Paediatric Renal Transplantation

1. Paediatric Renal Transplantation Dr Heather Maxwell Consultant Paediatric Nephrologist Royal Hospital for Sick Children Glasgow

2. Paediatric Renal Transplantation • Background information • Outcome of transplantation • Work up for transplantation • Access to transplantation

3. Renal Transplantation • First human to human renal transplant was in 1933 • The first successful adult renal transplant was performed in Boston in 1954 in twins • First paediatric renal transplant performed in 1959 from identical twin sister • First in Yorkhill was 1977 and 204 transplants have now been performed since

4. Patient survival Graft survival Parameters of Growth BP Haemoglobin Factors affecting outcome RHSC Audits NHSBT ODT (UKT) Centre-specific data Cohort studies 20 year review of paediatric renal Tx Renal Registry Paediatric Renal Transplant Outcome

5. Paediatric Renal Transplant Program RHSC Glasgow

6. Results of Audit from 1990’s • High incidence of vascular thromboses • Lower graft survival data than expected • Change in practice • Joint adult transplant and paediatric urologists • Multi-disciplinary team approach • Transplant work-up and protocol

7. Paediatric Renal Transplant Program RHSC Glasgow

8. UK Paediatric Renal Transplant Data NHSBT www.uktransplant.org.uk

9. RHSC Glasgow Data NHSBT www.uktransplant.org.uk

10. RHSC Audit 1998-2007 Female 37% Male 63% 37 LRD (46%) 43 DD (54%)

11. Cause of RenalFailure

12. RHSC Audit 1998-2007

13. 1998-2007 RHSC Audit - Outcome

14. Audit 2008-2011 • Higher incidence of graft thrombosis and vascular complications than expected • Particularly with LRD transplants • M&M reviews • Small number of transplants • High risk patients

15. RHSC Audit Surgical Complications * 3 grafts lost

16. RHSC Audit Medical Complications * 16 (55%) biopsied

17. Current Immunosuppression • Tacrolimus • Mycophenolate Mofitil • Treatment Arm • Daclizumab • Prednisolone for 5 days • Control Arm • Standard prednisolone Grenda et al, 2010

18. Rejection Rate NAPRTCS Report 2007

19. 2008-2011 RHSC Audit - Outcome

20. Audit 2008-2011 • Higher incidence of graft thrombosis and vascular complications than expected • Particularly with LRD transplants • M&M reviews • Small number of transplants • High risk patients • Internal and external review • Change in practice – smaller group of surgeons involved

21. Factors Affecting Outcome of Paediatric Renal Transplantation

22. Factors Affecting Outcome of Paediatric Renal Transplantation • An analysis of deceased donor paediatric renal transplants performed in the UK between 1986 and 1995 found that extremes of donor age, young recipient age and poor HLA matching were the major factors which adversely affected transplant outcome • Avoided transplants in the very young • Only used donors aged 5-50 years • Better matching Postlethwaite et al, 2002

23. UKT Study 1995 - 2001 • To investigate the influence of a variety of factors on five-year renal transplant survival in a more recent cohort of paediatric recipients 1995-2001 • To compare risk-adjusted outcome of adult and paediatric recipients at five years post-transplant • 7946 transplants (596 paediatric & 7350 adult) WTC 2006 Maxwell et al, 2006

24. Methods • Cox regression analysis of factors influencing five-year transplant survival (time from transplant to earlier of graft failure or patient death) • Factors considered in the analysis:

25. Methods • Cox regression analysis of factors influencing five-year transplant survival (time from transplant to earlier of graft failure or patient death) • Factors considered in the analysis:

26. Summary • Significant year-on-year improvement in transplant outcome of paediatric patients

27. 5-year transplant survival of paediatric patients by year of transplant

28. Improved Acute Graft Survival • Better pre-transplant management • Improved anaesthetic and operative care • Better organ selection • Size • Matching • Use of more living donors • Organ preservation and reduced cold ischaemia time (<20hours) • Reduced acute rejection • Reduced incidence of infection

29. Summary • Significant year-on-year improvement in transplant outcome of paediatric patients • Very young donors (0 – 10 years) and donors aged over 40 years confer the greatest risk of transplant failure in paediatric patients

30. 5-year transplant survival of paediatric patients by donor age group

31. Summary • Significant year-on-year improvement in transplant outcome of paediatric patients • Very young donors (0 – 10 years) and donors aged over 40 years confer the greatest risk of transplant failure in paediatric patients • Glomerulonephritis is associated with poorer outcome than other primary renal diseases

32. 5-year transplant survival of paediatric patients by primary renal disease group

33. Summary • Significant year-on-year improvement in transplant outcome of paediatric patients • Very young donors (0 – 10 years) and donors aged over 40 years confer the greatest risk of transplant failure in paediatric patients • Glomerulonephritis is associated with poorer outcome than other primary renal diseases • Risk of transplant failure associated with adolescents (14 – 17 years) similar to that for recipients aged over 60 years

34. 5-year transplant survival by recipient age – all patients

35. 5-year transplant survival by recipient age

36. 2006 Allocation Scheme • Increased availability of well-matched organs for children • Improved access for long waiters • Increased access for homozygous patients • Reduce shipping times • Still use deceased donors 5-50yrs • Paediatric donors would no longer preferentially given to paediatric recipients • Avoid very small recipients

38. UK PAEDIATRIC KIDNEY TRANSPLANTATION: A 20-YEAR REVIEW Lisa Mumford, Jane Tizard On behalf of the Kidney Advisory Group Paediatric Subgroup

39. Deceased and living paediatric kidney only transplants Number of transplants Year of graft

40. Deceased donors aged between 5 and 50 years Number of donors Year of donation

41. Donor age of deceased paediatric kidney only transplants Donor age Year of graft

42. HLA mismatch levels of deceased paediatric kidney only transplant patients Proportion of transplants Year of graft

43. HLA mismatch levels of deceased paediatric kidney only transplant patients

44. Waiting times of UK deceased paediatric kidney only transplants Waiting time (days) Year of graft

45. Waiting Times for Listed Patients • 2000 – 2002: median 153 days (95% CI: 119-187) • 2003 – 2005 median 264 days (95% CI: 201-327) 2006 – 2008 median 374 days (95% CI: 285-463) • In terms of the impact of the 2006 scheme on equity for paediatric patients, the number on the transplant list and the median waiting time have remained unchanged while the number of transplants for long-waiting patients has increased as a result of a change made in April 2008 such that only 3% of listed patients have been waiting in excess of 3 years compared to 12% in December 2005.

46. Waiting times of deceased paediatric kidney only transplants

47. Recipient ethnicity of deceased paediatric kidney only transplant patients Proportion of transplants 2010 34% ethnic minority patients registered on transplant list Year of graft

48. Sensitisation (cRF) of first deceased paediatric kidney only transplant patients Proportion of transplants 2010 48% patients with cRF 11-100 registered on transplant list Year of graft

49. Sensitisation (cRF) of first deceased paediatric kidney only transplant patients

50. Cold ischaemia time (hours) of DBD paediatric kidney only transplants Cold ischaemia time (hours) Year of graft