KDIGO Controversies Conference on Onco-Nephrology · 2020. 8. 13. · multidisciplinary clinical...
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1 KDIGO Controversies Conference on Onco-Nephrology December 13-16, 2018 Milan, Italy Kidney Disease: Improving Global Outcomes (KDIGO) is an international organization whose mission is to improve the care and outcomes of kidney disease patients worldwide by promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines. Periodically, KDIGO hosts conferences on topics of importance to patients with kidney disease. These conferences are designed to review the state of the art on a focused subject and to ask conference participants to determine what needs to be done in this area to improve patient care and outcomes. Sometimes the recommendations from these conferences lead to KDIGO guideline efforts and other times they highlight areas for which additional research is needed to produce evidence that might lead to guidelines in the future. Background In the 21 st century, patients with malignancy make up a growing number of the subjects seen for nephrology consult and/or critical care nephrology services. The outstanding progress in the therapy of malignancy presents new possibilities and challenges for both nephrologists and medical oncologists. It is important for nephrology services to be acknowledged and to take an active participation in the care of oncology patients. In addition, nephrology services need to better understand the biology of advanced malignancies and their treatment in order to become a valuable part of the teams working to yield the best possible outcome for cancer patients. The links between kidney disease and malignancy were observed quite some time ago. However, it was only recently that their importance was recognized and a new subspecialty in nephrology, namely ‘onco-nephrology’ was established [1]. Chronic kidney disease (CKD) is often diagnosed in the general population [2], however, its incidence and prevalence among patients with different malignancies is not extensively studied and data are limited. Half a century ago, increased incidence of cancer in CKD
Transcript of 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?
