【高血压精品英文课件】hypertension and kidney

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?,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 PO4 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,0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1,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 (PGC) is good, as it results in increased GFR. Increased PGC is not good in a kidney 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),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 plays a central role in organ damage,Renin Angiotensin Aldosterone System,Angiotensinogen,Non-ACE pathways (eg, chymase),Vasoconstriction Cell growth Na/H2O retention Sympathetic activation,Renin,Angiotensin I,Angiotensin II,ACE,Cough, angioedema Benefits?, Bradykinin,Inactive fragments,Vasodilation Antiproliferation (kinins),Aldosterone,AT2,AT1,PGC,AA,EA,A II,Angiotensin II Effects on Glomerular Capillary Pressure,PGC,AA,EA,A II,Angiotensin II Causes Glomerular Hypertension,PGC,AA,EA,How does blood pressure relate to progression of CKD?,In a sick kidney, increased glomerular capillary pressure (GLOMERULAR HYPERTENSION) causes progression of the CKD (increased fibrosis),Angiotensin II and CKD,Angiotensin II,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 data with diabetic rats at 70 weeks,ACE Inh/ARB AII BP Proteinuria/Renal Disease,Anderson S et al, Kidney Int 36:526, 1989,Glomerular Pressure 40s 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.,What should be the treatment goal?,For Individuals With:,BP Goal:,Hypertension (no diabetes or renal disease),Diabetes Mellitus,Renal Disease with proteinuria 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 BP1 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,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,2,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),-0.44ml/min per month,-0.10ml/min per month,-0.81ml/min per month,-0.14ml/min per 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 = 0.005,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 2.5) Prospective, double-blinded multicenter (30) trial randomized to captopril vs. placebo for 3 years,Lewis EJ et al , New Engl J Med 329:1456-62, 1993,ACE Inhibition and Type I DM Nephropathy,Lewis EJ et al, New Engl J Med 329:1456, 1993,3) These effects were independent of effects on blood pressure.,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 BP140/90 vs. placebo for 3.4 years,Brenner BM et al, New Engl J Med 345:861-869, 2001,RENAAL ARB Reduction of Renal Failure,Brenner BM et al, N Eng J Med 345:861, 2001,16%,25%,28%,20%,Irbesarten Diabetic Nephropathy Trial (IDNT),1715 Type II diabetics with hypertension (BP 135/85) 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,Losartan,Atenolol,Adjusted Risk Reduction 13.0%, P = 0.021 Unadjusted Risk Reduction 14.6%, P = 0.009,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 BP 101 8 to 91 9 mmHg Proteinuria 1.60 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: