Advanced CKD Study

Daniel FordUKRR Annual Audit Meeting

June 2009

Overview

Data collection issues– Definition of the date of start of dialysis

Pre-RRT study results– Associations with the rate of kidney function

decline in the final year pre-RRT

Pre-RRT Study

ObjectivesTo look at what factors are associated with:– eGFR decline– Hb decline– Survivalduring the final year prior to starting RRT

Methods4,722 incident RRT patients from 7 centres from 2001-2006Extracted laboratory data– 0, 1, 2, 3, 4, 5, 6, 12 months pre-RRT

Median eGFR pre-RRT (Centre 4)- (IQRs)

0

2

4

6

8

10

12

14

16

-15 -12 -9 -6 -3 0

Time pre-RRT (months)

eG

FR

(m

l/min

/1.7

3m

2)

.

Proportion of patients excluded from study because of anomalous timeline data

0

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2,000

a b c d e f g h i

Centre

Nu

mb

er

of

pa

tien

ts

Excluded

Included

Proportion of patients excluded from study because of anomalous timeline data

0

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2,000

a b c d e f g h i

Centre

Nu

mb

er

of

pa

tien

ts

Excluded

Included

n=826

• Distinction between “acute” and “chronic” HD• Definition of start of PD

Definition of “acute HD”

Of 826 records checked, 14.9% started RRT on “acute” HD with no retrospective timeline change

Definition of “acute HD”

“If a patient started as ‘acute’ renal failure and did not recover, the date of start of renal replacement should have been backdated to the start of acute dialysis.”

Definition of “acute HD”“If a patient started as ‘acute’ renal

failure and did not recover, the date of start of renal replacement should have been backdated to the start of acute dialysis.”

• Appendix B of Annual Report (online only)

• Methodology or instruction to clinicians?

Definition of start of PD

• 75/826 had some evidence of PD exchanges prior to documented start date

• What is the date of start of PD?

Definition of start of PD

• 75/826 had some evidence of PD exchanges prior to documented start date

• What is the date of start of PD?– Insertion of PD catheter?– First fluid exchange after PD catheter?– Date of start of CAPD training?– Date of PD independence?

Consequences of inaccurate RRT start date

• Dubious eGFR trend pre-RRT

• Existing eGFR at start studies

• Survival data• Late presentation

data

Median eGFR pre-RRT (Centre 4)- (IQRs)

0

2

4

6

8

10

12

14

16

-15 -12 -9 -6 -3 0

Time pre-RRT (months)

eG

FR

(m

l/min

/1.7

3m

2)

.

What needs to be done?

• UKRR– Redefine date of start of HD (acute/chronic)

• National– Consensus on date of start of PD

ISSN 1471-3349

The Renal Association

UK Renal Registry

The Eleventh Annual Report

December 2008

This report was prepared by Dr David Ansell, Professor John Feehally, Dr Damian Fogarty,

Dr Daniel Ford, Dr Alex Hodsman, Dr Charles Tomson, Dr Udaya Udayaraj, Dr Graham Warwick and Dr Andrew Williams

in association with F Caskey, K Farrington, R Fluck, M Lewis,

J Nicholas, R Ravanan, D Richardson and D Thomas

Date of start of HDIf a patient started as ‘acute’ renal

failure and did not recover, the date of start of renal replacement should have been backdated to the start of acute dialysis. Many nephrologists do not do this and where this period of acute dialysis has been recorded in local systems, the UKRR will use this data to backdate the start of RRT.

Appendix B UKRR 11th Annual Report, December 2008

ISSN 1471-3349

The Renal Association

UK Renal Registry

The Eleventh Annual Report

December 2008

This report was prepared by Dr David Ansell, Professor John Feehally, Dr Damian Fogarty,

Dr Daniel Ford, Dr Alex Hodsman, Dr Charles Tomson, Dr Udaya Udayaraj, Dr Graham Warwick and Dr Andrew Williams

in association with F Caskey, K Farrington, R Fluck, M Lewis,

J Nicholas, R Ravanan, D Richardson and D Thomas

Date of start of HDIf a patient started as ‘acute’ renal

failure and did not recover, the date of start of renal replacement should have been backdated to the start of acute dialysis. Many nephrologists do not do this and where this period of acute dialysis has been recorded in local systems, the UKRR will use this data to backdate the start of RRT.

Appendix B UKRR 11th Annual Report, December 2008

Letter to RA membershipC Tomson, M Raftery, 23rd March 2009

ISSN 1471-3349

The Renal Association

UK Renal Registry

The Eleventh Annual Report

December 2008

This report was prepared by Dr David Ansell, Professor John Feehally, Dr Damian Fogarty,

Dr Daniel Ford, Dr Alex Hodsman, Dr Charles Tomson, Dr Udaya Udayaraj, Dr Graham Warwick and Dr Andrew Williams

in association with F Caskey, K Farrington, R Fluck, M Lewis,

J Nicholas, R Ravanan, D Richardson and D Thomas

Date of start of HDIf a patient started as ‘acute’ renal

failure and did not recover, the date of start of renal replacement should have been backdated to the start of acute dialysis. Many nephrologists do not do this and where this period of acute dialysis has been recorded in local systems, the UKRR will use this data to backdate the start of RRT.

Appendix B UKRR 11th Annual Report, December 2008

Letter to RA membershipC Tomson, M Raftery, 23rd March 2009

Date of start of PD

The date of start of peritoneal dialysis is defined as the date of first PD fluid exchange given with the intention of causing solute or fluid clearance

This contrasts with an exchange solely for confirming or maintaining catheter patency. In general, exchanges which are part of PD training should be considered as the start of PD.

ISSN 1471-3349

The Renal Association

UK Renal Registry

The Eleventh Annual Report

December 2008

This report was prepared by Dr David Ansell, Professor John Feehally, Dr Damian Fogarty,

Dr Daniel Ford, Dr Alex Hodsman, Dr Charles Tomson, Dr Udaya Udayaraj, Dr Graham Warwick and Dr Andrew Williams

in association with F Caskey, K Farrington, R Fluck, M Lewis,

J Nicholas, R Ravanan, D Richardson and D Thomas

ISSN 1471-3349

The Renal Association

UK Renal Registry

The Eleventh Annual Report

December 2008

This report was prepared by Dr David Ansell, Professor John Feehally, Dr Damian Fogarty,

Dr Daniel Ford, Dr Alex Hodsman, Dr Charles Tomson, Dr Udaya Udayaraj, Dr Graham Warwick and Dr Andrew Williams

in association with F Caskey, K Farrington, R Fluck, M Lewis,

J Nicholas, R Ravanan, D Richardson and D Thomas

Chapter 7: Survival in UK RRT patients. UKRR 11th Annual Report, December 2008

Summary of timeline issues

Inaccurate timeline returns are common

This has implications for a number of UKRR analyses, including:– Survival– Rates of late presentation– eGFR at start of RRT

This may not be unique to the UKRR

Efforts are being made to re-define and publicise problematic definitions

Pre-RRT Study Results

Pre-RRT study

• 7 centres

• 2001-2006

• n=4,722

• Excluded patients – presenting late (<3m)– with missing data from relevant analyses– with anomalous timeline data– with fewer than 4 eGFR results

eGFR statistical analyses- Retha Steenkamp

• Least-square analysis– Linear regression line fitted on an individual-

patient basis– Mean rate of eGFR decline calculated

• Multi-level model– Quadratic model

Adjusted for:– Age, gender, ethnicity, PRD

Results

• Age

• Ethnicity

• Primary renal disease

• Systolic BP

• Diastolic BP

• Time from first renal presentation

0

1

2

3

4

5

6

7

8

18-34 35-44 45-54 55-64 65-74 75+

Age group (years)

eG

FR

de

clin

e (

ml/m

in/1

.73

m2

/ye

ar)

.

Rate of eGFR decline pre-RRT by age group (adjusted for gender, ethnicity and PRD) (95% CIs)

1. Hunsicker LG, et al. Kidney Int 1997;51:1908-1919. 2. Levin A, et al. American Journal of Kidney Diseases 2008;52:661-671. 3. Eriksen BO, et al. Kidney Int 2006;69:375-382.

Modelled eGFR pre-RRT by age group

6

8

10

12

14

16

18

-15 -12 -9 -6 -3 0Time pre-RRT (months)

eGF

R (

ml/m

in/1

.73m

2)

65-74

75+

Modelled eGFR pre-RRT by age group

6

8

10

12

14

16

18

-15 -12 -9 -6 -3 0Time pre-RRT (months)

eGF

R (

ml/m

in/1

.73m

2)

55-64

65-74

75+

Modelled eGFR pre-RRT by age group

6

8

10

12

14

16

18

-15 -12 -9 -6 -3 0Time pre-RRT (months)

eGF

R (

ml/m

in/1

.73m

2)

45-54

55-64

65-74

75+

Modelled eGFR pre-RRT by age group

6

8

10

12

14

16

18

-15 -12 -9 -6 -3 0Time pre-RRT (months)

eGF

R (

ml/m

in/1

.73m

2)

35-44

45-54

55-64

65-74

75+

Modelled eGFR pre-RRT by age group

6

8

10

12

14

16

18

-15 -12 -9 -6 -3 0Time pre-RRT (months)

eGF

R (

ml/m

in/1

.73m

2)

18-34

35-4445-54

55-6465-74

75+

Rate of eGFR decline pre-RRT by ethnicity (adjusted for age, gender and PRD) (95% CIs)

0

1

2

3

4

5

6

7

8

Asian Black White

eG

FR

de

clin

e (

ml/m

in/1

.73

m2

/ye

ar)

.

1. McClellan W, et al. J Am Soc Nephrol 2006;17:1710-1715. 2. Clase CM, et al. J Am Soc Nephrol 2002;13:1338-1349.3. Coresh J, et al. American Journal of Kidney Diseases 2003;41:1-12. 4. Hsu C-Y, et al. J Am Soc Nephrol 2003;14:2902-2907.

Modelled eGFR pre-RRT by ethnicity (adjusted for age, gender and PRD)

6

8

10

12

14

16

-15 -12 -9 -6 -3 0

Time pre-RRT (months)

eGF

R (

ml/m

in/1

.73m

2)

white

black

asian

Rate of eGFR decline pre-RRT by primary renal disease (adjusted for age, gender and ethnicity) (95% CIs)

0

1

2

3

4

5

6

7

DM GN PKD Pyelo RVD

eG

FR

de

clin

e (

ml/m

in/1

.73

m2

/ye

ar)

1. Hemmelgarn BR, et al. Kidney Int 2006;69:2155-2161. 2. Levin A, et al. American Journal of Kidney Diseases 2008;52:661-671.

3. Jungers P, et al. Nephrol Dial Transplant 1995;10:1353-1360.

Modelled eGFR pre-RRT by primary renal disease (adjusted for age, gender and ethnicity)

4

6

8

10

12

14

16

-15 -12 -9 -6 -3 0

Time pre-RRT (months)

eG

FR

(m

l/min

/1.7

3m

2)

.

DMGN

PyeloPKD

Rate of eGFR decline by systolic BP at 6 months pre-RRT (adjusted for age, gender, ethnicity and PRD) (95% CIs)

0

1

2

3

4

5

6

7

<120 120-139 140-159 ≥160

Systolic blood pressure (mmHg)

eG

FR

de

clin

e (

ml/m

in/1

.73

m2

/ye

ar)

.

Rate of eGFR decline by diastolic BP at 6 months pre-RRT (adjusted for age, gender, ethnicity and PRD) (95% CIs)

0

1

2

3

4

5

6

7

8

9

10

<70 70-79 80-89 90-99 ≥100

Diastolic blood pressure (mmHg)

eG

FR

de

clin

e (

ml/m

in/1

.73

m2

/ye

ar)

.

Rate of eGFR decline pre-RRT by time from first presentation (adjusted for age, gender, ethnicity and PRD)

(95% CIs)

0

2

4

6

8

10

12

<3m 3-6m 6-12m >12m

Time from first renal presentation to starting RRT (months)

eG

FR

de

clin

e (

ml/m

in/1

.73

m2

/ye

ar)

.

Modelled eGFR pre-RRT by time from first renal presentation (adjusted for age, gender, ethnicity and PRD)

6

8

10

12

14

16

18

-15 -12 -9 -6 -3 0

Time pre-RRT (months)

eG

FR

(m

l/min

/1.7

3m

2)

<3m

3-6m

6-12m

>12m

Discussion

Limitations– Retrospective, only includes patients on RRT– Missing data

• Date first seen, PRD, ethnicity, BP, co-morbidity• Timeline issues

Strengths– Largest study of patients in the final year pre-

RRT (4,722 vs. 159 & 342)– Unselected UK incident cohort

1. Jungers P, et al. NDT 1995; 10(8): 1353-60 [n=159]2. Ambrogi V, et al. Nephron Clin Prac 2009; 111: 95-101 [n=342]

Summary of findings

• Associations with faster eGFR decline are:– Younger age– Black and South Asian ethnicity– GN & diabetes– Higher systolic and diastolic BP– Late presentation

Acknowledgements

Statistics

Retha Steenkamp

Supervisors

Damian Fogarty, Yoav Ben-Shlomo, Charlie Tomson, David Ansell

Data collection

David Bull, Andy Webb and the UKRR systems team

UK renal centres and patients