Comparison of induction strategies in renal...

Comparisonofinductionstrategiesinrenaltransplantation:Whogetswhat?

RandallHinojosa

PGY1PharmacyResidentSt.David’sNorthAustinMedicalCenter,Austin,TX

TheUniversityofTexasatAustinCollegeofPharmacy

January8,2016

LearningObjectives

• Understandtheimmunetargetsimportantintransplantimmunology• Identifycommonimmunosuppressionagentsusedinkidneytransplantation• Recognizeimportantdonorandrecipientfactorsforrejection• Evaluateavailableinductionagentsandtheirevidenceinkidneytransplant

Comparisonofinductionstrategiesinrenaltransplantation

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I. KidneydiseaseintheUnitedStates1,2A. Estimated13.6%ofadultshavesomelevelofchronickidneydisease

(CKD)makingitmorecommonthandiabetesmellitus(12.3%)B. EndStageRenalDisease(ESRD)asof2013

1. Incidencerateof363newcasespermillion/year2. Prevalencerateof2034casespermillion/year3. DeathsfromESRDroseto90,119patientsin20124. Medicareexpendituresupto$30.9billion(7.1%ofclaims)

C. MostcommoncausesofESRD1. Diabetes(nephropathy)2. Hypertension3. Glomerulonephritis4. Otherdiseasesofgeneticetiology

II. OptionsforpatientswithESRD3,4A. Dialysis

1. Roughly400,000patientstreatedwithdialysiseachyear2. Deathratefordialysispatientsnow20%peryear3. Hemodialysisexpenditures>$80,000/patientin2009

B. Kidneytransplantation1. OptimaltreatmentmodalityforESRD

a. Longersurvival&betterqualityoflifeformostvs.dialysisb. Five-yearsurvival:transplant(85.5%)vs.dialysis(35.8%)

2. Surgicalinterventiona. One-yearcostofdialysisnearlytriplethatoftransplantb. Re-hospitalizationratehigherinfirstyear,thenlowerin

longitudinallyconsumingfewerhealthcareresources

www.niddk.nih.gov/health-information/health-statistics/documents


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3. Allograftoptionsa. Deceaseddonation(DD)–fromanimmunologically

compatiblecadaverafterbrainorcardiacdeathi. Considerationforcauseofdeath,ischemiatime,

anddonorhealthii. One-yearpatient(95%)andgraftsurvival(92%)

inferiortolivingdonationiii. KidneyDonorProfileIndex(KDPI)isanumerical

measuretoexpressdonorkidneyquality5• KDPI70%hashigherexpectedriskofgraft

failurethan70%ofkidneysrecovered• Allowscliniciantoallocateakidneytoa

recipientofsimilarsurvivalexpectations• Improvementuponandreplacedlessinclusive

expandedcriteriadonation(ECD)6b. Livingdonation(LD)–fromanimmunologicallycompatible

friend,familymember,oraltruisticdonori. Highlycoordinatedeffort(minimalischemiatime)ii. One-yearpatient(98%)andgraftsurvival(97%)

4. Prospectiverecipientsonthenationaltransplantwaitinglistgreatlyoutnumberdonorsupply4,7a. Over100,000patientsawaitingakidney(January2016)b. Only17,104kidneytransplantsbetweenin2014

5. 1-yeargraftsurvivalkeyinoutcomesIII. Transplantimmunology8-13

A. TargetcellsfortransplantationareoflymphocytelineageB. LymphocytesmatureintoT-andB-cells

1. T-cellsresponsibleforcellularrejection2. B-cellsresponsibleforantibody-mediatedrejection

http://www.textbookosacteriology.net/cellsindefenses75.jpg


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C. Cell-vs.antibody-mediatedrejection1. Hyperacute:occurswithinminutestohours

a. Pre-formeddonorspecificantibodies(DSA)reactwithdonorantigentoactivatecomplement

b. Mostlypreventedbypre-transplanttissue/bloodmatching2. Acute:occurswithinweekstomonths

a. Acutecellularrejection(ACR)i. Infiltrationofgraftbylymphocytesandother

inflammatorycellsii. Preventionisprimarygoalofmaintenance

immunosuppressioniii. MildACRtreatedwithsteroids,whereasmore

severeACRrequiresantibodytreatmentb. Antibody-mediatedrejection(AMR)

i. Causedbyde-novoDSAleadingtocomplementactivationinthegraft

ii. DiffersfromACR,butoftenmixedrejection3. ChronicAMR:occursovermonthstoyears

a. Slow,indolentprocessleadingtograftfunctiondeclineb. Oftenduetosub-optimalimmunosuppressionadherence

D. Immunediscrimination1. Humanleukocyteantigen(HLA)isacellsurfacemarkerthat

distinguishesselffromnon-selfa. Class1(HLA-A,-B,and-C)

i. Expressedonallnucleatedcellsii. Presentsantigenicintracellularpeptidesto

cytotoxicCD8+Tc-cellsb. Class2(HLA-DR,-DP,and-DQ)

i. Expressedonantigenpresentingcells(APC)whicharemacrophages,dendriticcells,B-cells

ii. PresentsprocessedextracellularpeptidestohelperCD4+Th-cells

c. HLA-A,-B,and–DRmatchinghistoricallyimportantforrejectionriskinkidneytransplantation

2. Innateimmunesystema. Fast(minutestohours),non-specificonset,shortdurationb. Primitiveandindiscriminateimmuneresponsec. Verylittleamplification;nomemoryofforeigncontacts

3. Adaptive(acquired)immunesystema. Slow(daystoweeks),highlyspecificresponse,long

duration(monthstoyears)b. Highlyorchestratedactivationofimmuneresponsec. Amplificationandcell-talkallowsantigenmemory


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4. CD4+Th-cellproliferationorchestratestherejectionresponsea. Focusofmaintenanceimmunosuppressionb. 3signalpathwayactivatedbyantigenpresentation

i. Signal1• AntigenpresentedtoCD4+Th-cell• BindingproducesIL-2chemokine

ii. Signal2• APCbindsco-stimulatoryCD28receptor• CD4+Th-cellactivationthresholdlowered

iii. Signal3• IL-2bindsCD25receptor• StimulatesmTOR–>CD4+Th-cellproliferation

E. Pre-transplantHLAantibodies1. Panelreactiveantibody(PRA):expressedasapercentageand

reflectsrecipients’abilitytoproduceantibodytoHLAingeneralpopulation,betterknownas“sensitization”

2. Sensitizationincreaseswithpriorexposuretonon-selfHLA:a. Previoustransplant,nephrectomyb. Bloodtransfusionsc. Pregnancy

3. Crossmatch(XM):determinecompatibilitywithaspecificdonorpriortotransplanta. PositiveXMindicatespresenceofpreformedDSAand

transplantistypicallynotsuitableb. DifferentXMtestsavailabletoclarifyquestionable

mismatchesandpredictimmunologicconsequencesIV. Donorandrecipientriskfactorsforacuterejection14-16

A. NumberofHLAmismatchesB. YoungerrecipientageandolderdonorageC. African-AmericanethnicityD. PRA>0%E. PresenceofDSAF. ABObloodgroupincompatibilityG. Delayedgraftfunction(DGF)

1. Influencedbyorganqualityandcoldischemiatime2. Definedasrequiringdialysisduringfirstpost-opweek

H. Coldischemiatime(CIT)1. Timewhendonororganisoniceduringtransportation2. SignificantlygreaterriskofDGFwhengreaterthan24hours


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V. Immunosuppression(IS)2,17-20A. Goalistopreventrejectionandprolonggraftsurvivalwhileminimizing

opportunisticinfections,malignancies,andsideeffectsB. ComponentsofIStherapy

1. Maintenance–chronicISusedtominimizerejection2. Induction–potentISusedperioperatively3. Rescue–treatmentofrejection

C. EvolutionofIS1. FirstkidneytransplantfailedduetolackofIS2. Introductionoffirstcalcineurininhibitor,cyclosporine

dramaticallyincreasedgraftsurvival3. ACRratesnowapproximately10%inthe1styear

D. Maintenance–chronicISusedtominimizerejection

1. Typicallyconsistsof2-3classesofmedicationswithdifferentimmunetargetsusedtogethertominimizedosesofeachand,thus,reducesideeffects

2. Recentnationaldatasuggeststhatmosttransplantcentersusea3drugregimenoftacrolimus(96.5%),mycophenolatemofetil(93%),andprednisone(65.6%)asof2013

3. MaintenanceIStherapy:a. Calcineurininhibitors(CNIs)

i. Mechanism–inhibitsCD4+Th-cells’abilitytoproduceIL-2foractivationofTandBlymphocytes

ii. Tacrolimus(TAC)• ~0.1mg/kg/daydosedevery12hrs• Troughlevels:5–12ng/mLwithhighergoal

levelsearlyandtaperedlater• Sideeffects:nephrotoxicity,neurotoxicity,and

metabolicsideeffectsiii. Cyclosporine(CyA)–2ndlineagentdueto

increasedrejectionb. Cellcycleinhibitors(antiproliferatives)


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i. Mechanism–inhibitSphaseofT-andB-cellproliferation

ii. Mycophenolicacid• 1000mgBID(mycophenolatemofetil,MMF)• Sideeffects:GIsideeffectsandbonemarrow

suppression(pancytopenias)iii. Azathioprine–2ndlineagentduetoincreased

rejectionandhematologicalsideeffectsc. Corticosteroids(CS)

i. Mechanism–interferewithimportantsignalsfortherecruitmentofimmunecellstotherejectionprocess

ii. Prednisone–onlymaintenanceoralsteroid• HighdosesofIVmethylprednisolonedoses

usedperioperatively,taperedoffortomaintenanceprednisonedose

• Limitedbymetaboliceffects,mainlyhyperglycemiaandhypertension

d. Opportunisticinfections(OI)commonandrequireprophylaxis(ppx)inkidneytransplantrecipients:

• UTI,PCP,Nocardiaspp.:SMZ/TMP• CMV:valganciclovir+/-adjuncts• BKvirus:ISreduction+/-adjuncts• Candidaspp.:nystatin,azoleantifungals

E. Induction–potentantibodiesusedintra-andperi-operativelytodepleteormodulatetoT-cellresponseatthetimeofantigenpresentation

1. Providesbackgroundprotectionwhilemaintenanceimmunosuppressionistitratedtotherapeuticlevels

2. Classificationofinductionagentsa. Antibodytarget

i. Monoclonal:basiliximab,alemtuzumabii. Polyclonal:antithymocyteglobulin

b. Depletionactivityi. Lymphocytedepleting:antithymocyteglobulin,

alemtuzumabii. Non-lymphocytedepleting:basiliximab


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VI. IL-2receptorantagonist(IL-2RA)17,21,24A. Mechanism

1. Monoclonal,non-lymphocytedepletingagent2. IL-2receptorantagonist(IL2-RA)foundonactivatedT-andB-

cellstostimulatelymphocyteproliferationB. Agent

1. Basiliximab(Simulect®)2. Daclizumab(Zenapax®):withdrawnfrommarketin2009

C. Dosing–basiliximab20mgIVintraoperativelyandpost-opday(POD)4D. Sideeffects–welltoleratedE. Cost–$6489.14forinduction(2doses)

VII. Antithymocyteglobulin17,22,24A. Mechanism

1. Polyclonal,lymphocytedepletingagent2. TargetHLAandmanyimmunecellreceptorstocausecellular

inactivation,lysis,anddepletionB. Agents

1. rATG(Thymoglobulin®)–rabbit2. ATG(ATGAM

®)–horse;notusedduetoincreasedrejection

C. Dose1. ~6mg/kgdividedintodoses(1stdoseintraoperatively)2. RequirespremedicationwithAPAP,diphenhydramine,steroids

D. Sideeffects–thrombocytopenia,leukopenia,infusionreactionsE. Cost–$12,757.60fora70-kgrecipient(6mg/kg)

VIII. Alemtuzumab,ALEM(Campath-1H®)17,23,24A. Mechanism

1. Monoclonalantibody,lymphocytedepletingagent2. TargetsCD52receptoranddirectsdestructionofT-andB-cells

B. Dose1. 30mgIVintra-operativelyx1dose2. RequirespremedicationwithAPAP,diphenhydramine,steroids

C. Sideeffects–cytopenias,infusionreactionsD. Cost–currentlynochargethroughCampath®DistributionProgramfrom

manufacturerfortheindicationoftransplantinduction


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Whatistheoptimalinductionagentinkidneytransplantrecipients?Ormoreappropriately...Whogetswhat!?

IX. Earlystudiescomparinginductionstrategies

A. Basiliximabvs.placebo(Lawen2003)251. Randomized,doubleblind,multicenterstudy2. Low-moderateriskreceivingDDorHLAnon-identicalkidneys3. Induction:basiliximab20mgx2(n=59)vs.placebo(n=54)4. IS:CyA,MMF,prednisone5. OIppx:SMZ/TMP;ganciclovir,acyclovir,orbothifhighCMVrisk6. Resultsat6months

a. Firstbiopsy-provenrejection(BPAR):basiliximab(15.3%)vs.placebo(26.6%),p=NS

b. Acuterejection(AR)treatedwithantibody:basiliximab(5.1%)vs.placebo(15.6%)

c. Basiliximabsignificantlyimprovedrenalfunctioninthefirsttwoweeksaftertransplant

d. Nodifferencebetweengraft(GS)andpatient(PS)survivalat12months

e. Adverseeventprofilesweresimilar7. Conclusion:basiliximabinductionshowsstrongtrendtoward

reductioninARinkidneytransplantrecipientsontripleIS;greatlydecreasedARratescomparedtobasiliximabtrialswithrecipientsmaintainedonCyAandprednisonealone

B. Basiliximabvs.rATG(Brennan2006,2008)26,271. Prospective,randomized,internationalstudy2. High-riskforARorDGFreceivingDDkidney3. Induction:basiliximab20mgx2(n=137)vs.rATG1.5

mg/kg/dayx5(n=141)4. IS:CyA,MMF,prednisone5. OIppx:IV/POganciclovirx3monthsifmoderate-highriskfor

CMV,andanti-fungal&anti-bacterialpercenterprotocol6. Resultsat12months

a. BPAR:basiliximab(25.5%)vs.rATG(15.6%),p=0.02b. ARtreatedwithantibody:basiliximab(8.0%)vs.rATG

(1.4%),p=0.005c. Greaterincidenceofinfection(85.8%vs.75.2%,p=0.03),

butlessCMVdisease(7.8%vs.17.5%,p=0.02)withrATGd. Moreleukopenia(33.3%vs.14.6%,p<0.001),andhigher

trendofcancer(3.5%vs.0.7%,p=NS)withrATGe. DGF,slowedgraftfunction,GS,andPSweresimilar


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7. Resultsat5yearsa. LessBPAR(15%vs.27%,p=0.03)andARtreatedwith

antibody(3%vs.12%,p=0.05)withrATGb. rATGgrouphadfewercasesoftreatedCMV(7%vs.17%,

p=0.04)c. Nodifferenceincancer,graftorpatientsurvival

8. Conclusion:whilerATGdidnotreduceDGFinhighriskrecipientscomparedtobasiliximab,rATGdidreducetheincidenceandseverityofARwithlastingresults

C. Basiliximabvs.alemtuzumab(Kaufman2005)281. Single-center,non-randomized,retrospective,sequentialstudy2. VariedriskrecipientsreceivingDDorLDkidneywhere37%of

basiliximabvs.25%ofalemtuzumabreceivedDDkidneys3. Induction:basiliximab20mgx1(n=155)vs.alemtuzumab30

mgx1(n=123)4. IS:TAC,MMF+3-daycourseofCS(nomaintenanceCS)

a. 2.5-3gMMF/dayinbasiliximabgroupb. 1.5-2gMMF/dayinalemtuzumabgroup

5. OIppx:SMZ/TMP,nystatin/clotrimazole,and(val)ganciclovirx3monthsifmoderate-highriskCMV

6. Resultsatminimumof30monthsa. FewerepisodesofARwithalemtuzumabinthefirst3

months(4.1%vs.11.6%),butequivalentat12months(14.9%vs.13.5%,p=NS)

b. MediandaytoARgreaterwithalemtuzumab(153vs.10)c. Recipientsinthealemtuzumabreceivedsignificantlyless

TACandMMFexposureatallpointsd. Infectionandcancerratesweresimilare. Nodifferenceingraftandpatientsurvivalat1and3years

7. Conclusion:currentrecommendeddoseofalemtuzumabinductionshowssimilarefficacyasbasiliximabinaprednisone-freemaintenanceprotocol,althoughwithincreasedratesofdelayedARepisodes

X. KDIGOClinicalPracticeGuidelinefortheCareofKidneyTransplantRecipients.AmJTransplant.2009.Chapter1:InductionTherapy.14

A. Startingacombinationofimmunosuppressivemedicationsbefore,oratthetimeof,kidneytransplantation(1A)

B. Includinginductiontherapywithabiologicagentaspartoftheinitialimmunosuppressiveregimeninrecipients(1A)

1. IL2-RAbethefirst-lineinduction(1B)2. Lymphocyte-depletingagent,ratherthananIL2-RA,forhigh-

immunologicriskrecipients(2B)C. Basemostrecommendationsondatafromsystematicreviewsandmeta-

analysesintheoldermaintenanceimmunosuppressionera


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XI. StudiesinthemoderneraofimmunosuppressionA. Alemtuzumabvs.basiliximabandrATG(Hanaway2011)29

1. Prospective,randomized,multicenter,risk-stratifiedstudy2. High-risk(repeattransplant,PRA>20%,orblackrace)andlow-

riskreceivingDDorLD(~60%)kidney;noECDorDCDkidneys3. Induction:

a. Alemtuzumab30mgx1(n=164lowrisk,n=70highrisk),b. Basiliximab20mgx2(n=171lowrisk)c. rATG1.5mg/kgx4(n=69highrisk)

4. IS:TAC,MMF+5daycourseofCS(nomaintenanceCS)5. OIppx:percenterprotocol6. Resultsat36months

a. Lowriski. BPARlesswithalemtuzumabat36months(10%vs.

22%,p=0.003)• Similarratesofsevererejectionandrejection

requiringantibody• Laterejection>12monthstrendedhigherwith

alemtuzumab(8%vs.3%,p=NS)ii. Seriousinfectionshigherwithalemtuzumab(35%

vs.22%,p=0.02)andmeanlymphocytecountwasloweratalltimepoints

iii. Graftandpatientsurvivalsimilarb. Highrisk

i. SimilarBPARat36monthsbetweenalemtuzumab(18%)andrATG(15%)• Similarratesofsevererejectionandrejection

requiringantibody• Laterejection>12monthstrendedhigherwith

alemtuzumab(10%vs.2%,p=NS)ii. Seriousinfectionsandmeanlymphocytecount

weresimilariii. Graftandpatientsurvivalsimilar

c. Post-hocanalysesofbiopsies:complement(C4d)staining,amarkerforAMR,positivein4%inthealemtuzumabvs.1%inthecombinedbasiliximabandrATGgroups

7. Conclusion:alemtuzumabinitiallyhaslessrejectionthanbasiliximabinlowriskrecipientsandequivalentrejectiontorATG,althoughlate-onsetrejectionmaybeconcerning


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B. MultivariatedatabaseanalysisofDDrecipients(Sureshkumar2012)301. Comparators:rATG(n=5348),alemtuzumab(n=2428),andIL-

2RA(n=1396)a. RecipientsweredischargedonaCNI(primarilyTAC)and

MMF,butwerenotmaintainedonCS;receivedDDkidneyb. Substantialdemographicdifferencesbetweengroups,

adjustedanalysisbasedoncovariatesknowntoadverselyimpactgraftoutcome

2. Resultsa. Lowrisk

i. SimilaradjustedGSforalemtuzumabandIL-2RAvs.rATG

ii. AlemtuzumabhadsimilaradjustedPS,butIL-2RAhadwaslower(HR1.16,1.02-1.31)vs.rATG

iii. Alemtuzumabhadincreasedadjustedgraftfailurevs.rATGwhenPRA>20%,ECD,andCIT>24hours

b. Highriski. Loweradjustedgraftsurvivalforalemtuzumab(HR

1.18,1.06-1.31)andIL-2RA(HR1.06,1.002-1.12)ii. AlemtuzumabhadsimilaradjustedPS,butIL-2RA

hadwaslower(HR1.08,1.004-1.17)vs.rATGiii. AlemtuzumabhadinferioradjustedPSvs.rATG

whenECDorCIT>24hours3. Conclusion:rATGseemstobeassociatedwithsuperior

outcomesamongDDkidneyrecipientsmaintainedonCNI/MMFC. rATGvs.alemtuzumabvs.IL-2RA,daclizumab(Ciancio2014)31

1. Prospective,randomized,singlecenterstudy2. Moderate-highriskrecipientsreceivingDDorLDkidney;

majorityAfrican-AmericanandHispanic3. Induction:rATG1mg/kgx7(n=43),alemtuzumab0.3mg/kgx2

(n=43),daclizumab1mg/kgx5(n=42)4. IS:

a. TAC,MMF,+/-CSb. Alemtuzumabgroup:lowerTACtarget,MMF500mgBID,

and7daycourseofCS(nomaintenanceCS)5. OIppx:notdescribed6. Results(medianfollowupto95months)

a. BPARsimilaramongthe3groups(19%vs.33%vs.29%)b. Biopsyprovenchronicallograftinjury(CAI)higherwith

alemtuzumab(44%)vs.rATG(21%)+daclizumab(17%),p=0.0008**HighergradeofCAI

c. Death-censoredgraftfailurehigherwithalemtuzumab(30%)vs.rATG(12%)+daclizumab(12%),p=0.009**ConsistentbetweenDD/LDandcompliance


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d. Morerecipientsinthealemtuzumab(33%)hadMMFwithheldordiscontinuedMMFat1monthvs.rATG(7%)+daclizumab(2%),p=0.00002**WBCsignificantlylowerinalemtuzumabgroup

e. 40%ofalemtuzumabrecipientsrequiredCSreinstitutionf. Similarrateofinfection,newonsetdiabetes,andPS

7. Conclusion:longtermresultsindicateinferiorresultswithalemtuzumabinductionwithregardtoCAIandgraftfailureinrecipientsmaintainedonreduceddoseTACandMMF

D. Alemtuzumabvs.rATG(Saull2015)321. Retrospective,singlecenterstudy2. Recipients:lowrisk(firsttransplant,PRA<20%);receivedDDor

LDkidneya. MoreECDinalemtuzumabgroup(likelyduetoexclusion

ofpatientswhoreceivedextendedrATGduetoDGF)b. Protocolbiopsyat1,4,and12months

3. Induction:alemtuzumab30mgx1(n=100)vs.rATG1.5mg/kgx4(n=100)

4. IS:TAC,MMF+5daycourseofCS(nomaintenanceCS)5. OIppx:SMZ/TMP,nystatin/clotrimazole,andvalganciclovirx3

monthsifmoderateandx6monthsinhighriskCMV6. Resultsat12months

a. BPARsimilarbetweenalemtuzumab(34%)vs.rATG(23%)b. MoreseveregradesofBPARwithalemtuzumab(p=0.047)

i. Independentlyassociated(OR3.7,1.2-10.5)regardlessofECDandDGF

ii. AlemtuzumabonlysignificantpredictorforBPARc. MediandaytoARgreaterwithalemtuzumab(182vs.30)d. Recurrentrejectionmorecommonwithalemtuzumab

(41%vs.17%,p=0.05)e. MorerecipientsinthealemtuzumabgroupwithanMMF

dose<1500mg/dayatfirstAR(84%vs.16%)duetohigherratesofBKvirus,CMVdisease,andleukopenia

f. SimilarratesofAMR:alemtuzumab(2%)andrATG(0%)g. Graftlossat3years:alemtuzumab(10)vs.rATG(5)

7. Conclusion:althoughratesofARwerecomparable,moresevereanddelayedrejectionswereobservedwithalemtuzumab,potentiallyduetohighratesofviralinfectionandleukopenia,withsubsequentreductioninmaintenanceIS


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XII. Costcomparisonofinductionandrejection24

rATG Alemtuzumab BasiliximabInductionCost $12,757.60(upto22,325.80) Free $6,489.14CostofRejection

IncrementalmarginalcostsperyearposttransplantinstandardcriteriadonorrecipientsWithantibodytherapy Withnon-antibodytherapy

1-year2-years3-years

$22,407$18,603$13,909

$14,122$7,852$8,234

CostofrATGforrejection

$22,325.80to$44,651.60PluscostofIVmethylprednisolone

CostofIVmethylprednisolone

Costofother +/-CostofotherantibodyrescueagentsTotals $$$$ $$$$ $$$ $$$ $$$ $$XIII. Conclusion

A. ALEMnotrecommendedforinclusionintokidneytransplantinductionprotocol

1. Maybearoleincertainpatients,althoughcurrentlynotclear2. PotentialforfuturestudiestooptimizemaintenanceIStobe

usedwithalemtuzumabB. Inductionagentselectedbasedonriskstratification

1. High-risk:rATG2. Low-risk:basiliximab

Low-risk-LowPRA(<20%)

-Infecwonormalignancyconcern

High-risk-HighPRA(>20%)-Re-transplant-Blackrace

-Othersatdiscrewon(prolongedCIT,highriskforDGF,sub-opwmalorgan

quality)

BasiliximabrATG


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