KDIGOControversiesConferenceonEarlyIdentification&InterventioninCKD

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AsofSeptember10,2019Industrycommentsarehighlightedinblue

JayShubrook-TouroUniversityCalifornia(Doctor/Physician)IhaveaprimarycareandDiabetologybackgroundandhavebeenworkingonbettertrainingtheprimarycareworkforceonmanagingdiabetesanditscomplications.Iamveryinterestedinlearningmoreaboutyourinitiative.Thankyou!JayShubrookCelesteBoucher-AlbanyMedicalCenterDialysis(RN,CDN)Iworkwithboththepediatricandadultpopulations.Ibelieveearlydetectionbymeansofspecifictargetedtests&medicationsiscrucialintreatinganddelayingkidneydiseaseprogressiontoESKD.Dialysisdependencyhassomanypotentialcomplicationsandtheimpactonlivesandhealthcaresystemisastronomical.Researchisimperativetodevelopmoreimprovedearliertestingandalsopotentialfordevelopmentandtransplantationofkidneysgrownfromstemcellsreducingimmunosuppressanttherapiesforimprovedlifespansandoutcomes.CarmenPeralta-CricketHealth(Doctor/Physician) Thankyoufortacklingthisgreattopic.OnemajorpiecethatismissingistotacklethequestionofHOWDOWEEVALUATESUCCESS?Tothatend,whatclinicaloutcomesshouldbefollowedafterdetectionandinterventions?(slowprogressionofdisease,delaydialysis,reducecardiovascularevents,forexample).Specifically,moreworkisrequiredtodefinehowtomeasuretheseoutcomeswithrealworlddata.MagdyElsharkawy-Ain-ShamsUniversity(Doctor/Physician) Topicsshouldfocuson:Mediaandgovernmentalinvolvementintoeveryscreeningandpreventionprogram.FoodindustryshouldbeinvolvedinallpreventiveprogramsItisofatmostimportancetoaddressschoolstudentsandtheirteachers

aboutkidneydisease.Screenyoungadultsintheschoolsevery3yearswithurineandbloodpressuremeasurement.RumeyzaKazancioglu-BezmialemVakifUniversity(Doctor/Physician) Ireallylikedyourtopicbutpleasepayattentiontogeographicalandresourcedifferencesworldwide.MonaAlrukhaimi-DubaiMedicalCollege(Doctor/Physician)Excellentscope.NothingtoaddJessiePavlinac-OregonHealth&ScienceUniversity(RenalDietitian)ThereisonecommentaboutdietintheScopeandnoreferencesconcerningnutritioninterventioninslowingtheprogressionofCKDandmanagingDM.AlsoIhopeyourinvitedattendeesincludeexpertsintheareaofnutritionalassessmentandinterventioninthispopulation.RodrigoBuenodeOliveira-UniversityofCampinas(Doctor/Physician)Whoitconcern,Iwouldaddresssomecomments/suggestionsforworkgroup1:EarlyCKDDetectionMeasures.1.CKDdiagnosisandclassificatonislargelybasedonmeasurementsofeGFR;2.GFRcanbeafectedbydrugswithintrarenalhemodynamiceffects(SGLTi,ACEi,etc.);3.Residualrenalfunctioncanbeaffectbythesamedrugsplusdietaryhabits(proteinload);4.GFRcanbeassessedindifferentcondictions:"basal"GFR(hipoproteicdiet)or"stressedGFR"(AAinfusion,dopamineorglucagoninfusion);Basedonthestatmentsaboveonecouldargue:

-IsRRFdeterminationimportanttoevaluationoftrueGFR?-IsRRFimportanttopredictprogressionrate?-WhataretheimplicationsofRRTatclinicalsetting?-ShoulddoctorsaccessRRF?

References1.deMoor.ClinicalKidneyJournal,2018,vol.11,no.5,623–654.2.InkerLA.KidneyInternational(2019)96,280–282.3.MayerGJ.KidneyInternational(2019)96,489–504.4.PalssonR.AdvChronicKidneyDis.2018;25(3):e1-e8.5.RoncoC.IntensiveCareMed(2017)43:917–920.6.vanBaarMGB.KidneyInternational(2019)96,283–286.

RichardGlassock-GeffenSchoolofMedicineatUCLA(Doctor/Physician)1)besuretotakeaverycarefulandcriticallookattheestimatesoftheglobalburdenofCKD-Ithinktheyareverymuchoverstated2)besuretotakeaverycriticallookatCKDlscreeningstrategies,especiallythosebasedoneGFR.TheevidencethattheydoverymuchtoimprovethelivesofpatientswithCKDisvery,veryweakandalmostallobservationalortheoretical.ItistimetomoveontoRCTofscreeninginaseriousway.3)sinceCKDislargelyadisease(ordiseases)oftheelderlyawarenessprogramsshouldfocusonthisgroup-usingage-adaptedcriteriaforCKDdefinition.4)willbetterrecognitionofHTNreducedtheprevalenceofCKDorESRDinnon-diabetics?Ithinknot-themessagefromSPRINTneedstobecarefullyexamined.5)don’tforgetmGFR-don’tspendtoomuchtimeoneGFR-CystatinC.ItisnobetterthananeGFR-creatinine+aC-RP.DianaGarcia-PrivatePractice&Teaching(Doctor/Physician) ItwillbeveryinterestingtohearsomethingaboutnephrologyspecificinLatinos.AlsoIthinkit’snecessarytoupdatetheCKDguidelines,andIhopeyoushowusthenewupdatesaboutthis.Iwillbewaitingthedetails.ArifKhwaja-SheffieldKidneyInstitute(Doctor/Physician) i)ThescopeofworktakesitasagiventhatearlydetectionofCKDdefactoleadstoimprovedoutcomes.Itwouldbegoodtoreviewtheevidenceforthistheimpactofearlydetectiononotherdiseases(egprostatecancer)remainsfarfromcertain.ii)ForthevastmajorityofpeopleCKDiseffectivelyasurrogateforageandvasculardiseaseandsoimportantthatthescopeofworkfocusesonacomprehensiveCVstrategyofwhichCKDisapartofratherthanaseparatestrategyforCKDiii)Wehaveanumberofsisterrenalcentresindevelopingcountriesanditsclearthattheproblemsareverydifferent.Inthosecountriesthereisnoearlydetection-justcrashlandingatCKD5-itispleasingtoseethescopeofworkseemstorecognisethatthereneedstobefundamentallydifferentmodelsofcareaccordingtoresourcesettingLindaMcCann–Nocurrentaffiliation(Dietitian) Thisisaveryambitiousundertaking,verywellthoughtoutandcomprehensive.Welldone.Thismaybealittleoffthegrid,butaquestionIhavebeenwonderingaboutisrelatedtodietarypatterns.WhenIwasinpracticeIsawacoupleexamplesofpatientswhowerelikelystage4orheadingintostage5whoseemedtoprecipitatetheirdeclineinkidneyfunctionwithproteinsparingfastforweightloss.Iamwonderingifthestrongreimergenceofhighprotein,verylowcarbohydrateweightlosseffortshavehadaneffectonprogressiontoneedingkidneyreplacement

therapy.Wehavealwayshadabitofamixedmessageaboutthebenefitofreducingproteinintaketopreservefunction(afterconfirmingsomeoneeatsalotofproteinmorethansuggestedamounts).DoestheexpandeduseofKetodiet,Atkinstypedietscreateanyproblems.Itmightbeofinteresttoatleastsuggestthatadietaryhistoryaskthequestionaboutrecentuseofsuchdiets.Mypracticealwaysincludedafulldiethistoryincludingadetailedassessmentofusualandrecentdietaryintaketounderstandwhatmodificationsmightbewarranted.Theprocessofobtaininganaccuratediethistoryistimeconsumingandneedsadefinitiveprocess.Onedownfallofamajorityofstudiestryingtodefineoptimalnutrientintakeseemstobethatwestruggletogetaccurateinformationaboutactualintake(i.e.usingestimatesofproteinintaketoestimatephosphorusintakewhichdoesn’tnecessarilyconsiderthephosphoruscontentordigestibilityoftheproteinsource)-butalsorecognizingthatfoodcompositiondatabasesarenotthataccurateforsomenutrients.Sorry-longdiatribejusttosayitmightbeinterestingtobeginadiscussionorsuggestsomeresearchquestionrelatedtouseoffaddiets.Again,thescopeofworkseemsverycomprehensiveandcompleteandpromisestohelpclinicalpracticeandpatientunderstandingofthediseaseanditscomplexity.Thankyouforyoureffortsonbehalfofthosewhohavekidneydisease.JamesTattersall-UKNationalHealthService(HealthcareArtificialIntelligenceConsultant) Ithinktheextentandmechanismsforpatientengagementshouldbediscussedexplicitly.Forexample,inGroup1,earlydetectionmeasures,thereshouldbeanitemtodiscusswhetherandhowscreeningshouldbeaccessedbypatientsdirectly(e.g.byhometestkit,orasanopenaccessserviceprovidedbypharmacy)oradministeredbythepatientshealthcareproviderasatpresent.ShouldscreeningbeadvertisedusingAI-targetedmethodsascurrentlyusedbygoogle,facebooketc.?Ingroup2:Theitem"Whatpromisingemergingopportunitiesortechnologies(e.g.,AI)existforautomatedandtargetedsurveillanceapproachestoidentifyat-riskindividuals?’isfartootimid.Thisshouldbeattoppositionandtitled"HowshouldwebeusingAItofacilitateidentificationandsurveillanceofat-riskindividuals?"Ingroup3:Theitem"Whatistheroleofself-managementandnewtechnologies(mobileapps)whendetecting/managingCKD?"isfartootimid.Itshouldbeatoppositionandtitled"HowcanwefacilitateselfmanagementindetectingandmanagingCKDusingmobileandwebapplications?"InGroup4:Isuggestanadditionalitemwithhighpriority"TowhatextentshouldpatientsbeabletoaccessCKDmanagementtoolsdirectly,independentlyofhealthcareproviders?"

RukshanaShroffConsultantinPaediatricNephrology(Doctor/Physician)Someareastoconsiderare:1.withreferencetopediatricpractice:-schoolscreeningprogrammestodetecthematuria/proteinuria-follow-upofchildrenwithmultipleUTIsorUTIscausedbyresistant/unusualorganisms-follow-upofpatientswithabnormalantenatalscans2.Foradultsandchildren:-follow-upforsurvivorsofAKI(egICUpatientswhorequiredCVVH)Thankyouforthisopportunitytosubmitcomments.KevinFowler-KidneyHealthInitiative(Patient) Iwouldliketheworkgrouptoconsideraddingthesemeetingtopics:Comparenephrology'sadoptionofnovelmedicationsandtherapiestootherspecialties.AcknowledgethattherearemultipleupstreaminterventionsforDiabeticKidneyDisease,ADPKD,FSGS,IGAN,Alportsyndrome,etcandthattheglobalnephrologycommunityisforthemostparttreatingthedownstreamconsequencesofkidneydisease.Ifnephrologydoesnotchangetheircaremodels,thenthepharmaceuticalindustrymaycutbackontheirinvestment.IsuggestthattheadoptionofACEs/ARBsbeincludedaspartofthediscussionbecauseaJanuary30,2019JASNarticlenotedthattheuseofACES/ARBshaveplateaued.Thisissignificantanddisconcertingbecausethesemedicationshavebeenoffpatentforoveradecade.Thereneedstobeadiscussionaboutreimbursementincentivesthatsupportdialysisratherthanearlyintervention.IreneMewburn-BEAT-CKDandAKTN(Patient)IfinvitedIhaveastronginterestinGroups1and3.AfterattendingtheAKIConference,Iambecomingmoreaffiliatedwithdifferentones.FromanAlliedHealthperspectiveIhaveaverystronginterestinMentalHealthasanearlyfollow-up(Group3).FromaPatientPerspectivewithearlydetection,theproblemsassociatedwithUraemiawerestronglyoverlooked.IfthishadbeendetectedearlierImaynothaveendedupwithRenalFailure(Group1).IwasunderDrP.DanbyinMelbourneatthattimeandhadmyBiopsyfordiagnosisdoneatMonash.LauraSola-CASMU-IAMPP(Doctor/Physician) Itisaverycomprehensiveagenda.IwouldonlyadforGROUP3:Additionally,toaskingwhen,how,andhowoftentomonitorpreventiveinterventions,weshouldknowwhichwouldbeanappropriatewaytomonitortheeffectivenessoftheinterventionsregardingCKDprogression.Howshouldwemonitorprogression,Δestimatedglomerularfiltrationrate?definingstabilizationorprogressionofCKD?

CibeleIsaacRodrigues-PontifíciaUniversidadeCatólicadeSãoPaulo(Doctor/Physician)Considerations:Group1:EarlyCKDDetectionMeasures:cystatinCisnotapossibilitymarkerofCKDinourcountry(Brasil),ontheotherhandserumcreatinineandGFReiseasilyavailableandisalowcostlaboratorymarkerwithwell-knownlimitations.Proteinuriaandalbuminuriacreatinineratioisalsoavailable,butnotinallstates.Group3:Fortheimplementationoftheguidelineithastobetranslatedbythelocalnephrologysocietiesandbereliable.Diagramsandflowchartsaremorelikelytobereadandtobefollowbyclinicians.InBrasilthemajorityofthepopulationhasmobilephone.DetectionandmanagementofCKDanditsriskfactorswithAppswillbepossible.Agreewiththescope.EiichiroKanda-KawasakiMedicalSchool(Doctor/Physician)Thankyouverymuchforyouraskingformycomments,whicharebelow:BackgroundThenumberofchronickidneydisease(CKD)patientshasbeenincreasing.TopreventtheprogressionofCKD,andimprovetheirprognosis,earlyidentificationofCKDpatientsandinterventionarenecessary.Thereareabout334,000dialysispatientsinJapan.Theunderlyingdiseasesrequiringdialysisarediabetickidneydisease(DKD)(42.5%),chronicnephritis(16.3%),andnephrosclerosis(14.7%),whichhavebeenincreasingwithaginginJapan.ForCKDprevention,itisakeystrategytoidentifyDKDandnephrosclerosispatientsandtreatthematanearlystage.However,becauseinnephrosclerosisandinsomecasesofDKD,proteinuriaisnotobserved,itisdifficulttoidentifythesepatientsatearlystage.MypreviousinvestigationsofearlyCKDIconductedseveralcohortstudiesofearlyCKD.Here,Idescribetheresultsoftwostudies.①・Importanceofglomerularfiltrationratechangeassurrogateendpointforthefutureincidenceofend-stagerenaldiseaseingeneralJapanesepopulation:community-basedcohortstudy(ClinExpNephrol(2018)22:318–327)・Guidelinesforclinicalevaluationofchronickidneydisease(ClinicalandExperimentalNephrology(2018)22:1446–1475)ThiscohortstudyinJapanfor15yearsincluded58,292healthypersonswithhigheGFR(>60ml/min/1.73m2)and10,946personswithloweGFR(<60ml/min/1.73m2).InhigheGFRgroup,whichisthetargetofthisKGIDOproject,end-stagekidneydisease(ESKD)wasonlyobservedin186persons(20.8/100,000person-years).TheriskofESKDandeGFRchangesshowedaU-shapedrelationship.Thatis,becausethepersonswithhighrisksofESKDmayshownotonlyadecreaseineGFRbutalsoanincreaseineGFR(improvedeGFR).ThisisouraimtoidentifythesepatientswithanincreaseineGFR

atanearlyCKDstage.Thefollowingdifficultiesofanalysiswereencountered:(1)Becausethenumberoftheeventsareverysmall,largesamplesizeandalongobservationperiodarerequired.(2)Thesmallnumberofeventsmakesanalysisusingclassicalstatistics(frequentist)difficult.(3)BecauseeGFRoftenchanges(increaseordecrease),alongobservationperiodisneededtoconfirmthetrendofdecreaseineGFR.②・IdentifyingprogressiveCKDfromhealthypopulationusingBayesiannetworkandartificialintelligence:Aworksite-basedcohortstudy(ScientificReportsvolume9,Articlenumber:5082(2019))Consideringthestudy①,weconductedanothercohortstudyinJapantoidentifypersonswithahighriskofearlyCKD.Inthisstudy,enrolledpersons(eGFR>60),7465,wereenrolled,andtheywerefollowedupfor9years.TrajectoryanalysisshowedthattheirGFRfluctuated(increaseordecrease).MostofthepersonsatstagesG1A1(70.8%)andG2A1(81.4%)showedstableCKD.Ontheotherhand,10.6%ofthepersons,whowereinitiallyatstageG2A1atthestartshowedimprovementinCKDstage(G1A1),and2.3%wereatstageG3A1oneyearlater.Moreover,9yearslater,6.6%ofthepersonsatstageG2A1showedimprovementineGFR(G1A1),and7.2%showedprogressionofCKD(G3aA1).PersonsatCKDstageG1A1showedgreaterprogressionthanthoseatstageG2A1.Then,thefactorsassociatedwithearlyCKDprogressionwereinvestigatedusingtheBayesiannetwork,becausethe“frequentistanalysis”wasinapplicable.Thetime-serieschangesintheprognosticcategoryofCKDweremorerelatedtotheoutcomethanthebaselinecharacteristics,suchashypertensionanddiabetesmellitus.Moreover,supportvectormachinesincludingtime-seriesdataoftheprognosticcategoryofCKDdetectedthehighpossibilityoftheprogressionofCKDnotonlyinpersonsatveryhighrisksbutalsointhoseatlowrisksatbaseline(G1A1andG2A1).Thisstudyshowedthat(1)eGFRandproteinuriaoftenchangeformanyyears.(2)Time-seriesobservationisnecessarytoidentifypersonswithahighriskofearlyCKD.(3)Aftertheevaluationofkidneyfunctionatahealthcheckup,itisnecessarytofollowupnotonlypatientsathighrisksbutalsothoseatlowrisksatbaselineformanyyears.CommentsConsideringthebackground,mycommentsareasfollows.Group1:EarlyCKDDetectionMeasures>WhatarestrengthsandweaknessesofcurrentlyavailablemeasurestoidentifyandcategorizeCKD;valuesofdiscriminatingrisk;specificity;andcosts?Asdescribedabove,eGFRchangesmarkedly,whichmakesitdifficulttopredictCKDprogression.PredictionofCKDprogressionusingsupportvectormachinesincludingtime-seriesdataonCKDstageshowedahighaccuracyof88%(logisticregressionmodelcouldnotidentifypersonsathighrisks).>What

aretheidealCKDdetectionmeasuresandtheinfluenceofdemographiccharacteristicson;therelativevalueofcreatinineonlyversusaddingcystatinC,albuminuria/proteinuria,oratriple-markerstrategy?eGFRbasedoncreatinine(eGFRcr)aloneisinsufficienttoidentifypersonsathighrisksofCKD.BecausemeasuredGFRcannotbemeasuredfrequently,itisnotappropriateforclinicalsettingsatmedicalfacilities.eGFRbasedoncystatinC(eGFRcyc)isinaccurateatstage5(GFR<10).Moreover,therearelimitationsofmeasurementofmGFRandeGFRcycdependingonthehealthinsurancecoverage.Therefore,thecombinationofeGFRcrandproteinuriaisusefulforevaluatingkidneyfunction.>Whatcriteriashouldbeusedtoevaluatepotentialscreeningstrategies:accuracyversusmeasuredGFR;predictionofadverseoutcomes;sensitivityversusspecificity;stageclassification?Thecriteriashouldbeselectedonthebasisofitspurpose.Toscreenpersonswithhighrisks,highsensitivitycriteriaareappropriate.Fordefinitivediagnosis,high-specificitycriteriaarebetter.>Whatarethecostsofcommonlyusedkidneyhealthmeasures,includingcreatinine,cystatinC,proteinuria,dipsticksandalbuminuria?>Whataretherelativeyields(utility)fromtestingproteinuriaversusalbuminuria;andaredipsticksadequate?>Isthereapotentialroleforpoint-of-care(POC)testing,suchasnovelPOCsforreal-timeGFRorcreatininemeasurements,ormeasuresofurinealbumin,inapublichealthCKDprogram?InJapan,athealthcheckups,dipsticksareusedforthegeneralpopulation.Then,apersonfoundtohaveproteinuriaisfurtherexaminedforserumcreatininelevel(eGFR)andproteinurialevel.AlbuminuriaisexaminedonlyindiabetesmellituspatientsinaccordancewiththeJapaneseNationalHealthInsuranceSystem.>WhereshouldtestingbeconductedandhowoftenshoulditberepeatedinaCKDdetectionandinterventionprogram?Whatnewtestsorbiomarkersarebeingdevelopedthatmightexpanddiagnosisbeyondglomerularmeasuresinordertodetectandmonitorkidneytubulehealth?Asdescribedabove,time-seriesmeasurementsofeGFRandproteinuria(onceayear)formorethan3yearsarerequiredtoidentifypersonswithhighrisksofCKD.>ProposeresearchagendarelatedtothissectionAlarge-scaleretrospectivecohortstudy.Group2:PopulationstoScreenandIdentifyingAt-RiskIndividuals>ShouldscreeningforoccultCKDinanearlydetectionprogrambedirectedtopopulationsortargetedtohigh-riskindividuals,usinganycombinationofkidneymeasures?CombinationofeGFRandproteinuriaareusefultoevaluatekidneyfunction.>Whataretheoptimumsettings(communitybasedvsprimarycarepractices)forcapturingatriskindividuals?Itdependsonthepurpose.ToscreenpersonswithhighrisksofearlyincidentCKD,acommunity-basedstudyisbetter.TopreventtheprogressionofCKD,aprimary-care-practice-basedstudyisbetter.>Whatisthedifferencebetweenasurveillanceprogramandascreening/detectionintervention,andwhatcanwelearnfrompriorprogramsincludingtheprevalenceofCKD?Asurveillance

programisusefulforinvestigatingtheprevalenceofCKDasapublichealthconcern.Ontheotherhand,screeningisimportantfortreatingCKDattheindividuallevel.>ShouldtheprevalenceofCKDortheabsoluteriskofCKDcomplicationsandESKDbeusedasthefirststepforanearlydetectioninterventionprogram?Across-sectionalstudyoftheprevalenceofCKDcaneasilybecarriedoutthanaresearch(cohortstudy)ontheabsoluterisksofCKDcomplicationsandESKD.>Ifhigh-riskgroupsaretobeidentified,shouldtheabsoluteriskestimatebebasedonlifetimeriskorwithinafiniteintervaloftime(e.g.,10-yrrisk),andshouldtheriskestimatesbedependentonlaboratorymeasures?ForearlyincidentCKD,afiniteintervaloftime(e.g.,10-yrrisk)isappropriate.Studiesoflifetimerisktakealongertimethanstudiesofthefiniteintervaloftime.>Howdoearlydetectionstrategiesapplyatextremesofage,suchasinpediatricsoramongolderadults?Agingisagrowingproblem.InJapan,thepopulationofpeopleagingmorethan80yearshasbeenincreasing.>Howmightweidentifyindividualsthatneedre-screeningafteraninitiallynegativescreen?Asdescribedabove,anincreaseineGFRdoesnotalwaysindicateanimprovementofkidneyfunction.Time-seriesdataareneededtoscreenforpersonswithhighrisks.>Aretheresocial,behavioral,occupationalorenvironmentalexposuresthatwouldwarrantpopulationscreeningratherthanindividualrisk-basedtargeting?InJapan,schoolandworkplacehealthcheckupsarecarriedout.>Shouldtherebearoleforreflexfamilyscreeningifancestralfactors,suchashigh-riskAPOL1genotype,arepresentamongscreenedindividuals?Thisshouldbeconsideredfromtheviewpointofcosteffectiveness.>Whatpromisingemergingopportunitiesortechnologies(e.g.,AI)existforautomatedandtargetedsurveillanceapproachestoidentifyat-riskindividuals?’Asdescribedabove,IhaveconductedacohortstudyofearlyCKDusingAI(supportvectormachine).Ifyouwillgivemeachance,Iwillbegladtopresenttheresultsofourstudyintheconference.>Proposeresearchagendarelatedtothissection.Alarge-scaleretrospectivecohortstudyincludingtime-seriesdataofhealthypopulationsuchascommunity-basedhealthcheckup.Group3:OptimalInterventionsandImplementationafterCKDDetection>WhatInterventions(e.g.,lifestyles,diet,pharmaceuticals)shouldweadopttopreventCKDonsetand/orslowCKDprogressionandtopreventCVDandHF?Acombinationofthesetherapiesshouldbeadopted.ItisdifficultforonlyasingletherapytopreventtheprogressionofCKD.>BeyondBP,glycemicandlipidcontrol,whatareotherriskfactorsthatweshouldbetargeting?(e.g.,metabolicacidosis,hyperuricemia,inflammation,anemia,etc.)>Whatadditionalriskfactors/interventionsshouldweconsideramongindividualswithCKDandothercomorbidities(e.g.,ASCVD,heartfailure,etc.)?Malnutritionisanadditionalriskfactor.ProteinenergywastingisariskfactorforESKDanddeath,andisoftenobservedinCKDpatients.Withaging,theprevalenceofPEWhasbeenincreasing.>When,how,andhowoftentomonitorpreventive

interventionsamongpeopleatriskorwithCKD?Itdependsonaperson’shealthcondition.Whenapersonhasaseverecomorbidcondition,monthlymonitoringisrequired.Whenapersonhasnocomorbidcondition,yearlyorhalf-yearlymonitoringissufficient.>Howcanweimprovedisseminationofguideline-basedcareviaimplementationorknowledgetranslationefforts?Conductinglecturestomedicalstaffmembersanddoctorsiseffective.>WhatriskalgorithmscanweusetostratifyrisklevelsamongpersonsatriskfororwithCKD?HowaboutdevelopingariskscoretopredictESKDorprogressionofCKD?>Howdopatientperspectivesandvaluesaffectdecisionsarounddetectionefforts,suchastherelativebenefitsfromearlyawarenessbalancedwithconcernsofoverdiagnosis,medicationsideeffects,monitoring,andlivingwithadiseaselabel?Thisisaffectedbythesocialandculturalbackgroundofpatients,whichmaybedifferentamongcountries,andmaybeaffectedbytheawarenessofactivitiesthatmaypreventCKD.>WhatistheroleofpatienteducationandCKDawarenessprogramstopreventCKDonsetandprogression,andtopreventCVD?PatienteducationhasanimpactonCKDpatientsintermsofadherencetoCKDtherapysuchasdietarytherapy,whichisespeciallydifficultforthemtoadhereto,becauseofrestrictiononsalt,protein,potassium,andphosphorus.>Whatistheroleofself-managementandnewtechnologies(mobileapps)whendetecting/managingCKD?MobileapplicationsareeffectiveforCKDpatientstoadheretothedietarytherapy.IhavedevelopedandreleasedamobileapplicationfordietarytherapyinJapancalled“gohancoach(mealcoach)”,whichiseffectiveformonitoringdietaryintake.Ifyouwillgivemeachance,Iwillbegladtopresentthesystem.>Whatdoessuccessfulimplementationofearlydetection/managementofCKDprogramslooklike,andwhatconstitutesaproofofconceptforsuchprograms?DetectionofpersonswithhighriskofearlyCKDand/orprogressionofCKD.Atindividuallevel,theproofisslow-downofdecreaseineGFRspeedorpreventionofESKD.Atpublichealth,decreaseinnumberofESKDpatientsandimprovementintheirprognosis.>Proposeresearchagendarelatedtothissection.Howaboutaprospectivecohortstudyusingpropensityscorematchingofpatienteducation?Group4:HealthSystemandEconomicFactors:MappingtheCascadeofCareforSuccessfulImplementationofScreening/DetectionandInterventions>AreearlyCKDdetectionandmonitoringstrategiescost-effective,andhowdoesthisdeterminationdifferindevelopingvsdevelopedcountries,andwhatinputs/metricsdrivethecost-effectivenessassessment?>WhatmodelsofchronicdiseasedetectionandmanagementcouldbeappliedtoCKDdetectionandmanagement,suchasscreening,treatingorpreventingCVD,diabetes,andHIV?InJapan,athealthcheckups,dipsticksareusedforthegeneralpopulation.Then,apersonfoundtohaveproteinuriaisfurtherexaminedforserumcreatininelevel(eGFR)andurinaryproteinlevel.Dipsticksarecheapforscreening,andcanbeusedindevelopingcountries.>Whatarethe

barriersandfacilitatorsofimplementationofevidence–basedCKDdetectionstrategies,includingtheroleofprimarycareproviders,integratedcareteams,specialistengagement,andcommunitypartners?>Whatistheroleofhealthsystemsinimprovinguseofevidence-basedtreatmentsinCKD,andhowcancost-effectivenessbeprojectedandmonitored?NephrologistsandNephrologyassociationssuchastheJapaneseSocietyofNephrology(JSN)takepartinprovidingevidence-basedmedicine.JSNprovidesCKDguidelinesforspecialistsandgeneralpractitioners,andgiveslecturesonCKDtogeneralpractitionersandgeneralpopulation.>WhatistheroleofinformationtechnologyandotherinnovationsinimprovingearlyCKDdetection,monitoringandclinicaldecision-making;howcantechnologybeintegrated;andhowwillcost-effectivenessbedemonstrated?JSNestablishedalargedatabaseofCKDpatients(>150,000)usingICTtechnology,whichisusedforareal-worlddatabase.Itiscost-effective.(Iamoneofthepersonsincharge.)>WhatistheroleofsocioeconomicfactorsinearlyCKDdetectionandmanagement,andwhatstrategiesandinterventionscanbeusedtobridgegapsacrosssocioeconomicgroups?InJapan,thecostofschool,workplaceandelderlyhealthcheckupsisminimal.Theitemsmeasuredatahealthcheckuparedeterminedbyeachmunicipalityorcompany,andthetreatmentofCKDiscoveredbythenationalhealthinsuranceonthebasisofCKDguidelines.StandardizedCKDguidelinesareusefulforbridgingthegaps.>WhatincentivescouldimproveearlyCKDdetection/management,suchasfinancialandnon-financialincentivesandalternatepaymentmodels?Asanexample,partialcoverageofmedicalfeesbyhealthinsuranceormunicipalitiescanbeanincentive.>Whataresomesuccessfulimplementationstrategiesthatwecanlearnfromotherdisciplinesandhowdidtheydemonstratetheircost-effectiveness?InJapan,hypertensionanddiabetesmellitusarescreenedathealthcheckups.Thecost-effectivenessofsuchscreeningisevaluatedbythedecreaseinmedicalfees.>ProposedresearchagendarelatedtothissectionHowaboutasurveyamongcountriestoinvestigatehealthsystemandhealthinsurance?HansPottel-KULeuvenKulak(Researcher/Biostatistician) “Theworldwideprevalenceiscurrentlyestimatedat7.2%to13.4%.”Comment:thisprevalenceisbasedoneGFRandthefixedthresholdof60mL/min/1.73m².Anage-dependentthresholdwillincreasetheprevalenceintheyounganddecreasetheprevalenceinanolderpopulation,resultinginanoveralldecreaseoftheworldwideprevalence.“Anotherstudyfoundthatonly14to28%ofpatientswithaninitialeGFR<60ml/min/1.73m2haveadocumenteddiagnosisofCKD.”Comment:thiswillcertainlydependontheageofthecohortinthestudy.Assaidbefore,olderadultswithstableeGFRbelow60mL/min/1.73m²maynothaveCKD.“Applicabilityofmeasurementsacrossageandrace/ethnicitymaychangethe

preferredmeasurementsaccordingtosetting.”Comment:thisshouldbeacalltoapplyand/ordevelopeGFRequationsapplicableforallages,sexesandrace/ethnicities.ThecurrentKDIGO-strategytousetheCKiDScrequationcombinedwiththeCKD-EPIequationshouldbeabandoned.Also,thepreferenceshouldbeonheight-independenteGFRequationssinceheightisnormallynotavailableintheclinicallaboratorydatabases.“Tothisend,theobjectivesofthisconferencearetodeterminetheoptimalstrategiesforearlydetectionandinterventionofCKD”Comment:thetopicsdefinedarenicebutIammissingthediscussiononfixedversusage-adaptedthresholdstodefineCKD.Theapplicationofanage-dependentthresholdhasamajoreffectonthediagnosisofCKD.“ThegoalofthisKDIGOconferenceistoidentifybestpracticesandareasofuncertainties,reviewkeyrelevantliterature,addressongoingcontroversialissues,…”Comment:1.Fixedversusage-dependentthresholdandtheirimpactontheprevalenceofCKD2.switchingeGFR-equationsatthetransitionfrompediatrictoadultnephrologycare3.flawsofthecurrenteGFR-equationsandhowtoremediatethem4.settingupacentralrepositoryofGFR-relateddata"Group2:"“Howdoearlydetectionstrategiesapplyatextremesofage,suchasinpediatricsoramongolderadults?”Comment:useofanage-dependentthresholdwouldincreasethedetectioninpediatrics,sincethethresholdwillbe75mL/min/1.73m²ratherthan60mL/min/1.73m²MichelleMazuranic–AstraZeneca(Pharma/Sponsor) Afewcommentstopleasebeconsideredforincorporationintotheagendaifappropriate:Whatarethecurrent/historicalbarrierstoimplementationoftestinganddiagnosticrecordingrecommendationsIpresumesection2willultimatelyarriveatrecommendationsonwho,how,whenandhowoftentotestidentifiedatriskindividualsorpopulations?Forpatientswithcomorbiditiesshouldjointmulti-disciplinarycarepathwaysbeaddressed(eg.JointEndo,Neph,Cardio)Whereavailableandsupportedbyevidencearerecommendationsforpreventativestrategiesinatriskindividualsorpopulationsinscope?WillCKDawarenessaddresstheimportanceofbothpublic(patient)awarenessandclinical(Endo/PCP)awarenessaroundtheimportanceofCKDandtheappropriatemethodsandrecommendationsfortesting?TheroleofpreventionandHCPinterventionRegards,MichelleBarbaraPhilips-BrightonandSussexMedicalSchool(Doctor/Physician)Readingthroughthe4groupsandthescopeofworkplanned,IcannotseeasectionontherelationshipbetweenAKIandCKD.AthowmuchgreaterriskofAKIisanacutelyillpatientwithunderlyingmildtomoderateCKDcomparedtopatientswithnounderlyingrenalpathology?Cananyriskbepredictedorquantified?Cantherisk

bemitigatedandifsohow?Similarly,whataretheriskfactorsfordevelopingsevereCKDfromepisodesofAKI?IknowyouhaveseparateconferencesforAKIbutwhereistheinterrelationshipdiscussed?JoannaHudson-TheUniversityofTennessee(Pharmacist)AsaprofessorofpharmacyattheUniversityofTennesseeCollegeofPharmacyandMedicine(DivisionofNephrology)andapharmacistspecializinginnephrologyfromtheresearch,teachingandpatientcareaspects,IhavehadtheopportunitytobeinvolvedinthenephrologycommunityandworkwithotherhealthcareprofessionalstoprovidecaretopatientwithchronickidneydiseaseandESRD.WhenreadingthescopeofworkfortheIdentificationandInterventioninCKD,Iwasexcitedtoseethemultidisciplinarycomponentemphasized.Iwasdisappointed,however,thatpharmacistswerenotidentifiedasakeymemberoftheteamtobeinvolvedinthisconference.Therewasmentionofinvolvinganindividualwithexpertiseinpharmacology,butthisisnotaclinicalpharmacistinvolvedinthedaytodaycareofCKDpatients.IhopethegroupconsidersincludinganindividualclinicalpharmacistwhocanprovideaprospectiveoncomprehensivemedicationmanagementintheCKDpatient.DoingsowillhelpmeetthegoalofthisconferenceindeterminingthebestmethodstodeliverintegratedcoordinatedcareforCKDpatientsandincorporatinganinterdisciplinaryapproach.Iamhappytoproviderecommendationsofindividualswhocanprovideaperspectiveofaclinicalpharmacistandbeinvolvedinthisconference.JyothiNayak-ManipalCollegeofNursing(PhDScholar) IappreciateyourcontributionforthecareofCKDpatient.Yourhardworkhelpedmetogainin-depthknowledgeonCKD.Iwouldliketoaddsomethingifitisdiscussedintheworkshop.SomeofthecomplementarytherapyusedforthepreventionofprogressionoftheCKDsuchasYoga.Thankingyou.WithRegards,JyothiPhDScholarManipalCollegeofNursing,MAHE,ManipalKarnataka,IndiaEmail:jyothikuledu@gmail.comDeepakSharma–KetavKalpHealthcare&ResearchPVTLTD(Doctor/Physician) Wellthoughtofandresearchedscopeofwork.MaartenTaal-UniversityofNottingham(Doctor/Physician)ThescopingdocumentisextremelywellwrittenandprovidesaclearframeworkfortheControversiesConferenceonEarlyIdentification&InterventioninCKD.MymaincommentisthatIwouldliketosuggestmorespecificfocusontheissuesofCKDinolderpersonsandcomorbidityinthecontextofCKD.Thisiscertainly

impliedinthecurrentscopebutbecauseoftheimportanceoftheseissues,perhapsshouldbemademoreexplicit.CKDintheelderly:TheprevalenceofCKDrisessharplywithagebuttherisksassociatedwithCKDalsochangewithadvancingage.TheriskofESKDdeclinesduetothecompetingriskofdeathbuttherisksofhospitalisationandcardiovasculareventsremainhigh.Forexampleinonecohortstudyofolderpersons(meanage73years)withCKDstage3atbaseline,theincidenceofESKDafter5yearswasonly0.2%(ShardlowAetal.PLOSMed2016;13(9):e1002128).InolderpersonsCKDisalsofrequentlyassociatedwithotherchronicconditions(seebelow).TheseconsiderationsshouldinformtheapproachtobothdetectionandoptimalmanagementofCKDinolderpeople.Comorbidity:CKDisassociatedwithaveryhighprevalenceofcomorbidconditions.Inonelargepopulation-basedstudy25%ofpersonswithCKDhad3ormorecomorbidities(TonelliMetal.KidneyInt2015;88:859-66)andinacohortstudyofolderpersons(meanage73years)withCKDstage3,only4%hadnocomorbiditiesand40%had3ormorecomorbidities(FraserSDSetal.BMCNephrology2015;16:193).Inbothstudiesagreaternumberofcomorbiditieswasassociatedwithreducedsurvival.Comorbiditiesareimportantbecausetheyimpactaperson’squalityoflifeandabilitytoengagewithhealthcareinterventions.TreatmentguidelinesshouldincludeconsiderationofhowtomanageCKDinthecontextofotherchronicconditionsandhowtheseconditionsmaynegativelyimpacttheoptimalmanagementofCKD.KunitoshiIseki-NakamuraClinic(Doctor/Physician) InJapan,wehavehighincidenceandprevalenceofESRD,inparticularDKD.Since2008,Nationwidescreeningprogramonearlydetectionandinterventionformetabolicsyndromehasstarted.InthisprogramnthetargetisthosecoveredbyNationalInsuranceHolders.Itcoverspeople;house-wife,farmers,fishemen,andnon-employees(Age40-74).Onethirdofthemhavebeenparicipatngoneayear(Totalnember>30miilions).Wehavebeenworkingonthedatabasesince2008.Follwingpapersarerelatedtothecost-benefitanalysisonCKDscreening.1.KondoM,YamagataK,HoshiSL,etal.Cost-effectivenessofchronickidneydiseasemassscreeningtestinJapan.ClinExpNephrol16:279-291,20122.KondoM,YamagataK,HoshiSL,etal.BudgetimpactanalysisofchronickidneydiseasemassscreeningtestinJapan.ClinExpNephrol18(6):885-891,20143.NagaiK,IsekiC,IsekiK,etal.HighermedicalcostsforCKDpatientswitharapiddeclineineGFR:AcohortstudyfromtheJapanesegeneralpopulation.PLoSOne(inpress)EiseiNoiri-UTokyo/NCGM(Doctor/Physician) Group1:EarlyCKDDetectionMeasuresQ:WhatarestrengthsandweaknessesofcurrentlyavailablemeasurestoidentifyandcategorizeCKD;valuesof

discriminatingrisk;specificity;andcosts?A:KDIGObasedCKDcategorizationiseasyindicatortounderstandbasalkidneyfunctionofindividuals.However,wecannottellwhomaygetworsefromonecategorytothenextwiththecurrentclassificationandthinkingway.Thisisbecausetheindicatorssuchasserumcreatinine,albuminuriaandcystatinC,donothaveanydata.ProteinuriareportedfromOkinawa,namedOCHIDstudy,thathighlypositiveproteinlevelshowsworseoutcome.Thisisepidemiologicalanalysis.StudiesofDKDinEuropeandJapanshowsthathighurineL-FABPlevelcandistinguishtheprogressorbetterthanalbuminuria.ThiswillbetipstothenextstageofCKDstaging.IcangiveasmalldataasahintaboutitincludingrecentdatainUKandSouth-EastAsia.Q:WhataretheidealCKDdetectionmeasuresandtheinfluenceofdemographiccharacteristicson;therelativevalueofcreatinineonlyversusaddingcystatinC,albuminuria/proteinuria,oratriple-markerstrategy?A:Thereisnorecommendationtothisquestion.Instead,wecanlearnfromtheevidenceinDKD.Inaddition,therearesmallstudieswhichdemonstratetheefficacyofL-FABPtopredicttheprogressoringlomerulardiseasesinJPN.lQ:Whatcriteriashouldbeusedtoevaluatepotentialscreeningstrategies:accuracyversusmeasuredGFR;predictionofadverseoutcomes;sensitivityversusspecificity;stageclassification?A:IwouldprefertousecurrentKDIGOcriteriaincombinationwiththedataofcyctatinC.ThiswaywilltellthepotentialityofcystatinCtodistinguishtheprogressorifreal.Likewise,thecombinationofalbuminuriaandL-FABPwilltelltheprogressor.ThecombinationofserumandurinewilltellthecohortwhoneedclosermanagementpresumablyshowingfastereGFRdecline.Q:Whatarethecostsofcommonlyusedkidneyhealthmeasures,includingcreatinine,cystatinC,proteinuria,dipsticksandalbuminuria?A:Dipstickincludingproteinuria<serumcreatinine<dipstickalbuminuria=dipstickL-FABP<quantitativealbuminuria<cystatinC=quantitativeL-FABPHowever,frequencywillbeonceinacoupleofmonthdependingontheabovementionedconsiderations.Q:Whataretherelativeyields(utility)fromtestingproteinuriaversusalbuminuria;andaredipsticksadequate?A:Proteinurianegativeandalbuminuriapositiveismostlynon-progressor.IwouldrecommendtomeasuringurineL-FABPthreetimesayeartodetectthechangeofphenotype.Proteinuriapositivecasesshouldnotmeasurealbuminuriaindipstick.Iwouldrecommendtocomparequantitationofproteinuriaanddipstickforjustincasetomissmyelomarelatedkidneydiseases.lQ:Isthereapotentialroleforpoint-of-care(POC)testing,suchasnovelPOCsforreal-timeGFRorcreatininemeasurements,ormeasuresofurinealbumin,inapublichealthCKDprogram?A:Yes.WehaveasmalldatainVietnamandBangladesh.UsingL-FABPdipstick,wecanprovisionallyshowCKDdiseaseburdenasNCD.Q:WhereshouldtestingbeconductedandhowoftenshoulditberepeatedinaCKDdetectionandinterventionprogram?Whatnewtestsorbiomarkersarebeingdevelopedthat

mightexpanddiagnosisbeyondglomerularmeasuresinordertodetectandmonitorkidneytubulehealth?A:InJapan,wehavealreadydevelopedtheproduct,urineL-FABPbothforPOCandclinicallaboratory.Thisproductisreimbursedfortheuseevery3month.L-FABPisconsideredasthemonitorofproximaltubularstressandinjury.So,IrecommendL-FABPmeasure3timesayear,ifstableCKD.IfapatientissuspectedasprogressorconcerningthedevelopmentofAKIwithCKD,physiciansareallowedtousewiththeirowndecisionfortheirpatients.Q:ProposeresearchagendarelatedtothissectionA:AsImentionedearlier,CKDpatientsofstage2and3awillbethecandidateforthestudy.Iwouldprefertoplace3yearperiodwiththeuseofinulinclearanceorequivalenteveryyear.Thisisbecauseserumcreatininelevelinlowerresourcecountryisnotthelevelofhighresourcecountry.Then5indicators,serumcreatinine,serumcystatinC,urinealbumin,urineL-FABP,urineprotein,arecandidatesforthefollowupstudy.BothserumcreatinineandcystatinC(2x2)highgroupisdefinitelytheprogressor.Bothlowispresumablynon-progressor.OthertwoconditionsarethetargetofurinealbuminandL-FABP(2x2)basedonthepreviousdataofDKD.AlvaroGarcia–InternistaNefrologo(Doctor/Physician)Group1:EarlyCKDDetectionMeasures�WhatarestrengthsandweaknessesofcurrentlyavailablemeasurestoidentifyandcategorizeCKD;valuesofdiscriminatingrisk;specificity;¿andcosts?TheCKDstillpersistswithaveryhighincidenceandprevalence,especiallyindevelopingcountriesandLatinAmericans;inwhich50to70%ofpatientsconsultinlatestagesofCKD(G5),toinitiateRRTprograms,forcomplicationsthatprecipitatetheonsetofthistypeofhigh-costtherapies(Hemodialysis,peritonealdialysis);ThemostcommoncomplicationsofthepatientwithCKDare:congestiveheartfailure,acutecoronaryevent,stroke,hydroelectrolyticormetabolicdisorders,whichincreasethecostsofinitiationoftherapybyahigh%duetotheneedfor:intensivecareICU,catheterforonsetofdialysis,treatmentbyintensives,cardiologist,nephrologist,nursingetc.,andalsowithaverypoorpatientsurvivalexpectationsinthefirst3monthsafterstartingRRT.HassanR.showsthisbeginningofRRT,notcontrolledinhisworkon:RiskfactorsforUnplannedDialysisinitiation:AsystematicreviewoftheLiterature:whereitisshownthat(10.4%)ofdialysisbeganduringhospitalization,ordialysisbeganwithoutpriorvascularaccess(18.8%),orbymedicalemergency(14,6),other27%,etc.(3).Althoughpre-dialytictherapyisanepidemiological,medical,social,andeconomicsolution,etc.,whichavoidsadisorderlyandunscheduledadmissionofpatientswithCKDtoRRTinstageG5,andprovidesacomprehensivemedicaltherapytopatientsatdifferentstagesofCKDandtheircomorbidities;Healthprovidersarenotconvincedoftheeconomic/medicalbenefitsofthistypeoftherapyduetothelackofwell-designedstudies(RTCs),inwhichthesebenefitsare

revealed.ThestudyCanadianssober,thecostofcareforpeoplewithchronickidneydisease.Onacourtof219,641patientswithCKD,forayearonaveragepre-dialysisthecostoftheintegraltreatmentofUS$14,634perpatient/yearintheinitialstagesandshowshowthiscostisincreasingastheCKDprogresses,uptoreachanexponentialvalueofUS$95,000,toUS$100,000accordingtothetherapyusedHDorPDpatient/yearinstageG5.Thatiswhy:Isitimportantthatthetreatmentofthepre-dialysispatientbepartoftheRRTofthepatientwithCKD?�WhataretheidealCKDdetectionmeasuresandtheinfluenceofdemographiccharacteristicson;therelativevalueofcreatinineonlyversusaddingCystatinC,albuminuria/proteinuria,oratriple-markerstrategy?–Quantifytheglomerularfiltrationrate(GFR≥or≤of60ml/min/1.73m²)inthepatientwithCKD;Itisthestartingpointtostratifyitinto6subgroupsaccordingtotheGRF,whichisdirectlyproportionaltothedegreeofkidneydamagethepatienthas.ThereareseveralmarkersusedtodetermineGFR,eithermeasured(m)orestimated(e),bymeansofvalidatedformulas(MDRD;CKD-EPI);thesemarkerscanbedividedintoexogenous:Inulin,Cr-51-EDTA,Iothalamate,iohexolandothers;itsuseiscomplex,highcostanddifficulttoimplementinclinicalpractice,despitehavingaveryhighspecificityvalue.Themostcommonmarkersinmedicalpracticeareendogenous(Cr,CystatinC,andalbuminuria).Creatinine(Cr),isa113-Dabreakdown,aproductofmusclemetabolism,identifiedin1847,proposedasamarkerofglomerularfiltration1926.TheeGFRcrisamathematicalformulawhichcombinesnotonlybloodlevelsbutage,sex,race;totrytocorrectthesevariables.CystatinC(CysC)isa13-kDacysteineprotease,ubiquitousinallnucleatedcellsthatisproducedataconstantrate,freelyfiltered,notreabsorbed,andnotsecretedinrenaltubules.Itwasidentifiedin1979andproposedasamarkerofglomerularfiltrationin1985.CystatinCislessinfluencedwiththepatient'smusclemass,andeGFRisbettercorrelated,especiallyinspecialgroupsofthepopulationsuchas:vegetarians,musclewasting,diseaseschronicles,orlimbamputation;TheclearanceofCystatinC(eGFRcys)isnotmoresignificantthanthatdeterminedwitheGFRcr,instandardpopulations,butthecombinationofeGFRcr-cysissuperiortoeither(CrorCys).DetermineGRFonlywithcreatinine(Cr),eGFRcrlevelsinblood;Thismaybeunderestimatedespeciallyinthosepatientswithmusculardisorders,dietandmedicationsthataltertheconcentrationofCrinblood;TheUKguidelinesrecommenddeterminingrenalclearanceusingCystatinC,eGRFcysore-GRFcr-cys,especiallyinthosepatients,classifiedasG3aa1,(clearancebetween45to59ml/min/1.73m²,withoutproteinuria).TheeGRFcr-cysreclassifiesasmallproportion(7.7%)ofpatientsnotclassifiedwiththee-GRF-cr,butdoesnotpredicthigher%mortalityfromallcauses,or%intheprogressionofCKD.Theincreaseincostsis23pounds’patient/year,thereforemorestudiesarerecommendedtoclarifyitsimplementationTriple-markerstrategy:asamarkerofchronicrenaldamageverylittlehasbeenused,the

worksonthissubjectdemonstrateahighdegreeofsuperioritywhencomparedwithanyoftheothermarkers.ThecombinationofCr,CystatinC,andurinealbumin-to-creatinineratio(ACR),wouldimprovenotonlyidentifyingpatientswithCKDbuttherisksassociatedwithCKDcomparedwithCralone.TheReasonsforgeographicandRacialDifferencesinstroke(REGARDS),isaprospectivestudyin26,643patientsandtheMainoutcomemeasure:All–causemortalityandincidentin-stagerenaldiseasewithmedianfollow-upof4.6years,theconclusionwas:addingcysCtothecombinationofCrandACRmeasuresimprovedthepredictiveaccuracyforall-causemortalityandend-stagerenaldisease.�Whatcriteriashouldbeusedtoevaluatepotentialscreeningstrategies:accuracyversusmeasuredGFR;predictionofadverseoutcomes;sensitivityversusspecificity;¿stageclassification?ItisimportanttoplanthestrategiestofollowwhenmeasuringGFR.Thequantificationofthistest,bymeansofurinary,bloodcollection,orothertechniques,maynotbespecifiedbythecollectionbiasortooexpensiveandnotpractical.Atpresent,theeGFRestimate,throughformulas,whichhavebeenperfectedovertime,addingaseriesofvariablessuchasage,sex,bodymass,ethnicity,makesthemmorepreciseandisawaytodeterminetheGFRisusedthroughouttheworld.DuetothecostsandeaseofthetracertodetermineGFR,todateendogenousmarkerssuchasCrandCysarethemostused.ThemethodusedtodeterminetheGFRmustbehighlysensitive,ratherthanspecific;thisallowsusahighnegativepredictivepower,whichwecancorrectwithothermorespecifictests;inthecaseofeGRFcr,usingtheeGFRcyswhichcorrectsproblemsinspecialpopulationsinwhichCrlevelsarealteredasinvegetarians,amputees,orinthosewithmuscleproblemsetc.ThepressurepowerofeGRFincreasessignificantlyineitherofthetwoformulaswhenweaddthealbumin/creatinineradioACR,butdespitethis,thereareseveralcombinationsthathavebeenmadetoevaluateandclassifypatientsinstage1and2,andtheG3aa1(GFRbetween45-59ml/min)withoutproteinuria,withpoorresults,thatiswhyprecisemarkersareneeded.�Whatarethecostsofcommonlyusedkidneyhealthmeasures,includingCreatinine,CystatinC,proteinuria,dipsticksandalbuminuria?ThecostsofthedifferentmarkersusedinthediagnosisofCKDanditscontrolovertimevary,indifferentcountries;Itdependsonthehealthproviderthatmakesitstateorprivateentity:AsingledeterminationofCr$3.8US,CysC$73.3US,proteinuria$5.8US,Albuminuria/creatinine(ACR):$14.2US,dipsticks$3.1US,foratotalof$100USTheCanadianstudyoncostsperyearinpre-dialysisisUS$14,630�Whataretherelativeyields(utility)fromtestingproteinuriaversusalbuminuria;¿andaredipsticksadequate?Dip-stikproteinuriaisonlysensitivetoalbuminuriaandispoorlycorrelatedwiththequantificationofproteinuriain24h.Dip-stikisusedinRTCsofrenopro-tectivecharacter.Decideurineproteintocreatinineradio(UPCR)oralbumintocreatinineradio(UACR),correlateswithexcretionin24hours,Dip-stikcorrelatespoorlywithUPCR,and

moderatelywithUACR.TheUCARandUPCR,increasethediagnosisofeGFR,andareassociatedwithcardiovascularriskandhighmortalityinthepatientwithCKD.ProteinuriaoralbuminurianotonlyincreasesthediagnosisofCKD,whenweuseeGFRasamethod,butalsodeterminestheriskforRRTandcardiovascularrisk.TheUACRisamoresensitivemarkerinthediagnosisandfollow-upindiabetics,hypertensivepatients,glomerulardisease;butwhenweuseUPCRwecanidentify16%morepatientswithCKD,whoalsohaveahighriskofallcausesofmortality�Isthereapotentialroleforpoint-of-care(POC)testing,suchasnovelPOCsforreal-timeGFRorcreatininemeasurements,ormeasuresofurinealbumin,inapublichealthCKDprogram?AsimplescreeningmethodtodeterminethepresenceornotofCKDistomeasureCreatininelevels,withondrybloodspotonfilterpaperfollowedbytheclearancequantificationestimatedbyeMDRDcroreCKD-EPIcr.PatientswithGFR<60ml/min,couldbedeterminedin76%ofhypertensivepatients,30%indiabetics,37%ofpatientswithafamilyhistoryofCKD.Thesensitivityusingtheequation:e-MDRDwas96%,anditsspecificitywas55%.Bythee-CKD-EPIequationthesensitivepositivevaluewas94%,specificity55%.ThissimplemethodcanbeappliedasscreeningincommunitieswithhighriskofCKD.TheIwate–KENCOisaprospectivestudy,inacommunityof22,975patientswith5.6yearsoffollow-up,thediagnosisofCKD,determinedbyeGFR,improvedsignificantlywhentheUACRwasadded,ratherthanwhentheDip-stickproteinuriawasused,thiswasnotsoblunt,butbothpredictedthepossibilityofcardiovasculareventsinthefuture.Findinghighlysimple/specificdiagnosticmethodstoevaluatepopulationsatriskofCKDisthechallengewehavetofaceinthecomingyears.�WhereshouldtestingbeconductedandhowoftenshoulditberepeatedinaCKDdetectionandinterventionprogram?Whatnewtestsorbiomarkersarebeingdevelopedthatmightexpanddiagnosisbeyondglomerularmeasuresinordertodetectandmonitorkidneytubulehealth?AprogramforthepromotionandpreventionofCKDshouldbedevelopedineachofthecountriesoftheworld,withlocationsfullyidentifiedorsimilartohemodialysisorperitonealdialysisunits,andmakepre-dialysisapartofthepatient'sRRTwithCKD.TheserenalhealthentitieswouldbetheplaceswherethedevelopmentofCKDisdiagnosedandfollowedatthesametime(stages/interventions);theymusthavealltheprogramsoftheintegraltreatmentofthepatientwhichwillbederivedinaphasedmannertoRRTinstages5.Primaryorsecondaryinvolvementattheglomerular,tubularorinterstitiallevelcanleadtoaCKDovertime;thatiswhywemusthavesimplemarkersofeasyapplicationthatallowustoidentifythiscommitmentearly:1-Thesalivaureanitrogen(SUN)dipstick,hasbeensuggestedasascreeningtoolforacuteorchronickidneydiseasediagnosis,ishighlysensitiveinCKD2-AsymmetricDimethylarginine(ADMA),isanovelbiomarkerinCKD,isananalogueofL-arginine,itshighlevelsinhibittheproductionofnitricoxide(NO),causingendothelial

dysfunctiontypicalofpatientswithCKD3-SymmetricDimethylarginine(SDMA),isaproductofthemetabolismofmethylargininethatiseliminatedbythekidney,bloodlevelsandglomerularfiltrationcorrelatewiththedegreeofCKD.4-Uromodulin(Tamm-Horsfallprotein),itisproducedforthetubularcellsofthethickascendinglimb-isapromisingmarkerforthenumberofintactnephrons.5-KidneyInjurymolecule-1(KIM-1)isknownasaregulatorofthedifferentiationofproximaltubulecellsafteranischemicortoxicinjury,thismarkerisusedtoidentifyglomerulartabulardamageandisapredictoroftimedamageoftheKCD.6-NeutrophilGelatinase-associatedlipocalin(NEGAL)-itisafirstmoleculethathelpstheembryogeneticformationofthekidneyispartofthemesenchymecellandtubularepithelialcells-itslevelsfrequentlyincreaseintubulointerstitialdiseases7-miRNA,ncRNa,IncRNAandlicRNAbiomarkers-epigeneticapproachestowardstheexaminationofregulationofgenesinvolvedindiseasedetectionandprogressionarenowwideinterest.8-ProteomicandMetabolomicsBiomarkers:SerumCrandurinaryalbumin-proteomicbiomarkersmayfacilitatemoreaccurateandearlierdetectionofrenalpathologyBIBLIOGRAPHY1-CanadianSocietyofNephrology2014Clinicalpracticeguidelinefortimingtheinitiationofchronicdialysis.CMAJ,February4,2014,186(2)2-Whentostartdialysis:updatedguidancefollowingpublicationoftheinitiationDialysisEarlyandLate(IDEAL).TattersallJ.NephrolDialltransplant(2011)26:2082-20863-RiskfactorsforUnplannedDialysisinitiation:AsystematicreviewoftheLiterature:HassanR.etal,CanadianJournalofkidneyHealthanddisease.Vol6:1-14,20194-ThecostofcareforpeoplewithChronicKidneyDisease.CanadianJournalofkidneyHealthanddiseasevol6:1-11,20195-Creatininemeasurementondrybloodspotsampleforchronickidneydiseasescreening.SilvaAC.JBrasNfrol2016Mar,38(1):15-216-TheclinicalutilityandcostimpactofCystatincmeasurementinthediagnosisandmanagementofchronickidneydisease:Aprimarycarecohortstudy.PlosMed.2017Oct10;14(10).e10024007-CystatinCforglomerularfiltrationrateestimation:Comingofage.LeveyAS,ClinicalChemistry60:7,P16-919(2014)8-DetectionofChronickidneydiseasewithCreatinine,CystatinC,andUrineAlbumin-to-CreatinineradioandassociationwithprogressiontoEnd-StageRenaldiseaseandmortality.PeraltaCetal.Jama2011,April20;305(15)1545-15529-Proteinuriaversusalbuminuriainchronickidneydisease.GuhJY.Nephrology(carton).2010Jun;15;suppl2:53-6

10-9Stratifyingriskinchronickidneydisease:anobservationalstudyofUKguidelinesformeasuringtotalproteinuriaandalbuminuria.MsthvenS.QJM.W,2011Aug;104(8):663-7011-Comparisonbetweenurinealbumin-to-creatinineratioandurineproteindipsticktestingforprevalenceandabilitytopredicttheriskforchronickidneydiseaseinthegeneralpopulation(Iwate-KENCOstudy):aprospectivecommunity–basedcohortstudy.KoedaY.etal,BCMNephrology(2016)17:4612-NovelBiomarkersintheDiagnosisofchronicKidneydiseaseandthepredictionofitsOutcome.RyszJ.Int.J.Mol.Sci.2017,18,1702PierreDelanaye-UniversityofLiège(Doctor/Physician)IagreewiththeeffortsofKDIGOtoimproveearlydetectionofCKDatthepopulationlevel.Inthisview,severalpointsneedtobediscussed.FirsttheCKDdefinitionisbasedonafixed,uniquethresholdof60mL/min/1.73m².Thispointishoweververydebatable.Severalauthorshavearguedthatanage-adapteddefinitionisrequired,notablytobetterreflectthenaturaltrendofGFRwithaging1–21.Withsuchage-adapteddefinition,lessoldsubjectswillbediagnosedasCKD,butmanyyoungpatientswillbediagnosedearlierthanwiththefixeddefinition19,22.Forexample:justconsidera35-yearsoldman(orwoman)withGFRat65ml/min/1.73m²:isthisGFRlevelreally“normal”?AchangeintheCKDdefinitionisneeded(seeareviewpaperthatwillbesoonpublishedinJASN,10thSeptember).ThisisalsoveryimportantfordevelopingcountrieswhereCKDisimportantandfrequentinyoungpeople(demographicrepartitionofemergingcountriesbeingdifferentfromdevelopingcountries).ItisalsotimetoreconsidertheequationpromoteduntilnowbytheKDIGO:theCKD-EPIequations23.TheperformanceoftheCKD-EPIequationisveryquestionableatthetransitionbetweenadolescencetoadults24.TheethnicfactorintheMDRDorCKD-EPIequationsisquestionableinAfricanpeople25–29,butalsoinAfrican-Americans29,30.Therearereasonstothinkthatthe“toohigh”ethnicfactorinAfricanAmericansleadstolatereferral(theirGFRbeing“toohigh”,“toogood”).Otherequations(revisedLundMalmö/CAPAequations31,32andFullAgeSpectrum33,34)arebetterthanCKD-EPIinAfricans26,35,andalsosolvetheproblemduetotransition24.Eventually,themetricsusedinthecurrentliteraturetotestthepotentialsuperiorityofonegivenequationonanothershouldbedebated.1.DelanayeP,SchaeffnerE,EbertNetal.Normalreferencevaluesforglomerularfiltrationrate:whatdowereallyknow?NephrolDialTransplant2012;27:2664–2672.2.DelanayeP,GlassockRJ,PottelHetal.AnAge-CalibratedDefinitionofChronicKidneyDisease:RationaleandBenefits.ClinBiochemRev2016;37:17–26.

3.RuleAD,GlassockRJ.Chronickidneydisease:ClassificationofCKDshouldbeaboutmorethanprognosis.NatRevNephrol2013;9:697–8.4.GlassockRJ,WinearlsC.Anepidemicofchronickidneydisease:factorfiction?NephrolDialTransplant2008;23:1117–1121.5.GlassockRJ.Con:Thresholdstodefinechronickidneydiseaseshouldnotbeagedependent.NephrolDialTransplant2014;29:774–779.6.HallYN,HimmelfarbJ.TheCKDClassificationSysteminthePrecisionMedicineEra.ClinJAmSocNephrol2016;12:19–21.7.DenicA,MathewJ,LermanLOetal.Single-NephronGlomerularFiltrationRateinHealthyAdults.NEnglJMed2017;376:2349–2357.8.DelanayeP,CavalierE.Stagingchronickidneydiseaseandestimatingglomerularfiltrationrate:anopinionpaperaboutthenewinternationalrecommendations.ClinChemLabMed2013;51:1911–1917.9.GlassockRJ,RuleAD.Theimplicationsofanatomicalandfunctionalchangesoftheagingkidney:withanemphasisontheglomeruli.KidneyInt2012;82:270–277.10.PoggioED,RuleAD.CanwedobetterthanasingleestimatedGFRthresholdwhenscreeningforchronickidneydisease?KidneyInt2007;72:534–536.11.vandenBrandJA,vanBoekelGA,WillemsHLetal.IntroductionoftheCKD-EPIequationtoestimateglomerularfiltrationrateinaCaucasianpopulation.NephrolDialTransplant2011;26:3176–3181.12.WetzelsJF,KiemeneyLA,SwinkelsDWetal.Age-andgender-specificreferencevaluesofestimatedGFRinCaucasians:theNijmegenBiomedicalStudy.KidneyInt2007;72:632–637.13.WetzelsJF,WillemsHL,denHeijerM.Age-andgender-specificreferencevaluesofestimatedglomerularfiltrationrateinaCaucasianpopulation:ResultsoftheNijmegenBiomedicalStudy.KidneyInt2008;73:657–658.14.BauerC,MelamedML,HostetterTH.Stagingofchronickidneydisease:timeforacoursecorrection.JAmSocNephrol2008;19:844–846.15.O’HareAM,BertenthalD,CovinskyKEetal.Mortalityriskstratificationinchronickidneydisease:onesizeforallages?JAmSocNephrol2006;17:846–853.16.EllamT,TwohigH,KhwajaA.Chronickidneydiseaseinelderlypeople:diseaseordiseaselabel?BMJ2016;352:h6559.17.MoynihanR,GlassockR,DoustJ.Chronickidneydiseasecontroversy:howexpandingdefinitionsareunnecessarilylabellingmanypeopleasdiseased.BMJ2013;347:f4298.18.BotevR,MallieJP,WetzelsJFetal.TheClinicianandEstimationofGlomerularFiltrationRatebyCreatinine-basedFormulas:CurrentLimitationsandQuoVadis.ClinJAmSocNephrol2011;6:937–950.

19.DeBroeME,GharbiMB,ZamdMetal.Whyoverestimateorunderestimatechronickidneydiseasewhencorrectestimationispossible?NephrolDialTransplant2017;32:ii136-ii141.20.RoderickPJ,AtkinsRJ,SmeethLetal.Detectingchronickidneydiseaseinolderpeople;whataretheimplications?Ageandageing2008;37:179–86.21.DenicA,GlassockRJ,RuleAD.Structuralandfunctionalchangeswiththeagingkidney.AdvChronicKidneyDis2016;23:19–28.22.BenghanemGharbiM,ElseviersM,ZamdMetal.Chronickidneydisease,hypertension,diabetes,andobesityintheadultpopulationofMorocco:howtoavoid“over”-and“under”-diagnosisofCKD.KidneyInt2016;89:1363–1371.23.LeveyAS,StevensLA,SchmidCHetal.Anewequationtoestimateglomerularfiltrationrate.AnnInternMed2009;150:604–612.24.PottelH,BjörkJ,BökenkampAetal.Estimatingglomerularfiltrationrateatthetransitionfrompediatrictoadultcare.KidneyInt2019;95:1234–1243.25.YayoE,AyéM,YaoCetal.Measured(andestimated)glomerularfiltrationrate:referencevaluesinWestAfrica.NephrolDialTransplant2018;33:1176–1180.26.BukabauJB,YayoE,GnionsahéAetal.Performanceofcreatinine-orcystatinC–basedequationstoestimateglomerularfiltrationrateinsub-SaharanAfricanpopulations.KidneyInt2019;95:1181–1189.27.BukabauJB,SumailiEK,CavalierEetal.PerformanceofglomerularfiltrationrateestimationequationsinCongolesehealthyadults:Theinopportunityoftheethniccorrection.PloSOne2018;13:e0193384.28.MoodleyN,HariparshadS,PeerFetal.EvaluationoftheCKD-EPIcreatininebasedglomerularfiltrationrateestimatingequationinBlackAfricanandIndianadultsinKwaZulu-Natal,SouthAfrica.ClinBiochem2018;59:43–49.29.AnkerN,ScherzerR,PeraltaCetal.RacialDisparitiesinCreatinine-basedKidneyFunctionEstimatesAmongHIV-infectedAdults.EthnDis2016;26:213–20.30.DelanayeP,MariatC,MaillardNetal.Arethecreatinine-basedequationsaccuratetoestimateglomerularfiltrationrateinafricanamericanpopulations?ClinJAmSocNephrol2011;6:906–912.31.GrubbA,HorioM,HanssonLOetal.GenerationofaNewCystatinC-BasedEstimatingEquationforGlomerularFiltrationRatebyUseof7AssaysStandardizedtotheInternationalCalibrator.ClinChem2014;60:974–986.32.BjorkJ,GrubbA,SternerGetal.RevisedequationsforestimatingglomerularfiltrationratebasedontheLund-MalmöStudycohort.ScandJClinLabInvest2011;71:232–239.33.PottelH,DelanayeP,SchaeffnerESetal.EstimatingGlomerularFiltrationRatefortheFullAgeSpectrumfromSerumcreatinineandcystatinC.NephrolDialTransplant2017;32:497–507.

34.PottelH,HosteL,DubourgLetal.Anewestimatingglomerularfiltrationrateequationforthefullagespectrum.NephrolDialTransplant2016;31:798–806.35.PottelH,HosteL,DelanayePetal.Demystifyingethnic/sexdifferencesinkidneyfunction:isthedifferencein(estimating)glomerularfiltrationrateorinserumcreatinineconcentration?ClinChimActa2012;413:1612–1617.AlvaroGarcia–InternistaNefrologo(Doctor/Physician) Group2:PopulationstoScreenandIdentifyingAt-RiskIndividuals�ShouldscreeningforoccultCKDinanearlydetectionprogrambedirectedtoPopulationsortargetedtohigh-riskindividuals,usinganycombinationofkidneyMeasuresIthasbeenestimatedthat40%,ofthepopulationwithCKD,isnotdiagnosed(hiddenpopulation),especiallyintheinitialstages1,2,3,thispopulationwillbesubjecttopresenting,cardiovascularmorbidityandmortalityby20%,morefrequentthatthegeneralpopulationandtheywillconsultforCKDatlatestages,whichincreasesthecostsoftheirtreatmentfortheimplementationofRRT.Alloftheaboveconditionstoidentifyandtointervenethispopulationasquicklyaspossible.Alltheguidesagreethatitismorepractical,ofgreatercoverage,andmoreeconomicaltoidentifyhigh-riskpopulations:HT,Diabetics2,cardiovasculardisease,hereditarykidneydiseasesorwithfamilyassociations(glomerulopathies,interstitialnephropathies),indigenouscommunities,blacksetc.;thisinordertoclassifythestageoftheCKDandbeabletointervenethemmedically;ideally,makealow-costrapidscreeningtest:eGFR+DipsticksforUrineproteinsoraUPCRdetermination,whichincreasesthepowerofsensitivityandspecificity�Whataretheoptimumsettings(communitybasedvsprimarycarepractices)forcapturingatriskindividuals?CommunitypracticesondiseasesrelatedtoCKDsuchasdiabetesday,hypertension,heartdisease,kidneyday,areveryusefulnotonlytopromotetheeducationalpartaboutthem,butitisatimelyandkeymomenttoevaluatepatientsonCKD,usingfastandsimplescreeningmethods;activitiesthatcanincreasetheincidenceofCKDandknowthesocio-economicandculturalenvironmentofthepopulation.PrimarycareprogramsareoptimalfordiagnosingnewpatientswithCKD,theyhavedefinedevaluationandstratificationtechnology,butthenumberofpatientswhoattendtheseprogramsisnothighandissubjecttothehealthprogramsofeachcountryorregion.�WhatisthedifferencebetweenasurveillanceprogramandaScreening/detectionintervention,andwhatcanwelearnfrompriorprogramsincludingtheprevalenceofCKD?AnepidemiologicalsurveillanceprogramoftheCKDimpliesasystematicandpermanentcollectionoftheessentialdataoftheCKD(age,sex,race,mostfrequentetiology,stagesaccordingtotheGFR,etc.),toperformananalysisandinterpretationofyourdata;whichwillallowustoelaborateawell-definedplanning,thisallowstoimplementandevaluatethestrategiestofollowinaCKDprogram.Detentionandinterventiongoesbeyondidentifyingtheincidence

andprevalenceofCKD.Aninterventionprogrammustestablishpreventionstrategies,managementofCKDanditscomplicationsbyprimaryhealthcare;fullydefinedcriteriamustbetakentoreferpatientstoalevelofgreatercomplexityandtreatmentbynephrology,whichwillimprovetherenalhealthandprognosisofourpatients.Thereareseveralaspectsthatmustbetakenintoaccountinthisprogramamongothers:Susceptibilityfactors:whichincreasethepossibilityofkidneydamage?InitiatingFactors:thosethatdirectlyinitiatekidneydamage.Progressionfactors:worsenkidneydamageandaccelerateitsdeteriorationFinalstagefactors:Increasemorbidityinrenalfailuresituations(Spanishmodel).Thehighprevalenceofthisentity(CKD),itstreatmentcostsandtheassociatedcardiovascularcomplicationsmakeitnecessarytodevelopscreeningandinterventionprograms.�ShouldtheprevalenceofCKDortheabsoluteriskofCKDcomplicationsandESKDbeusedasthefirststepforanearlydetectioninterventionprogram?CKDisapublichealthandforpublichealthproblem,duetoitshighprevalenceestimatedbetween7and14%oftheworld'spopulation;duetoitshighmorbidityandmortalityintheadvancedstagesG4,G5;Itisalsoanimportantconsumerofhealthresourcesinallcountriesoftheworld,duetothehighcostsofRRT.Finallyitisassociatedasthemaincauseofcardiovasculardisease,vascularbrainandperipheralvascularinashorttime.AllthesesituationsmaketheCKD,animportantglobalhealthproblem,whichshouldbeapriorityinterventioninprimaryhealthcareprogramsintheinitialstages1,2,3;wheretheirdiagnosis,theirpossibleetiologyandtheeventsthatperpetuatedoracceleratethedeteriorationofrenalfunctionovertimearefullydefined,tocorrectandtreatthemmedically�Ifhigh-riskgroupsaretobeidentified,shouldtheabsoluteriskestimatebebasedonlifetimeriskorwithinafiniteintervaloftime(e.g.,10-yrrisk),andshouldtheriskestimatesbedependentonlaboratorymeasures?GiventheprevalenceofCKD,thevarietyofitsetiology,andtheneedforaclassificationindifferentstages(G6);ItisimportanttodetermineifduringthewholejourneyofCKDfromstage1to5,thesamefactorsofprogressionofCKDact,whichcanworsenoracceleratethedeteriorationofrenalfunctionandevaluatewhetherwecanmeasureorquantifythesefactorswithlabtests?Butalthoughmanyofthesefactorscalledtraditionalrisk,haveabundantRCTsoncardiovascularriskanddeath,inthegeneralpopulationandinitialstagesofCKD,manyofthemdonotinfluencetheprogressionofthedisease,intheadvancedstages.Traditionalmarkersofriskquantification,BUN,CR,glycemia,uricacid,k,Ca,P,urinecytochemical,albuminuria/proteinuria,Hblevels,Hto,arterialgases,Cholesterol-triglycerides,HDL,LDLetc.,areimportantintheinitialstagesoftheCKD,GFR>of30ml/min/1.73mts²;butinstagesG4,G5,theyareotherimportantfactorsthatinfluencethemorbidityandmortalityofthepatientwithCKD:(hyperparathyroidism,coronaryheartdisease,andvascularcalcifications,especiallyatthecoronarylevel).Theirdeterminationnot

onlyhelpsthediagnosisbuttheyaremarkersclarifythepathophysiologyofcomorbidity;quantifythe%risk,andsurviveatthisstageoftheCKC;thesemarkersaretotallydifferent:bloodlevelsofPhosphorus,Ca,vitaminD3,PTH,23FGF,MO,CarbamylatedLDL,ADMA,P-CresylsultatoFetuin,Osteopontin,osteocalcin,matrixgla-protein,matrixmetalloprotease3,24hydroxylase,homocysteine,amongothers,arebloodlevelmarkersthatareassociatedwiththeriskofCKDinadvancedstages.�Howdoearlydetectionstrategiesapplyatextremesofage,suchasinpediatricsoramongolderadults?Thestrategiestofollowinextremeagesaretotallydifferent.Inpopulationsatrisk,eGFRandalbuminuriashouldbeperformedeveryyear(ifitispositive,itmustbeconfirmed2or3timesin3months).Thisdeterminationshouldbemadeinpopulationssuchas:type2DM,HTa,orestablishedcardiovasculardisease.Itisadvisabletoevaluaterenalfunctioninpeopleover60,obese(BMI>35kg/m²)withtype1DM,withmorethan5yearsofevolution,relativesin1degreeofhereditarykidneydiseases,obstructiveurinarytractdisease,treatmentprolongedwithnephrotoxicdrugs(nonsteroidalanti-inflammatorydrugs,antineoplasticdrugs);patientswithcardiovascularrisk(hyperlipidemia,metabolicsyndrome,smokers),historyofAKI,chronicinfections,autoimmunediseasesandmalignanciesassociatedwithCKD.TheCKDstage(fromG1toG5),plusthedeterminationofalbuminuria(<30,30-299,>300mg/g),allowsustomonitorpatientsandrefertothenephrologistforprogressionofCKD,>thannormaldeteriorationovertime,forexample:decreaseineGFR>5ml/min/yearor>10ml/minin5years.Youshouldalwaysdetermineyourprogressionwithtwovariables:impairmentoftheGFR>25%orincrease>50%oftheUACR.ThecriteriaforreferraltothenephrologistaredeterminedbytheGFRorUACR,aGFR<30ml/min/1.73mts²oraproteinuria>300mgr/gr,exceptinpatients>80yearsofage,withoutprogressionofCKD.RRTcandidatesmustbesenttothenephrologist1yearbeforestartingthistherapy.Patients<70yearswithGFRbetween30-45ml/min/1.73mts²,shouldbemonitoredevery3-6monthsandthosewithlessthan30ml/min/1.73mts²every3months;Inaddition,allpatientswithanaccelerateddeteriorationofGFRoralbuminuria,whoareoutsidetheproposedrange,shouldbereferred.Wehavelittleexperienceinpediatrics,butchildrenwithahistoryoffamilyinheriteddiseases(Allportsyndrome,Ochoafacialurosyndrome,ADPKD,congenitalglomerulopathiesetc.)shouldbeevaluated,theirfollow-upmustbefullydefinedbynephronpediatricians.�Howmightweidentifyindividualsthatneedre-screeningafteraninitiallynegativescreen?Ingenerale-GFR,itisinadequateinaseriesofclinicalsituationswhichmustbetakenintoaccountforexample:patientswithanextremeBMIbodyweight<19kg/mts²or>35kg/mts²,peoplewithspecialdiets(vegetarians,creatinesupplements),malnutrition,impairedmusclemass,<18years,liverdisease,ascites,AKI,adjustmentofrenaleliminationdrugs,metabolicsyndromeetc.ManyoftheseGFR

determinationscanbecorrectedwithasecondtest,UACR,oruseofcysC.Asecondre-screeningscenariocanoccurinpatientswithclinicalconditionsinwhichrenalinvolvementisfullydemonstratedinahighpercentageovertime:typeDMwithmorethan10yearsofevolution,orDM1withmorethan5years,poorlycontrolledhypertension,cardiovasculardisease,rheumaticdiseases,neoplasmsassociatedwithkidneydamage,familyinheriteddisease(Allportsyndrome,ADPKD,urofacialurosyndrome,someglomerulopathies,),blackpatients,specialethnicities,etc.Inwhich,itisnecessarytomonitoryourrenalfunctiontodetermineyourGFR.�Aretheresocial,behavioral,occupationalorenvironmentalexposuresthatwouldwarrantpopulationscreeningratherthanindividualrisk-basedtargeting?Thesocial,culturalenvironmentandtheworkenvironmentareimportant,ascontributingfactors,whichcanactonageneticbasis,toconfigurerenaldamageovertimeleadingthepatienttoCKD;Aclearexampleofthisisintheso-calledBalkannephropathy,orMesoamericannephropathyofCentralAmerica,wherethetriggersofthemarefullystudied.InColombiarecentlyaNephrologistDr.EdgarSanClemente,didanexcellentjob(book),onenvironmentaltoxic,medicinesandCKD.Throughrenalbiopsytakeninminerswhoexploitriversandquarriesinsearchofgoldusingmercuryandcyanide,hewasabletorelatethepresenceofglomerulopathiesinthesepatients;Theuseofpesticidesattheleveloftheagriculturalindustry(Cañaduzales)wasanotherimportantscenariotoevaluatefactorsthatinducerenaldamage;finallyairpollutioninlargecitiesinthenumberofdissolvedparticlesintheenvironment,notonlycausediseasesoftheairway,butpossiblekidneydamage.WesuggesttoKDIGOaspecialsegmentintheguidelinesonCKD,includingtheworkenvironment,andnephrotoxinsasapossibleetiologyofCKD,onapreviousgeneticbasis�Shouldtherebearoleforreflexfamilyscreeningifancestralfactors,suchashigh-riskAPOL1genotype,arepresentamongscreenedindividuals?Attheliteratureleveltherearemanyarticles,whichrelategeneticfactors,totheenvironment;thisallowsustoexplainwhythereareregionswithahigherincidenceofCKDwhencomparedtoothers(3)Bothgenomicfactorsandenvironmentalfactorscontributetothiscomplexheterogeneousdisease.CKDheritabilityhasbeenestimatedat30to75%.Genome-wideassociationstudies(GWAS)andGWASMeta-analyzeshamidentificationgeneticlociassociatedwithCKD(1)InaCanadianstudy(2),ongeneticriskfactorsofCKD,Iconcludethat5SNPsisaproteinrelatedto(Osteopontin,osteocalcin,matrixglaprotein,matrixmetalloprottease3and24hydroxylase)whichisassociatedwithanincreaseinCKD,producingvascularcalcificationstypicalofstagesG4,G5.AswecanseeinadditiontotheAPOL-1gene,therearemanystudiesthatshowahighassociationbetweenthegeneticpartandenvironmentalfactorsasanadjunctinthedevelopmentofCKD.�Whatpromisingemergingopportunitiesortechnologies(e.g.,AI)existforautomatedandtargetedsurveillanceapproachestoidentifyat-riskindividuals?’

TheAI,incellulartablets,PC,others;whichhavesmallprogramsformonitoringbloodpressure,heartrate,electrocardiograms;orestimatetheGFRorpossibilityofreachingtheCKDinawhile;theyareimportantelectronicmeasures;whichmustbecorrected,makethemmoresensitiveandeffectiveintheirmeasurements.Aplaceofformalconsultationoftheusermustbeprovidedtoresolvetheirconcerns,thisapproachmustbeusedtocapturethesepatients,anddetermineiftheyhaveorCKD,toenterthemintoaformalprogram.Weonlyhaveonedoubt,theseelectronicresourcesarenotsopopularinthirdworldcountriesbecauseofthecosts,andstrategiesfortheirendowmentshouldbestudied.Bibliography1-Geneticsusceptibilitytochronickidneydisease–somemorepiecesfortheheritabilitypuzzle.Cañadas-GarreM.etal.FrontGenet.2019may31,10.4532-AssociationofCandidategenepolymorphismwithkidneydisease.Resultsofacase-controlanalysisinthenefronacohort.VallsJ.FrontGenet2019feb26;10:1183-Geneticanddevelopmentalfactorsinchronickidneydiseasehostspost.FridmanDetal.SeminNephrol.2019May,39(3):244-2554-CoronaryArteryDiseaseinPatientswithChronicKidneyDisease:AClinicalUpdate.QiangjunCaietal.CurrentCardiologyRevews,2013,vol9,No4:331-339LingyunLi-Relypsa(MedicalDirector)ThankyouforprovidingusanopportunitytocommentontheScopeofWorkfortheKDIGOControversiesConferenceonEarlyIdentification&InterventioninCKD.Wehavereviewedtheselectedtopicsthatwillbecoveredduringthemeetingandwouldliketorecommendthatthefollowingtopicbeaddressedduringthecontroversiesconference.RAASinhibitoruseindelayingCKDprogressionandmanagementoftheassociatedriskofhyperkalemiaGroup3Topic1intheproposedScopeofWorkcommentoninterventions(e.g.,lifestyles,diet,pharmaceuticals)weshouldadopttopreventCKDonsetand/orslowCKDprogressionandtopreventCVDandHF.Apartofthisdiscussionshouldfocusontheutilityandoptimizationofrenin-angiotensin-aldosterone-system(RAAS)inhibitorsindelayingdiseaseprogressioninthispatientpopulation,theassociatedriskofhyperkalemia,andmanagementstrategiesforhyperkalemia.RAASinhibitors,includingangiotensin-converting-enzyme(ACE)inhibitorsandangiotensin-receptor-blockers(ARBs)arerecommendedbyKDIGOguidelineasfirst-lineagentstopreventCKDprogressionindiabeticandnon-diabeticadultswithCKDandurinealbuminexcretion>300mg/24hours(1B)andindiabeticadultswithCKDandurinealbuminexcretion30–300mg/24hours(2D)(KDIGO2012CKDguideline).RAASinhibitorshavebeenshowntosignificantlyreducethedegreeofproteinuriaandtherateoflossofrenalfunction,reducetheriskofdevelopingend-

stagerenaldisease,andmostimportantly,reducetheriskforkidneyfailure,cardiovascularevents,andall-causemortalityinCKDpatients(Brenneretal,2001;Lewisetal,2001;Xieetal,2016).Inaddition,mineralocorticoidreceptorantagonists(MRA)havebeenshowntodecreaseurinealbuminexcretionwhenaddedtoACEiorARBtherapyinpatientswithCKD(KDIGO2012BPguideline).ManypatientswithCKDhaveco-morbidheartfailure;inthissetting,MRAarealsoClass1ArecommendedtherapiestoreducemorbidityandmortalityforsymptomaticpatientswithHF-REF,andClassIIBrecommendedtherapiestoreducehospitalizationsinpatientswithHF-PEF(Yancyetal,2013;Yancyetal,2017;Ponikowski,2016).DespitethebenefitsofRAASinhibitorsinCKDpatients,hyperkalemiahasbeenreportedinclinicaltrialswithRAASinhibitorsandconstitutesthemajorbarrierfortheutilizationofguideline-recommendedRAASitreatment(Epstein,2016).Sub-maximumdosesanddiscontinuationofRAASitherapyresultinworsepatientoutcomes(Epstein,2015).Recently,theemergingnewpotassiumbinders(patiromerandSZC)provideoptionsforsafeandeffectivetreatmentofhyperkalemia(Bakrisetal,2015;Weiretal,2015;Kosiborodetal,2014;Spinowitzetal,2019),andmayfacilitatemaintainingpatientsonoptimaldosesofRAASinhibitorsasrecommendedinthecurrenttreatmentguidelines.Forthesereasons,wesuggestthatthefollowingquestionsbeaddressedwithintheproposedScopeofWork:•HowdoweimproveuseofRAASinhibitorstoslowCKDprogression,anduseofMRAattheguidelinerecommendeddosesamongindividualswithCKDandHF-rEF?•DoesdiscontinuationofRAASinhibitorsasthemethodofcorrectionforhyperkalemiaaffectpatientoutcomesinCKDandHF?Ifyes,howdoweensurethatthepatientsgetoptimalRAASitreatment?•WhataretherecommendationsforthemanagementofhyperkalemiaforCKDpatientsonRAASinhibitors?References:BakrisGL,PittB,WeirMR,etal.EffectofPatiromeronSerumPotassiumLevelinPatientsWithHyperkalemiaandDiabeticKidneyDisease:TheAMETHYST-DNRandomizedClinicalTrial.JAMA.2015;314:151-161BrennerBM,CooperME,deZeeuwD,etal.fortheRENAALStudyInvestigators;EffectsofLosartanonRenalandCardiovascularOutcomesinPatientswithType2DiabetesandNephropathy.NEnglJMed.2001;345(12):861-869EpsteinM,ReavenNL,FunkSE,etal.Evaluationofthetreatmentgapbetweenclinicalguidelinesandtheutilizationofrenin-angiotensin-aldosteronesysteminhibitors.AmJManagCare.2015;21(11):S212–S220EpsteinM.Hyperkalemiaconstitutesaconstraintforimplementingreninangiotensin-aldosteroneinhibition:thewideninggapbetweenmandated

treatmentguidelinesandthereal-worldclinicalarena.KidneyIntSuppl.2016;6(1):20–8KidneyDiseaseImprovingGlobalOutcomes(KDIGO)CKDworkgroup.KDIGO2012clinicalpracticeguidelinefortheevaluationandmanagementofchronickidneydisease.KidneyIntSuppl.2013;3(1):1–150KidneyDiseaseImprovingGlobalOutcomes(KDIGO)WorkingGroup.KDIGOclinicalpracticeguidelineforthemanagementofbloodpressureinchronickidneydisease.KidneyIntSuppl.2012;2(5):337–414KosiborodM,RasmussenHS,LavinP,etal.Effectofsodiumzirconiumcyclosilicateonpotassiumloweringfor28daysamongoutpatientswithhyperkalemia:theHARMONIZErandomizedclinicaltrial.JAMA.2014;312(21):2223-2233LewisEJ,HunsickerLG,ClarkeWR,etal.CollaborativeStudyGroup.Renoprotectiveeffectoftheangiotensin-receptorantagonistirbesartaninpatientswithnephropathyduetotype2diabetes.NEnglJMed.2001;345(12):851-860PonikowskiP,VoorsAA,AnkerSD,etal.2016ESCGuidelinesforthediagnosisandtreatmentofacuteandchronicheartfailure:TheTaskForceforthediagnosisandtreatmentofacuteandchronicheartfailureoftheEuropeanSocietyofCardiology(ESC).EurHeartJ.2016;37(27):2129-2200SpinowitzBS,FishbaneS,PergolaPE,etal.SodiumZirconiumCyclosilicateamongIndividualswithHyperkalemia:A12-MonthPhase3Study.ClinJAmSocNephrol.2019;14(6):798-809WeirMR,BakrisGL,BushinskyDA,etal.PatiromerinpatientswithkidneydiseaseandhyperkalemiareceivingRAASinhibitors.NEnglJMed.2015;372:211-221XieX,LiuY,PerkovicV,etal.Renin-angiotensinsysteminhibitorsandkidneyandcardiovascularoutcomesinpatientswithCKD:aBayesiannetworkmeta-analysisofrandomizedclinicaltrials.AmJKidneyDis.2016;67(5):728–41YancyCW,JessupM,BozkurtB,etal.2013ACCF/AHAguidelineforthemanagementofheartfailure:areportoftheAmericanCollegeofCardiologyFoundation/AmericanHeartAssociationTaskForceonPracticeGuidelines.JAmCollCardiol.2013;62(16):e147–e239YancyCW,JessupM,BozkurtB,etal.2017ACC/AHA/HFSAFocusedUpdateofthe2013ACCF/AHAGuidelinefortheManagementofHeartFailure:AReportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceonClinicalPracticeGuidelinesandtheHeartFailureSocietyofAmerica.JAmCollCardiol.2017;70(6):776-803FrancescoLocatelli-AlessandroManzoniHospital(Doctor/Physician) Ifullyagreewiththeverygoodquestionsforthe4groups:youdidawonderfuljob!IwouldliketounderlinethatthepresentmethodsformeasuringGFRareabletodetectakidneydamageonlywhenthereisalreadyanimportantdamageofthe

kidneys.Therefore,weneednewmethodsforevaluatingtherenalfunction.Thesceeningforalbuminuriaismuchmoreimportantfordetectingearlykidneydamage.Eventualythemarkersoftubulardamagecouldbemoreimportantfordetectingrenaldamagerelatedtotheworkeractivities.Theworkersintheagicolture(andtheproductstheyareusing(KidneyIntRep(2018)3,271–280;https://doi.org/10.1016/j.ekir.2017.10.006)andtheclimatewheretheyareworking)shouldbecarefullyconsidered,takingintoaccounttheprevalenceofCKDindifferentpopulationsandconsideringtheirlifeexpectancy(inpopulationwithoutapparentreasonsfordifferentlifeexpectancy)forselectingtheprioritiesamongthepopulationtobetested.Thepossiblekidneydamageassociatedwithplasticcontaminationisanotherinterestingtopicforresearch(DOI:10.1056/NEJMc1907676).JosephVassalotti-NationalKidneyFoundation&IcahnSchoolofMedicineatMountSinai(Doctor/Physician)Overall,thisisaclear,well-organizedandcomprehensiveScopeofWorkforEarlyIdentification&InterventioninCKD.IcommendKDIGOandtheorganizersforaddressingthistopic.Themostimportantaspectofthisworkisthatthetargetpopulationisnotthegeneralpopulation,norisitrestrictedtointerventionsinCKD.MethodsthatCKDidentification&interventioncanbeintegratedintopopulationhealth,qualityimprovementandothersystematicapproachestocareinchronicdiseasesorriskconditionsisclearlydescribedinthisscopeofwork.ThisallowsCKDidentificationandinterventionstobeintegratedintoexistingworkflows,ratherthancreatingdenovoCKDcareplan.Thisiscrucialfordisseminationandscale.Specificcommentstoconsiderforstrengtheninganalreadyexcellentscopeofwork.MajorPage3:DietitiansandnutritionisimportantenoughtoearlyCKDinterventiontobenotedspecifically.Page5:Group1earlyCKDdetectionmeasures-abulletonthestatusofinternationalstandardizationoflaboratorymethodsisimportant-sCrstandarized-internationalimplementationstatus?,uACR(pendingstatus?),sCystatinC(pendingstatus?),uPCR(likelynotfeasible).Page6:Group2PopulationstoScreenandIdentifyingAt-RiskIndividualsIntroducingtheconceptofperceived-riskforCKDhereisworthconsidering.Thisisaconceptthatcouldbesystematicallypromotedorassessed.Inotherwords,doesthepopulationwithDMandorHTNknowthattheyareatriskforsubsequentCKD?(SeeBoulwareLE,CarsonKA,TrollMU,PoweNR,CooperLA.Perceivedsusceptibilitytochronickidneydiseaseamonghigh-riskpatientsseeninprimary

carepractices.JGenInternMed.2009;24(10):1123-9.)ThisisdistinctfromtheconceptofCKDawareness.Page7:Group3OptimalInterventionsandImplementationafterCKDDetection.ThedistinctionbetweenslowingprogressionandpreventingCVeventsandparticularlypreventingHFisimportant.Accordingly,CKDmetabolicacidosisisimportanttonoteassmallRCTssupportalkalitreatmentslowsprogression,whereashyperuricemia,inflammation,CKDanemiatherapiesareimportantbuthavenocompellingRCTdatathatdemonstratetreatmentslowsCKDprogression.Page8:Healthsystemandeconomicfactors-theconditionsthatarelistedhereasmodelsforintegrationofCKDcareareCVD,DMandHIV.Theseareimportant.Obesityisnotmentionedanywhereinthisscopeofworkandmaybeworthincludinghereand/orelsewhere.Also,thereisanobviousinter-dependenceofthisdiscussionwiththeGroup2at-riskpopulationstoscreen.Ideally,alltheconditionsnotedinthediseasemanagementsectiongroup4wouldbeaddressedbythescreeninggroup2.Althoughthelistofthelattercouldbemoreextensiveorcomplete.MinorPage1:USCDCdescribes15%ofthepopulationwithCKDinthe2019kidneydiseasefactsheet.Seehyperlink:https://www.cdc.gov/kidneydisease/pdf/2019_National-Chronic-Kidney-Disease-Fact-Sheet.pdfAdditionalReferencestoconsiderotherthanthe8intheSoW-pdfprovidedonrequest,asapplicable.Iamgenuinelyhonoredandexcitedtobeabletoparticipateandcontributetothisdiscussion.GolestanehL,AlvarezPJ,ReavenNL,etal.All-causecostsincreaseexponentiallywithincreasedchronickidneydiseasestage.AmJManagCare.2017;23(10Suppl):S163-S172.ChenRA,ScottS,MatternWD,etal.Thecasefordiseasemanagementinchronickidneydisease.DisManag.2006Apr;9(2):86-92.LacsonE,WangW,et.al.Effectsofanationwidepre-dialysiseducationalprogramonmodalitychoice,vascularaccess,andpatientoutcomes.AmJKidneyDis.2011;58:235–242.DixonJ,BordenP,KanekoTM,etal.MultidisciplinaryCKDcareenhancesoutcomesatdialysisinitiation.NephrolNursingJ.2011;38(2):165-171.NorfolkE,HartleJ.NephrologyCareinaFullyIntegratedCareModel:LessonsfromtheGeisingerHealthSystem.ClinJAmSocNephrol.2013;8(4):687-693.JohnsonDS,KapoianT,TaylorR,et.al.GoingUpstream:CoordinationtoImproveCKDCare.SeminDial.2016;29(2):125-34.

FishbaneS,AgoritsasS,BellucciA,etal.AugmentedNurseCareManagementinCKDStage4to5:ARandomizedTrial.AmJKidneyDis.2017;70(4):498–505.NarvaA.PopulationHealthforCKDandDiabetes:LessonsfromtheIndianHealthService.AmJKidneyDis.2018;71(3):407-411.CarrollJK,PulverG,DickinsonLM,etal.Effectof2ClinicalDecisionSupportStrategiesonChronicKidneyDiseaseOutcomesinPrimaryCare:AClusterRandomizedTrial.JAMANetwOpen.2018;1(6):e183377.KramerH,JimenezEY,BrommageD,etal.MedicalNutritionTherapyforPatientswithNon-Dialysis-DependentChronicKidneyDisease:BarriersandSolutions.JAcadNutrDiet.2018;118(10):1958-1965.BanalN,ZelnickL,BhatZ,etal.BurdenandOutcomesofHeartFailureHospitalizationsinAdultsWithChronicKidneyDisease.JAmCollCardiol.2019;73(21):2691-2700.NationalKidneyFoundation.LaboratoryEngagementInitiative.Hyperlink:https://www.kidney.org/CKDintercept/laboratoryengagementAmericanSocietyforClinicalPathology.Twenty-fiveThingsPhysiciansandPatientsShouldQuestion.Hyperlink:https://www.ascp.org/content/docs/default-source/get-involved-pdfs/25-things-to-question.pdf(seekidneyprofile21of25)NationalKidneyFoundationKidneyHealthEvaluationMeasure.Hyperlink:https://www.kidney.org/sites/default/files/nkf-kidney-health-evaluation-measure-worksheet.pdfVassalotti,JA,DeVinneyR,LukasikC,etal.CKDQualityImprovementInterventionwithPCMHIntegration:HealthPlanResults.AmJofManagedCare2019November(inpress)CesarLoza-PeruvianUniversityCayetanoHeredia(Doctor/Physician)Allquestionsorquestionsareverywellfocused:ButIthinkthatanimportantquestionthatcouldbeincorporatedwouldbe;IfthenationalhealthsurveysimplementedbysomecountriestoperiodicallyassesstheprevalenceofCKDisarecommendedpractice,tobeimplementedinallcountriesoftheworldGuillermoGarciaGarcia-UniversityofGuadalajara(Doctor/Physician)Someadditionalquestions:andonecomment.RoleofIntegrationofCKDintoNCDsprograms?AnyprogresssincetheBangkokKDIGOConference?RoleofCKDdetectionaspartofNationalHealthSurveys.RoleofmandatoryCKDdetectionbydialysisproviders(theexampleofColombia)Whatistheroleofkidneyfoundations,especiallyinLMIC?Roleoffragmented,dysfunctionalHealthSystems(Mexico,India,SouthAfrica)asbarrierstosuccessfulimplementation)MainbarriersinLMICarethoselinkedtopoverty(socalledsocialdeterminantsofhealth):lackorcosttoaccesstohealthcare,includingmedicationsandlabtests;geographicbarriers;healthliteracy;culturalbeliefs;barriersimposedbythehealth

system(ie.enMexico,patientswithSeguroPopulararedeniedtreatmentwhentheyareidentifiedashavingkidneydisease),losingtheopportunitytointervenetoretardCKDprogression)SijieZheng-KaiserPermanente/ThePermanenteMedicalGroup(Doctor/Physician) Group3:OptimalInterventionsandImplementationafterCKDDetection•WhatInterventions(e.g.,lifestyles,diet,pharmaceuticals)shouldweadopttopreventCKDonsetand/orslowCKDprogressionandtopreventCVDandHF?1.Stopsmoking2.StopNSAIDs3.Avoidprocessedfood,4.Avoiddairyproduct5.Plantbaseddiet6.Weightloss7.Exerciseastolerates8.ACE-I/ARB9.Lowsaltdiet10.Statin11.NotsureaboutSGLT-2inhibitorsyet,especiallyinlowresourcecountries.12.ControlDM13.TreatOSA•BeyondBP,glycemicandlipidcontrol,whatareotherriskfactorsthatweshouldbetargeting?(e.g.,metabolicacidosis,hyperuricemia,inflammation,anemia,etc.)Metabolicacidosis,theothershavenostrongevidence•Whatadditionalriskfactors/interventionsshouldweconsideramongindividualswithCKDandothercomorbidities(e.g.,ASCVD,heartfailure,etc.)?ASCVD,CHF,OSA,Obesity,smokecessation,•When,how,andhowoftentomonitorpreventiveinterventionsamongpeopleatriskorwithCKD?CKD3a:every6monthsCKD3b-4:every4monthsCKD5:every2-3months•Howcanweimprovedisseminationofguideline-basedcareviaimplementationorknowledgetranslationefforts?Notunderstandingthequestion•WhatriskalgorithmscanweusetostratifyrisklevelsamongpersonsatriskfororwithCKD?PCR/ACR•Howdopatientperspectivesandvaluesaffectdecisionsarounddetectionefforts,suchastherelativebenefitsfromearlyawarenessbalancedwithconcernsofoverdiagnosis,medicationsideeffects,monitoring,andlivingwithadiseaselabel?IfthereisresourcethatabletochangetheprogressionofCKD,thenearlydetection

canbedone.Inresourcechallengedsituation,wheninterventionisnotfeasible,earlydetectionmaynotbebeneficious.•WhatistheroleofpatienteducationandCKDawarenessprogramstopreventCKDonsetandprogression,andtopreventCVD?Veryimportant,highyield•Whatistheroleofself-managementandnewtechnologies(mobileapps)whendetecting/managingCKD?Yes,needeasyusemobileapps•Whatdoessuccessfulimplementationofearlydetection/managementofCKDprogramslooklike,andwhatconstitutesaproofofconceptforsuchprograms?KaiserPermanentehasaverygoodupstreamCKDmanagementprogram,focusonbloodpressurecontrol,avoidnephrotoxins,cholesterolcontrol,measureUrineprotein,makesureCKDpatientsareonACE-I/ARB.•ProposeresearchagendarelatedtothissectionRadicaAlicic-ProvidenceHealthCare(Doctor/Physician)Thankyoufordevelopingclearobjectivesandexcellentdiscussionquestions.I'mthrilledtoseehealthsystems,caredeliveryandeconomicfactorsincludedindiscussion.Recognitionofobstaclesforimplementationofanymajorinitiativeiscrucialforitssuccess,butitisfrequentlymissingformourdiscussions.Inclusionofthistopicwillhelpestablishclearpathwayforimplementationofsuggestedmeasures.Iwouldliketomakesuggestionforincludingfewreferencesforsuggestedreview-NortonJM1etal.DevelopmentandValidationofaPragmaticElectronicPhenotypeforCKD.ClinJAmSocNephrol20196:1306-1314Epub2019Aug12.-InkerLAetal.GFRSlopeasaSurrogateEndPointforKidneyDiseaseProgessioninClinicalTRials:AMeta-AnalysisofTreatmentEffectsofRadnomizedControlledTrails.JASN201930:1735-1745-MorganEGetal.EvaluatingGlomerualFiltrationRateSlopeasaSurrogateEndPointfroESKDinClinicalTrials:AnIndividualParticipantsMeta-AnalysisofObservationalDataJASN201930:1746-1755-GreeneTatal.PerformanceofGFRSloeasaSurrogateEndPointforKidneyDiseasePtogressioninClinicalTrials:AstatisticalStimulation.JASN201930:1756-1769JoseErnestoLopez-Almaraz-FreseniusMedicalCare(Doctor/Physician)Group1:itisfundamentaltodifferentiatebetweenscreeningand"confirmandcategorize"CKD,perhapswithanalgorithmthatmakescleartheimplicationsoftheprocess(i.e.thescreeningwon'tallowsustoprovideaprognosis,buttocatchearlystagesandpromoteinterventionstostop/slowprogression.Thegroupshouldworkonsimpleguidesinordertomakeiteasiertodecide(forPCP's)whatstudiestheyshoulduseinthediagnosisandstratificationofCKD.SerumCreatinine(with

eGFR),ACR(spotor24H),urinaryoutput,urinarysediment,renalultrasoundshouldbeconsideredasasecondstepafterscreeningforconfirmatory(andclassification)purposes.Group2:geographical,ethnicalandetiologyfactorsshouldbeconsideredwhenaddressingscreeningforCKDsinceinhighriskpopulations(i.e.diabetes)shouldleadtosupportcommunitybasedprogramswhereaslessprevalentetiologiesshouldbedirectedtoprimarycare-basedscreening.Group3:-Analgorithmand/ora"checklist"formodifiableriskfactorsthatmaybeusedshouldbeconsidered,perhapswithfocuson(a)PrimaryCare,(b)InternalMedicine/Pediatritian,(c)Nephrologist(Adult&Pediatric).-Selfmanagementshouldincludeinthediscussiontoolsrelatedtoself-monitorprogressionofCKD(eGFRandproteinuria)oncethediseaseisestablished,alongwithEducationalProgramsbothfromHCP'sandalsowithcollaborationofPatient'sgroupsorassociations.Group4:-Insteadof"developingvs.developedcountries"weshouldtalkaboutHealthcareSystemsandCoverageforEarly(andthereforeAdvanced)CKD.Screeningprogramsmaybe"uncomfortable"forthosecountrieslackingofUniversalHealthCoveragesincetheseprogramsmayincreasetheprevalenceofthediseaseandtherequirementfortreatment.-WhatwouldbetheimplicationsofbeingclassifiedasCKDpatientduringascreeningprocessforInsuranceeligibilityandcostrelatedtoit?Shouldweconsiderotherkidneydiseasemarkers(ACR,hematuria,structural)beforelabelandclassifyapatientwithCKDbasedsolelyontheeGFR?