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Paul E de Jong, nephrologist University Medical Center Groningen The Netherlands Screening for Chronic Kidney Disease Where does Europe go?
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Screening for Chronic Kidney disease

Nov 26, 2021

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Page 1: Screening for Chronic Kidney disease

Paul E de Jong, nephrologist

University Medical Center GroningenThe Netherlands

Screening for Chronic Kidney Disease

Where does Europe go?

Page 2: Screening for Chronic Kidney disease

Lysaght, JASN, 2002

1990 2000 2010

426,000

1,490,000

2,500,000

Patients in chronic dialysis world-widedialysis costs ~ € 50.000/year

Page 3: Screening for Chronic Kidney disease

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

PREVENDThe stages 1-5 of Chronic Kidney Disease

Page 4: Screening for 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

Page 5: Screening for Chronic Kidney disease

CKD as predictor of renal events,

GFR or albuminuria?

PREVEND

Page 6: Screening for Chronic Kidney disease

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

Page 7: Screening for Chronic Kidney disease

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

Page 8: Screening for Chronic Kidney disease

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

Page 9: Screening for Chronic Kidney disease

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

Page 10: Screening for Chronic Kidney disease

CKD as predictor of CV events:

GFR or albuminuria?

PREVEND

Page 11: Screening for Chronic Kidney disease

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

Page 12: Screening for Chronic Kidney disease

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-

Page 13: Screening for Chronic Kidney disease

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

Page 14: Screening for Chronic Kidney disease

Is it just identification of a subject with increased risk

or, ...

can we offer him a treatment?

PREVEND

Page 15: Screening for Chronic Kidney disease

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

Page 16: Screening for Chronic Kidney disease

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

Page 17: Screening for Chronic Kidney disease

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

Page 18: Screening for Chronic Kidney disease

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

Page 19: Screening for Chronic Kidney disease

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

Page 20: Screening for Chronic Kidney disease

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

Page 21: Screening for Chronic Kidney disease

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

Page 22: Screening for Chronic Kidney disease

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

Page 23: Screening for Chronic Kidney disease

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

Page 24: Screening for Chronic Kidney disease

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

Page 25: Screening for Chronic Kidney disease

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

Page 26: Screening for Chronic Kidney disease

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

Page 27: Screening for Chronic Kidney disease

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

Page 28: Screening for Chronic Kidney disease

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 - -

Page 29: Screening for Chronic Kidney disease

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