高血压英文PPT精品课件TherapeuticsinRenal 62页

TherapeuticsinRenalDiseaseDrMichaelClarksonConsultantRenalPhysician–CUH ChronicKidneyDiseaseCommonEasytoDiagnoseEffectiveTherapiesAvailableCKDCareSuboptimal SerumCreatinineisaPoorMarkerofGFR MDRDeGFRMDRDequation–ComplexlogrhythmicequationIntegrateskeyvariablesAgeSexCreatinineRaceUreaAlbumin GFRistheacceptedmeasureofkidneyfunctionGFRisdifficulttoinferfromserumcreatininealoneAutomaticreportingidentifiesCKDpatientswithapparently“normal”serumcreatinineReducesbarriertoearlydetectionMDRDeGFR ThreesimpletestsidentifyCKDinadultsDipstickUrinalysis–Haematuria/MacroalbuminuriaUrinePCR-Urineproteintocreatinineratioona“spot”urinesample24-hoururinecollectionsareNOTneededeGFR-EstimatedGFRfromserumcreatinineusingtheMDRDequation SpotRatios!24hourcollectionscumbersomeExcretionofcreatinineandproteinisreasonablyconstantthroughoutthedayArandomurineprotein:creatinineratiohasbeenshowntocorrelatewitha24-hrestimationExpressedeitherasmg/mg(easy)ormg/mmol(multiplyx0.0088) SpotRatios!24yoladywithankleoedema,proteinuriaandhypercholesterolaemiaSpoturineprotein924mg/LSpoturinecreatinine3343µmol/LRatio=276mg/mmol(normal:0-45)Converttomg/mg(276x0.0088)=2.4g/24hr IdentifyingCKDBISHBASHBOSH StagingofChronicKidneyDisease StageDescriptionGFREvaluation/Plan0Atrisk>90Modifyriskfactors1Kidneydamage/>90Diagnose/Treatcause.SlownormalGFRprogressionandevaluateCVrisk.2Mild60-89Estimateprogression3Moderate30-59Evaluateandtreatcomplications4Severe15-29PrepareforRRT5ESRD<15InitiateRRTNKF,USA FactorsMediatingEvolutionofCKDSusceptibilityFactorsInitiationFactorsProgressionFactors SusceptibilityFactorsMalegenderHypertensionAge1ml/yearlossnormallyGeneticBackgroundACEpolymorphismsReducedNephronMassatBirth DiabeticNephropathy>GlomerularDisease>TubulointerstitialDisease>HypertensiveNephrosclerosisInitiationFactors ProgressionFactorsProgressivelossofrenalfunctionwilloccurevenintheabsenceofovertactivityoftheprimaryrenaldisorder ProgressionFactorsHypertensionGlomerularHypertensionProteinuriaHyperlipidemiaGeneticFactorsMiscellaneousExacerbatingEffectofRiskFactorClustering MaladaptiveResponsetoLossofNephronMassInitialRenalInsultLossofNephronMassCompensatoryGlomerularHypertrophy/HyperfiltrationMaximisationofGFRIntraglomerularHypertensionPodocyteInjury/MesangialMatrixExpansionSecondaryFSGSProteinuria/HypertensionRAASBlockadeBPControlDietaryProteinRestriction HypertensionandCKD RoleofHypertensioninCKDProgression50-75%ofpatientswithCKDhaveBP>140/90mmHgGoalsoftherapyRetardCKDprogressionReduceoverallcardiovascularrisk RoleofHypertensioninCKDProgressionStrongassociationwithpoorrenaloutcomesesp.indiabeticnephropathyMicroalbuminuriaprogressionMorphologicinjuryPredictslossofrenalfunctioninnon-diabeticglomerulardisordersandinAPKD.Confoundingeffectofproteinuriamakeaccurateassessmentofindependenteffectdifficult HypertensionandCKDTargetBloodPressure RelationshipbetweenBPControlandRateofDeclineinGFRBakrisetalAJKD,2000. DeclineinGFRandHTN:StratificationforProteinuriaMDRDStudy:ArchIntMed,1995 EffectiveControlofHypertensioninCKD:MultipleAgentsRequiredBakrisetalAJKD,2000 EffectiveControlofHypertensionYieldsMajorBenefitinCKD Earlytreatmentcanmakeadifference100100NoTreatmentDelayedTreatmentEarlyTreatment47914KidneyFailureGFR(mL/min/1.732)283 BloodPressureGoalsinCKDStratifyAccordingtoProteinuriaProteinuria<3gGoal<130/80Proteinuria>3gGoal<125/75OptimalBloodPressureUnknownDiureticsEssential120/80?? ProteinuriaandCKD MicroalbuminuriaandMacroalbuminuriaMicroalbuminuriaMacroalbuminuriaDefinition>30-299mg/day>300mg/dayRoutineDipstickNegativePositiveRenalSignificanceRiskMarkerMarkerofprogressionCardiovascularRiskIncreasedIncreased MaladaptiveResponsetoLossofNephronMassInitialRenalInsultLossofNephronMassCompensatoryGlomerularHypertrophy/HyperfiltrationMaximisationofGFRIntraglomerularHypertensionPodocyteInjury/MesangialMatrixExpansionSecondaryFSGSProteinuria/Hypertension ProteinuriaandCKDProteinuriaevaluationmandatoryinallpatientswithCKDIndependentriskfactorforCKDprogressionBestpredictorofESRD AdverseConsequencesofProteinuriavsloweGFRAll-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. ProteinuriaInCKDInterventionStudiesPharmacologicApproachesDietaryApproaches ReductioninproteinuriaReductioninproteinuriaiskeytosuccessfulrenoprotectivestrategy.Anti-hypertensiveregimenswithbetterreductioninproteinuriaaffordgreaterrenoprotectivebenefits.BenefitpersistsevenwhenBPwithinthe‘normalrange’. ProteinuriaandCKDPharmacologicApproaches ACE-IDecreaseProteinuriaMorethanConventionalAnti-HypertensiveTherapyJafaretal,MetaAnalysisAnnIntMed2001 RAASBlockadeinCKD-MechanismofActionReductioninintraglomerularhypertensionEfferentarteriolarvasodilatationImprovedglomerularpermselectivityAttenuationofAII-stimulatedgrowthfactorandinflammatorycytokinesecretionPreventionofextracellularmatrixaccumulation AfferentEfferentVasodilatorsProstaglandinsNitricOxideVasoconstrictorsEndothelinCatecholaminesAdenosineVasoconstrictorsAngiotensin-II AfferentEfferentVasodilatorsProstaglandinsNitricOxideVasoconstrictorsAngiotensin-IIPGcHyperfiltrationMechanicalStrain2ºFSGS EfferentRAASBlockadePGcHypertensionControlBPLowerGFRReductioninProteinuria AngiotensinRecptorBlockadeMoreRisk,MoreBenefit! InitiationofACE-IorARB“AlthoughACEinhibitorsnowhaveaspecialisedroleinsomeformsofrenaldiseasetheyalsooccasionallycauseimpairmentofrenalfunctionwhichmayprogressandbecomesevereinothercircumstances”BNF InitiationofACE-IorARBCaseExample42yearoldladyHypertensionRecurrentUTIAtrophicleftkidneyPre-eclampsiax2BP=155/95MAP=115SeCr=145umol/L.MDRDGFR=50ml/minUrineProteintoCreatinineratio:1.4 InitiationofACE-IorARBInitiatedonRamipril5mgqd+lowsaltdietDay7.BP=145/90Ramiprilincreasedto10mgqdDay14BP140/85RepeatCreatinine=175umol/L,K+5.4mmol/LEstimatedGFR=42mls/min InitiationofACE-IorARBClinicalDilemmaSubstantialfallinGFRfollowingRAASblockadeHyperkalaemiaDonotsuspectrenovasculardiseaseWithdrawACE-I/ARB? InitiationofRAASBlockade:InitialreductioninGFRpredictsbetteroutcomeAperlooetal,KidInt,1997 InitiationofACEi/ARB10010047914KidneyFailureGFR(mL/min/1.732)283 InitiationofACE-IorARBContinueRAASBlockade.Accept<25%fallinGFR.Ensureitisnotprogressive.Goal130/80ReviewMedicationsDietaryK+RestrictionDiureticAddsecondagentDiureticNon-dihydroperidineCCBBetaBlocker GoalProteinuriaIndependentRiskMarkerThereforeNeedsIndependentTherapeuticGoalIrrespectiveofBPControlProteinuriaDoseResponsetoRAASBlockadeMayNotParallellThatofBP GoalProteinuria<300mg/24hoursorRatioof<0.3RAASBlockadeBPControl±ProteinRestriction CaseExample56yearoldBachelorFarmerTypeIIDMMx2yearsRetinopathyProteinuriaLivingaloneHighsaltintakeReferredformanagementofrisingserumcreatinine CaseExampleMedicationsBasalBolusInsulinAmlodipine10mgdaily24hoururinarysodium160mmol/L 01/200509/200601/200702/2009Creat87120140247eGFR78564723PCRBP160/90165/95165/93170/95CaseExample RelationshipbetweenBPControlandRateofDeclineinGFRBakrisetalAJKD,2000. Interventions:Tightsaltrestriction(100mmol/5g)NoaddedsaltNosaltincookingMinimisepre-preparedfoodRamipril5mg40/3mmHgBPdropCaseexample 01/200509/200601/200702/200904/200907/200902/201006/2010Creat87120140247268270260298eGFR7856472321212219PCR2.80.60.70.1BP160/90165/95165/93170/95160/75135/70130/70122/72CaseExampleNephrologyReferral CaseExample ‘Givingupthesaltmadeanawfuldifference’‘Saltisapoison!’‘Bytheway,DrHorgantellsmemyeyesarewaybetter’Caseexample SummaryInproteinuricCKDACE-inhibition+5gsaltrestrictionDiuretic(thiazideorloop~eGFR)Non-dihydropyridineCCBOthersGoal<130/80mmHgatleastARBinTypeIIDMorifACEi→cough SummaryInnon-proteinuricCKD5gsaltrestrictionACE-inotmandatoryDiuretic(thiazideorloop~eGFR)Non-dihydropyridineCCBOthersGoal<130/80mmHg?BewareARVD Questions?