Paul E de Jong, nephrologist University Medical Center Groningen The Netherlands Screening for Chronic Kidney Disease Where does Europe go?
Paul E de Jong, nephrologist
University Medical Center GroningenThe Netherlands
Screening for Chronic Kidney Disease
Where does Europe go?
Lysaght, JASN, 2002
1990 2000 2010
426,000
1,490,000
2,500,000
Patients in chronic dialysis world-widedialysis costs ~ € 50.000/year
n= 85421 n= 85421
age 28age 28--75 yrs75 yrs
n= 40856n= 40856
-- morning urine samplemorning urine sample-- short questionnaireshort questionnaire
n= 8592n= 8592
oversamplingoversamplingelevated UAEelevated UAE
PREVEND: PREVEND: PPrevention of revention of RRenal enal and and VVascular ascular EEnd stage nd stage DDiseaseisease
www.prevend.orgpermanent follow up of this cohort
1997
Iseki et al; Am J Kidney Dis 2004;44:806-14
eGFR as predictor of end stage renal disease
n=95.252, follow-up: 7 years
0.01
0.1
1.0
10
100
1000
eGFR (mL/min)0 30 60 90 120
proteinuria negativeInci
denc
e of
ESR
D p
er 1
000
15
5 4 3 CKD stages
Iseki et al; Am J Kidney Dis 2004;44:806-814
eGFR and dipstick proteinuria as predictorof end stage renal disease
n=95.252, follow-up: 7 years
0.01
0.1
1.0
10
100
1000
proteinuria positive
eGFR (mL/min)0 30 60 90 120
proteinuria negativeInci
denc
e of
ESR
D p
er 1
000
15
5 4 3 2 1 CKD stages
PREVEND
Albuminuria predicts rate of renal function decline in the general population
-2
-1,8
-1,6
-1,4
-1,2
-1
-0,8
-0,6
-0,4
-0,2
00-15 15-30 30-150 150-300 >300
Slop
e of
rena
l fun
ctio
n de
clin
e (m
l/min
/yea
r)
Crude
Adjusted for age and sex
Adjusted for age, sex, BP,BPLD, lipids, LLD, glucoseand CV history
= UAE class
Van der Velde et al; JASN 2009; 20: 852-62 N=6.894
P<0.05
P<0.01
P<0.01
P<0.01
microalbuminuria macro
Total Medicare
Diabetes
Heart Failure
Dialysis/Tx
CKD
41.3% 48.1%
19%
7.8%
Alan Collins, USRDS database
Costs for kidney failure overlap with costs for diabetes and heart failure in age >60
Go et al, New Eng J Med 2004;351:1296-1305 Kayser-Permanente Study; n=1.120.295
0
1
2
3
4
5
6
7
>60
45-60
30-45
15-30 <1
5
>60
45-60
30-45
15-30 <1
5
Adj
uste
d H
azar
d R
atio
All cause mortality
CV events
GFR(mL/min/1.73m2)
eGFR as predictor of all cause mortality and cardiovascular events
Albuminuria as predictor of cardiovascular mortalityPREVEND
albumin concentration (mg/L)
1
2
3
4
5
2 10 100 1000
CV
mor
talit
y(a
ge a
nd s
ex a
djus
terd
rela
tive
risk)
Hillege et al; Circulation 2002;106:1777-82 N = 40.856
normo- micro- macro-
Brantsma et al, NDT 2008;23:3851-8
PREVEND
0 2 4 6 8
0,90
0,92
0,94
0,96
0,98
1,00
No CKD
Stage 1*
Stage 2*
Stage 3 and MA–
Stage 3 and MA+*
Follow-up in years
Prop
ortio
n fr
ee o
f car
diov
ascu
lar e
vent
CV outcome according to CKD class- age and sex adjusted -
*p <0.001 vs no CKD
Is it just identification of a subject with increased risk
or, ...
can we offer him a treatment?
PREVEND
Asselbergs et al; Circulation 2004;110:2809-16
Lowering albuminuria reduces CV events in “healthy” microalbuminurics (n=864)
0 10 20 30 40
0.10
0.05
0
Placebo
ACEi (fosinopril)C
V M
orb/
mor
t (%
)
Months
RiskReduction
44%
Del
ta A
lbum
inur
ia (%
)
0
- 10
- 20
- 30
3 Months 4 Years
ACEiEffect on albuminuria
- 29.5 *- 31.43 *
* p < 0.001
ACEiEffect on CV morb/mort
PREVEND
eGFR
0
10
Follow-up (years)
Late intervention
Early intervention
GFR slope calculation affords early intervention
Need for dialysis
90
60
30
No albuminuria normal ageing
With albuminuria
PREVEND
Gansevoort et al. JASN 2009, 20: 465-8
Cost-effectiveness plane
0
400
800
1200
1600
2000
0 10 20 30
∆ Effect (in LYGs)
∆ C
ost
(100
0 x
in €
’s)
Low CostsLow Effects
High CostsHigh Effects
Low CostsHigh Effects
High CostsLow Effects
Cost vs effects: PREVEND
0
400
800
1200
1600
2000
0 10 20 30
∆ Effect (in LYGs)
∆ C
ost
(100
0 x
in €
’s)
€80,000 per LYG
€50,000 per LYG
€20,000 per LYG
UAE ≥ 300 mg/dUAE ≥ 30 mg/dUAE ≥ 15 mg/d
Boersma C et al. Clin Therapeutics 2010, in press
Cost vs effects: impact of pre-selection on one morning urinePREVEND
0
400
800
1200
1600
2000
0 10 20 30
∆ Effect (in LYGs)
∆ C
ost
(100
0 x
in €
’s)
€80,000 per LYG
€50,000 per LYG
€20,000 per LYG
UAE ≥ 300 mg/dUAE ≥ 30 mg/dUAE ≥ 15 mg/d
Unselected population
Boersma C et al. Clin Therapeutics 2010, in press
Cost vs effects: impact of pre-selection on one morning urinePREVEND
0
400
800
1200
1600
2000
0 10 20 30
∆ Effect (in LYGs)
∆ C
ost
(100
0 x
in €
’s)
€80,000 per LYG
€50,000 per LYG
€20,000 per LYG
UAE ≥ 300 mg/dUAE ≥ 30 mg/dUAE ≥ 15 mg/d
Unselected populationPre-selection on UAC ≥10 mg/L
Boersma C et al. Clin Therapeutics 2010, in press
Cost versus Effects:impact of age-limitationPREVEND
0
400
800
1200
1600
2000
0 20 40 60 80 100
∆ Effect (in LYGs)
∆ C
ost
(100
0 x
in €
’s)
€80,000 per LYG €50,000 per LYG €20,000 per LYG
€10,000 per LYG
All subjects
UAE ≥ 300 mg/dUAE ≥ 30 mg/dUAE ≥ 15 mg/d
Boersma C et al. Clin Therapeutics 2010, in press
Cost versus Effects:impact of age-limitationPREVEND
0
400
800
1200
1600
2000
0 20 40 60 80 100
∆ Effect (in LYGs)
∆ C
ost
(100
0 x
in €
’s)
€80,000 per LYG €50,000 per LYG €20,000 per LYG
€10,000 per LYG
All subjectsAge >50 years UAE ≥ 300 mg/d
UAE ≥ 30 mg/dUAE ≥ 15 mg/d
Boersma C et al. Clin Therapeutics 2010, in press
APPROACH-USA
Overall population
Percentage visiting GP
Measurements
Action
Target population
30-50%
History on renal and cardiovascular end organ damage
Measure renal and cardiovascular risk factors
Measure eGFR and albuminuria
When suspicion of primary renal disease: additional investigations + specific treatment
In case of CKD without suspicion of primary renal disease: treat CV risk factors
APPROACH-UK APPROACH-Netherlands
If known with DM, HT, CV-history, or age>50 yr
SCREENING
De Jong et al. CJASN 2008;3:616-23
APPROACH-USA
Overall population
Percentage visiting GP
Target population
30-50%
Disadvantage: - the patients diagnosed mostly are on treatment yet
Advantage: - being aware of CKD requires more aggressive treatment goals
APPROACH-UK APPROACH-Netherlands
If known with DM, HT, CV-history, or age>50 yr
SCREENING
De Jong et al. CJASN 2008;3:616-23
APPROACH-USA
Overall population
Percentage visiting GP
Measurements
Action
Target population If known with eGFR <60:
Confirm impaired eGFR; If positive
30-50% 2-3%
History on renal and cardiovascular end organ damage
Measure renal and cardiovascular risk factors
Measure eGFR and albuminuria
When suspicion of primary renal disease: additional investigations + specific treatment
In case of CKD without suspicion of primary renal disease: treat CV risk factors
3-4%
APPROACH-UK APPROACH-Netherlands
If known with DM, HT, CV-history, or age>50 yr
SCREENING
De Jong et al. CJASN 2008;3:616-23
APPROACH-USA
Overall population
Percentage visiting GP
Target population If known with eGFR <60:
Confirm impaired eGFR; If positive
30-50% 2-3%
Disadvantage: - there is just detection of stage 3 or more CKD
- focus might be incorrect as it detects only patients with a reason to do serum creatinine measurements
Advantage: - it does not require prior selection
3-4%
APPROACH-UK APPROACH-Netherlands
If known with DM, HT, CV-history, or age>50 yr
SCREENING
De Jong et al. CJASN 2008;3:616-23
APPROACH-USA
Overall population
Percentage visiting GP
Measurements
Action
Target population If known with eGFR <60:
Confirm impaired eGFR; If positive
30-50% 2-3% 7-8%
History on renal and cardiovascular end organ damage
Measure renal and cardiovascular risk factors
Measure eGFR and albuminuria
When suspicion of primary renal disease: additional investigations + specific treatment
In case of CKD without suspicion of primary renal disease: treat CV risk factors
15-20%
3-4%
APPROACH-UK APPROACH-Netherlands
Confirm microalbuminuria: If positive
Preselection on dipstick or albuminuria; If positive:
If known with DM, HT, CV-history, or age>50 yr
SCREENING
De Jong et al. CJASN 2008;3:616-23
age < 65 age > 65
Dutch GP-nephrologist CKD cooperation
green = GP follows DM and CVD guideliness whenever appropriateyellow = CKD guideliness followed by GP, unless x1; orange = consultation between GP and nephrologistred = nephrologist
x1 = rapid eGFR decline, underlying kidney disease, or metabolic complications
figures in cells refer to the number of subjects per 1000 population
Normoalbuminuria
Microalbuminuria
Macroalbuminuria
GFR > 90 254 15 -
GFR 60-90 678 27 2
GFR 45-60 20 2 1
GFR 30-45 - - -
GFR < 30 - - -
Normoalbuminuria
Microalbuminuria
Macroalbuminuria
GFR > 90 66 10 -
GFR 60-90 687 72 8
GFR 45-60 119 21 6
GFR 30-45 5 3 1
GFR < 30 1 - -
ConclusionsPREVEND
• CKD is found in about 10% of the population• The level of albuminuria is of more impact than
the level of GFR to predict both renal and CV prognosis
• Lowering albuminuria prevents CV events• Screening for albuminuria is cost-effective to
prevent CV events• Screening for albuminuria affords early
intervention• It can be implemented in GP practice