Ø david’s current posions include professor of kidney ... · 3/1/2017 · david c wheeler Ø...

KidneyDisease:ImprovingGlobalOutcomes

David C Wheeler

Ø  David’scurrentposi1onsincludeProfessorofKidneyMedicineatUniversityCollegeLondon,UKandHonoraryConsultantNephrologistattheRoyalFreeLondonNHSFounda1onTrust.

Ø  HeisClinicalLeadforDivision2oftheNorthThamesClinicalResearchNetworkandheadsa

teamofeightclinicaltrialsnurses/prac11onersattheCentreforNephrology,RoyalFreeHospitalinLondon.Hehasbeeninvolvedinclinicalprac1ceguidelinedevelopmentforseveralorganisa1ons,

mostrecentlyforKDIGO,ofwhichheiscurrentlyCo-Chair.

KDIGO

GUIDELINEOVERVIEWANDOBJECTIVES

KDIGO2016ClinicalPrac?ceGuidelineUpdate

KDIGO


WHYUPDATE?

ClinicalPrac?ceGuidelinesshouldbeupdatedif:

•  newevidenceshowsthatarecommendedinterven?oncausespreviouslyunknownsubstan?alharm;

•  anewinterven?onissignificantlysuperiortoapreviouslyrecommendedinterven?onfromanefficacyorharmsperspec?ve;or

•  arecommenda?oncanbeappliedtonewpopula?ons.

Ins?tuteofMedicine,2011ClinicalPrac*ceGuidelinesWeCanTrust

KDIGO


WHYUPDATE?Addi?onalconsidera?onsforupda?ng:

•  Changesintherelevanceofaclinicalques?ontotheprac?ceofmedicine

•  Changesinavailableinterven?ons(e.g.newdrugsordevices)•  Changesinevidenceontheexis?ngbenefitsandharmsof

interven?ons

•  Changesinoutcomesconsideredimportant

•  Changesinvaluesplacesonoutcomes

•  Changesinevidencethatcurrentprac?ceisop?mal

•  Changesinresourcesavailableforhealthcare

KDIGO


HOWLONGDOESITTAKEUNTILCLINICALPRACTICEGUIDELINESAREOUTOFDATE?

ShojaniaKGetal.AnnInternMed2007

KDIGO


KDIGO2009CKD-MBDGUIDELINE

ShojaniaKGetal.AnnInternMed2007

ThefirstKDIGOclinicalprac?ceguidelineonCKD-MBDwaspublished

inAugust2009.KDIGO


KDIGOCONTROVERSIESCONFERENCEONCKD-MBD,2013(MADRID,SPAIN)

•  74aQendeesfrom5con1nentsand19countries

•  Representedexpertsinadult,pediatricandtransplantnephrology,endocrinology,cardiology,bonehistomorphometry,andepidemiology

•  Dividedinto4BreakoutGroups–  BoneQuality

–  CalciumandPhosphate

–  VitaminDandPTH

–  VascularCalcifica?on

KDIGO


CONTROVERSIESCONFERENCEOBJECTIVE

Theoverallgoalwastoprovideasuggestedroadmapforthenextguidelineupdategroupbyiden?fyingwhichrecommenda?onspoten?allywarrantrevisions(ordele?ons)andwhatnewscopetopicsorrecommenda?onscouldbeconsideredinafuturesystema?creview.

KDIGO


CONTROVERSIESCONFERENCEOBJECTIVEQues?onstobeaddressedforallguidelinerecommenda?onsunderreviewbytopicgroups:•Hastherebeennewevidencesincetheoriginalreportthatbegersubstan?atesorconflictswithcurrentrecommenda?ons?Aretherelarge-scalestudiesthatmaysignificantlyimprovethecertaintyormagnitudeofnetbenefit/harm?•Shouldanyoftheguidelinestatementsbemodified/createdorremovedbecauseofnewdataornewinterven?ons,strategiesortechniquesnotpreviouslyconsidered?•Shouldanyoftheguidelinestatementsbemodified/createdtoaddressspecificCKDpopula?onsbylevelsofseverityorCKDpopula?onsnotpreviouslycovered(e.g.,elderly,pediatric,transplantrecipients)?

KDIGO


CONTROVERSIESCONFERENCEPUBLICATION

KDIGO


GUIDELINERECOMMENDATIONSTOREVISITBoneQuality3.2.1 Inpa?entswithCKDstages3–5D,itisreasonabletoperformabonebiopsyinvariousselngsincluding,butnotlimitedto:unexplainedfractures,persistentbonepain,unexplainedhypercalcemia,unexplainedhypophosphatemia,possiblealuminumtoxicity,andpriortotherapywithbisphosphonatesinpa?entswithCKD-MBD(NotGraded).3.2.2 Inpa?entswithCKDstages3–5DwithevidenceofCKD–MBD,wesuggestthatBMDtes?ngnotbeperformedrou?nely,becauseBMDdoesnotpredictfractureriskasitdoesinthegeneralpopula?on,andBMDdoesnotpredictthetypeofrenalosteodystrophy(2B).

KDIGO


GUIDELINERECOMMENDATIONSTOREVISITBoneQuality4.3.4 Inpa?entswithCKDstages4–5Dhavingbiochemicalabnormali?esofCKD–MBD,andlowBMDand/orfragilityfractures,wesuggestaddi?onalinves?ga?onwithbonebiopsypriortotherapywithan?resorp?veagents(2C).5.5 Inpa?entswithanes?matedglomerularfiltra?onrategreaterthanapproximately30ml/min/1.73m2,wesuggestmeasuringBMDinthefirst3monthsamerkidneytransplantiftheyreceivecor?costeroids,orhaveriskfactorsforosteoporosisasinthegeneralpopula?on(2D).5.7 Inpa?entswithCKDstages4–5T,wesuggestthatBMDtes?ngnotbeperformedrou?nely,becauseBMDdoesnotpredictfractureriskasitdoesinthegeneralpopula?onandBMDdoesnotpredictthetypeofkidneytransplantbonedisease(2B).

KDIGO


GUIDELINERECOMMENDATIONSTOREVISITBoneQuality4.3.4Inpa?entswithCKDstages4–5Dhavingbiochemicalabnormali?esofCKD–MBD,andlowBMDand/orfragilityfractures,wesuggestaddi?onalinves?ga?onwithbonebiopsypriortotherapywithan?resorp?veagents(2C).5.5Inpa?entswithanes?matedglomerularfiltra?onrategreaterthanapproximately30ml/min/1.73m2,wesuggestmeasuringBMDinthefirst3monthsamerkidneytransplantiftheyreceivecor?costeroids,orhaveriskfactorsforosteoporosisasinthegeneralpopula?on(2D).5.7Inpa?entswithCKDstages4–5T,wesuggestthatBMDtes?ngnotbeperformedrou?nely,becauseBMDdoesnotpredictfractureriskasitdoesinthegeneralpopula?onandBMDdoesnotpredictthetypeofkidneytransplantbonedisease(2B).

KDIGO


BONEQUALITY:WHYUPDATING?•  2009Guidelinewaslargelylimitedtobisphosphonates

•  Clinicaltrialdataarenowavailablefordenosumabandteripara?de

•  Therearerecentdatafromatleasttwostudiessugges?ngthatlowBMDisassociatedwithhigherriskoffractures;whetherthisisapplicabletotransplantrecipientsisunknownandawaitsformalsystema?creviewbytheEvidenceReviewTeam(ERT)

KDIGO


GUIDELINERECOMMENDATIONSTOREVISITCalciumandPhosphate4.1.1 Inpa?entswithCKDstages3–5,wesuggestmaintainingserumphosphorusinthenormalrange(2C).Inpa?entswithCKDstage5D,wesuggestloweringelevatedphosphoruslevelstowardthenormalrange(2C).4.1.2 Inpa?entswithCKDstages3–5D,wesuggestmaintainingserumcalciuminthenormalrange(2D).4.1.3 Inpa?entswithCKDstage5D,wesuggestusingadialysatecalciumconcentra?onbetween1.25and1.50mmol/l(2.5and3.0mEq/l)(2D).

KDIGO


GUIDELINERECOMMENDATIONSTOREVISITCalciumandPhosphate4.1.4 Inpa?entswithCKDstages3–5(2D)and5D(2B),wesuggestusingphosphate-bindingagentsinthetreatmentofhyperphosphatemia.ItisreasonablethatthechoiceofphosphatebindertakesintoaccountCKDstage,presenceofothercomponentsofCKD–MBD,concomitanttherapies,andside-effectprofile(notgraded).4.1.7 Inpa?entswithCKDstages3–5D,wesuggestlimi?ngdietaryphosphateintakeinthetreatmentofhyperphosphatemiaaloneorincombina?onwithothertreatments(2D).

KDIGO


CALCIUMANDPHOSPHATE:WHYUPDATING?•  Renewedsafetyconcernsconcerningliberalexposureto

calciuminbothpredialysisanddialysispa?ents

•  Effectofcalciumbalanceonendpointssuchasvascularcalcifica?on,mortality,andprogressiontoESRD

•  Poten?alnewdataondialysiscalciummasstransferduringhemodiafiltra?on/nocturnalhemodialysis.Anybenefitsforuseoflowcalciumdialysate?

•  Newevidencesugges?ngthatcalcimime?csmayalterclinicalsignificanceoflowcalcium

KDIGO


CALCIUMANDPHOSPHATE:WHYUPDATING?•  Relevanceofaboveissuesforthepediatricpopula?onsascalcium

balanceisexpectedtobemoredynamicforthisgroup?

•  Relevanceofaboveissuesforthetransplantrecipients?Anydataonmanagementofhypercalcemiaforthispa?entgroup?

•  Datatosupportseparaterecommenda?onsonuseofphosphatebindersformanagementofhyperphosphatemiainpredialysisanddialysispa?ents?

•  Datatoprovidemoreguidanceonlimi?ngdietaryphosphateintakebytarge?ngspecificphosphoproteinsources?

KDIGO


GUIDELINERECOMMENDATIONSTOREVISITVitaminDandPTH4.2.1 Inpa?entswithCKDstages3–5notondialysis,theop?malPTHlevelisnotknown.However,wesuggestthatpa?entswithlevelsofintactPTH(iPTH)abovetheuppernormallimitoftheassayarefirstevaluatedforhyperphosphatemia,hypocalcemia,andvitaminDdeficiency(2C).Itisreasonabletocorrecttheseabnormali?eswithanyorallofthefollowing:reducingdietaryphosphateintakeandadministeringphosphatebinders,calciumsupplements,and/orna?vevitaminD(notgraded).4.2.2 Inpa?entswithCKDstages3–5notondialysis,inwhomserumPTHisprogressivelyrisingandremainspersistentlyabovetheupperlimitofnormalfortheassaydespitecorrec?onofmodifiablefactors,wesuggesttreatmentwithcalcitriolorvitaminDanalogs(2C).

KDIGO


VITAMINDANDPTH:WHYUPDATING?•  BothPRIMOandOPERAfailedtoshowabeneficialeffectoflowering

PTHwithparicalcitoloncardiacstructureandfunc?on,butdiddemonstrateanincreasedriskofhypercalcemia.

•  TherearealsoconcernsabouttreatmenttolowerPTHvaluestowithinthenormalrangeinCKDstages3to5,whilemoderatePTHeleva?onsmayserveasabeneficialadap?veresponse(e.g.,phosphaturia,boneturnover).Forthisreason,alongwithissuesmen?onedpreviouslyrela?ngtoappropriatecalciumbalanceandload,supportedrevisi?ngthesetworecommenda?ons

KDIGO


WHATABOUTVASCULARCALCIFICATION?3.3.1 Inpa?entswithCKDstages3–5D,wesuggestthatalateralabdominalradiographcanbeusedtodetectthepresenceorabsenceofvascularcalcifica?on,andanechocardiogramcanbeusedtodetectthepresenceorabsenceofvalvularcalcifica?on,asreasonablealterna?vestocomputedtomography-basedimaging(2C).3.3.2 Wesuggestthatpa?entswithCKDstages3–5Dwithknownvascular/valvularcalcifica?onbeconsideredathighestcardiovascularrisk(2A).Itisreasonabletousethisinforma?ontoguidethemanagementofCKD–MBD(notgraded).

KDIGO


WHATNOUPDATEFORVASCULARCALCIFICATION?

•  Nohighqualitydatatojus?fyrou?nescreeningforcardiovascularcalcifica?oninCKD

•  Nonewdatacomparingdifferentimagingmethodshaveemerged

KDIGO


CONFERENCERECOMMENDATIONS

•  Selec?veupdateofthe2009CKD-MBDGuideline.

•  Mostofthe2009guidelinerecommenda?onswereunchanged.

•  12recommenda?onswereiden?fiedforre-evalua?on.

•  Addi?onalrecommenda?onswereproposedforrevisi?ngsincecompletetrialdataanalyses(e.g.,EVOLVE)werepublishedamertheMadridconferenceandarenowavailableforformalsystema?creview.

•  Largegapsofknowledges?llpersist,despitethecomple?onofseveralRCTssince2009.

KDIGO


CKD-MBDGUIDELINEUPDATE2016

WorkGroup

•  GeoffreyBlock(USA)•  PieterEvenepoel(Belgium)•  MasafumiFukagawa(Japan)•  CharlesA.Herzog(USA)•  LindaMcCann(USA)

•  SharonM.Moe(USA)•  RukshanaShroff(UK)•  MarcelloA.Tonelli(Canada)•  NigelD.Toussaint(Australia)•  MarcG.Vervloet(TheNetherlands)

GuidelineChairsMarkusKegeler(Germany)

MaryBLeonard(USA)

KDIGO


EVIDENCEREVIEWTEAMLeader

KarenA.RobinsonDirector,JohnsHopkinsUniversity

AHRQEvidence-BasedPrac?ceCenter

EvidenceReviewTeamCaseyM.Rebholz,PhD,MPHMS

LisaM.Wilson,ScMErmiasJirru,MD,MPHMarisaChiLiu,MD,MPH

JessicaGayleard,BSAllenZhang,BS

KDIGO


METHODOLOGY

•  Refineandupdateguidelineclinicalques?ons

•  Reviewpriorsearchstrategy,inclusion/exclusioncriteria,andamendifnecessary

•  Performdataextrac?ononstudiesfulfillinginclusioncriteria

•  RelevantoutcomesandevidenceappraisalaresummarizedintheformofEvidenceMatricesandEvidenceProfiles

•  WorkGroupreviewedERTdataandrevisedrelevantguidelinerecommenda?ons

•  WorkGrouprevisitedthestrengthoftherecommenda?on

•  ERTassistedwiththeevidencegradingoftheindividualrecommenda?ons

KDIGO


GRADINGRECOMMENDATIONS

Ungradedrecommenda?onsarealsoissuedtoprovideguidancebasedoncommonsenseorwherethetopicdoesnotlenditselfforsystema?creview.Themostcommonexamplesincluderecommenda?onsregardingmonitoringintervals,counseling,andreferraltootherclinicalspecialists.recommenda?ons.

KDIGO


THEGRADESYSTEM

KDIGO


FINALGRADEFOROVERALLEVIDENCEQUALITY

KDIGO


SUMMARYOFERTSEARCHYIELD

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SIGNUPTOREVIEWCKD-MBDGUIDELINEUPDATEDRAFT

http://kdigo.org/home/kdigoreviewer/

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FOLLOW KDIGO

www.kdigo.org

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Ø david’s current posions include professor of kidney ... · 3/1/2017 · david c wheeler Ø...

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