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1、UnderstandingandManagingMethotrexateNephrotoxicity：BrigitteC.ethotrexate,toxicityaPediatricOncologyBranch,NationalCancerInstitute,Bethesda,Maryland,USA;bDivisionofClinicalPharmacologyTherapeutics,Children’sHospitalofPhiladelphia,Philadelphia,Pennsylvania,USAKeyethotrexatetoxicity;Renaldysfunction;
2、Carboxypeptidase-G2;Hemodialysis;Hemoperfusion;Thymidine;High-dosechemotherapy;RescueagentsABSTRACTMethotrexate(MTX)isoneofthemostinistrationofhigh-dosemethotrexate(HDMTX)folloportantponentinthetreatmentofavarietyofchildhoodandadultcancers.HDMTXcanbesafelyadministeredtopatientsalrenalfunctionbythe
3、useofalkalinization,hydration,andpharmacokiicallyguidedLVrescue.Despitethesemeasures,HDMTX-inducedrenaldysfunctioncontinuestooccurinapproximately1.8%ofpatientsptrecognitionandtreatmentofMTX-inducedrenaldysfunctionareessentialtopreventpotentiallylife-threateningMTX-associatedtoxicities,especiallymy
4、elosuppression,mucositis,anddermatitis.Inadditiontoconventionaltreatmentapproaches,dialysis-basedmethodshavebeenusedtoremoveMTXitedeffectiveness.Morerecentlycarboxypeptidase-G2(CPDG2),arebinantbacterialenzymethatrapidlyhydrolyzesMTXtoinactivemetabolites,hasbeeavailableforthetreatmentofHDMTX-induce
5、drenaldysfunction.CPDG2administrationhasbeenaMTXconcentrationsbyamedianof98.7%(range,84%99.5%).TheearlyadministrationofCPDG2inadditiontoLVmaybebeneficialforpatientsaMTXconcentrations.INTRODUCTIONMethotrexate(MTX),aclassicalantifolate,isoneofthemostinisteredovera20mg/m2peraintenancechemotherapyfora
6、cutelymphoblasticleukemiaandtreatmentofnononcologicdiseasesincludingrheumatoidarthritisorpsoriasis[46],andg/m2[7].Thelatter,termedhigh-dosemethotrexate(HDMTX)isusuallyadministeredasaprolongedi.v.infusionandisanimportantponentinthetreatmentregimensforavarietyofcancers,includingacutelymphoblasticleu
7、kemia,lymphoma,osteosara,breastcancer,andheadandneckcancer[3,811].HDMTXcanbesafelyadministeredtopatientsalrenalfunctionbyvigorouslyhydratingandalkalinizingthepatienttoenhancethesolubilityofMTXinurineandthroughthe
