高血压与糖尿病肾病进展.ppt

1、Hypertension and Diabetic Kidney Disease Progression,George L. Bakris, MD Professor and Vice-Chairman Dept. of Preventive Medicine Director, Hypertension/Clinical Research Center Rush University Medical Center Chicago, IL 60612,2006. American College of Physicians. All Rights Reserved.,Disclosure of

2、 Relationships with Commercial Companies:,George L. Bakris, MD, FACP Research Grants/Contracts: NIH (NIDDK/NHLBI), AstraZeneca, Abbott, Alteon, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Novartis, Lilly, Sankyo Consultantship: Astra-Zeneca, AusAm, Abbott, Alteon, Biovail, Boehringer-Ingelheim, BM

3、S/Sanofi, GlaxoSmithKline, Merck, Novartis, Lilly Speakers Bureau: Boehringer-Ingelheim, BMS/Sanofi, GlaxoSmithKline, Merck, Novartis, Lilly,2006. American College of Physicians. All Rights Reserved.,Increasing Prevalence of Diagnosed Diabetes in US Adults,Centers for Disease Control and Prevention

4、Web site. Available at:/diabetes/statistics/prev/state/fig61994and2002.htm. Accessed August 30, 2004.,1994,2002,4% 44.9% 55.9% 6%,2006. American College of Physicians. All Rights Reserved.,Increasing Prevalence of Obesity* Among US Adults,Centers for Disease Control and Prevention W

5、eb site. Available at: /nccdphp/dnpa/obesity/trend/maps/index.htm. Accessed August 30, 2004.,*BMI 30 kg/m2.,10%14% 15%19% 20%24% 25%,2002,2006. American College of Physicians. All Rights Reserved.,Walking the dog,2006. American College of Physicians. All Rights Reserved.,Incidence o

6、f Kidney Failure per million population, 1990, by HSA, unadjusted,2006. American College of Physicians. All Rights Reserved.,Incidence of Kidney Failureper million population, 2000, by HSA, unadjusted,2006. American College of Physicians. All Rights Reserved.,Diabetes:The Most Common Cause of ESRD,P

7、rimary Diagnosis for Patients Who Start Dialysis,Glomerulonephritis,13%,Other,10%,United States Renal Data System. Annual data report. 2000.,No. of patients,Projection,95% CI,1984,1988,1992,1996,2000,2004,2008,0,100,200,300,400,500,600,700,r2=99.8%,243,524,281,355,520,240,No. of dialysis patients (t

8、housands),2006. American College of Physicians. All Rights Reserved.,Cardiovascular Comorbidities, 5% Medicare sample, by Diabetes and CKD status, 1999-2000,%Stroke/TIA,%ASHD,%Amputation/PVD,%Heart Failure,2006. American College of Physicians. All Rights Reserved.,Level of Kidney Function Is an Inde

9、pendent Risk Factor For CV Risk,N=15,350 Mean follow-up=6.2 years Age -45-64,Stage of Kidney Disease N,Stage 2 (GFR-60-89) 7,665,Stage 3 41:47-55,0.75,2006. American College of Physicians. All Rights Reserved.,Go, A. S. et al. N Engl J Med 2004;351:1296-1305,2006. American College of Physicians. All

10、 Rights Reserved.,CKD Hospitalization Rates for Cardiovascular Disease,CHF admission rates are 5 times higher in patients with a diagnosis of CKD vs non-CKD Ischemic heart disease admissions at 2-2.5 times higher in the CKD population Cardiac arrhythmia admission rates are twice as common in CKD pop

11、ulations,2006. American College of Physicians. All Rights Reserved.,CKD Prevalence in US (AJKD 2002),GFR (ml/min) 90,2006. American College of Physicians. All Rights Reserved.,CVD Risk Factors,Hypertension* Cigarette smoking Obesity* (BMI 30 kg/m2) Physical inactivity Dyslipidemia* Diabetes mellitus

12、* Microalbuminuria Estimated GFR 60 ml/min Age (older than 55 for men, 65 for women) Family history of premature CVD (men under age 55 or women under age 65),*Components of the metabolic syndrome.,Chobanian A et.al Hypertension, Dec. 2003,2006. American College of Physicians. All Rights Reserved.,Mi

13、croalbuminuria,Albuminuria (Proteinuria),mg/day,CV Risk and Vascular Dysfunction,CV Risk and Presence of Renal Dysfunction and Vascular Dysfunction,Normal,2006. American College of Physicians. All Rights Reserved.,Proteinuria Predicts Stroke and CHD Events in Type 2 Diabetes,P0.001,40,30,20,10,0,Str

14、oke,CHD Events,80,60,40,20,0,0.5,0.6,0.7,0.8,0.9,1,Survival Curves For CV Mortality,Overall: P0.001,C,B,A,Incidence(%),Months,Miettinen H et al. Stroke. 1996;27:2033-2039.,B: U-Prot 150300 mg/L,A: U-Prot 150 mg/L,C: U-Prot 300 mg/L,0,U-Prot = Urinary protein concentration.,100,2006. American College

15、 of Physicians. All Rights Reserved.,Berton G et.al. Diabetologia, Aug. 2004,Kaplan-Meier curves of 3-year all-cause mortality in the AMI patients stratified by DM status and ACR 30g/mg or 30g/mg on the 3rd day after admission,2006. American College of Physicians. All Rights Reserved.,Mortality,Haza

16、rd Ratio ( 95% CI ) for Values Above 80th Percentile,Use of MAU, CRP, and BNP as Predictors of Mortality and CV Events,NT-proBNP,CRP,MAU,First Major CV Event,NT-proBNP,CRP,MAU,P=.007,P=014,P=.008,P=.003,P=.96,P=.001,Adjusted for age, sex, smoking, DM, HTN, Afib, LVEF50%, LVH, total cholesterol, seru

17、m creatinine. Mortality analysis based on 91 deaths, and CV event data based on 63 events due to missing covariates. The 80th percentile corresponds to values more than 5.85 pg/mL for NT-proBNP, 5.76 mg/L for CRP, and 18.4 mg/g for MAU. Kistorp K, et al. JAMA. 2005;293:1609-1616.,2006. American Coll

18、ege of Physicians. All Rights Reserved.,0,-5,5,10,15,-100,-50,0,50,100,Rate of decline in GFR,(ml/min/ year),r = 0.47,p 0.011,delta Proteinuria (% change from pretreatment),Predictive value of antiproteinuric effect on renal protection,Apperloo AJ et al; Kidney Int 1994; 45:S174-8.,Rossing P et al.

19、Diabetologia. 1994;37:511-516.,15,10,5,0,-5,-100,-50,0,50,100,r=0.73 p.001.,Diabetes,Non-Diabetes,2006. American College of Physicians. All Rights Reserved.,Clinical Trials and Renal Outcomes Based on Proteinuria Reduction,Increased Time to Dialysis (30-35% proteinuria reduction) Captopril Trial-N E

20、ngl J Med, 1993 AASK Trial-JAMA, 2001 RENAAL-N Engl J Med, 2001 IDNT-N Engl J Med, 2001 COOPERATE-Lancet, 2003,No Change in Time to Dialysis (NO proteinuria reduction) DHPCCB arm-IDNT DHPCCB arm-AASK,Hart P 345(12):851-860. 2001 Massachusetts Medical Society. All rights reserved.,2006. American Coll

21、ege of Physicians. All Rights Reserved.,Relationship Between Rate of Decline in Renal Function and Change in Proteinuria in IDNT,Lewis EJ et al. N Engl J Med. 2001;345:851-860.,Amlodipine,Irbesartan,Placebo,Creatinine clearance (mL/min/1.73 m2),Proteinuria (g/d),2006. American College of Physicians.

22、 All Rights Reserved.,RENAAL; Baseline Proteinuria as a Determinant for Cardiac Events in Type 2 diabetes,CV Endpoint,Heart Failure,0,2,4,6,Hazard ratio,5.25,Albuminuria (g/g),0,2,4,6,.5,2.0,2.95,4.4,5.25,Albuminuria (g/g),.5,2.0,2.95,4.4,Hazard ratio,De Zeeuw et al; Circulation 2004,(adjusted for a

23、ll conventional risk factors),2006. American College of Physicians. All Rights Reserved.,RENAAL; Baseline Proteinuria as a Determinant for RENAL Events in Type 2 Diabetes,De Zeeuw et al; Kidney Int 2004,Primary composite Endpoint,0,10,15,5,Hazard ratio,.5,2.0,2.95,4.4,5.25,Baseline Albuminuria (g/g)

24、,Baseline Albuminuria (g/g),0,.5,2.0,2.95,4.4,5.25,ESRD,Hazard ratio,(adjusted for all conventional risk factors),2006. American College of Physicians. All Rights Reserved.,De Zeeuw D, et al. Kidney Int. 2004; 65:2309.,60,50,40,30,20,10,0,% with ERSD,0,12,24,36,48,Month,60,50,40,30,20,10,0,% with re

25、nal end point,0,12,24,36,48,Month,0%,030%,30%,0%,030%,30%, Alb: 030 vs. 0% Alb: 30 vs. 0% Alb: 30 vs. 030%,0.880.600.68,0.1570.00010.0003,HR,P values,Unadjusted,Renal End Point,0.760.460.61,0.0028.0001 .0001,HR,P values,Adjusted, Alb: 030 vs. 0% Alb: 30 vs. 0% Alb: 30 vs. 030%,0.820.510.62,0.1242.00

26、010.0019,HR,P values,Unadjusted,Renal End Point,0.620.370.60,0.0003.0001 .0010,HR,P values,Adjusted,RENAAL: Renal End Points By 6-Month Changes in Albuminuria,2006. American College of Physicians. All Rights Reserved.,De Zeeuw D, et al. Circulation. 2004;110:921.,40,% with CV endpoints,30,20,10,0,0,

27、12,24,36,48,Month,CV Endpoint,40,% with CV endpoints,30,20,10,0,0,12,24,36,48,Month,Heart Failure,0%,30%,0%,30%,RENAAL: Cardiovascular End Points by 6-Month Changes in Albuminuria,2006. American College of Physicians. All Rights Reserved.,Most Common Cause of Failing to Reduce Proteinuria with ACE I

28、nhibitor or ARB,High SALT intake (5 grams/day),DeZeeuw D et.al Kidney Int., 1989, Mishra SI et.al, Curr Hypertens Rep, 2005,2006. American College of Physicians. All Rights Reserved.,What is the Goal BP and Initial Therapy in Kidney Disease or Diabetes to Reduce CV Risk?,Group Goal BP (mmHg) Initial

29、 Therapy Am. Diabetes Assoc (2006) 130/80 ACE Inhibitor or ARB* KDOQI (NKF) (2004) 130/80 ACE Inhibitor or ARB* JNC 7 (2003) 130/80 ACE Inhibitor or ARB* Canadian HTN Soc. (2002) 130/80 ACE Inhibitor or ARB Am. Diabetes Assoc (2002) 130/80 ACE Inhibitor or ARB Natl. Kidney Fdn.-CKD(2002) 130/80 ACE

30、Inhibitor or ARB* Natl. Kidney Fdn. (2000) 130/80 ACE Inhibitor* British HTN Soc. (1999) 140/80 ACE Inhibitor WHO/ISH(1999) 130/85 ACE Inhibitor JNC VI (1997) 130/85 ACE Inhibitor,* Indicates use with diuretic,2006. American College of Physicians. All Rights Reserved.,DETAIL, a prospective, multicen

31、ter, non-inferiority trial randomized 250 patients with type 2 diabetes, hypertension (BP 70 mL/min/1.73 m2) to either telmisartan or enalapril. Followed for 5 years,Barnett AH et.al N Engl J Med 2004;351:1952-1961.,Angiotensin-Receptor Blockade versus ConvertingEnzyme Inhibition in Type 2 Diabetes

32、and Nephropathy,2006. American College of Physicians. All Rights Reserved.,Barnett AH et.al N Engl J Med 2004;351:1952-1961.,Angiotensin-Receptor Blockade versus ConvertingEnzyme Inhibition in Type 2 Diabetes and Nephropathy-RESULTS,Baseline GFR 91 ml/min,2006. American College of Physicians. All Ri

33、ghts Reserved.,Effects of ACE Inhibitors or ARBs on Renal Disease Progression: A Meta-Analysis Cases J et.al. Lancet 2005;366:2026,ESRD,2X SCr,2006. American College of Physicians. All Rights Reserved.,Effects of ACE Inhibitors or ARBs on Renal Disease Progression: A Meta-Analysis Cases J et.al. Lan

34、cet 2005;366:2026,ESRD,2X SCr,2006. American College of Physicians. All Rights Reserved.,-9.4,-1.3,-4,-7,-10,-8,-6,-4,-2,0,mL/min/yr.,mm Hg,Initial GFR Rateof Decline4 Months,130,140,150,Systolic PressureTrial End,Bakris(N = 18),Nielsen(N = 21),Final GFR Rateof DeclineTrial End (16 years),136,154,Ba

35、kris GL follow-up = 7.8 years,Patients with Type 2 Diabetes and Microalbuminuria,Aggressive treatment of: Microalbuminuria with ACEIs, ARBs, or combination Hypertension Hyperglycemia Dyslipidemia Secondary prevention of CVD,Adapted from Gde P et al. N Eng J Med. 2003;348:383-393,2006. American Colle

36、ge of Physicians. All Rights Reserved.,Saydah S et.al JAMA 2004;291:335,Percentage of Adults with Diabetes Who Achieved Recommended Goals of Cardiovascular Risk Factors in NHANES,%,2006. American College of Physicians. All Rights Reserved.,(if systolic BP 20 mmHg above goal) START with ACEI or ARB/thiazide diuretic*),If BP Still Not at Goal (130/80 mm Hg),If BP