Sirolimus Induced Phosphaturia is Not Caused by Inhibition of Renal Apical Sodium Phosphate Cotransporters 英文参考文献.docVIP

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Sirolimus Induced Phosphaturia is Not Caused by Inhibition of Renal Apical Sodium Phosphate Cotransporters 英文参考文献.doc

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Sirolimus Induced Phosphaturia is Not Caused by Inhibition of Renal Apical Sodium Phosphate Cotransporters 英文参考文献

SirolimusInducedPhosphaturiaisNotCausedby InhibitionofRenalApicalSodiumPhosphate Cotransporters MariaHaller1,2,3,StefanAmatschek1,JuliaWilflingseder1,AlexanderKainz1,BerndBielesz1,IvanaPavik2, AndreasSerra2,NilufarMohebbi2,Ju¨rgBiber2,CarstenA.Wagner2,RainerOberbauer1,3,4* 1DepartmentofNephrology,MedicalUniversityofVienna,Vienna,Austria,2InstituteofPhysiology,ZurichCenterforIntegrativeHumanPhysiology(ZIHP),Universityof Zurich,Zurich,Switzerland,3DepartmentofNephrologyandTransplantation,KHElisabethinenLinz,Linz,Austria,4AustrianDialysisandTransplantRegistry,Linz,Austria Abstract The vast majority of glomerular filtrated phosphateis reabsorbed in theproximal tubule.Posttransplant phosphaturia is commonandaggravatedbysirolimusimmunosuppression.Thecauseofsirolimusinducedphosphaturiahoweverremains elusive.MaleWistarratsreceivedsirolimusorvehiclefor2or7days(1.5mg/kg).Theurinephosphate/creatinineratiowas higherandserumphosphatewaslowerinsirolimustreatedrats,fractionalexcretionofphosphatewaselevatedandrenal tubularphosphatereabsorptionwasreducedsuggestingarenalcauseforhypophosphatemia.PTHwaslowerinsirolimus treatedrats.FGF23levelswereunchangedatday2butlowerinsirolimustreatedratsafter7days.Brushbordermembrane vesiclephosphateuptakewasnotalteredinsirolimustreatedgroupsorbydirectincubationwithsirolimus.mRNA,protein abundance,andsubcellulartransporterdistributionofNaPi-IIa,Pit-2andNHE3werenotdifferentbetweengroupsbutNaPi- IIcmRNAexpressionwasloweratday7.Transcriptomeanalysesrevealedcandidategenesthatcouldbeinvolvedinthe phosphaturicresponse.Sirolimuscausedaselectiverenalphosphateleakage,whichwasnotmediatedbyNaPi-IIaorNaPi- IIcregulationorlocalization.Wehypothesizethatanothermechanismsuchasabasolateralphosphatetransportermaybe responsibleforthesirolimusinducedphosphaturia. Citation: Haller M, Amatschek S, Wilflingseder J, Kainz A, Bielesz B, et al. (2012) Sirolimus Induced Phosphaturia is Not Caused by Inhibition of Renal Apical SodiumPhosphateCotransporters.PLoSONE7(7):e39229