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KDIGOControversiesConferenceonBloodPressure&VolumeManagementinDialysis

February7-10,2019Lisbon,Portugal

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

Increasingevidenceoverthelastdecadehashighlightedbloodpressure(BP)andfluidvolumestatusaskeymediatorsofpooroutcomesamongindividualsreceivingmaintenancedialysis.1-6Concomitantly,thedialysiscommunityhasbeguntoexpandthedefinitionof“adequatedialysis”,aconcepttraditionallydefinedbysmallmoleculeclearance,tootheraspectsofdialysiscare,includingBPandvolumemanagement.1,7InthefirstoffourplannedKDIGOdialysiscontroversiesconferences(DialysisInitiation,January2018),participantsproposedaparadigmshifttowardacultureofmoreindividualizedorpersonalizeddialysiscare.Inthisseconddialysisconference,wewillbuildontheDialysisInitiationConferencebyconsideringhowBPandvolumestatusmanagementcanbeoptimizedandindividualizedacrossdialysismodalitiesandresourcesettings.Indoingso,wewillconsiderexistingevidenceandapproachesbutalsolooktothefuturetoidentifypromisingnewtechnologiesandgapsinknowledgethatdemanddedicatedresearch.

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RelevanceoftheTopic

Bloodpressureandvolumecontrolarecriticalcomponentsofdialysiscare.Howevertheabsenceofwidelyavailable,accurateandobjectivemeasuresofextracellularvolumestatusinadditiontothelackofhighqualityevidencefortherapeuticinterventionshavehamperedeffortstodevelopconsensusbestpractices.Assuch,practicepatternsrelatedtoBP(i.e.optimalBPtargets,non-pharmacologicandpharmacologicmanagement)andvolume-relatedaspectsofthedialysisprescription(i.e.treatmenttime,ultrafiltrationrate,dialysatecompositionandextracellularvolumestatusassessment)varywidelyacrosstheworld.Thereisalsosubstantialvariationinuptakeofvolume-relevantdialysistechnologiesincludingbutnotlimitedtohemodiafiltration,temperaturebiofeedback,bioimpedance,bloodvolumemonitors,andremotehometreatmentmonitoring.Furthermore,qualitativedatasuggestthatpatientsbearsubstantialsymptomburdensthat,inpart,stemfromsuboptimalBPandvolumemanagement.8,9,10Similarly,patientshaveciteddietaryrestrictions,commonreflexvolumemitigationstrategies,ashavingdeleteriouseffectsonqualityoflife.11Thesevolume-relatedpatientburdensoftengounrecognizedbyproviders,9,12

suggestingthatmoreindividualizeddialysisprescriptionsmustalsoaccountforpatientsymptomsandpreferences.

ConferenceOverview

TheKDIGOControversiesConferenceonBloodPressure(BP)andVolumeManagementinDialysiswillexamineBPmeasurementandtargetsforindividualsreceivingmaintenancedialysis;pharmacologicinterventionsforBPabnormalities;dialysisprescriptionsastheyrelatetoBPandvolume;extracellularvolumeassessmentandmanagementwithafocusontechnology-basedsolutions;andvolume-relatedpatientsymptomsandexperiences.TheobjectivesofthisconferencearetoassessthecurrentstateofknowledgerelatedtoBPandvolumemanagementandidentifyexistingandfutureopportunitiestoimproverelatedclinicalandpatient-reportedoutcomesamongindividualsreceivingmaintenancedialysis.

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Drs.JennyFlythe(UniversityofNorthCarolina,USA)andKevanPolkinghorne(MonashUniversity,Australia)willco-chairthisconference.Theformatoftheconferencewillinvolvetopicalplenarysessionpresentationsfollowedbyfocuseddiscussiongroupsthatwillreportbacktothefullgroupforconsensusbuilding.Thishighlyinteractiveconferencewillinvitekeythoughtleadersandrelevantstakeholders,includingpatients,innephrologyandotherrelateddisciplineswhowillcomprehensivelyreviewtheliteratureandcurrentstateofunderstandinginthisarea,andaddressclinicalissueasoutlinedintheAppendix:ScopeofCoverage.TheconferenceoutputwillincludepublicationofapositionstatementthatwillhelpguideKDIGOandothersonmanagementandfutureresearchinthisarea.Therewillbefourworkinggroupsthatwilleachaddress:Group1 BPMeasurementandTargetsandPharmacologicApproachestoBPand

VolumeManagementAmongIndividualsReceivingMaintenanceDialysisGroup2 TheDialysisPrescriptionasitRelatestoBPandVolumeGroup3 ExtracellularVolumeManagementandTechnology-BasedConsiderations

RelevanttoVolumeManagementGroup4 Volume-RelatedPatientSymptomsandExperiencesandNon-

pharmacologicInterventionsforBPandVolumeAbnormalities

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APPENDIX:SCOPEOFCOVERAGE

Group1:BloodPressure(BP)MeasurementandTargetsandPharmacologicApproachestoBPandVolumeManagementAmongIndividualsReceivingMaintenanceDialysisBPMeasurement

1. HowandwhenshouldBPbemeasuredamongindividualsreceivingdialysis?a. Whatapproach,ifany,isconsideredthegoldstandardtomeasureBP

amongindividualsreceivingdialysis?WhatarethebarrierstoimplementingthegoldstandardmethodofBPmeasurement?

b. Whengoldstandardmeasurementsarenotavailable/feasible,whatalternativeBPmeasurementsshouldbeusedtodiagnosehypertension?

c. Dotheanswerstoquestions1a-1bdifferbydialysismodality(e.g.,in-centerhemodialysis(HD),homeHD,peritonealdialysis(PD))?

DefinitionsofHypertensionandIntradialyticHypotensionandHypertension

2. Whatisthethresholdforthediagnosisofhypertensionamongdialysispatients(includediscussionofexistingguidelinedefinitions)?a.DoesthisthresholdvarydependingonBPmeasurementtechnique?b.Doesthisthresholdapplyirrespectiveofdialysismodality?Acrossall

patients?Ifnot,howshouldthresholdsbeindividualized?

3. Whatistheoptimaldefinitionofintradialytichypotension(includediscussionofexistingguidelinedefinitions)?Basedonwhatevidence?

a. Doesthisdefinitionapplyacrossdialysismodalities-HDandPD?

4. Whatistheoptimaldefinitionofintradialytichypertension(includediscussionofexistingguidelinedefinitions)?Basedonwhatevidence?

a. Doesthisdefinitionapplyacrossdialysismodalities-HDandPD?

5.WhatisthedefinitionofBPvariability?Basedonwhatevidence?a.Doesthisdefinitionapplyacrossdialysismodalities-HDandPD?

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b.Whatapproach,ifany,isconsideredthegoldstandardapproachtomeasuringBPvariability?Whengoldstandardmeasurementsarenotavailable/feasible,whatalternativemeasurementsshouldbeused? c.WhatistheevidencesupportinganassociationbetweenBPvariabilityandoutcomes?d.CanandshouldBPvariabilitybetargetedforidentificationandinterventionamongdialysispatients?

PharmacologicApproachestoBPandVolumeAbnormalities

6.Whenshouldanti-hypertensiveagentsbeused?7.Howshouldanti-hypertensiveagentsbeselected?

a. Comparativeeffectivenessofanti-hypertensiveagents?b. Whatanti-hypertensiveagentshavebeenshowntoimprove

cardiovascularoutcomes(e.g.leftventricularhypertrophy/leftventricularmass,myocardialinfarction,cardiovascularmortality)orall-causemortalityinpatientsreceivingdialysis?

c. RegardlessoftheireffectonBP,whatistheroleofdiureticsinvolumemanagement?

d. Howdoesdialysismodalityfactorintoanti-hypertensiveagentselection(e.g.removalbydialysis)?

e. Whatanti-hypertensiveagentstrategiesshouldbeusedtotreatintradialytichypertension?

f. Howcananti-hypertensivetherapystrategiesbeindividualized?

8.Whatistheoptimaltimingofanti-hypertensiveadministration?a. Howdoesdialysismodalityfactorintotimingofanti-hypertensiveagent

administration?

9.Whatgapsremaininourunderstandingofantihypertensivemedicationsindialysisandwhattype(s)ofresearchis(are)neededtofillthesegaps?

10.ShouldpharmacologicagentsbeusedtoraiseBP?

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a. If,yes,inwhatclinicalsituationsandwhatagents?If,no,why,andwhatarealternativemanagementstrategies?

b. ComparativeeffectivenessofBP-raisingagents?Group2:TheDialysisPrescriptionasitRelatestoBPandVolumePreventionandManagementofIntradialyticHypotensionandHypertension

1. Howmightthehemodialysis(HD)prescription(centreHDandhomeHD)bemodifiedtopreventintradialytichypotension?[Note:thedefinitionofintradialytichypotensionwillbecoveredbygroup1andshouldbeomittedfromdiscussion.]

2. Howmighttheperitonealdialysis(PD)prescriptionbemodifiedtopreventhypotension(chronicandacute)?

a. Howshouldthesestrategiesbeindividualized?

3. Whatarethecurrentrecommendationsfornon-pharmacologicmanagementofintra-hemodialytichypotension(centreHDandhomeHD)?

a. Howshouldpreventiveintra-hemodialytichypotensionstrategiesbeindividualized?

4. HowmighttheHDprescriptions(centreHDandhomeHD)bemodifiedtoprevent/controlintradialytichypertension?[Note:thedefinitionofintradialytichypertensionwillbecoveredbygroup1andshouldbeomittedfromdiscussion.]

5. Howmighttheperitonealdialysis(PD)prescriptionbemodifiedto

prevent/controlhypertension?a. Howshouldthesestrategiesbeindividualized?

6. Outsideofdietaryrestrictions,whatarethecurrentrecommendationsfornon-

pharmacologicmanagementofintra-hemodialytichypertension(centreHDandhomeHD)?

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a. Howshouldpreventiveintradialytichypertensionstrategiesbeindividualized?

UltrafiltrationRate,TreatmentTimeandResidualKidneyFunction

7. IsthereanoptimalultrafiltrationrateforHD?a. Whatrole,ifany,isthereforultrafiltrationprofiling,and/orsequential

therapy(ultrafiltrationonly,thenultrafiltration+dialysis)inHD?b. HowshouldthepotentialrisksfromhigherHDultrafiltrationratesbe

balancedwiththerisksfromvolumeoverload(apotentialconsequenceoflowerultrafiltrationrates)?

c. Whatarethebeststrategiestolowerultrafiltrationrates?d. Howcanultrafiltrationratesbeloweredinresource-constrained

environmentswithlimitedrun-timesandfewhometherapyoptions?

8. WhatfactorsshouldbeconsideredwhenprescribingHDtreatmenttime?a. IsthereanoptimalHDtreatmenttimeindependentofultrafiltration

rate?b. HowdoesonereconciletheinternationaldifferencesinHDtreatment

times?

9. WithregardtoultrafiltrationinPD:a. IsthereanoptimalultrafiltrationratewiththePDsolutionsofdifferent

glucoseconcentrationsandglucosepolymerPDsolutions?b. Howdoesperitonealmembranefunctionfactorintoultrafiltration?How

shoulditbeassessed?c. HowdoeschoiceofPDmodalities(CAPDvs.automatedPD)influencethe

ultrafiltrationandfactorintovolumemanagement?

10. Howdoesresidualkidneyfunction(RKF)factorintovolumemanagementinbothPDandHD?

a. ShouldRKFbemeasuredroutinely?Ifso,bywhatmethodsandhowoften?

b. WhatstrategiescanbeusedtopreserveRKF(considerallmodalities)?

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DialysateCompositionandPrescription

11. WhatarethestrategiesforHDdialysatecompositionmanipulationtooptimizeBPandvolumecontrol?[e.g.sodium,potassium,calcium,dialysatetemperature]

12. WhatarethestrategiesforPDsolutionmanipulationtooptimizeBPandvolumecontrol?[e.g.glucoseconcentration,non-glucoseosmoticagents]

Group3:ExtracellularVolumeManagementandTechnology-BasedConsiderationsRelevanttoVolumeManagementExtracellularVolumeMeasurement

1. Howshouldextracellularvolumestatusbemeasured?[Considerintheabsenceofandpresenceoftechnologyaidsandconsideralldialysismodalities]

a. Howoften?Bywhom?Whattrainingisrequired?b. Doesthisdifferacrossmodalities?c. Docomorbidmedicalconditionsaffecttheaccuracyextracellularvolume

statusmeasurementandinfluenceanyassociatedclinicaldecision-making?

2. Whataretheexistingandon-the-horizontoolsforextracellularvolume

assessment?a. Whatisthequalityoftheirsupportingevidence?b. Whatarethebarrierstotheiruseinclinicalpracticeandhowcantheybe

overcome?c. Whatfactorscontributetointernationaldifferencesinclinicaluptakeof

suchtools?d. Arethereinexpensive,readilyavailabletoolsthatcouldbeimplemented

inresource-constrainedenvironments?Aretherelativecosteffectivenessofdifferenttoolsdefined?

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IntradialyticVolume-RelatedTechnologies3. HowmightdifferentdialyticstrategiesbeusedforBPandvolumemanagement?

Whenrelevant,considerhowsuchtechnologiesmightbeimplemented.[Note:thedialysatecompositionwillbecoveredbygroup2andshouldbeomittedfromdiscussion.]

a. Hemodiafiltration(AllformsincludingPre,Post,Mixed,&Mid-Dilution,MixedandIntermittentInfusionHDF?

b. Temperaturebiofeedback?c. Bloodvolumemonitoringd. Ultrafiltrationprofiling?e. Isolatedultrafiltration?f. Bioimpedance?g. Others?

4. Howmighttechnologybeusedtoreliablyidentifyindividualsatriskfor

impendingclinicalcomplications(e.g.intradialytichypotension)andtherebyreducedownstreamclinicaleventsincludinghospitalizationsanddeath?

Home-BasedMonitoringTechnologies

5. Howmighthome-basedmonitoringbeusedtoimproveBPandvolumemanagementamongindividualsonhome-basedtherapies?Istherearoleforhome-basedmonitoringamongcentre-basedpatients?

6. Whattypeofrolesmightwearablehealthtechnologies(existingorfuture)playinBPandvolumemanagement?

Group4:Volume-RelatedPatientSymptomsandExperiencesandNon-PharmacologicInterventionsforBPandVolumeAbnormalities

1. Whatclinicalsymptomsplausiblyrelatetovolumeaberrationsand/orBPaberrationsamongdialysispatients(considerallmodalities;potentialsymptomsinclude:edema,breathlessness,thirst/drymouth,cramping,etc.)?

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a. Howstrongistheevidencesupportingtheseassociations?b. Whattypesofadditionalresearchareneededtoestablishassociations

betweensymptomsandaspectsofBPand/orvolumemanagement?c. Dosuchsymptomsvarybypatient-specificfactorsandhealthconditions?d. Howshouldthesesymptomsbeassessed/measured?Bywhom?Atwhat

frequency?e. Howshouldthesesymptomsbemanaged?

2. Howshouldvolume-relatedsymptomconsiderationsbeincorporatedinto

dialysisprescriptions?a. Howshouldpatient-reportedsymptomsbefactoredintodecisionsabout

maximumvolumeremoval,ultrafiltrationratesortreatmenttime?b. Couldsymptom-driventreatmentdecisionshaveunintended

consequencesforotheraspectsofBPand/orvolumecontrol?c. Howmightthedialysisprescription(allmodalities)bealteredtomitigate

symptoms?d. Howdowenegotiatepotentialconflictsbetweenmeetingclinical

benchmarks(e.g.clearancethreshold)andpatientsymptoms(e.g.crampingorprolongedrecoverytimewithlongertreatments)?

e. Howcantheinterdisciplinarycareteambeusedtoovercometheseconflictsandchallenges?

3. Shouldpatient-reportedoutcomes/experiencesbeusedtoratethequalityof

volumemanagementatadialysisclinic/program?a. Aretheresymptommeasurementtools?(Howshouldsymptomsbe

assessedandwithwhatinstruments?)b. Howcanmetricsbeindividualizedtoavoida“one-size-fits-all”approach?

4. WhatroledofluidandsaltrestrictionshaveinBPand/orvolumemanagement?

a. What,ifany,arethebestevidence-basedapproachesfordietaryrestrictioncounseling/motivation/education?

b. Howdodietaryrestrictionsinfluencepatientqualityoflife/lifesatisfaction?

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c. Howmightpatientsbeempoweredtoadheretodietaryrestrictions?

5. Whatroledoesexercise(interdialyticorintradialytic)haveinBPand/orvolumemanagement?

6. Howdowebalancevolume-relateddietaryrestrictionsandnutritionalstatus?a. Doesthebalancevarybypatientcharacteristics(e.g.child,pregnancy,

residualkidneyfunction,frailty)?

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