【高血壓英文課件】Hypertension-and-Kidney

ManagementofhypertensioninCKDManagementofhypertensionin1HypertensionisanimportantcauseofESRDHypertensioniscommoninpatientswithCKDandacceleratetheprogressionofrenalfailureKeyQuestionCaneffectiveantihypertensivetherapypreventthedevelopmentofESRDandretardtheprogressionofCKD?Hypertensionisanimportantc2Ageandchangeofrenalfunctionoverall diabeteshypertension noDMandnoHTPrevalenceoflowGFR<60ml/mkn/1.73㎡,%>Ageandchangeofrenalfuncti3【高血壓英文課件】Hypertension-and-Kidney4【高血壓英文課件】Hypertension-and-Kidney5RENALINJURY

NephronmassGlomerularcapillaryhypertension

Glomerularpermeabilitytomacromolecules

Filtrationofplasmaproteins

ProteinuriaExcessivetubularproteinreabsorbtionTubulo-interstitialinflammationRENALSCARRINGSYSTEMICHYPERTENSION

CKD:

CommonpathwayindiseaseprogressionRENALINJURYNephronmassRENAL6MAJORRISKFACTORSFORCARDIOVASCULARDISEASEHYPERTENSIONHYPERLIPIDEMIASMOKINGFAMILYHISTORYOBESITYDIABETESCHRONICKIDNEY DISEASEPHYSICALINACTIVITYAGE>55INMEN,>65INWOMENMAJORRISKFACTORSFORCARDIOV7WhyareCKD/ESRDPatientsPredisposedtoCVDisease?INFLAMMATIONplusCaPdepositionCVDISEASEANDDEATHCKD/ESRDANEMIALVH/CHFLIPIDSHTNCADandPVDWhyareCKD/ESRDPatientsPred8WhyareCKD/ESRDPatientsPredisposedtoCVDisease?30-50%ofESRDpatientshave

INFLAMMATION

(increasedCRP,increasedIL-6,decreasedalbumin)IncreasedCRPisaprimarymarkerforinflammationpredictingcardiovasculardiseaseinnormaladultsIncreasedCRPistheprimarymarkerforincreasedcardiovascularmortalityondialysisCKD/ESRDpatientshave

metastaticcalcification

(coronaryarteries)

becauseofsecondaryhyperparathyroidismandelevatedPO4levels.WhyareCKD/ESRDPatientsPred9MicroalbuminuriaandproteinuriaasariskfactorforCADandCVA–markerofendovascularhealthMiettinenHetal,Stroke27:2033,1996

Microalbuminuriaandproteinur10PrevalenceofHTNinCKD80%ofpatientswithglomerulonephritisand30%ofpatientswithchronicinterstitialdiseasearehypertensive.PrevalenceofHTNinCKD80%of110102030405060708090stage1stage2stage3stage4%normalhypertensionHypertensionandrenalfunction00.10.20.30.40.50.60.70.80.91stage1stage2stage3stage4ProbabilityofHT0102030405060708090stage1stag12RelativeriskofESRDaccordingtoquintileBPMRFITstudyN=332,544men

Howimportantis

systemicbloodpressurecontrol?RelativeriskofESRDaccordin13HypertensioninCKDPathophysiologythoughttobebothpressor-andvolume-related,thusCKDpatientsrespondtobothvasodilatorsaswellasdiuretics/sodiumrestriction.

AskidneyfunctiondeclinesclosertoESRD,volume-dependenthypertensionbecomesmoreimportant.Oftenondialysis,wecanremoveantihypertensiveagentsaswebringthepatientdowntotheirdryweightwithultrafiltration.HypertensioninCKDPathophysio14ConceptofGlomerularHypertensionNormally,increasedglomerularcapillarypressure(PGC)isgood,asitresultsinincreasedGFR.IncreasedPGCisnotgoodinakidneythatisalreadydamaged=GLOMERULARHYPERTENSION.IncreasedPGCoccurswith:IncreasedsystemicbloodpressureIncreasedefferentarteryvasoconstriction(angiotensinII)Increasedafferentarterydilation(proteinloads,calciumchannelblockers)ConceptofGlomerularHyperten15GFRProteinuriaAldosteronereleaseGlomerularsclerosisAIIAtherosclerosis*VasoconstrictionVascularhypertrophyEndothelialdysfunctionLVhypertrophyFibrosisRemodelingApoptosisStrokeDeath*Preclinicaldata.LV=leftventricular;MI=myocardialinfarction;GFR=glomerularfiltrationrate.HypertensionHeartFailureMIRenalFailureAngiotensinIIplaysacentralroleinorgandamageGFRAIIAtherosclerosis*LVhype16ReninAngiotensinAldosteroneSystemAngiotensinogenNon-ACEpathways

(eg,chymase)VasoconstrictionCellgrowthNa/H2OretentionSympatheticactivationReninAngiotensinIAngiotensinIIACECough,

angioedemaBenefits?

BradykininInactive

fragmentsVasodilationAntiproliferation

(kinins)AldosteroneAT2AT1ReninAngiotensinAldosterone17PGCAAEAAIIAngiotensinIIEffectsonGlomerularCapillaryPressurePGCAAEAAIIAngiotensinIIEffe18PGCAAEAAIIAngiotensinIICausesGlomerularHypertensionPGCAAEAAIIAngiotensinIICaus19PGCAAEAHowdoesbloodpressurerelatetoprogressionofCKD?BPInasickkidney,increasedglomerularcapillarypressure(GLOMERULARHYPERTENSION)causesprogressionoftheCKD(increasedfibrosis)PGCAAEAHowdoesbloodpressure20AngiotensinIIandCKDAngiotensinIIPGC

InjurytoGlomerularcellsProteinuriaO2.

and

TGF-

Scarring/FibrosisAngiotensinIIandCKDAngioten21AngiotensinII

Oneofthemostpotentvasoconstrictors–criticalinmaintenanceofbloodpressureRenalactionsIncreasedsodiumreabsorptionIncreasedGFRbyincreasingglomerularcapillarypressureAngiotensinIIOneofthemost22AIIBlockade–Experimentaldata

withdiabeticratsat70weeksACEInh/ARBAIIBPProteinuria/RenalDiseaseAndersonSetal,KidneyInt36:526,1989GlomerularPressure 40s 64 46 56AIIBlockade–Experimentald23Topreserverenalfunction:maintainGFRandreduceproteinuriaToreduceCVmorbidityandmortality:mostclinicaltrialsinpasthaveexcludedpatientswithCKDGoalsofTreatmentofHTNinCKDTopreserverenalfunction:ma24

Treatmentgoalforhypertensioninthegeneralpopulationhasremainedrelativelythesameforthelastdecade.GuidelinesBPtargetBritishHypertensionSociety(2004)<140/85JNCVII(2003)<140/90Whatshouldbethetreatmentgoal? Treatmentgoalforhypertensi25ForIndividualsWith:BPGoal:

Hypertension

(nodiabetesorrenaldisease)DiabetesMellitusRenalDiseasewithproteinuria>1gram/24hoursordiabetickidneydisease<140/90mmHg(JNC7)<130/80mmHg(ADA,JNC7)<130/80mmHg(JNC7,K/DOQI)

<125/75mmHg(NKF)

ChobanianAVetal.JAMA.2003;289:2560–2571.AmericanDiabetesAssociation.DiabetesCare.2002;25:134–147.NationalKidneyFoundatrion.AmJKidDis.2002;39(suppl1):S1–S266.TargetBloodPressure

ForIndividualsWith:BPGoal: 26Shouldbelower

thanthegeneralpopulationShouldbetailoredaccordingto:Whatshouldbethetreatmentgoalforrenaldisease?theseverityofrenalfailuretheseverityoftheproteinuriaShouldbelowerthanthegener27AggressiveBPControl,ProteinuriaandCKDProgression

–whatistheoptimalBPforCKD?KlahrSetal,NEnglJMed330:877,1994**GOALBP<125/75if>1gmproteinuriaAggressiveBPControl,Protein28Stepseveryclinicianshouldtaketoreducetheincidenceand/orprogressionofCKDAggressiveBPreductionUseofagentsthatinterferewiththeRAASStepstoReduceRenalDiseaseStepseveryclinicianshouldt29BPcontrol,GFRdeclineandproteinuriaIntenseBPcontrolAninitialreductioninproteinuriaof1.0g/d

slowermeandecreaseinGFR by0.92±0.31mL/min·y,GFR25-55 by1.32±0.46mL/min·y,GFR15-24BPcontrol,GFRdeclineandpr30ProgressionofCKDandBPProgressionofCKDandBP31ContinuedramiprilSwitchedtoramipril2Ruggenentietal.Lancet1998;352:1252-1256.REINfollow-uptrialchronicnephropathyandproteinuria>3g/day2530354045CorestudyFollow-uptrialGFRdecline(mL/min/1.73m/month)-0.44ml/minpermonth-0.10ml/minpermonth-0.81ml/minpermonth-0.14ml/minpermonthContinuedramiprilSwitchedto32AASK:ACEIvsCCB

inHypertensiveRenalDiseaseAgodoaLYetal.JAMA.2001;285:2719–2728.GFREvent,ESRD,orDeath252015105003122436AmlodipineRamiprilCumulativeIncidence,%MonthsP=0.005CCBarmterminatedprematurelybecauseACEIandbetablockerdemonstratedclearsuperiorityAASK:ACEIvsCCB

inHyperten33CardiovascularmortalityNon-cardiovascularmortalityHansL.Hillege,etal.,Circulation,2002,106:1777End-organdamageandmortalityingeneralpopulationCardiovascularmortalityNon-ca34TheEffectofAngiotensin-ConvertingEnzymeInhibitiononDiabeticNephropathy409TypeIdiabeticsages18-49withnephropathy(Uprotein>500mgandSCr<2.5)Prospective,double-blindedmulticenter(30)trialrandomizedtocaptoprilvs.placebofor3yearsLewisEJetal,NewEnglJMed329:1456-62,1993TheEffectofAngiotensin-Conv35ACEInhibitionandTypeIDMNephropathyLewisEJetal,NewEnglJMed329:1456,19933)

Theseeffectswere independentof

effectsonbloodpressure.IfSCr>1.5mg/dl:CaptoprilreduceddoublingofSCrby48%over4years.CaptoprilreducedESRD(dialysisor transplant)ordeathby50%over4years.ACEInhibitionandTypeIDMN36ReductionofEndpointsinNIDDMwiththeAngiotensinIIAntagonistLosartan–RENAAL

1513TypeIIdiabeticswithnephropathy(Ualb/Crratio>300orUprot>500mgandSCr1.3-3.0mg/dl)Prospective,randomized,double-blindedmulticenter(250)trialTwoarms–Losartan(50-100mg)tokeepBP<140/90vs.placebofor3.4yearsBrennerBMetal,NewEnglJMed345:861-869,2001ReductionofEndpointsinNIDD37RENAAL–ARBReductionofRenalFailure

BrennerBMetal,NEngJMed345:861,200116%25%28%20%RENAAL–ARBReductionofRena38IrbesartenDiabeticNephropathyTrial(IDNT)

1715TypeIIdiabeticswithhypertension(BP>135/85)andnephropathy(proteinuria>900mg,SCr1.0-3.0 mg/dl)Prospective,randomized,double-blinded,multicenter(210)trialThreearms:Irbesarten,amlodipine,andplaceboLewisEJetal,NewEnglJMed345:851,2001IrbesartenDiabeticNephropath39IDNT–ARBReductionofRenalFailure

LewisEJetal,NEngJMed345:851,200120%33%23%IDNT–ARBReductionofRenal40

ARBEffectsofTypeIIDMNephropathy-RENAALandIDNTEndpoints

RENAAL

IDNTComposite 16% 20%SCrDoubling 25% 33%ESRD 28% 23%ARBEffectsofTypeIIDMNe41ACEInhibitorsandCKDProgression

Meta-analysis-JafarT,AnnInternMed135:73-87,200111randomizedcontrolledtrialscomparingACEinhibitorsvs.othermedicationsintreatmentofhypertensionin1860nondiabeticpatientswithCKD(SCr=2.3).Results:ACEInhibitorsloweredBPandproteinuria.Results:ACEinhibitorsdecreasedriskofESRDby31%,combinedriskofprogressionofrenalinsufficiencyanddevelopmentofESRDby30%independentofBPloweringeffects.ACEInhibitorsandCKDProgres42ProportionofPatientsWithFirstEvent,%LIFE:PrimaryCompositeEndpointMonthsDahl?fBetal.Lancet.2002;359:995–1003.0612182430364248546066Intent-to-Treat0246810121416LosartanAtenololAdjustedRiskReduction13.0%,P=0.021UnadjustedRiskReduction14.6%,P=0.009TherewasnosignificantdifferenceinBPbetweengroupsatalltimepointsProportionofPatientsWithFi43Patients;non-diabeticpatientsaffectedbyproteinuricrenaldiseaseMAP>

98mmHgTreatment;telmisartan80mg,oncedailySystolicBPchange 135±11to122±13mmHgDiastolicBPchange 84.4±8.1to75.9±8.5mmHg

meanBP 101±8to91±9mmHgProteinuria 1.60±0.90to1.06±0.63g/24hCupistiAetal.,BiomedPharmacother,2003,57:169Patients;non-diabeticpatient44WhatistheevidencethatcombininganACEIandanARBwillhaveadditivebenefits?

Whatistheevidencethatcomb45COOPERATE:StudyDesignDesign:

Randomized,double-blindtrialin263

patientswithnon-diabeticrenaldiseasePrimary

CompositeoftimetodoublingofsCr/ESRD