Transcript Microalbuminuria: Heeding the Alarm to Reduce Risk of

The PREVEND Study:
Screening for micro-albuminuria
Towards targeted “primary” prevention
to improve renal and cardiovascular care ?
The PREVEND Study Group
University Medical Center Groningen
PREVEND
PREVEND
The design of the PREVEND Study
PREVEND
The PREVEND Study
Acronym for:
Prevention of REnal and Vascular
ENd-stage Disease Study
Since 1997
Groningen, The Netherlands
www.PREVEND.org
PREVEND Study
Selection procedure
PREVEND
1997
85.421
All inhabitants of the city of Groningen,
aged 28 - 75 years, invited for study
40.856
Positive response
- spot morning urine sample, sent in a vial by post to a
central laboratory, short questionnaire
Inclusion criteria:
- All with urinary albumin concentration >10 mg/L
- Random sample with UAC <10 mg/L
Exclusion criteria:
- Diabetes mellitus
- Pregnancy
8.592
Screening in an outpatient clinic (once per 3 years)
Albuminuria, renal function, BP, morbidity, mortality etc
Micro-albuminuria:
Definition and classification
Morning urine
Albumin
(mg/l)
Normal
< 20
24h urine
Alb/creat
ratio
(mg/mmol)
M
< 2.5
F
< 3.5
Albumin
(mg/24h)
Overnight
urine (timed)
Albumin
(g/min)
< 30
< 20
Micro-albuminuria
20 – 200
M
F
> 2.5-25
> 3.5-35
30 – 300
20 – 200
Macro-albuminuria
> 200
M
F
> 25
> 35
> 300
> 200
PREVEND
The PREVEND Study
Aknowledgements
Other sponsors:
Dutch Heart Foundation
Bristol Myers Squibb
de Cock Fund
Dade Behring
Ausam
Roche
Dutch Government (NWO)
US National Institutes of Health (NIH)
University Medical Center Groningen (UMCG)
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Introductory slides
The history of renal care
De Jong PE, Brenner B: Kidney Int 2004;66:2109-2118
EARLY RENAL
DAMAGE
ESTABLISHED
RENAL DISEASE
END-STAGE RENAL
FAILURE
1960-1980
TERTIARY
PREVENTION
Prevention of
complications of
ESRF in dialysis
The history of renal care
De Jong PE, Brenner B: Kidney Int 2004;66:2109-2118
EARLY RENAL
DAMAGE
ESTABLISHED
RENAL DISEASE
END-STAGE RENAL
FAILURE
1980-2000
1960-1980
SECONDARY
TERTIARY
PREVENTION
PREVENTION
Prevention of
progression to ESRF
Prevention of
complications of
ESRF in dialysis
The history of renal care
De Jong PE, Brenner B: Kidney Int 2004;66:2109-2118
EARLY RENAL
DAMAGE
ESTABLISHED
RENAL DISEASE
END-STAGE RENAL
FAILURE
1980-2000
1960-1980
“PRIMARY”
SECONDARY
TERTIARY
PREVENTION
PREVENTION
PREVENTION
Prevention of renal
function loss in a
very early phase
Prevention of
progression to ESRF
Prevention of
complications of
ESRF in dialysis
> 2000
Number of subjects in dialysis increases
2,500,000
1,490,000
426,000
1990
Lysaght et al; J Am Soc Nephrol 2002
2000
2010
Incidence of dialysis in The Netherlands
- Classical causes for ESRD decrease !!! 400
All age groups
Crude incidence per year
350
300
250
200
150
Diabetes type 1
100
Interstitial nephritis
50
Glomerulonephritis
0
'69-'73
'74-'78
Gansevoort et al; Kidney Int 2004
'79-'83
'84-'88
'89-'93
'94-'98
'99-'03
Incidence of dialysis in The Netherlands
- Atherosclerosis related causes increase 400
350
Crude incidence per year
Renal Vascular
Disease
All age groups
300
Unknown (probably
atherosclerosis related)
250
200
DM type 2
150
100
50
0
'69-'73
'74-'78
Gansevoort et al; Kidney Int 2004
'79-'83
'84-'88
'89-'93
'94-'98
'99-'03
Renoprotection
Especially effective when started early
Renal function (%)
Necessity for
dialysis
10
0
0
1
2
3
4
5
6
7
Follow-up (years)
8
9
10
Albuminuria (mg/24hr)
Renal function (mL/min)
Natural course of untreated diabetic nephropathy
150
Hyperfiltration
125
Normal renal function
100
75
50
Overt nephropathy
25
0
10.000
3.000
Macro-albuminuria
1.000
300
100
Micro-albuminuria
30
Normo-albuminuria
10
0
Mogensen et al; Diabetes 1990
4
8
12
16
20
24
28
Duration of diabetes (years)
PREVEND
Slides from the publications of 2000
Renal function in relation to albuminuria
in the non-diabetic general population
PREVEND
120
n= 8,592
100
80
0-7.5
7.5-15
15-22.5
Pinto-Sietsma et al; JASN 2000;11:1882-1888
22.5-30
30-175
175-300
>300
UAE
mg/d
Renal function (mL/min)
Albuminuria (mg/24hr)
PREVEND
The natural course of renal function
in the non-diabetic general population
150
Hyperfiltration
125
Normal renal function
100
75
50
Overt nephropathy
25
0
10.000
3.000
Macro-albuminuria
1.000
300
Micro-albuminuria
100
30
Normo-albuminuria
10
Increasing age (years)
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Slides from the publications of 2001
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Prevalence of albuminuria in the
general population
Macro-albuminuria
>200 mg/l
Micro-albuminuria
0.7%
20-200 mg/l
7.2%
High-normal
albuminuria
10-20 mg/l
16.6%
n=40,856
Hillege et al; J Int Med 2001;249:519-526
Normal
0-10mg/l
75%
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Microalbuminuria in relation to underlying
mechanism in the general population
Diabetes
6.2%
Hypertension
18.9%
n=2,918
“Healthy”
75%
Hillege et al; J Int Med 2001;249:519-526
PREVEND
Slides from the publications of 2002
PREVEND
Albuminuria as predictor of CV mortality
in the general population
Risk of CV mortality (HR)
5
N=40.856
4
3
2
1
2
10
100
1000
Albumin concentration (mg/L)
Hillege et al; Circulation 2002;106:1777-1782
PREVEND
Albuminuria predicts cardiovascular
death in the general population
CV death (% per 1000 pj)
35
29.1
30
25
20
15
11.2
10
5
3.5
4.5
0
0 - 14
Hillege et al; Circulation 2002;106:1777-1782
15 – 29
30 - 300
>300
PREVEND
Slides from the publications of 2004
Blood pressure and proteinuria lowering effect
of antihypertensives: a meta-analysis
Proteinuria (% change)
- 10
-5
- 20
- 10
- 30
- 15
- 40
- 20
- 50
ACEi
Others
CCB
BB
Rest
N=34
N=593
N=40
N=632
N=23
N=394
N=8
N=129
N=9
N=109
Gansevoort et al; Nephrol Dial Transplant 1995
- 25
Mean Arterial Pressure (% change)
0
0
PREVEND IT
PREVEND IT Study
Baseline characteristics
Placebo (n=429)
Fosinopril (n=425)
51.5 ± 11.4
51.0 ± 12.1
Male gender
63.9 %
66.1 %
Smoking, past
current
31.2 %
34.4 %
34.4 %
36.0 %
Obesity (BMI > 30 kg/m2)
18.6 %
14.6 %
Cholesterol, mg/dl
(mmol/l)
220 ± 39
(5.7 ± 1.0)
224 ± 39
(5.8 ± 1.0)
SBP, mmHg
130 ± 17.9
129 ± 17.1
DBP, mmHg
76 ± 9.7
76 ± 9.7
Prior CV event
2.3 %
4.0 %
Cardiovascular drugs
5.8 %
3.8 %
Albuminuria, mg/24h *
21.7 (15.2- 39.6)
23.7 (16.9- 44.5)
Age, years
Asselbergs et al; Circulation 2004
* Expressed as median (interquartile range)
PREVEND IT
Effects of ACEi
in the “healthy” with albuminuria
Change from baseline
with Fosinopril
0
Change in
albuminuria
(%)
- 10
- 20
- 30
- 29.5 *
- 31.43 *
* p < 0.001
3 Months
Asselbergs et al; Circulation 2004
4 Years
PREVEND IT
Treatment that lowers albuminuria reduces
CV risk in the “healthy” with albuminuria
7.5
Placebo
5
2.5
0
ACEi
0
Combined CV endpoint (%)
10
10
20
30
(fosinopril)
40
Months
Asselbergs et al; Circulation 2004
Risk
Reduction
40%
NNT
29
Incidence of Stage 3 CKD (%)
PREVEND
Albuminuria predicts CKD
in the non-diabetic general population
70
58
60
50
40
30
22
20
9
13
10
0
0 - 14
Verhave et al; Kidney Int 2004;66(suppl 92):1-4
15 – 29
30 - 300
>300
3 CKD = creatinine clearance < 60 mL/min
AlbuminuriaStage
(mg/day)
PREVEND
Slides from the publications of 2005
PREVEND
Albuminuria predicts new onset diabetes
in the general population
New onset Diabetes (%)
14
11.8
12
10
7.9
8
6
4.3
4
2.2
2
0
0 - 14
Brantsma et al; Diabetes Care 2005
15 – 29
30 - 300
Albuminuria (mg/day)
>300