Advanced CKD Study Daniel Ford UKRR 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 Objectives T o look at what factors are associated with: –eGFR decline –Hb decline –Survival during the final year prior to starting RRT Methods 4,722 incident RRT patients from 7 centres from Extracted laboratory data –0, 1, 2, 3, 4, 5, 6, 12 months pre-RRT

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

What needs to be done? UKRR –Redefine date of start of HD (acute/chronic) National –Consensus on date of start of PD

Date of start of 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. 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

Date of start of 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. 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 membership C Tomson, M Raftery, 23rd March 2009

Date of start of 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. 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 membership C 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. 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 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

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: Levin A, et al. American Journal of Kidney Diseases 2008;52: Eriksen BO, et al. Kidney Int 2006;69:

Modelled eGFR pre-RRT by age group

Rate of eGFR decline pre-RRT by ethnicity (adjusted for age, gender and PRD) (95% CIs) 1.McClellan W, et al. J Am Soc Nephrol 2006;17: Clase CM, et al. J Am Soc Nephrol 2002;13: Coresh J, et al. American Journal of Kidney Diseases 2003;41: Hsu C-Y, et al. J Am Soc Nephrol 2003;14:

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

Rate of eGFR decline pre-RRT by primary renal disease (adjusted for age, gender and ethnicity) (95% CIs) 1.Hemmelgarn BR, et al. Kidney Int 2006;69: Levin A, et al. American Journal of Kidney Diseases 2008;52: Jungers P, et al. Nephrol Dial Transplant 1995;10:

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

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

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

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

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

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): [n=159] 2.Ambrogi V, et al. Nephron Clin Prac 2009; 111: [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