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Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury.doc

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Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Kashanietal.CriticalCare2013,17:R25 /content/17/1/R25 RESEARCH OpenAccess Discoveryandvalidationofcellcyclearrest biomarkersinhumanacutekidneyinjury KianoushKashani1,AliAl-Khafaji2,ThomasArdiles3,AntonioArtigas4,SeanMBagshaw5,MaxBell6,AzraBihorac7, RobertBirkhahn8,CynthiaMCely9,LakhmirSChawla10,DanielleLDavison10,ThorstenFeldkamp11,LuiGForni12, MichelleNgGong13,KyleJGunnerson14,MichaelHaase15,JamesHackett16,PatrickMHonore17,EricAJHoste18, OlivierJoannes-Boyau19,MichaelJoannidis20,PatrickKim21,JayLKoyner22,DanielTLaskowitz23,MatthewELissauer24, GernotMarx25,PeterAMcCullough26,ScottMullaney27,MarliesOstermann28,ThomasRimmelé29,NathanIShapiro30, AndrewDShaw31,JingShi32,AmyMSprague33,Jean-LouisVincent34,ChristopheVinsonneau35,LudwigWagner36, MichaelGWalker32,RGentryWilkerson37,KaiZacharowski38andJohnAKellum39* SeerelatedcommentarybyRoncoetal.,/content/17/1/117 Abstract Introduction:Acutekidneyinjury(AKI)canevolvequicklyandclinicalmeasuresoffunctionoftenfailtodetectAKI atatimewheninterventionsarelikelytoprovidebenefit.Identifyingearlymarkersofkidneydamagehasbeen difficultduetothecomplexnatureofhumanAKI,inwhichmultipleetiologiesexist.Theobjectiveofthisstudy wastoidentifyandvalidatenovelbiomarkersofAKI. Methods:WeperformedtwomulticenterobservationalstudiesincriticallyillpatientsatriskforAKI-discoveryand validation.Thetoptwomarkersfromdiscoverywerevalidatedinasecondstudy(Sapphire)andcomparedtoa numberofpreviouslydescribedbiomarkers.Inthediscoveryphase,weenrolled522adultsinthreedistinctcohorts includingpatientswithsepsis,shock,majorsurgery,andtraumaandexaminedover300markers.IntheSapphire validationstudy,weenrolled744adultsubjectswithcriticalillnessandwithoutevidenceofAKIatenrollment;the finalanalysiscohortwasaheterogeneoussampleof728criticallyillpatients.Theprimaryendpointwasmoderate tosevereAKI(KDIGOstage2to3)within12hoursofsamplecollection. Results:ModeratetosevereAKIoccurredin14%ofSapphiresubjects.Thetwotopbiomarkersfromdiscovery werevalidated.Urineinsulin-likegrowthfac