kdigo controversies conference on onco-nephrology · 2020. 8. 13. · multidisciplinary clinical...

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KDIGOControversiesConferenceonOnco-Nephrology

December13-16,2018Milan,Italy

KidneyDisease:ImprovingGlobalOutcomes(KDIGO)isaninternationalorganizationwhosemissionistoimprovethecareandoutcomesofkidneydiseasepatientsworldwidebypromotingcoordination,collaboration,andintegrationofinitiativestodevelopandimplementclinicalpracticeguidelines.Periodically,KDIGOhostsconferencesontopicsofimportancetopatientswithkidneydisease.Theseconferencesaredesignedtoreviewthestateoftheartonafocusedsubjectandtoaskconferenceparticipantstodeterminewhatneedstobedoneinthisareatoimprovepatientcareandoutcomes.SometimestherecommendationsfromtheseconferencesleadtoKDIGOguidelineeffortsandothertimestheyhighlightareasforwhichadditionalresearchisneededtoproduceevidencethatmightleadtoguidelinesinthefuture.Background

Inthe21stcentury,patientswithmalignancymakeupagrowingnumberofthesubjectsseenfornephrologyconsultand/orcriticalcarenephrologyservices.Theoutstandingprogressinthetherapyofmalignancypresentsnewpossibilitiesandchallengesforbothnephrologistsandmedicaloncologists.Itisimportantfornephrologyservicestobeacknowledgedandtotakeanactiveparticipationinthecareofoncologypatients.Inaddition,nephrologyservicesneedtobetterunderstandthebiologyofadvancedmalignanciesandtheirtreatmentinordertobecomeavaluablepartoftheteamsworkingtoyieldthebestpossibleoutcomeforcancerpatients.

Thelinksbetweenkidneydiseaseandmalignancywereobservedquitesometimeago.However,itwasonlyrecentlythattheirimportancewasrecognizedandanewsubspecialtyinnephrology,namely‘onco-nephrology’wasestablished[1].Chronickidneydisease(CKD)isoftendiagnosedinthegeneralpopulation[2],however,itsincidenceandprevalenceamongpatientswithdifferentmalignanciesisnotextensivelystudiedanddataarelimited.Halfacenturyago,increasedincidenceofcancerinCKD

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patientswasdiscussedbySutherlandetal.[3]andotherreportsalsolinkedCKDwithanincreasedincidenceofcancer[4-10].

Aplethoraofrenalproblemsmaybefoundinpatientswithmalignancy.Theymayinfluencenotonlytheirshort-termoutcomesbutalsotheadequatetreatmentoftheunderlyingoncologicaldisease.Thus,allkidney-relatedissuesposeanimportantchallengeforbothoncologyandnephrologyspecialities.Indeed,theincidenceratesformanymalignanciesareincreasedandtheameliorationincancermortality,duetomoreeffectivechemotherapyincludingtargeteddrugsandtreatmentwithstemcells,hasresultedinariseinthecancersurvivors’population[12].Someofthesesurvivorsdevelopacutekidneyinjury(AKI)orCKDduetoeitherthecanceritselfand/oritstherapy[13].Thekidneysmaythusbedirectlyorindirectlydamagedbythemalignancyorbyoneormoreofthenoveltherapeuticsthatprolonglives,howeveratthecostofdevelopingAKIorCKD.Inaddition,multiorganfailuremaybealsoseenincancerpatients.Asaconsequence,theymayrequireintensivecareunit(ICU)careandkidneyreplacementtherapy(KRT).Inthesettingofadvancedmalignancycomplicatedbymultiorganillness,theappropriatenessofaggressivetreatmentin‘‘futilesituations’’andtheroleofpalliativetherapyremainsanopenquestion.Thus,thecareforoncologypatientshasbecomemorespecializedandcomplicated,requiringcollaborationamongnephrology,medicaloncology,criticalcare,andpalliativecare.Thequestionofpersistenttherapy(e.g.,continuationofKRTinadvancedmalignancy)vs.end-of-lifecareisalsoonethatmorecliniciansarefacingtoday.

Relevanceofthetopicandtheconference

Theprevalenceofbothcancerandkidneydiseaseishighandassuchitrequiresawarenessfrombothoncologistsandnephrologistsconcerningnewcancertreatmentsandtheirpotentialadverseeffectsonkidneyfunction.Therefore,thenecessityofsuchmultidisciplinaryexpertscallsfortheneedofanewsubspecialtyfieldofonconephrology.

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IncreasedincidenceofCKD,inparticularintheelderly,isofutmostconcern.Manyantineoplasticagentsareclearedprimarilybythekidneysasunchangeddrugsoractivemetabolites.Therefore,adeclineinkidneyfunctioncanpotentiallyleadtoalterationsinpharmacokinetics,resultinginelevatedbloodlevelsofthedrugsandincreasedtoxicity.IthasbeenshownthataremarkablenumberofCKDsubjectstreatedwithchemotherapyrequiredosereductionincaseofCKD,buttheyarenotadministeredtheappropriateadjusteddose[14].Thus,itshouldbestressedthatCKDisanunder-recognizedproblemintheoncologypopulationandestimatedglomerularfiltrationrateistobeassessedsimultaneously,notonlyinoncologywardsbutalsoineverydepartment.Thisisduetothefactthatpatientsaregettingolder,exhibitmorecomorbidities,areadministeredwithmorepotentiallynephrotoxicdrugsandundergomorepotentiallynephrotoxicproceduressuchaspercutaneouscoronaryinterventionsorCTwithintravenouscontrastagentsetc.[15]Itisofparamountimportancetobeawareofthekidneyfunctioninpatientsreceivingpotentiallynephrotoxicagentsandtomonitortheirkidneyfunctionregularlybeforeeachcourseofchemotherapy.Oncologistsshouldadjustthedoseofcytotoxicdrugsaccordingtoactualkidneyfunction.EspeciallyinCKDpatientswithimpairedkidneyfunctiontreatedwithnephrotoxicchemotherapeuticagents,concomitantdrugsshouldbecarefullyevaluated(e.g.,NSAIDS).Theyshouldbeavoided,ifpossible,astheymaycontributetothenephrotoxicityofchemotherapeutics.

ConferenceOverview

Tothisend,thisKDIGOconferenceononco-nephrologywillgatheraglobalpanelofmultidisciplinaryclinicalandscientificexpertise(e.g.,nephrology,oncology,intensivecare,hematology,pharmacology,etc.)thatwillidentifykeymanagementissuesinnephrologyrelevanttopatientswithmalignancy.Itisunderstoodthatthedevelopmentofnewerandmoreeffectivecancertreatmentshasledtoanincreasingnumberofcancersurvivorsbutunfortunatelymanyofthesetreatmentscanalsobenephrotoxic.Therefore,prevention,earlydetection,long-termmonitoringandtreatmentofensuingproblemsinthesepatientsisagrowingneedinthispopulation.

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TheobjectiveofthisconferenceistohighlighttheneedtopreventorslowkidneydamageduetovarioustreatmenttherapiesandtoassessourcurrentstateofknowledgerelatedtoAKIandCKDarisingfromvariousmalignancies(e.g.,hematologicalcancerssuchasmultiplemyelomaandsolid-organcancers)includingthemanagementofcancerafterkidneytransplantation.Careforoncologypatientshasbecomemorespecializedandcomplicated,requiringcollaborationamongnephrologists,oncologists,intensivists,andpalliativecarespecialists.Theremarkableadvancesincancermanagementpresentnewopportunitiesandcomplexchallengesfortheoncologyandnephrologycommunities.Itisessentialfornephrologiststobeinformedandactivelyinvolvedincertainfacetsofcancercare;abetterunderstandingoftherapidlyevolvingfieldofcancerbiologyanditstherapyisrequiredfornephrologiststobecomevaluablemembersofthecancercareteamandtoprovidethebestnephrologycarepossible.Drs.JolantaMałyszko(WarsawMedicalUniversity,WarsawPoland)andCamilloPorta(IRCCSSanMatteoUniversityHospitalFoundation,Pavia,Italy)willco-chairthisconference.Theformatoftheconferencewillinvolvetopicalplenarysessionpresentationsfollowedbyfocuseddiscussiongroupsthatwillreportbacktothefullgroupforconsensusbuilding.InvitedparticipantsandspeakerswillincludeworldwideleadingexpertswhowilladdresskeyclinicalissuesasoutlinedintheAppendix:ScopeofCoverage.TheconferenceoutputwillincludepublicationofapositionstatementthatwillhelpguideKDIGOandothersontherapeuticmanagementandfutureresearchinthisarea.

References

1. SalahudeenAK,BonventreJV.Onconephrology:thelatestfrontierinthewaragainstkidneydisease.JAmSocNephrol.2013;24:26-30.

2. JonesCA,McQuillanGM,KusekJW,EberhardtMS,HermanWH,CoreshJ,SaliveM,JonesCP,AgodoaLY.SerumcreatininelevelsintheUSpopulation:thirdNationalHealthandNutritionExaminationSurvey.AmJKidneyDis.1998;32:992-9.

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3. SutherlandGA,GlassJ,GabrielR.Increasedincidenceofmalignancyinchronicrenalfailure.Nephron.1977;18:182-4.

4. DenkerB,Robles-OsorioML,SabathE.Recentadvancesindiagnosisandtreatmentofacutekidneyinjuryinpatientswithcancer.EurJInternMed.2011;22:348-54.

5. LameireN,VanBiesenW,VanholderR.Electrolytedisturbancesandacutekidneyinjuryinpatientswithcancer.SeminNephrol.2010;30:534-47.

6. SalahudeenAK,DoshiSM,PawarT,NowshadG,LahotiA,ShahP.Incidencerate,clinicalcorrelates,andoutcomesofAKIinpatientsadmittedtoacomprehensivecancercenter.ClinJAmSocNephrol.2013;8:347-54.

7. SamuelsJ,NgCS,NatesJ,PriceK,FinkelK,SalahudeenA,ShawA.SmallincreasesinserumcreatinineareassociatedwithprolongedICUstayandincreasedhospitalmortalityincriticallyillpatientswithcancer.SupportCareCancer.2011;19:1527-32.

8. Janssen-HeijnenML,MaasHA,HoutermanS,LemmensVE,RuttenHJ,CoeberghJW.Comorbidityinoldersurgicalcancerpatients:influenceonpatientcareandoutcome.EurJCancer.2007;43:2179-93.

9. HunterC,JohnsonK,MussH,SatarianoW.Comorbiditiesandcancer.In:HunterC,JohnsonK,MussH,editors.CancerintheElderly.NewYork:Dekker,M;2000.p.477-500.

10. YungKC,PiccirilloJF.Theincidenceandimpactofcomorbiditydiagnosedaftertheonsetofheadandneckcancer.ArchOtolaryngolHeadNeckSurg.2008;134:1045-9.

11. CengizK.Increasedincidenceofneoplasiainchronicrenalfailure(20-yearexperience).IntUrolNephrol.2002;33:121-6.

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12. NationalCancerInstitute.SurveillanceEpidemiologyandEndResults:SEERstatfactsheets:Allsites.Availableat:http://seer.cancer.gov/statfacts/html/all.html.AccessedJanuary16,2017.

13. NationalCancerInstitute:Findcancerstatistics.Availableat:www.cancer.gov/statistics/find.AccessedMay16,2018.

14. JanusN,Launay-VacherV,ByloosE,MachielsJP,DuckL,KergerJ,WynendaeleW,CanonJL,LybaertW,NortierJ,DerayG,WildiersH.CancerandrenalinsufficiencyresultsoftheBIRMAstudy.BrJCancer.2010;103:1815-21.

15. AbujudehHH,GeeMS,KaewlaiR.Inemergencysituations,shouldserumcreatininebecheckedinallpatientsbeforeperformingsecondcontrastCTexaminationswithin24hours?JAmCollRadiol.2009;6:268-73.

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APPENDIX:SCOPEOFCOVERAGE

BreakoutGroup1:KidneyProblemsinHematology

1. Howdowerecognizeandpreventtumorlysissyndrome?Whatrenaltesting/investigationsshouldpatientsscheduledtoinitiatechemotherapyhave?

2. Istherearolefortotalplasmaexchangeinthemanagementofmultiplemyelomacastnephropathy?HowdowemanageMM-relatedbonedisease?Howdoesonedecideonbisphosphonateordenosumabtherapy?HowdoweminimizeriskofESRDinMM?

3. Howdoweoptimallymanagecalcineurininhibitorsintherecipientsofallogeneicstemcelltransplant?

4. Isarenalbiopsyrequiredtoinitiatechemotherapyinsuspectimmunoglobulincastnephropathy?

5. Whichpatientswithmonoclonalgammopathyofrenalsignificanceshouldbeofferedtreatment?

6. Whenarepatientswithmyelomaandamyloidosisondialysiscandidatesforkidneytransplantation?

7. Whatistheappropriatechemotherapyselectionfortreatmentofmonoclonalgammopathyofrenalsignificance?

8. WhatistheoptimaldosingofcytotoxicagentsinpatientswithCKDG3b-G5D?

9. Whataretherolesofhighcutoffmembranesandnewsorbentdevices(CytoSorb)inHSCTpatients?

10. Inpatientswithcancerrelatedpainwhatanalgesicsareappropriateforlongtermmanagement?

11. WhichhematologicalcancerpatientswithCKDcanbetreatedwitherythropoietin-stimulatingagents(ESAs)?

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12. Todialyseornot:Iswithholdingdialysisavalidtreatmentoptionforhematologicalcancerpatientsandwhenisittheoptimaltimetoinitiatedialysis?

BreakoutGroup2:KidneyImpairmentandSolid-OrganMalignancies

Assessmentofkidneyfunction

1. WhatistheepidemiologyofCKDinsolid-organtumors?

2. Whicharethemainpathophysiologiccausesandmechanismsofkidneyimpairmentinsolid-organtumors?

3. Howiskidneyimpairment(GFRandbiomarkersofcelldamage)bestmeasured

incancerpatients?

Applicability&efficacyofvariousdiagnostics

4. Whatarethekeyrenalinvestigationsforpatientswithsolid-organmalignancy?Consider:a. Atcancerdiagnosisb. Duringoncologicaltreatmentc. Duringfollow-up

5. Cancerscreeningindialysispatients:Underwhichcircumstancesisitindicated?

Whenitis,whichexamsshouldbedoneandhowoften?

6. Cancerscreeninginpatientswithglomerulopathies:Whenandhowshoulditbedone?(Considermembranousnephropathyandotherpossibleparaneoplasticglomerulopathies)

7. Whenisakidneybiopsyindicatedincancerpatientswithurinaryabnormalities?

PreventionofAKI&CKDortheirprogression

8. ShouldACEinhibitors/ARBsbeusedforslowingkidneydiseaseprogressioninCKDand/ornephrectomizedcancerpatients?

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9. Ispreventionofpost-surgicalAKIdifferentincancerpatientscomparedtonon-

cancersurgery?10. Iscontrast-inducedAKIarelevantissueincancerpatients?ShouldCKDpatients

withcancerreceivefewercontrastmediaCTscans?HowcancontrastinducedAKIbepreventedinCKDpatientswithcancer?

Managingrenaltoxicitiesfromtreatments

11. Whatarethenephrotoxicitiesofvariousoncologicaltreatments(e.g.,chemotherapy,radiotherapy,targetedtherapies,immunotherapy,bonetargetingagents)?

12. ESAandirontherapyinCKDpatientswithsolid-organmalignancies:Arethe

indicationsfortreatmentanydifferentthanthoseofCKDpatientswithoutmalignancy?Whatistheappropriatehemoglobintarget?WhatESAdoseshouldbeconsidered?WhicharetheeffectsofironandESAtreatmentsonsurvivalincancerpatients?

13. Whicharetheoptimaltimingandthenecessarydoseadjustmentsofanticancer

drugsinpatientswithCKDstage3to5D?Doesthedialysisregimenaffectdosingofanti-cancerdrugs?

Ethics

14. Todialyseornot:Iswithholdingdialysisavalidtreatmentoptionforsolid-organcancerpatientsandwhenisittheoptimaltimetoinitiatedialysis?

BreakoutGroup3:ManagementandTreatmentofKidneyCancer

Epidemiology,prevalence,typeofrenalcellcarcinoma(RCC)

1. HastheepidemiologyofRCCchangedinrecentyears?

2. WhatarethehistologicalsubtypesofRCCandunderlyingmolecularcharacteristics?

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KidneyfunctioninRCC

3. WhataretheriskfactorsforimpairedkidneyfunctioninRCC?

4. IsCKDasariskfactorand/orprognosticfactorforRCC?IfCKDisariskfactor,atwhatstageofCKDisariskfactor(e.g.,ESKD)?

5. Howcanweoptimizetreatmentofcancerpatientsondialysisandrenaldysfunctionwithtyrosinekinaseandcheckpointinhibitortherapies?

Typeofsurgery(e.g.,nephronsparing,nephrectomy)anditseffectonkidneyoutcomes

6. Whoarecandidatesfornephron-sparingsurgery?

7. WhatistheroleofcytoreductivenephrectomyinmetastaticRCC(mRCC)?Newtargetedtherapiesandrenalsideeffects

8. WhataretheclassesoftargetingagentsinthetreatmentofmRCCandtheirimpactontheoutcomeofRCC?

9. Whatarethemostfrequentsideeffectsoftargetingagentsinthecontextof

renaltoxicityandhowcanoneamelioratethem?

10. CanweovercomeunderrepresentationofpatientswithCKDincancertrials?Whatisthereal-worldevidenceonefficacyandtoxicityinthesepopulations?

Follow-upaftersurgery(urologist,oncologist,nephrologistordedicatedteam)

11. Whatistheroleofadjuvantsystemictherapyinhigh-risklocalizedRCC?

12. Canwepredictandpreventchangesinrenalfunction-CKDfollowingsurgery?

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BreakoutGroup4:MalignancyandKidneyTransplantation Epidemiology

1.Whatistheincidence,cancerriskfactorsandmortalityratesofcancersinkidneytransplantrecipientscomparedwiththegeneralpopulation?

Donor-derivedcancers

2.Whatistheincidenceofdonor-derivedmalignancyinkidneytransplantrecipientsandhowmaytheserisksdifferbycancertypes?

3.Inwhatcircumstancescanadonorwithactiveorhistoricalneoplasiabeacceptedfordonation?

4.Whatarethecurrentstrategiesforreporting,screening,management,ofthoseatriskandhadacquiredthediseaseafterdonortransmissionofcancerhasoccurred?

5.Whataretheshort-andlonger-termoutcomesofrecipientswhodevelopedadonor-derivedcancer?

Recipientswithapriorcancerhistory

6.Inpatientswithapriorcancerhistory,whataretheeligibilitycriteriafortransplantation?

7.Whatistheriskofcancerrecurrenceandtheprognosisofthosewithrecurrence?

8.Whataresomeofthemethodswecouldusetopredictandprognosticatecancerrecurrenceinatriskpatients?

Cancerscreeninginkidneytransplantrecipients

9.Shouldcancerscreeninginkidneytransplantrecipientsdifferfromthatimplementedinthegeneralpopulation?

10.Inadditiontothestandardpopulationcancerscreeningtestssuggestedinthegeneral(forbreast,colorectalandcervicalcancer),shouldroutinescreening/monitoringbesuggestedforothercancerssuchasrenalcellcarcinoma,PTLDandlungcancer?

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11.Whatistheroleofeducationincancerprotection?

Managementofcancerafterkidneytransplantation

12.Arethereanydifferencesandlimitationindiagnosticsofcancerinkidneytransplantrecipients(e.g.,roleofbiomarkers,imaging,biopsies,etc.)?

13.WhatarethemethodstoassessgraftfunctionandpreventAKI/progressionofCKDinkidneytransplantrecipientswhenonanticancertherapy(chemo,radio,targeted/immunomodulatorytherapies)?Forexample,theriskofacuterejectioninthecontextofCTL4andPD1inhibitors.

14.Whatarethelimitationsincancertherapyinkidneytransplantrecipients?

15.Whataretheoptimalstrategiesformanagingatransplantrecipientwithcancerbeforeandaftertransplantationasfarasthedoesandtypesofimmunosuppressionareconcerned?Howdocancertreatments(e.g.,chemotherapy,radiation,targetedtherapies)impactimmunosuppressionstrategies?