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The PREVEND Study Group University Medical Center Groningen The PREVEND Study: Screening for micro-albuminuria PREVEND Towards targeted “primary” prevention.

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Presentation on theme: "The PREVEND Study Group University Medical Center Groningen The PREVEND Study: Screening for micro-albuminuria PREVEND Towards targeted “primary” prevention."— Presentation transcript:

1 The PREVEND Study Group University Medical Center Groningen The PREVEND Study: Screening for micro-albuminuria PREVEND Towards targeted “primary” prevention to improve renal and cardiovascular care ?

2 The design of the PREVEND Study PREVEND

3 The PREVEND Study Acronym for: Prevention of REnal and Vascular ENd-stage Disease Study Since 1997 Groningen, The Netherlands PREVEND

4 All inhabitants of the city of Groningen, All inhabitants of the city of Groningen, aged years, invited for study aged years, invited for study Positive response - spot morning urine sample, sent in a vial by post to a central laboratory, short questionnaire - spot morning urine sample, sent in a vial by post to a central laboratory, short questionnaire Screening in an outpatient clinic (once per 3 years) Inclusion criteria: Inclusion criteria: - All with urinary albumin concentration >10 mg/L - All with urinary albumin concentration >10 mg/L - Random sample with UAC <10 mg/L - Random sample with UAC <10 mg/L Exclusion criteria: Exclusion criteria: - Diabetes mellitus - Diabetes mellitus - Pregnancy - Pregnancy PREVEND Study Selection procedure PREVEND 1997 Albuminuria, renal function, BP, morbidity, mortality etc

5 Micro-albuminuria: Definition and classification Morning urine > > < 2.5 < 3.5 Alb/creat ratio (mg/mmol) > 200> 300> 200Macro-albuminuria 20 – – 300MFMF 20 – 200Micro-albuminuria < 20< 30MFMF < 20Normal Albumin (  g/min) Albumin (mg/24h) Albumin (mg/l) Overnight urine (timed) 24h urine > 25 > 35 MFMF

6 The PREVEND Study Aknowledgements Other sponsors: Dutch Heart Foundation Bristol Myers Squibb de Cock Fund Dade Behring AusamRoche Dutch Government (NWO) US National Institutes of Health (NIH) University Medical Center Groningen (UMCG) PREVEND

7 Introductory slides PREVEND

8 The history of renal care De Jong PE, Brenner B: Kidney Int 2004;66: EARLY RENAL DAMAGE ESTABLISHED RENAL DISEASE END-STAGE RENAL FAILURE TERTIARYPREVENTION Prevention of complications of ESRF in dialysis

9 EARLY RENAL DAMAGE ESTABLISHED RENAL DISEASE END-STAGE RENAL FAILURE TERTIARYPREVENTION Prevention of complications of ESRF in dialysis SECONDARYPREVENTION Prevention of progression to ESRF The history of renal care De Jong PE, Brenner B: Kidney Int 2004;66:

10 EARLY RENAL DAMAGE ESTABLISHED RENAL DISEASE END-STAGE RENAL FAILURE TERTIARYPREVENTION Prevention of complications of ESRF in dialysis SECONDARYPREVENTION Prevention of progression to ESRF “PRIMARY”PREVENTION Prevention of renal function loss in a very early phase > 2000 The history of renal care De Jong PE, Brenner B: Kidney Int 2004;66:

11 Lysaght et al; J Am Soc Nephrol ,000 1,490,000 2,500,000 Number of subjects in dialysis increases

12 Crude incidence per year Interstitial nephritis Glomerulonephritis All age groups Gansevoort et al; Kidney Int 2004 Diabetes type 1 Incidence of dialysis in The Netherlands - Classical causes for ESRD decrease !!! - Incidence of dialysis in The Netherlands - Classical causes for ESRD decrease !!! -

13 Crude incidence per year Renal Vascular Disease Unknown (probably atherosclerosis related) DM type 2 All age groups Gansevoort et al; Kidney Int 2004 Incidence of dialysis in The Netherlands - Atherosclerosis related causes increase - Incidence of dialysis in The Netherlands - Atherosclerosis related causes increase -

14 Renal function (%) 0 10 Follow-up (years) Renoprotection Especially effective when started early Renoprotection Late treatment Early treatment Necessity for dialysis

15 Natural course of untreated diabetic nephropathy Mogensen et al; Diabetes 1990 Duration of diabetes (years) Albuminuria (mg/24hr) Renal function (mL/min) Normo-albuminuria Micro-albuminuria Macro-albuminuria Normal renal function Overt nephropathy Hyperfiltration

16 Slides from the publications of 2000 PREVEND

17 >300 Renal function in relation to albuminuria in the non-diabetic general population n= 8,592 Pinto-Sietsma et al; JASN 2000;11: creatinine clearance (ml/min) UAE mg/d PREVEND

18 The natural course of renal function in the non-diabetic general population Increasing age (years) Albuminuria (mg/24hr) Renal function (mL/min) PREVEND Normo-albuminuria Micro-albuminuria Macro-albuminuria Normal renal function Overt nephropathy Hyperfiltration

19 Slides from the publications of 2001 PREVEND

20 Prevalence of albuminuria in the general population Normal0-10mg/l75% Macro-albuminuria >200 mg/l 0.7% Micro-albuminuria Micro-albuminuria mg/l mg/l7.2% H igh-normal H igh-normal albuminuria albuminuria mg/l mg/l16.6% Hillege et al; J Int Med 2001;249: n=40,856 PREVEND

21 Microalbuminuria in relation to underlying mechanism in the general population Hypertension18.9% Diabetes6.2% “Healthy”75% PREVEND n=2,918 Hillege et al; J Int Med 2001;249:

22 Slides from the publications of 2002 PREVEND

23 Albuminuria as predictor of CV mortality in the general population PREVEND Hillege et al; Circulation 2002;106:

24 Albuminuria predicts cardiovascular death in the general population > – CV death (% per 1000 pj) Albuminuria (mg/day) PREVEND Hillege et al; Circulation 2002;106:

25 Slides from the publications of 2004 PREVEND

26 Proteinuria (% change) Mean Arterial Pressure (% change) ACEi N=34 N=593 Others N=40 N=632 CCB N=23 N=394 BB N=8 N=129 Rest N=9 N=109 Gansevoort et al; Nephrol Dial Transplant 1995 Blood pressure and proteinuria lowering effect of antihypertensives: a meta-analysis

27 Placebo (n=429) Fosinopril (n=425) Smoking, past current current 31.2 % 34.4 % 36.0 % SBP, mmHg 130 ± ± 17.1 Obesity (BMI > 30 kg/m 2 ) 18.6 % 14.6 % Age, years 51.5 ± ± 12.1 DBP, mmHg 76 ± 9.7 Prior CV event 2.3 % 4.0 % PREVEND IT Study Baseline characteristics Cholesterol, mg/dl (mmol/l) 220 ± 39 (5.7 ± 1.0) 224 ± 39 (5.8 ± 1.0) Albuminuria, mg/24h * 21.7 ( ) 23.7 ( ) * Expressed as median (interquartile range) Cardiovascular drugs 5.8 % 3.8 % Male gender 63.9 % 66.1 % Asselbergs et al; Circulation 2004 PREVEND IT

28 Effects of ACEi in the “healthy” with albuminuria Change in albuminuria(%) Months 4 Years with Fosinopril Change from baseline * * * * * p < Asselbergs et al; Circulation 2004 PREVEND IT

29 Asselbergs et al; Circulation Placebo ACEi (fosinopril) Combined CV endpoint (%) Months RiskReduction40%NNT29 Treatment that lowers albuminuria reduces CV risk in the “healthy” with albuminuria PREVEND IT

30 Albuminuria predicts CKD in the non-diabetic general population > – Incidence of Stage 3 CKD (%) Incidence of Stage 3 CKD (%) Albuminuria (mg/day) Verhave et al; Kidney Int 2004;66(suppl 92):1-4 PREVEND Stage 3 CKD = creatinine clearance < 60 mL/min

31 Slides from the publications of 2005 PREVEND

32 Albuminuria predicts new onset diabetes in the general population > – New onset Diabetes (%) Albuminuria (mg/day) Brantsma et al; Diabetes Care PREVEND


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