comparison of induction strategies in renal...
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Comparisonofinductionstrategiesinrenaltransplantation:Whogetswhat?
RandallHinojosa
PGY1PharmacyResidentSt.David’sNorthAustinMedicalCenter,Austin,TX
TheUniversityofTexasatAustinCollegeofPharmacy
January8,2016
LearningObjectives
• Understandtheimmunetargetsimportantintransplantimmunology• Identifycommonimmunosuppressionagentsusedinkidneytransplantation• Recognizeimportantdonorandrecipientfactorsforrejection• Evaluateavailableinductionagentsandtheirevidenceinkidneytransplant
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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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