高血壓英文課件TherapeuticsinRenal

TherapeuticsinRenalDiseaseDrMichaelClarksonConsultantRenalPhysician–CUHTherapeuticsinRenalDiseaseDChronicKidneyDiseaseCommonEasytoDiagnoseEffectiveTherapiesAvailableCKDCareSuboptimalChronicKidneyDiseaseCommonSerumCreatinineisaPoorMarkerofGFRSerumCreatinineisaPoorMarMDRDeGFRMDRDequation–ComplexlogrhythmicequationIntegrateskeyvariablesAgeSexCreatinineRaceUreaAlbuminMDRDeGFRMDRDequation–ComplGFRistheacceptedmeasureofkidneyfunctionGFRisdifficulttoinferfromserumcreatininealoneAutomaticreportingidentifiesCKDpatientswithapparently“normal”serumcreatinineReducesbarriertoearlydetectionMDRDeGFRGFRistheacceptedmeasureofThreesimpletestsidentifyCKDinadultsDipstickUrinalysis–Haematuria/MacroalbuminuriaUrinePCR-Urineproteintocreatinineratioona“spot”urinesample24-hoururinecollectionsareNOTneededeGFR-EstimatedGFRfromserumcreatinineusingtheMDRDequationThreesimpletestsidentifyCKSpotRatios!24hourcollectionscumbersomeExcretionofcreatinineandproteinisreasonablyconstantthroughoutthedayArandomurineprotein:creatinine

ratiohasbeenshowntocorrelatewitha24-hrestimation

Expressedeitherasmg/mg(easy)ormg/mmol(multiplyx0.0088)SpotRatios!24hourcollectionSpotRatios!24yoladywithankleoedema,proteinuriaandhypercholesterolaemiaSpoturineprotein 924mg/LSpoturinecreatinine 3343μmol/LRatio=276mg/mmol(normal:0-45)Converttomg/mg(276x0.0088)=2.4g/24hrSpotRatios!24yoladywithankIdentifyingCKDBISH BASH BOSH IdentifyingCKDBISH BASH BOSH StagingofChronicKidneyDiseaseStagingofChronicKidneyDiseStage Description GFR Evaluation/Plan

0 Atrisk >90 Modifyriskfactors1 Kidneydamage/ >90 Diagnose/Treatcause.Slow normalGFR progressionandevaluateCV risk.2 Mild 60-89 Estimateprogression 3 Moderate 30-59 Evaluateandtreat complications4 Severe 15-29 PrepareforRRT 5 ESRD <15 InitiateRRTNKF,USAStage Description GFR EvaluatFactorsMediatingEvolutionofCKDSusceptibilityFactorsInitiationFactorsProgressionFactorsFactorsMediatingEvolutionofSusceptibilityFactorsMalegenderHypertensionAge1ml/yearlossnormallyGeneticBackgroundACEpolymorphismsReducedNephronMassatBirthSusceptibilityFactorsMalegen DiabeticNephropathy>GlomerularDisease>TubulointerstitialDisease>HypertensiveNephrosclerosisInitiationFactors DiabeticNephropathy>GlomerProgressionFactorsProgressivelossofrenalfunctionwilloccurevenintheabsenceofovertactivity

oftheprimaryrenaldisorderProgressionFactorsProgressiveProgressionFactorsHypertensionGlomerularHypertensionProteinuriaHyperlipidemiaGeneticFactorsMiscellaneousExacerbatingEffectofRiskFactorClusteringProgressionFactorsHypertensioMaladaptiveResponsetoLossofNephronMassInitialRenalInsultLossofNephronMassCompensatoryGlomerularHypertrophy/HyperfiltrationMaximisationofGFR

IntraglomerularHypertensionPodocyteInjury/MesangialMatrixExpansionSecondaryFSGS

Proteinuria/HypertensionRAASBlockadeBPControlDietaryProteinRestrictionMaladaptiveResponsetoLossoHypertensionandCKDHypertensionandCKDRoleofHypertensioninCKDProgression50-75%ofpatientswithCKDhaveBP>140/90mmHgGoalsoftherapyRetardCKDprogressionReduceoverallcardiovascularriskRoleofHypertensioninCKDPrRoleofHypertensioninCKDProgressionStrongassociationwithpoorrenaloutcomesesp.indiabeticnephropathyMicroalbuminuriaprogressionMorphologicinjuryPredictslossofrenalfunctioninnon-diabeticglomerulardisordersandinAPKD.ConfoundingeffectofproteinuriamakeaccurateassessmentofindependenteffectdifficultRoleofHypertensioninCKDPrHypertensionandCKDTargetBloodPressureHypertensionandCKDTargetBloRelationshipbetweenBPControlandRateofDeclineinGFR

BakrisetalAJKD,2000.RelationshipbetweenBPControDeclineinGFRandHTN:StratificationforProteinuriaMDRDStudy:ArchIntMed,1995DeclineinGFRandHTN:StratiEffectiveControlofHypertensioninCKD:

MultipleAgentsRequiredBakrisetalAJKD,2000EffectiveControlofHypertensEffectiveControlofHypertensionYieldsMajorBenefitinCKDEffectiveControlofHypertensEarlytreatmentcanmakeadifference100100NoTreatmentDelayedTreatmentEarlyTreatment47914KidneyFailureGFR(mL/min/1.732)283EarlytreatmentcanmakeadifBloodPressureGoalsinCKDStratifyAccordingtoProteinuriaProteinuria<3g Goal<130/80Proteinuria>3g Goal<125/75OptimalBloodPressureUnknownDiureticsEssential120/80??BloodPressureGoalsinCKDStrProteinuriaandCKDProteinuriaandCKDMicroalbuminuriaandMacroalbuminuria

Microalbuminuria

MacroalbuminuriaDefinition >30-299mg/day >300mg/day

RoutineDipstick Negative PositiveRenalSignificance RiskMarker Markerof progressionCardiovascularRisk Increased IncreasedMicroalbuminuriaandMacroalbuMaladaptiveResponsetoLossofNephronMassInitialRenalInsultLossofNephronMassCompensatoryGlomerularHypertrophy/HyperfiltrationMaximisationofGFR

IntraglomerularHypertensionPodocyteInjury/MesangialMatrixExpansionSecondaryFSGS

Proteinuria/HypertensionMaladaptiveResponsetoLossoProteinuriaandCKDProteinuriaevaluationmandatoryinallpatientswithCKDIndependentriskfactorforCKDprogressionBestpredictorofESRD

ProteinuriaandCKDProteinuriaAdverseConsequencesofProteinuriavsloweGFRAll-CauseMortality(per1000patientyrs–rate(95%CI))NormalMildHeavyeGFR>602.7(2.6-2.8)5.8(5.5-6.0)7.2(6.6-7.8)eGFR45-592.9(2.7-3.0)5.2(5.5-6.0)7.2(6.5-7.8)eGFR30-444.0(3.7-4.2)5.8(5.4-6.2)7.5(6.8-8.2)eGFR15-306.7(6.2-7.3)9.1(8.2-10.0)10.4(9.3-11.6)Hemmelgarnetal.JAMA.2010;303(5):423-429.AdverseConsequencesofProteiProteinuriaInCKDInterventionStudiesPharmacologicApproachesDietaryApproachesProteinuriaInCKDInterventionReductioninproteinuriaReductioninproteinuriaiskeytosuccessfulrenoprotectivestrategy.Anti-hypertensiveregimenswithbetterreductioninproteinuriaaffordgreaterrenoprotectivebenefits.BenefitpersistsevenwhenBPwithinthe‘normalrange’.ReductioninproteinuriaReductProteinuriaandCKDPharmacologicApproachesProteinuriaandCKDPharmacologACE-IDecreaseProteinuriaMorethanConventionalAnti-HypertensiveTherapyJafaretal,MetaAnalysisAnnIntMed2001ACE-IDecreaseProteinuriaMorRAASBlockadeinCKD-

MechanismofActionReductioninintraglomerularhypertensionEfferentarteriolarvasodilatationImprovedglomerularpermselectivityAttenuationofAII-stimulatedgrowthfactorandinflammatorycytokinesecretionPreventionofextracellularmatrixaccumulationRAASBlockadeinCKD-

Mechani高血壓英文課件TherapeuticsinRenalAfferentEfferentVasodilatorsProstaglandinsNitricOxideVasoconstrictorsEndothelinCatecholaminesAdenosineVasoconstrictorsAngiotensin-IIAfferentEfferentVasodilatorsVaAfferentEfferentVasodilatorsProstaglandinsNitricOxideVasoconstrictorsAngiotensin-IIPGc

HyperfiltrationMechanicalStrain

2oFSGSAfferentEfferentVasodilatorsVaEfferentRAASBlockadePGc

HypertensionControlBPLowerGFRReductioninProteinuriaEfferentRAASBlockadePGcHypeAngiotensinRecptorBlockade

MoreRisk,MoreBenefit!AngiotensinRecptorBlockade

MInitiationofACE-IorARB“AlthoughACEinhibitorsnowhaveaspecialisedroleinsomeformsofrenaldiseasetheyalsooccasionallycauseimpairmentofrenalfunctionwhichmayprogressandbecomesevereinothercircumstances” BNF InitiationofACE-IorARB“AltInitiationofACE-IorARBCaseExample42yearoldladyHypertensionRecurrentUTIAtrophicleftkidneyPre-eclampsiax2BP=155/95 MAP=115SeCr=145umol/L. MDRDGFR=50ml/minUrineProteintoCreatinineratio:1.4InitiationofACE-IorARBCaseInitiationofACE-IorARBInitiatedonRamipril5mgqd+lowsaltdietDay7.BP=145/90Ramiprilincreasedto10mgqdDay14BP140/85RepeatCreatinine=175umol/L,K+5.4mmol/LEstimatedGFR=42mls/minInitiationofACE-IorARBInitInitiationofACE-IorARBClinicalDilemmaSubstantialfallinGFRfollowingRAASblockadeHyperkalaemiaDonotsuspectrenovasculardiseaseWithdrawACE-I/ARB?InitiationofACE-IorARBCliInitiationofRAASBlockade:

InitialreductioninGFRpredictsbetteroutcomeAperlooetal,KidInt,1997InitiationofRAASBlockade:

InitiationofACEi/ARB10010047914KidneyFailureGFR(mL/min/1.732)283InitiationofACEi/ARB100100InitiationofACE-IorARBContinueRAASBlockade.Accept<25%fallinGFR.Ensureitisnotprogressive.Goal130/80ReviewMedicationsDietaryK+RestrictionDiuretic

AddsecondagentDiureticNon-dihydroperidineCCBBetaBlockerInitiationofACE-IorARBContGoalProteinuriaIndependentRiskMarkerThereforeNeedsIndependentTherapeuticGoalIrrespectiveofBPControlProteinuriaDoseResponsetoRAASBlockadeMayNotParallellThatofBPGoalProteinuriaIndependentRiGoalProteinuria<300mg/24hoursorRatioof<0.3RAASBlockadeBPControl±ProteinRestrictionGoalProteinuria<300mg/24hoursCaseExample56yearoldBachelorFarmerTypeIIDMMx2yearsRetinopathyProteinuriaLivingaloneHighsaltintakeReferredformanagementofrisingserumcreatinineCaseExample56yearoldBacheloCaseExampleMedicationsBasalBolusInsulinAmlodipine10mgdaily24hoururinarysodium160mmol/L

CaseExampleMedications01/200509/200601/200702/2009Creat87120140247eGFR78564723PCRBP160/90165/95165/93170/95CaseExample01/200509/200601/200702/2009CrRelationshipbetweenBPControlandRateofDeclineinGFR

BakrisetalAJKD,2000.