Dialysis vs Transplant: the Australia & New Zealand experience

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

2. 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 Dialysis Transplant mortality, Darwin 2001

3. 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 1st 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 Dialysis Transplant mortality, Darwin 2001

4. 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• Separate terms for survival early and late stages post transplantation • “Intent-to-treat” analysis • Not censored if withdrawn from list Dialysis Transplant mortality, Darwin 2001

5. 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 Dialysis Transplant mortality, Darwin 2001

6. Kaplan-Meier survival estimates, by waitlist 1.00 Active list at least once 0.75 0.50 Never active 0.25 0.00 0 5 10 Analysis time (years) Waiting list and mortality 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 Dialysis Transplant mortality, Darwin 2001

7. 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 Dialysis Transplant mortality, Darwin 2001

8. 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 Dialysis Transplant mortality, Darwin 2001

9. Survival rates YearsDialysisTransplant 3 months 0.99 0.97 12 months 0.97 0.95 2 0.91 0.93 3 0.83 0.91 5 0.66 0.87 10 0.33 0.74 Actuarial survival on dialysis post Tx listing and post-transplant, 1981-2000. Crude comparisons. Dialysis Transplant mortality, Darwin 2001

10. 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. Dialysis Transplant mortality, Darwin 2001

11. 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=.01 1.99 [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 Dialysis Transplant mortality, Darwin 2001

12. Absolute Rates Marginal 20 Non-marginal 15 Mortality rate / 100 / yr 10 5 0 Dialysis 0-3 3-6 6-12 >12 months Post transplant status Dialysis Transplant mortality, Darwin 2001

13. 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 Dialysis Transplant mortality, Darwin 2001

14. 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 Dialysis Transplant mortality, Darwin 2001

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