Proposed Scope of Work for KDIGO Clinical ... - KIDNEY DISEASE€¦ · Management of Diabetes and...
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1 Proposed Scope of Work for KDIGO Clinical Practice Guideline on the Management of Diabetes and Chronic Kidney Disease Introduction Kidney Disease: Improving Global Outcomes (KDIGO) is a not-for-profit organization established to develop and implement global clinical practice guidelines for patients with kidney disease. Since its inception in 2003, KDIGO has published ten guidelines, beginning with the KDIGO Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease (CKD). This proposed Scope of Work is designed to briefly describe the rationale for development of a guideline on the management of patients with diabetes and CKD and to outline the topics that this guideline intends to address. We are now seeking public comments on the proposed Scope of Work presented here to ensure that feedback from all relevant stakeholders of this global guideline is duly considered before a formal systematic review of the literature is undertaken. Background The prevalence of diabetes around the world has reached epidemic proportions. While diabetes is already estimated to affect more than 8% of the global population − more than 425 million people− this is projected to grow to over 629 million people by 2045. 1 It has also been estimated that 40% or more of people with diabetes will develop CKD, including a significant number who will develop end-stage kidney disease (ESKD) requiring dialysis and transplantation. 2 Prevention of CKD in diabetes is therefore a high priority. Diabetes is already the leading cause of ESKD in most developed countries, and the growth in the number of people with ESKD around the world over recent decades has been driven primarily by growth in the number of people with diabetes as the underlying cause. 3,4 In people with diabetes, increasing albuminuria and declining GFR
Transcript of Proposed Scope of Work for KDIGO Clinical ... - KIDNEY DISEASE€¦ · Management of Diabetes and...
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ProposedScopeofWorkforKDIGOClinicalPracticeGuidelineonthe
ManagementofDiabetesandChronicKidneyDisease
Introduction
KidneyDisease:ImprovingGlobalOutcomes(KDIGO)isanot-for-profitorganizationestablishedtodevelopandimplementglobalclinicalpracticeguidelinesforpatientswithkidneydisease.Sinceitsinceptionin2003,KDIGOhaspublishedtenguidelines,beginningwiththeKDIGOClinicalPracticeGuidelineforthePrevention,Diagnosis,Evaluation,andTreatmentofHepatitisCinChronicKidneyDisease(CKD).ThisproposedScopeofWorkisdesignedtobrieflydescribetherationalefordevelopmentofaguidelineonthemanagementofpatientswithdiabetesandCKDandtooutlinethetopicsthatthisguidelineintendstoaddress.WearenowseekingpubliccommentsontheproposedScopeofWorkpresentedheretoensurethatfeedbackfromallrelevantstakeholdersofthisglobalguidelineisdulyconsideredbeforeaformalsystematicreviewoftheliteratureisundertaken.
Background
Theprevalenceofdiabetesaroundtheworldhasreachedepidemicproportions.Whilediabetesisalreadyestimatedtoaffectmorethan8%oftheglobalpopulation−morethan425millionpeople−thisisprojectedtogrowtoover629millionpeopleby2045.1Ithasalsobeenestimatedthat40%ormoreofpeoplewithdiabeteswilldevelopCKD,includingasignificantnumberwhowilldevelopend-stagekidneydisease(ESKD)requiringdialysisandtransplantation.2PreventionofCKDindiabetesisthereforeahighpriority.DiabetesisalreadytheleadingcauseofESKDinmostdevelopedcountries,andthegrowthinthenumberofpeoplewithESKDaroundtheworldoverrecentdecadeshasbeendrivenprimarilybygrowthinthenumberofpeoplewithdiabetesastheunderlyingcause.3,4Inpeoplewithdiabetes,increasingalbuminuriaanddecliningGFR
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canbeduetoclassicdiabeticglomerulopathy.However,reducedGFRwithoutalbuminuriaisanincreasinglyrecognizedphenotypethatmayhavedifferentunderlyingmechanisms,andpeoplewithdiabetescandevelopkidneydiseaseforreasonsotherthandiabetesitself.Assuchtheneedfordiagnosticandprognostickidneybiopsiesinpeoplewithdiabetesremainsamatterofdiscussion.Thepresenceofkidneydiseaseisassociatedwithamarkedlyincreasedriskofcardiovasculardiseaseanddeathinpeoplewithdiabetes.5,6ThereforeaggressiveinterventionagainstcardiovascularriskfactorsisveryimportantinpeoplewithdiabetesandCKD.7Recentdatademonstratedeclineinincidenceofcardiovascularandothercomplicationsinsomepopulationsprobablyduetobetterscreeningforandtreatmentofriskfactors,butdespitethis,adeclineinESKDismuchlessapparent.8
AsprovisionofdialysistopeoplewithESKDconsumesapproximately6%ofallhealthcarecostsintheUSandmoreinsomeothercountries,4thereisastrongeconomicimperativetoimproveoutcomesforpeoplewithdiabetesandkidneydiseaseinadditiontothestrongpersonalandsocietalhealthrationale.Whiletheidentificationofrenin-angiotensinblockadeasaneffectivestrategyforthepreventionofESKDintype1andtype2diabetesmellitusalmost2decadesagowasamajorstepforward,9-11subsequentresearchhashadlimitedsuccessatmostinbuildinguponthesegains.Anumberofpromisingtreatmentshavebeenfoundtobeineffectiveorharmful,manyofwhichhavenowbeenabandonedinthispopulation.Ontheotherhand,anumberofnewagentsarecurrentlybeingtested,whichmayhopefullyimproveoutcomesforpeoplewithdiabetesandkidneydisease.TreatinghyperglycemiainpeoplewithdiabetesandCKDischallengingduetotheriskofhypoglycemiaandtheneedtoadjustselectionanddosingofmedicationsaccordingtolevelofGFR.Furthermore,assessingmeanbloodglucoseiscomplicatedinadvancedCKDbecauseoflimitationsofhemoglobinA1c(HbA1c).
Importantlysomeofthenewdrugclassesnowavailableforreducingbloodglucoseintype2diabetessuchassodium-glucosecotransportertype2(SGLT2)inhibitorsandglucagon-like-peptide-1(GLP-1)receptoragonistshaveturnedouttohavebeneficialeffectsoncardiovascularoutcomeinpeoplewithpreviouscardiovasculardisease,includingpatientswithmoderateCKD.12,13Inaddition,someoftheseagentsexertedbeneficialeffectsonrenaloutcomeparametersmeasuredassecondaryendpoints.14,15Thisincludedreductioninprogressionofalbuminuria,asurrogateforapotentialrenalbenefit,butforSGLT2inhibitorsareductioninlossofGFRwasalsodemonstrated.16,17
GiventhehighprevalenceofdiabetesandCKD,thelargehealthimpactofESKD,andthestrongrelationshipsofCKDwithcardiovascularmorbidityanddeath,KDIGOhas
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determinedthatthedevelopmentofaclinicalpracticeguidelineforthispatientpopulationistimelyandappropriateinviewofrecentdevelopmentinvariousmanagementandtreatmentoptions.
Topic1:PrimarypreventionofCKDamongpeoplewithdiabetesCKD,asrepresentedbyalbuminuriaorreducedGFR,isacommoncomplicationoftype1andtype2diabetes.Durationofdiabetes,glycemiccontrol,andotherCKDriskfactorsareknowntobeassociatedwiththeprevalenceandincidenceofCKD.Randomizedcontrolledtrialshaveshownthatintensiveglycemiccontrolandspecificglucose-loweringagentsreducetheriskofdevelopingCKDornew-onsetalbuminuria,18whileresultsoftrialsoflifestyleinterventionsandRASblockadeforprimaryCKDpreventionarelessclear.Relevantkeyquestions:HowcanwepreventonsetofCKDinpatientswithdiabetes?Whatistheevidenceforglycemiccontrolandarethereothereffectivestrategies?IsRASblockadeindicatedinpatientswithalbuminuriaA1category(<30mg/gor<3mg/mmol)forCKDprevention,regardlessofbloodpressure?Whatisthedefinitionofdiabetickidneydisease(DKD)?HowisDKDdiagnosedandwhatistheroleofkidneybiopsyindiagnosis?IsthereutilityinthestagingofDKD?Topic2:SecondarypreventionofCKDprogressionamongpeoplewithdiabetesPatientswithdiabetesandeitheralbuminuriaorreducedGFRareatriskofprogressingtoESKD.Infact,diabetesisthemostcommoncauseofESKDinmanycountries.Inaddition,riskofCKDcomplications(includingcardiovasculardisease)increaseswithseverityofCKD.Therefore,interventionstohaltorslowprogressionofCKDareimportanttoimprovetheoutcomesofpeoplewithdiabetesandCKD.Currenttherapeutictargetsincluderenin-angiotensinsystemandbloodpressurecontrol,aswellasglycemiccontrol.Othertherapeuticagentsunderdevelopmentnowtargettheroleofendothelialfunction,oxidativestress,andfibrosis.
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Relevantkeyquestions:ForwhichpatientswithdiabetesandprevalentCKDisthereastrongindicationforRASinhibition?DoestreatmentofglycemiapreventprogressionofestablishedCKDtoESKD?WhatistheoptimalapproachtoimplementRAASblockadeindiabetesandCKD?IstherearemainingrolefordualRASblockadeamongpatientswithdiabetesandCKD?WhatistheroleofmineralocorticoidreceptorantagonistsinthetreatmentofdiabetesandCKD?ArethereadditionaltreatmentsthatshouldbeconsideredforpreventingprogressionofCKDindiabetes(e.g.,SGLT2inhibitors,dipeptidylpeptidase-4inhibitors,endothelinantagonists,bardoxolone,pentoxifyline,anti-inflammatoryagents,etc.)?Topic3:MeasurementofglycemiainCKDHbA1cistheacceptedtherapeutictargetfortitratingglucosecontrolamongpeoplewithdiabetes.InadvancedCKD,changestohemoglobinkineticscomplicateinterpretationofHbA1c.Alternativebiomarkersofmeanglycemiahavenowbeendevelopedandevaluatedinobservationalstudies.However,itisunclearwhetherusingthesealternativebiomarkersimprovesglycemiamanagement.Withtheadvanceofcontinuousglucosemonitoringtechnology,measuringglucoseitselfhasbeenshowntoimproveglycemiccontrolamongpeoplewithdiabetes(withoutCKD).Oftheseoptionsformeasuringglycemia,theoptimalapproachamongpeoplewithdiabetesandCKDisnotclear.Relevantkeyquestions:DoesCKDmodifytheaccuracyandprecisionofHbA1cinascertainingglycemiaamongpeoplewithdiabetes?InCKDandthoseondialysistherapy,doalternativebiomarkerssuchasglycatedalbuminorfructosaminecorrelatemorepreciselywithglycemiathanHbA1c?
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InCKDandthoseondialysistherapy,doalternativebiomarkerssuchasglycatedalbuminorfructosaminecorrelatemorepreciselywithclinicaldiabetescomplicationsorbetterguideglucose-loweringtreatmentintensitycomparedwithHbA1c?IsselfmonitoredbloodglucoseorcontinuousglucosemonitoringofaddedvalueinpatientswithdiabetesandCKD?Topic4:GlycemiamanagementinCKDIngeneral,intensiveglycemiccontrolreducestheriskofdiabetescomplications(e.g.,CKD,retinopathy,neuropathy,andcardiovasculardisease)attheexpenseincreasedriskofhypoglycemia.Inaddition,individualglucose-loweringmedicationshavespecificbenefitsandrisks.Forexample,someSGLT2inhibitorsandGLP-1receptoragonistsreducetheriskofCKDorcardiovasculareventswithotherbeneficialeffects(e.g.,bloodpressureandweightreduction),thoughadverseeffects(e.g.,hypoglycemia,bonedisease)couldalsovary.InCKD,benefitsandrisksofintensiveglycemiccontrolingeneralandspecificglucose-loweringdrugsmayvary,andsomedrugsrequiredosereductionsorarecontraindicated.TheimpactofCKDonglycemiamanagementalsodiffersacrossthespectrumofCKDseverity,beinglargestamongpatientsondialysistherapy.Therefore,amongpeoplewithdiabetesandCKD,optimalglycemiatargetsandthepreferredagentsusedtoachievethemarenotclear.Relevantkeyquestions:WhatistheoptimaltargetrangeforHbA1c(oralternativeglycemiamarkers)inCKD?DotargetsvaryinaccordancetoseverityofCKD(e.g.,GFRcategories)?Aretherepreferredclasses/agentsfortreatinghyperglycemiainpatientswithdiabetesandCKD?HowdoestheselectionofagentsdifferbyseverityofCKD?Aretherepreferredclasses/agentsinpatientswithdiabetesandCKDtopreventrenal,cardiovascularandothermicrovascularcomplications?WhatistheimpactofhypoglycemiainpatientswithdiabetesandCKD?TowhatextentshouldinsulindosesbemodifiedinadvancedCKD?ShouldtreatmentbechangedwhenpatientswithCKDG5transition/startdialysis?
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Topic5:LifestyleandnutritionamongpeoplewithdiabetesandCKDExercise,weightloss,smokingcessation,andmodificationofdietaryprotein,sodium,andpotassiumareoftenadvisedtopreventCKDprogressionandcardiovascularcomplications.However,effectivenessoftheseinterventionsremainsunclear.Relevantkeyquestions:Isthereevidenceforabenefitoflifestyleintervention(e.g.,weightloss,exercise,physicalactivity)ondeclineinGFRorcardiovascularriskamongpatientswithdiabetesandCKD?Isthereanoptimaldietaryprotein,sodiumandpotassiumintakeinpatientswithdiabetesandCKD?WhatistheroleofpotassiumbindersinpatientswithdiabetesandCKD?Topic6:CardiovascularriskreductionamongpeoplewithdiabetesandCKDPatientswithdiabetesandCKDareathighriskofcardiovascularevents,includingcoronaryheartdisease,stroke,peripheralvasculardisease,heartfailure,andarrhythmia.Inadditiontoglycemiccontrolandlifestyleinterventions,bloodpressurelowering,lipidlowering,andantiplateletmedicationsarecommonlyusedtoreducecardiovascularrisk.BloodpressureloweringalsoaffectsCKDprogression.Itisnotclearwhetherdiabetesaltersoptimalbloodpressuretargets.RASinhibitorsarerecommendedforbloodpressureloweringamongpatientswithalbuminuria,butit’snotclearforexactlywhichpatientsRASinhibitorsshouldberecommendedoverotherantihypertensivemedications.QuestionssurroundingbloodpressuremanagementinCKDpatientswithdiabeteswillbeaddressedbytheupcomingKDIGOBloodPressureguidelineupdatingWorkGroup.Recentclinicaltrialshavealsodemonstratedcardiovascularbenefittointensifyinglipid-loweringtherapybeyondtypicalstatintherapy,targetinglowLDLcholesterolconcentrationsoraddingadditionalagentstostatintherapy.TheextenttowhichthisapproachmaybeusefulforpatientswithDKDisnotclear.
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Relevantkeyquestions:WhatistheoptimaltreatmentforCVDriskreductioninCKDG3a-G5Dpatientswithdiabetes?WhatistheoptimallipidinterventionstrategyinCKDG3a-5Dpatientswithdiabetes?Whatisknownabouttherisk-benefitratioofanti-plateletagentsandanticoagulantsinpatientswithCKDanddiabetes?Aretherenewagentsindevelopment(e.g.,CETPinhibitors,PCSK9inhibitors,mineralocorticoid-receptorantagonists)thatmightbeparticularlypromisingforpeoplewithdiabetesandCKD?
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