screening for chronic kidney disease

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

De Zeeuw et al. Kidney Int 2005;98:S25-29

PREVENDThe stages 1-5 of Chronic Kidney Disease

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

CKD as predictor of renal events,

GFR or albuminuria?

PREVEND

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

CKD as predictor of CV events:

GFR or albuminuria?

PREVEND

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


∆ 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


∆ C

ost

(100

0 x

in €

’s)

€80,000 per LYG

€50,000 per LYG

€20,000 per LYG


Unselected population


Cost vs effects: impact of pre-selection on one morning urinePREVEND

0

400

800

1200

1600

2000

0 10 20 30


∆ C

ost

(100

0 x

in €

’s)

€80,000 per LYG

€50,000 per LYG

€20,000 per LYG


Unselected populationPre-selection on UAC ≥10 mg/L


Cost versus Effects:impact of age-limitationPREVEND

0

400

800

1200

1600

2000

0 20 40 60 80 100


∆ 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



Cost versus Effects:impact of age-limitationPREVEND

0

400

800

1200

1600

2000

0 20 40 60 80 100


∆ 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


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


Target population

30-50%

Disadvantage: - the patients diagnosed mostly are on treatment yet

Advantage: - being aware of CKD requires more aggressive treatment goals



SCREENING


APPROACH-USA

Overall population


Measurements

Action

Target population If known with eGFR <60:

Confirm impaired eGFR; If positive

30-50% 2-3%






3-4%



SCREENING


APPROACH-USA

Overall population




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%



SCREENING


APPROACH-USA

Overall population


Measurements

Action



30-50% 2-3% 7-8%






15-20%

3-4%


Confirm microalbuminuria: If positive

Preselection on dipstick or albuminuria; If positive:


SCREENING


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

screening for chronic kidney disease

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