Improving outcomes in advanced

CKD and the transition to dialysis

Elodie Speyer, PhD

on behalf of CKDopps and CKD-REIN Investigators

EDTNA 2017 Congress, DOPPS Clinical Symposium

Krakow, Poland

Sept, 10th 2017

CKDopps: Outline

1. Study overview

2. Practice patterns

3. What patients tell us

CKDopps – Overall goal and design

• The CKD Outcomes and Practices Patterns Study (CKDopps)

• International, prospective cohort study of CKD patients receiving

nephrologist care (based on national samples of nephrology

clinics)

• Identify nephrologist practices associated with better outcomes in

advanced CKD patients and during kidney failure transition

• CKDopps initiative may have a lasting influence on CKD care, as

DOPPS has had on HD care since its launch in 1996.

• Public and industry funding

Design Target ≈ 12,000 CKD patients

Inclusion

criteria

• Adult patients ( ≥18 years)

• All causes of CKD stage 3b to 5 (non dialysis,

non-renal transplant)

- Stage 3-4 in France

• 60-80 per clinic

Follow-up • 3 years (up to 5 years in France)

• Before and after starting RRT

Extensive data

collection

(longitudinal)

• Patient-level data (medical records & PRO) - Routine lab data (vs requested in France)

- No patient-questionnaire in Germany

• Physician-, and clinic-level data

Outcomes • Mortality and morbidity

• Progression and transition to kidney failure

• Patient-reported outcomes and experience

Patients and information

More details in Mariani et al. Am J Kidney Dis. 2016 Sep;68(3):402-13

Brazil

France

Germany

United States

CKDopps participating countries Current as of August 24, 2017

32 clinics

(target=30)

1,810 patients

(target = 1,800)

40 clinics

(target=40)

3,033 patients

(target=3,200)

32 clinics

(target=40)

1,425 patients

(target=3,200)

18 clinics

(target=20)

995 patients

(target=1,600)

Japan

31 clinics

(target=30)

2,201 patients

(target=2,400)

Currently enrolled ~ 9,465 of targeted 12,000 patients

Baseline patient characteristics

Brazil France Germany US

Patients, N 909 3,033 1,829 1,251

Median age (years) 67 69 75 71

Women 47% 35% 42% 47%

Diabetesa 48% 41% 43% 59%

Mean eGFR, mL/min/1.73 m2

25.8 32.9 27.7 26.4

CKD Cause

Diabetes 32% 20% 27% 35%

Glomerular Disease 8% 17% 10% 6%

Hypertension 30% 21% 33% 33%

Other/Unknown 30% 42% 30% 26%

a. 5, 2, 2, 4 % of all patients in Brazil, France, Germany, US were type 1 diabetics

b. ** Japanese data not available yet (enrollment started in 2016)

Country N Pts Follow-up Time,

Median years

Dialysis

Starts,

% (n)

Deaths**,

% (n)

Hospitalizations†,

% (n)

Brazil 909 1.20 9% (78) 6% (51) 17% (155)

France 3,012 1.99 8% (258) 8% (237) 58% (1774)

Germany 1,829 3.10 22% (396) 13% (234) -

United States 1,251 1.21 13% (168) 12% (156) 28% (345)

CKDopps Total 6,894 13% (900) 10% (678) 32% (2274)

CKDopps Outcomes*

* Japanese data not available yet (enrollment started in 2016)

** Deaths captured during study follow-up (including up to 12 months after start of dialysis) † Inpatient hospitalization

CKDopps: Outline

1. Study overview

2. Practice patterns

3. What patients tell us

49

34 27 24 29 26

42 36

21

21 21

19 22 27

22 20

18

31 33

36

41 33

25 31

14 14 19 21 8

14 11 13

0

25

50

75

100

3 4/5 3 4/5 3 4/5 3 4/5

160+

140-159

130-139

< 130

SBP, mmHg

Stage

Systolic blood pressure, by CKD stage

KDIGO 2012: Individualize BP targets; avoid postural hypotension

% of patients

Brazil

N=714

France

N=2898

Germany

N=1230

US

N=1160

Timing of first nephrology visit before starting

dialysis

KDIGO 2012

Timely referral for RRT planning if

progressive CKD with 1-year ESKD

risk at least 10-20% (using validated

risk prediction tool)

19

1 13

28

12

25

23

28

31

19

28

15

11

31

17

0

20

40

60

80

100

Brazil 74

France 251

US 159

>10 years

6-10 years

3-6 year

1-3 years

eGFR at dialysis initiation (DOPPS)*

7 4 10 10

17 10 13 9

17 18 22

28 31 34

13 17

19 19

29

29 31

33

35 39

39

37 30

43

22 25

21 26

22 33 31 33

27 21

20 14 24

18

23 21 18

24

12

14 13

18 10 12 9 11

6

3

35 33 33

22 20 14 13

8 12 11 10 10 9

2

0

20

40

60

80

100

Bel

227 …

Ger

346 …

US

526 …

Can

218 …

ANZ

90 …

Spa

319 …

UK

197 …

Fra

89 …

Ita

202 …

Swe

286 …

Jpn

446 …

Chi

120 …

Rus

70 …

GCC

145 …

12.5+

10-12.4

7.5-9.9

5.0-7.4

< 5.0

N Pts: Mean:

Adapted from Bieber et al. ASN abstract (2013) * 2009-2014

% of patients 20% 60%

CKDopps: Outline

1. Study overview

2. Practice patterns

3. What patients tell us

Patient’s general health

1 2 0 1 1 2 10 5 4 3

15 12

47

39

63 53

45 38

32

34

28

36 32

39

10 20

5 8 7 9

0

20

40

60

80

100

3 183

4/5 370

3 1 328

4/5 1 098

3 244

4/5 445

Poor

Fair

Good

Very good

Excellent

N Pts =

Enrollment Patient Questionnaire data

Stage

Brazil US

% of patients

France

23 21 22

39

25 21

36

26 30

47

34 36

0

20

40

60

80

100

Brazil France** US

3a 3b 4 5 CKD stage

Enrollment Patient Questionnaire data

Patients reporting to have

seen a dietician at least once during past year

% of patients

KDIGO 2012

Provide expert dietary advice and

information in the context of an education

program, … on salt, phosphate,

potassium, and protein intake (1B)

5 5 10

23

10 15

22 19

31

21

40

53

0

20

40

60

80

100

Brazil France** US

3a 3b 4 5 CKD stage

Percentage of patients who reported

receiving education sessions* about treatment

options for kidney failure

* Either one-on-one or a classroom education sessions

% of patients

“Which of treatment options for kidney failure has

your doctor discussed with you?” Among patients with eGFR

“Which of treatment options for kidney failure has

your doctor discussed with you?” Among patients with eGFR

CKDopps: Take-Home Messages

Early data show:

• Important variations already identified across countries

About practice patterns:

• Study is ongoing, but a high number of outcomes have already been recorded

• Uncontrolled SBP > 140 mm Hg remains high

• Late nephrologist referral is most common in Brazil

What patients tell us:

• A certain burden of kidney disease for patients

• Many don’t regurlarly see a dietician or receive advice regarding treatment options for kidney failure (recall bias?)

CKDopps: Special Thanks

• CKDopps Investigators

– Arbor Research: B. Robinson, R. Perlman, RL. Pisoni, F. Port

– Brazil: R. Bueno de Oliveira, AA. Lopes, J. Lugon, R. Pecoits-Filho, R. Sesso,

D. Rinaldo dos Santos

– France: B. Stengel, ZA. Massy, C. Combe, C. Jacquelinet, M. Laville, D.

Fouque, L. Frimat, S. Briançon, C. Pascal, YE Herpe, JF. Deleuze, J. Schanstra,

P. Morel

– Germany: H. Reichel, D. Fliser, J. Duttlinger, G. Lonnemann

– Japan: K. Yamagata, T. Wada

• All clinical investigators and CRAs for invaluable contributions.

• All patients for their participation.

CKDopps: Special Thanks

• Sponsorship – Brazil – Support provided in part by Keryx

– France – Affiliated with CKD-REIN which is funded by a public-private partnership including grants from Agence Nationale de la Recherche Programme "Investissements Avenir",

Programme Hospitalier de Recherche Clinique PHRC 2010 and 6 industrial partners : Amgen,

Baxter, Fresenius, Lilly, MSD, Otsuka

– Germany – Affiliated with the Scientific Institute for Nephrology (WiNe Institute)

– Japan – Affiliated with Reach-J supported in part by a Grant-in-Aid for Research

on Advanced CKD, Practical Research Project for Renal Diseases from Japan

Agency for Medical Research and Development (AMED)

– U.S. – Support provided in part by Keryx