

relativelyrarepediatricdisease.61Oneretrospectivestudyofchildrenwith
ADHFrevealedthat48%(35of73)ofchildrenwithADHFhadAKI(≥0.3
mg/dLincreaseincreatinine)andthatAKIwasassociatedwithincreased
mortalityandtheneedformechanicalventricularassistance.62Arecentstudy
assessedthecardiorenalsyndromeinpatientsfromthePediatric
CardiomyopathyRegistrywithapresentingdiagnosisofdilatedcardiomyopathy
(DCM).63Thecardiorenalsyndromewasdefinedasanestimatedglomerular
filtrationrateoflessthan90mL/minper1.73m2andwaspresentin61%of
childrenatthetimeofDCMdiagnosis.Thepresenceofthecardiorenal