【高血压英文课件】hypertension and kidney

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,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 failure,Key Question,Can effective antihypertensive therapy prevent the development of ESRD and retard the progression of CKD ?,Age and change of renal function,overall diabetes,hypertension no DM and no HT,Prevalence of low GFR,Three major causes of ESRD,Renal disease,loss of nephrons,Systemic,hypertension,Proteinuria,Progressive,decline,in GFR,RENAL INJURY,Nephron mass,Glomerular capillary hypertension,Glomerular permeability to macromolecules,Filtration of plasma proteins,Proteinuria,Excessive tubular protein reabsorbtion,Tubulo-interstitial inflammation,RENAL SCARRING,SYSTEMIC,HYPERTENSION,CKD: Common pathway in disease progression,MAJOR RISK FACTORS FOR CARDIOVASCULAR DISEASE,HYPERTENSION,HYPERLIPIDEMIA,SMOKING,FAMILY HISTORY,OBESITY,DIABETES,CHRONIC KIDNEY DISEASE,PHYSICAL INACTIVITY,AGE 55 IN MEN, 65 IN WOMEN,Why are CKD/ESRD Patients Predisposed to CV Disease?,INFLAMMATION plus CaP deposition,CV DISEASE AND DEATH,CKD/ESRD,ANEMIA,LVH/CHF,LIPIDS,HTN,CAD and PVD,Why are CKD/ESRD Patients Predisposed to CV Disease?,30-50% of ESRD patients have,INFLAMMATION,(,increased 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),because of secondary hyperparathyroidism and elevated PO,4,levels.,Microalbuminuria and proteinuria as a risk factor for CAD and CVA ,marker of endovascular health,Miettinen H et al, Stroke 27:2033, 1996,Prevalence of HTN in CKD,80% of patients with glomerulonephritis and 30% of patients with chronic interstitial disease are,hypertensive,.,0,10,20,30,40,50,60,70,80,90,stage 1,stage 2,stage 3,stage 4,%,normal,hypertension,Hypertension and renal function,0,1,stage 1,stage 2,stage 3,stage 4,Probability of HT,Relative risk of ESRD according to quintile BP,MRFIT study,N= 332,544 men,How important is systemic blood pressure control?,Hypertension in CKD,Pathophysiology 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, we can remove antihypertensive agents as we bring the patient down to their dry weight with ultrafiltration.,Concept of Glomerular Hypertension,Normally, increased glomerular capillary pressure (P,GC,) is good, as it results in increased GFR.,Increased P,GC,is,not good,in a kidney that is already damaged =,GLOMERULAR,HYPERTENSION,.,Increased P,GC,occurs with:,Increased systemic blood pressure,Increased efferent artery vasoconstriction,(,angiotensin,II),Increased afferent artery dilation,(protein loads, calcium channel blockers),GFR,Proteinuria,Aldosterone release,Glomerular sclerosis,A II,Atherosclerosis*,Vasoconstriction,Vascular hypertrophy,Endothelial dysfunction,LV hypertrophy,Fibrosis,Remodeling,Apoptosis,Stroke,Death,*Preclinical data.,LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate.,Hypertension,Heart Failure,MI,Renal Failure,Angiotensin II,p,lays a,c,entral,r,ole in,o,rgan,d,amage,Renin Angiotensin Aldosterone System,Angiotensinogen,Non-ACE pathways,(eg, chymase),Vasoconstriction,Cell growth,Na/H,2,O retention,Sympathetic activation,Renin,Angiotensin I,Angiotensin II,ACE,Cough,angioedema,Benefits?,Bradykinin,Inactivefragments,Vasodilation,Antiproliferation,(,kinins,),Aldosterone,AT,2,AT,1,P,GC,AA,EA,A II,Angiotensin II Effects on Glomerular Capillary Pressure,P,GC,AA,EA,A II,Angiotensin II Causes,Glomerular Hypertension,P,GC,AA,EA,How does blood pressure relate to progression of CKD?,BP,In a sick kidney, increased glomerular capillary pressure,(GLOMERULAR HYPERTENSION),causes,progression,of the CKD (increased fibrosis),Angiotensin II and CKD,Angiotensin II,P,GC, Injury to Glomerular cells ,Proteinuria,O,2,.,and,TGF-,Scarring/Fibrosis,Angiotensin II,One of the most potent,vasoconstrictors, critical in maintenance of blood pressure,Renal actions,Increased sodium,reabsorption,Increased GFR by increasing,glomerular,capillary pressure,A II Blockade Experimental datawith diabetic rats at 70 weeks,ACE Inh/ARB, AII BP Proteinuria/Renal Disease,Anderson S et al, Kidney Int 36:526, 1989,Glomerular Pressure40s 64 46 56,To preserve renal function:,maintain GFR and reduce proteinuria,To reduce CV morbidity and mortality,:most clinical trials in past have excluded patients with CKD,Goals of Treatment of HTN in CKD,Treatment goal for hypertension in the general population has remained relatively the same for the last decade.,Guidelines,BP target,British Hypertension Society (2004), 140/85,JNC VII (2003),1 gram/24 hours or diabetic kidney disease,140/90 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 Foundatrion. Am J Kid Dis. 2002;39(suppl 1):S1S266.,Target Blood Pressure,Should be,lower,than the general population,Should be tailored according to :,What should be the treatment goal,for renal disease?,the severity of renal failure,the severity of the,proteinuria,Aggressive BP Control, Proteinuria and CKD Progression,what is the optimal BP for CKD?,Klahr S et al, N Engl J Med 330:877, 1994,*,*,GOAL BP,1 gm proteinuria,Steps every clinician should take to reduce the incidence and/or progression of CKD,Aggressive BP reduction,Use of agents that interfere with the RAAS,Steps to Reduce Renal Disease,BP control, GFR decline and proteinuria,Intense BP control,An initial reduction in proteinuria of 1.0 g/d,slower mean decrease in GFR,by 0.92 0.31 mL/miny, GFR 25-55,by 1.32 0.46 mL/miny, GFR 15-24,Progression of CKD and BP,Continued ramipril,Switched to ramipril,2,Ruggenenti et al. Lancet 1998;352:1252-1256.,REIN follow-up trial,chronic nephropathy and proteinuria3g/day,25,30,35,40,45,Core study Follow-up trial,GFR decline (mL/min/1.73m /month),AASK: ACEI vs CCB in Hypertensive Renal Disease,Agodoa LY et al. JAMA. 2001;285:27192728.,GFR Event, ESRD, or Death,25,20,15,10,5,0,0,3,12,24,36,Amlodipine,Ramipril,Cumulative Incidence, %,Months,P,CCB arm terminated prematurely because ACEI and beta blocker demonstrated clear superiority,Cardiovascular mortality,Non-cardiovascular mortality,Hans L. Hillege, et al., Circulation, 2002, 106:1777,End-organ damage and mortality in general population,The 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% over 4 years.,R,eduction of,E,ndpoints in,N,IDDM with the,A,ngiotensin II,A,ntagonist,L,osartan 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) 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 placebo,Lewis EJ et al, New Engl J Med 345:851, 2001,IDNT ARB Reduction of Renal Failure,Lewis EJ et al, N Eng J Med 345:851, 2001,20%,33%,23%,ARB Effects of Type II DM Nephropathy - RENAAL and IDNT,Endpoints,RENAAL,IDNT,Composite,16% 20%,S Cr Doubling,25% 33%,ESRD,28% 23%,ACE Inhibitors and CKD Progression,Meta-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 1860 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 Event, %,LIFE: Primary Composite Endpoint,Months,Dahlf B et al. Lancet. 2002;359:9951003,.,0,6,12,18,24,30,36,42,48,54,60,66,Intent-to-Treat,0,2,4,6,8,10,12,14,16,Losartan,Atenolol,Adjusted Risk Reduction 13.0%,P,Unadjusted Risk Reduction 14.6%,P,There was no significant difference in BP between groups at all time points,Patients; non-diabetic patients affected by proteinuric renal disease,MAP 98 mmHg,Treatment; telmisartan 80mg, once daily,Systolic BP change 135 11 to 122 13 mmHg,Diastolic BP change 84.4 8.1 to 75.9 8.5 mmHg,mean BP101 8 to 91 9 mmHg,Proteinuria1.60 0.90 to 1.06 0.63 g/24 h,Cupisti A et al., Biomed Pharmacother, 2003, 57:169,What is the evidence that combining an ACEI and an ARB will have additive benefits?,COOPERATE: Study Design,Design:,Randomized, double-blind trial in 263,patients with non,-,diabetic renal disease,Primary,Composite of time to doubling of s,Cr/ESRD,Endpoint:,Randomization:,Losartan 100 mg/day + AHT* as needed,Trandolapril 3 mg/day + AHT* as needed,Duration:,3 yrs,Target BP:,SBP 130 mmHg,DBP 80 mmHg,Nakao 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 ESRD,0,5,10,15,0,5,12,18,24,30,3,6,20,25,30,Proportion Reaching End,p,oint,%,Months,a,fter Randomization,67,73,76,83,86,87,88,Combination,58,63,72,75,83,85,86,Trandolapril,47,59,65,79,84,88,89,Losartan,Number at Risk,Trandolapril,Losartan,Combination,P,Additive 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 monitored,Hypertension and CKD: summary,Thank You,