（高血压英文课件）Hypertension-and-Kidney.ppt

1、Management of hypertension in CKD Hypertension is an important cause of ESRD Hypertension is common in patients with CKD and accelerate the progression of renal failureKey QuestionCan effective antihypertensive therapy prevent the development of ESRD and retard the progression of CKD?Age and change

2、of renal functionoverall diabeteshypertension no DM and no HTPrevalence of low GFRRENAL INJURYProteinuriaRENAL SCARRINGSYSTEMIC HYPERTENSION CKD:Common pathway in disease progressionMAJOR RISK FACTORS FOR CARDIOVASCULAR DISEASEHYPERTENSIONHYPERLIPIDEMIASMOKINGFAMILY HISTORYOBESITYDIABETESCHRONIC KID

3、NEY DISEASEPHYSICAL INACTIVITYAGE 55 IN MEN,65 IN WOMENWhy are CKD/ESRD Patients Predisposed to CV Disease?INFLAMMATION plus CaP depositionCV DISEASE AND DEATHCKD/ESRDANEMIALVH/CHFLIPIDSHTNCAD and PVDWhy are CKD/ESRD Patients Predisposed to CV Disease?30-50%of ESRD patients have INFLAMMATION(increas

4、ed CRP,increased IL-6,decreased albumin)Increased CRP is a primary marker for inflammation predicting cardiovascular disease in normal adults Increased CRP is the primary marker for increased cardiovascular mortality on dialysis CKD/ESRD patients have metastatic calcification(coronary arteries)becau

5、se of secondary hyperparathyroidism and elevated PO4 levels.Microalbuminuria and proteinuria as a risk factor for CAD and CVA marker of endovascular healthMiettinen H et al,Stroke 27:2033,1996 Prevalence of HTN in CKD80%of patients with glomerulonephritis and 30%of patients with chronic interstitial

6、 disease are hypertensive.0102030405060708090stage 1stage 2stage 3stage 4%normalhypertensionHypertension and renal function00.10.20.30.40.50.60.70.80.91stage 1stage 2stage 3stage 4Probability of HTRelative risk of ESRD according to quintile BPMRFIT studyN=332,544 men How important is systemic blood

7、pressure control?Hypertension in CKDPathophysiology thought to be both pressor-and volume-related,thus CKD patients respond to both vasodilators as well as diuretics/sodium restriction.As kidney function declines closer to ESRD,volume-dependent hypertension becomes more important.Often on dialysis,w

8、e can remove antihypertensive agents as we bring the patient down to their dry weight with ultrafiltration.Concept of Glomerular HypertensionConcept of Glomerular Hypertension Normally,increased glomerular capillary pressure(PGC)is good,as it results in increased GFR.Increased PGC is not good in a k

9、idney that is already damaged=GLOMERULAR HYPERTENSION.Increased PGC occurs with:Increased systemic blood pressure Increased efferent artery vasoconstriction(angiotensin II)Increased afferent artery dilation(protein loads,calcium channel blockers)GFRProteinuriaAldosterone releaseGlomerular sclerosisA

10、 IIAtherosclerosis*VasoconstrictionVascular hypertrophyEndothelial dysfunctionLV hypertrophyFibrosisRemodelingApoptosisStrokeDeath*Preclinical data.LV=left ventricular;MI=myocardial infarction;GFR=glomerular filtration rate.HypertensionHeart FailureMIRenal FailureAngiotensin II plays a central role

11、in organ damageRenin Angiotensin Aldosterone SystemAngiotensinogenNon-ACE pathways(eg,chymase)Vasoconstriction Cell growth Na/H2O retention Sympathetic activationReninAngiotensin IAngiotensin IIACECough,angioedemaBenefits?BradykininInactivefragments Vasodilation Antiproliferation(kinins)AldosteroneA

12、T2AT1PGCAAEAA IIAngiotensin II Effects on Glomerular Capillary PressurePGCAAEAA IIAngiotensin II Causes Glomerular HypertensionPGCAAEAHow does blood pressure relate to progression of CKD?BPIn a sick kidney,increased glomerular capillary pressure(GLOMERULAR HYPERTENSION)causes progression of the CKD(

13、increased fibrosis)Angiotensin II and CKDAngiotensin IIPGC Injury to Glomerular cells ProteinuriaO2.and TGF-Scarring/FibrosisAngiotensin II One of the most potent vasoconstrictors critical in maintenance of blood pressure Renal actionsIncreased sodium reabsorptionIncreased sodium reabsorptionIncreas

14、ed GFR by increasing glomerular capillary Increased GFR by increasing glomerular capillary pressurepressureA II Blockade Experimental datawith diabetic rats at 70 weeksACE Inh/ARB AII BP Proteinuria/Renal DiseaseAnderson S et al,Kidney Int 36:526,1989Glomerular Pressure40s 64 46 56 To preserve renal

15、 function:maintain GFR and reduce proteinuria To reduce CV morbidity and mortality :most clinical trials in past have excluded patients with CKDGoals of Treatment of HTN in CKDTreatment goal for hypertension in the general population has remained relatively the same for the last decade.GuidelinesBP

16、targetBritish Hypertension Society(2004)140/85JNC VII(2003)1 gram/24 hours or diabetic kidney disease140/90 mmHg(JNC 7)130/80 mmHg(ADA,JNC 7)130/80 mmHg(JNC 7,K/DOQI)125/75 mmHg(NKF)Chobanian AV et al.JAMA.2003;289:25602571.American Diabetes Association.Diabetes Care.2002;25:134147.National Kidney F

17、oundatrion.Am J Kid Dis.2002;39(suppl 1):S1S266.Target Blood Pressure vShould be lower than the general populationvShould be tailored according to:What should be the treatment goal for renal disease?the severity of renal failure the severity of the proteinuriaAggressive BP Control,Proteinuria and CK

18、D Progression what is the optimal BP for CKD?Klahr S et al,N Engl J Med 330:877,1994*GOAL BP1 gm proteinuriaSteps every clinician should take to reduce the incidence and/or progression of CKDn Aggressive BP reductionn Use of agents that interfere with the RAASSteps to Reduce Renal DiseaseBP control,

19、GFR decline and proteinuriaIntense BP controlAn initial reduction in proteinuria of 1.0 g/d slower mean decrease in GFR by 0.92 0.31 mL/miny,GFR 25-55by 1.32 0.46 mL/miny,GFR 15-24Progression of CKD and BPContinued ramiprilSwitched to ramipril2Ruggenenti et al.Lancet 1998;352:1252-1256.REIN follow-u

20、p trialchronic nephropathy and proteinuria3g/day2530354045Core study Follow-up trialGFR decline(mL/min/1.73m /month)-0.44ml/min per month-0.10ml/min per month-0.81ml/min per month-0.14ml/min per monthAASK:ACEI vs CCB in Hypertensive Renal DiseaseAgodoa LY et al.JAMA.2001;285:27192728.GFR Event,ESRD,

21、or Death252015105003122436AmlodipineRamiprilCumulative Incidence,%MonthsP=0.005CCB arm terminated prematurely because ACEI and beta blocker demonstrated clear superiorityCardiovascular mortalityNon-cardiovascular mortalityHans L.Hillege,et al.,Circulation,2002,106:1777 End-organ damage and mortality

22、 in general populationThe Effect of Angiotensin-Converting Enzyme Inhibition on Diabetic Nephropathy 409 Type I diabetics ages 18-49 with nephropathy(U protein500 mg and S Cr 1.5 mg/dl:Captopril reduced doubling of S Cr by 48%over 4 years.Captopril reduced ESRD(dialysis or transplant)or death by 50%

23、over 4 years.Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan RENAAL 1513 Type II diabetics with nephropathy (U alb/Cr ratio 300 or U prot 500 mg and S Cr 1.3-3.0 mg/dl)Prospective,randomized,double-blinded multicenter(250)trial Two arms Losartan(50-100 mg)to keep BP135/85

24、)and nephropathy(proteinuria 900 mg,S Cr 1.0-3.0 mg/dl)Prospective,randomized,double-blinded,multicenter(210)trial Three arms:Irbesarten,amlodipine,and placeboLewis EJ et al,New Engl J Med 345:851,2001IDNT ARB Reduction of Renal Failure Lewis EJ et al,N Eng J Med 345:851,200120%33%23%ARB Effects of

25、Type II DM Nephropathy-RENAAL and IDNTEndpoints RENAALIDNTComposite16%20%S Cr Doubling25%33%ESRD28%23%ACE Inhibitors and CKD ProgressionMeta-analysis-Jafar T,Ann Intern Med 135:73-87,2001 11 randomized controlled trials comparing ACE inhibitors vs.other medications in treatment of hypertension in 18

26、60 nondiabetic patients with CKD(S Cr=2.3).Results:ACE Inhibitors lowered BP and proteinuria.Results:ACE inhibitors decreased risk of ESRD by 31%,combined risk of progression of renal insufficiency and development of ESRD by 30%independent of BP lowering effects.Proportion of Patients With First Eve

27、nt,%LIFE:Primary Composite EndpointMonthsDahlf B et al.Lancet.2002;359:9951003.0612182430364248546066Intent-to-Treat0246810121416LosartanAtenololAdjusted Risk Reduction 13.0%,P=0.021Unadjusted Risk Reduction 14.6%,P=0.009There was no significant difference in BP between groups at all time pointsPati

28、ents;non-diabetic patients affected by proteinuric renal diseaseMAP 98 mmHgTreatment;telmisartan 80mg,once dailySystolic BP change 135 11 to 122 13 mmHgDiastolic BP change 84.4 8.1 to 75.9 8.5 mmHgmean BP101 8 to 91 9 mmHg Proteinuria1.60 0.90 to 1.06 0.63 g/24 hCupisti A et al.,Biomed Pharmacother,

29、2003,57:169What is the evidence that combining an ACEI and an ARB will have additive benefits?COOPERATE:Study DesignDesign:Randomized,double-blind trial in 263 patients with non-diabetic renal diseasePrimary Composite of time to doubling of sCr/ESRDEndpoint:Randomization:Losartan 100 mg/day+AHT*as n

30、eededTrandolapril 3 mg/day+AHT*as neededDuration:3 yrsTarget BP:SBP 130 mmHgDBP 80 mmHgNakao N et al.Lancet.2003;361:117124.*Antihypertensive therapy(excluding other ACEIs or other ARBs).Nakao N et al.Lancet.2003;361:117124.Doubling of Serum Creatinine or Progression to ESRD051015051218243036202530P

31、roportion Reaching Endpoint,%Months after Randomization67737683868788Combination58637275838586Trandolapril47596579848889LosartanNumber at RiskTrandolaprilLosartanCombinationP=0.02Additive antiproteinuric effect of ACEI and ARB in patients with IgA nephropathy Russo,et al.,Am J Kid Dis,1999,33 Most patients with CKD have hypertension Lowering BP(2 drugs are often needed Blood pressure response as well as proteinuria should be monitoredHypertension and CKD:summary