1. Dialysis vs Transplant: the Australia & New Zealand experience Stephen McDonald ANZDATA Registry Adelaide, South Australia

2. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Background Reports from USRDS have shown a survival advantage for renal transplant recipients (RTR) both overall and in higher risk group (blacks) Those on waiting list have 50% mortality of others (<70 years) Increased risk of mortality higher in initial phase (2.8), equalise at 3 months and equal cumulative survival at 8 months (long term HR 0.32) Australia data have shown a similar survival advantage for older cadaveric RTR in one centre Johnson et al, 2000

3. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Methods Inclusion criteria “likelihood of transplantation” recorded from 1 Nov 1981 All ESRD entrants where first treatment recorded after this date Likelihood of transplantation = 10 “on waiting list” on at least one occasion –or 92 “Excellent match desired” –Date of listing not available Midpoint of 1 st survey period when “On list” recorded used as surrogate for time of listing (unless transplanted earlier) –Outcome=Death Deaths < 60 days post transplant failure attributed to transplantation Patients censored at return to dialysis

4. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Methods Comparison of dialysis and transplant group survival –Using time of transplant as time 0 Cox survival analysis with time-varying covariates –Looks at survival difference, allowing for time post ESRD entry by “crossing over” at time of grafting –Separate terms for survival early and late stages post transplantation “Intent-to-treat” analysis –Not censored if withdrawn from list

5. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Cohort 1 All people “waitlisted” post 1981 –No account taken of co-morbidity These records only available post 1991 All ages 15-65, first graft, multiple & OS grafts excluded –n=10642 (of 24402 entries to ESRD) Cohort 2-all waitlisted people post 1991 –2 groups compared “low risk” – first grafts, no co-morbidities, age 15-50 –N=2560 “marginal” – diabetes (any type), age 50-65 –N=2732

6. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Waiting list and mortality Kaplan-Meier survival estimates, by waitlist Analysis time (years) 0510 0.00 0.25 0.50 0.75 1.00 Never active Active list at least once Kaplan Meier curve of survival on dialysis (censored at transplantation) of patients <40 y.o. at ESRD entry 1981-2000, grouped by active transplant status at least once

7. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Cohort characteristics 3581/10642 (34%) people did not receive a graft at some stage –1167 (20%) received LD, 5714 CD Those grafted more likely to be –Male (67 vs 63%, p<0.0001) –Younger – CD recipients 4.5 years younger on average than non-grafted group

8. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Outcomes Dialysis group –6881 transplanted –1654 deaths –1921 alive at censor date Transplant group –Median duration of dialysis pre transplant 18 months for CD, 7 months for LD –924 deaths with functioning graft, + 177 within “60 day rule” –1370 fails -> dialysis –4026 alive at censor date –77 (1.1%) lost to follow-up

9. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Survival rates Years DialysisTransplant 3 months0.990.97 12 months0.970.95 20.910.93 30.830.91 50.660.87 100.330.74 Actuarial survival on dialysis post Tx listing and post-transplant, 1981-2000. Crude comparisons.

10. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Time varying covariates Cox analysis of mortality post transplantation (CD recipients only). Transplantation inserted as 4 level time-varying covariate. Referent HR=dialysis group. Gender not significant predictor. Months post TxHazard ratio (crude) Hazard Ratio (Age adjusted) 0-3 2.06 [1.78-2.40]2.34 [2.01-2.71] 3-6.72 [.56-.91].82 [.65-1.05] 6-12.32 [.25-.41].37 [.28-.47] 12-.20 [.18-.22].23 [.21-.26]

11. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Cohort 2 - TVC Survival advantage similar in “good” and “ marginal” recipients –Age adjusted figures MonthsHR (non-marginal)HR (marginal) 0-3 2.00 [1.17-3.44], p=.011.99 [1.43-2.76] p<0.001 3-6.40 [.13-1.27], p=.12.79 [.48-1.30], p=.36 6-12.43 [.20-.92],p=.03.27 [.15-.48], p<0.001 12-.18 [.12-.28], p<0.001.16 [.12-.21], p<0.001

12. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Absolute Rates Post transplant status Mortality rate / 100 / yr Dialysis0-33-66-12>12 months 0 5 10 15 20 Marginal Non-marginal

13. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Discussion After initial higher risk of mortality, there is a survival advantage for transplant recipients from 3 months post surgery Cumulative survival advantage begins from 2 years post transplantation –Due to very high early survival rates in dialysis group The survival advantage applies comparably across the cohorts examined –Detailed examination of subgroups not presented –Stratification used to approach co-morbids

14. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Discussion Methodologic issues –time varying covariates accounts for time on waiting list –“cross over” at Tx date –Should you adjust for age? –What should be done with those who drop off the list? –How far post Tx failure should you count deaths? 60 days, 3 months, 12 months? Further work –Prospective follow-up of cohorts from time of listing More detailed acquisition of co-morbid information

15. ANZDATA Registry Dialysis Transplant mortality, Darwin 2001 Acknowledgements ANZDATA Registry staff –Lee Excell, Brian Livingston, Liz Steinmetz Don’t forget our website: www.anzdata.org.au