【高血压精品英文课件】肾性高血压 hypertension in nephrology

HypertensioninNEPHROLOGY Renaldisease lossofnephrons Systemichypertension Proteinuria ProgressivedeclineinGFR Introduction ParallelsBetweenHypertensionin1972andKidneyDiseasein2005 RecentdocumentationofeffectivetherapyTreatmentofasilentdiseasetoreduceriskforadisastrousoutcomeSimplescreeningAdvantagesforpatients physicians industry RENALINJURY NephronmassGlomerularcapillaryhypertension Glomerularpermeabilitytomacromolecules Filtrationofplasmaproteins ProteinuriaExcessivetubularproteinreabsorbtionTubulo interstitialinflammation RENALSCARRING SYSTEMICHYPERTENSION KidneyDisease Commonpathwayindiseaseprogression DefinitionandPrevalenceofCKD DefinitionofCKDKidneydamage abnormalitiesinblood urineorimagingstudies oreGFR3months ChronicKidneyDiseaseStage1 GFR 90mL min 1 73m2Stage2 GFR60 90mL min 1 73m2Stage3 GFR30 60mL min 1 73m2Stage4 GFR15 30mL min 1 73m2Stage5 GFR 15mL min 1 73m2 Cockcroft Gaultequation 140 age xweightinkgCreatinineclearance x0 85 ifwomen 72Xserumcreatinine ModifiedMDRDGFRGFR mL min 1 73m2 186xsCr 1 154xage 0 203x0 742 ifwomen StagesofChronicKidneyDisease 3 6Million 6 5Million 15 5Million 700 000 300 000 NHANES2004 StageVGFR 15mL min m2 DIALYSIS StageIVGFR15 29ml min m2 StageIIIGFR30 59ml min m2 StageII pathology GFR60 89ml min m2 StageI pathology 90ml min m2 Walkingthedog 2006 AmericanCollegeofPhysicians AllRightsReserved MAJORRISKFACTORSFORCARDIOVASCULARDISEASE HYPERTENSIONHYPERLIPIDEMIASMOKINGFAMILYHISTORY OBESITYDIABETESCHRONICKIDNEYDISEASEPHYSICALINACTIVITYAGE 55INMEN 65INWOMEN WhyareCKD ESRDPatientsPredisposedtoCVDisease WhyareCKD ESRDPatientsPredisposedtoCVDisease 30 50 ofESRDpatientshaveINFLAMMATION increasedCRP increasedIL 6 decreasedalbumin IncreasedCRPisaprimarymarkerforinflammationpredictingcardiovasculardiseaseinnormaladultsIncreasedCRPistheprimarymarkerforincreasedcardiovascularmortalityondialysisCKD ESRDpatientshavemetastaticcalcification coronaryarteries becauseofsecondaryhyperparathyroidismandelevatedPO4levels MicroalbuminuriaandproteinuriaasariskfactorforCADandCVA markerofendovascularhealth MiettinenHetal Stroke27 2033 1996 PrevalenceofHTNinCKD 80 ofpatientswithglomerulonephritisand30 ofpatientswithchronicinterstitialdiseasearehypertensive 0 10 20 30 40 50 60 70 80 90 stage1 stage2 stage3 stage4 normal hypertension Hypertensionandrenalfunction 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 1 stage1 stage2 stage3 stage4 ProbabilityofHT RelativeriskofESRDaccordingtoquintileBP MRFITstudyN 332 544men Howimportantissystemicbloodpressurecontrol HypertensioninCKD Pathophysiologythoughttobebothpressor andvolume related thusCKDpatientsrespondtobothvasodilatorsaswellasdiuretics sodiumrestriction AskidneyfunctiondeclinesclosertoESRD volume dependenthypertensionbecomesmoreimportant Oftenondialysis wecanremoveantihypertensiveagentsaswebringthepatientdowntotheirdryweightwithultrafiltration ConceptofGlomerularHypertension Normally increasedglomerularcapillarypressure PGC isgood asitresultsinincreasedGFR IncreasedPGCisnotgoodinakidneythatisalreadydamaged GLOMERULARHYPERTENSION IncreasedPGCoccurswith IncreasedsystemicbloodpressureIncreasedefferentarteryvasoconstriction angiotensinII Increasedafferentarterydilation proteinloads calciumchannelblockers GFRProteinuriaAldosteronereleaseGlomerularsclerosis AII Atherosclerosis VasoconstrictionVascularhypertrophyEndothelialdysfunction LVhypertrophyFibrosisRemodelingApoptosis Stroke Death Preclinicaldata LV leftventricular MI myocardialinfarction GFR glomerularfiltrationrate Hypertension HeartFailureMI RenalFailure AngiotensinIIplaysacentralroleinorgandamage ReninAngiotensinAldosteroneSystem Angiotensinogen Non ACEpathways eg chymase VasoconstrictionCellgrowthNa H2OretentionSympatheticactivation Renin AngiotensinI AngiotensinII ACE Cough angioedemaBenefits Bradykinin Inactivefragments VasodilationAntiproliferation kinins Aldosterone AT2 AT1 PGC AA EA AII AngiotensinIIEffectsonGlomerularCapillaryPressure PGC AA EA AII AngiotensinIICausesGlomerularHypertension PGC AA EA HowdoesbloodpressurerelatetoprogressionofCKD Inasickkidney increasedglomerularcapillarypressure GLOMERULARHYPERTENSION causesprogressionoftheCKD increasedfibrosis AngiotensinIIandCKD AngiotensinII AngiotensinII Oneofthemostpotentvasoconstrictors criticalinmaintenanceofbloodpressureRenalactionsIncreasedsodiumreabsorptionIncreasedGFRbyincreasingglomerularcapillarypressure AIIBlockade Experimentaldatawithdiabeticratsat70weeks ACEInh ARB AII BP Proteinuria RenalDisease AndersonSetal KidneyInt36 526 1989 GlomerularPressure40s644656 TreatmenttoPreventProgressionofCKDtoKidneyFailure Intensiveglycemiccontrollessensprogressionfrommicroalbuminuriaintype1diabetes DCCT 1993AntihypertensivetherapywithACEInhibitorslessensproteinuriaandprogression Giatras etal 1997 Psait etal 2000 Jafar etal 2001Lowproteindietslessenprogression Fouque etal 1992 Pedrini etal 1996 Kasiske etal 1998 Meta Analyses Meta Analyses Treatmentgoalforhypertensioninthegeneralpopulationhasremainedrelativelythesameforthelastdecade Whatshouldbethetreatmentgoal ForIndividualsWith BPGoal Hypertension nodiabetesorrenaldisease DiabetesMellitus RenalDiseasewithproteinuria 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 ShouldbelowerthanthegeneralpopulationShouldbetailoredaccordingto Whatshouldbethetreatmentgoalforrenaldisease theseverityofrenalfailuretheseverityoftheproteinuria AggressiveBPControl ProteinuriaandCKDProgression whatistheoptimalBPforCKD KlahrSetal NEnglJMed330 877 1994 GOALBP1gmproteinuria Stepseveryclinicianshouldtaketoreducetheincidenceand orprogressionofCKDAggressiveBPreductionUseofagentsthatinterferewiththeRAAS StepstoReduceRenalDisease BPcontrol GFRdeclineandproteinuria Aninitialreductioninproteinuriaof1 0g d slowermeandecreaseinGFRby0 92 0 31mL min y GFR25 55by1 32 0 46mL min y GFR15 24 ProgressionofCKDandBP 2 REINfollow uptrialchronicnephropathyandproteinuria 3g day 25 30 35 40 45 CorestudyFollow uptrial GFRdecline mL min 1 73m month 0 44ml minpermonth 0 10ml minpermonth 0 81ml minpermonth 0 14ml minpermonth AASK ACEIvsCCBinHypertensiveRenalDisease AgodoaLYetal JAMA 2001 285 2719 2728 GFREvent ESRD orDeath 25 20 15 10 5 0 0 3 12 24 36 Amlodipine Ramipril CumulativeIncidence Months P 0 005 CCBarmterminatedprematurelybecauseACEIandbetablockerdemonstratedclearsuperiority Cardiovascularmortality Non cardiovascularmortality HansL Hillege etal Circulation 2002 106 1777 End organdamageandmortalityingeneralpopulation TheEffectofAngiotensin ConvertingEnzymeInhibitiononDiabeticNephropathy 409TypeIdiabeticsages18 49withnephropathy Uprotein 500mgandSCr 2 5 Prospective double blindedmulticenter 30 trialrandomizedtocaptoprilvs placebofor3years LewisEJetal NewEnglJMed329 1456 62 1993 ACEInhibitionandTypeIDMNephropathy LewisEJetal NewEnglJMed329 1456 1993 3 Theseeffectswereindependentofeffectsonbloodpressure ReductionofEndpointsinNIDDMwiththeAngiotensinIIAntagonistLosartan RENAAL 1513TypeIIdiabeticswithnephropathy Ualb Crratio 300orUprot 500mgandSCr1 3 3 0mg dl Prospective randomized double blindedmulticenter 250 trialTwoarms Losartan 50 100mg tokeepBP 140 90vs placebofor3 4years BrennerBMetal NewEnglJMed345 861 869 2001 RENAAL ARBReductionofRenalFailure BrennerBMetal NEngJMed345 861 2001 16 25 28 20 IrbesartenDiabeticNephropathyTrial IDNT 1715TypeIIdiabeticswithhypertension BP 135 85 andnephropathy proteinuria 900mg SCr1 0 3 0mg dl Prospective randomized double blinded multicenter 210 trialThreearms Irbesarten amlodipine andplacebo LewisEJetal NewEnglJMed345 851 2001 IDNT ARBReductionofRenalFailure LewisEJetal NEngJMed345 851 2001 20 33 23 ARBEffectsofTypeIIDMNephropathy RENAALandIDNT EndpointsRENAALIDNT Composite16 20 SCrDoubling25 33 ESRD28 23 ACEInhibitorsandCKDProgressionMeta analysis JafarT AnnInternMed135 73 87 2001 11randomizedcontrolledtrialscomparingACEinhibitorsvs othermedicationsintreatmentofhypertensionin1860nondiabeticpatientswithCKD SCr 2 3 Results ACEInhibitorsloweredBPandproteinuria Results ACEinhibitorsdecreasedriskofESRDby31 combinedriskofprogressionofrenalinsufficiencyanddevelopmentofESRDby30 independentofBPloweringeffects ProportionofPatientsWithFirstEvent LIFE PrimaryCompositeEndpoint Months Dahl fBetal Lancet 2002 359 995 1003 0 6 12 18 24 30 36 42 48 54 60 66 Intent to Treat Losartan Atenolol AdjustedRiskReduction13 0 P 0 021UnadjustedRiskReduction14 6 P 0 009 TherewasnosignificantdifferenceinBPbetweengroupsatalltimepoints Patients non diabeticpatientsaffectedbyproteinuricrenaldiseaseMAP 98mmHgTreatment telmisartan80mg oncedailySystolicBPchange135 11to122 13mmHgDiastolicBPchange84 4 8 1to75 9 8 5mmHgmeanBP101 8to91 9mmHgProteinuria1 60 0 90to1 06 0 63g 24h CupistiAetal BiomedPharmacother 2003 57 169 WhatistheevidencethatcombininganACEIandanARBwillhaveadditivebenefits COOPERATE StudyDesign Design Randomized double blindtrialin263patientswithnon diabeticrenaldiseasePrimaryCompositeoftimetodoublingofsCr ESRDEndpoint Randomization Losartan100mg day AHT asneededTrandolapril3mg day AHT asneededDuration 3yrsTargetBP SBP 130mmHgDBP 80mmHg NakaoNetal Lancet 2003 361 117 124 Antihypertensivetherapy excludingotherACEIsorotherARBs NakaoNetal Lancet 2003 3