1. Paediatric Renal Transplantation
Thank you for asking me to talk about our experience of paediatric renal transplantation at Yorkhill.
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. Paediatric Renal Transplant Outcome
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

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
DECEASED DONOR
LIVING DONOR
Jan 2005 – Dec 2009
Patient Survival 1yr
99% (97-100)
Graft Survival 1yr
94% (90-96)
97% (94-98)
Jan 2001 – Dec 2005
Patient Survival 5yrs
97% (94-99)
Graft Survival 5yrs
81% (77-85)
91% (86-94)
However what can our patients expect when they receive a renal transplant?
NHSBT

9. RHSC Glasgow Data
NHSBT

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

11. Cause of Renal Failure

12. RHSC Audit

13. RHSC Audit - Outcome

14. Audit
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
N=52
N=28
N=29
Haematoma
4 (8%)
2 (7%)
1 (3%)
Lymphocoele
3 (6%)
1 (2%)
Ureteric Problems
4 (14%)
AV Fistula
Thrombosis
4 (14%)*
Kinked Renal vein
Re-exploration
6 (12%)
6 (21%)
8 (28%)
* 3 grafts lost

16. RHSC Audit Medical Complications
N=52
N=28
N=29
Rejection Episodes
18 (35%)
8 (29%)
3 (10%) *
Infections
14 (27%)
3 (11%)
5 (17%)
PTLD
6 (12%)
Diabetes
5 (10%) 1
CAN
1 (4%)
Recurrence of FSGS
* 16 (55%) biopsied

17. Current Immunosuppression
Tacrolimus
Mycophenolate Mofitil
Treatment Arm
Daclizumab
Prednisolone for 5 days
Control Arm
Standard prednisolone
Treatment Arm
Control
Graft Survival
97%
BPAR
10% 7%
Growth
0.17SD
0.04SD
Adverse Glucose Metabolism 3%
16%
Grenda et al, 2010

18. Probability of First Rejection at 12 Months
Rejection Rate
Probability of First Rejection at 12 Months
Transplant Year
LIVING DONOR
DECEASED DONOR % SE
54.1
1.7
69.3
1.4
45.8
1.5
61.0
33.6
1.3
42.5
1.6
22.9
26.9
13.7
17.9
As an example…
Reduced ARR is associated with better graft survival and better graft function
NAPRTCS Report 2007

19. RHSC Audit - Outcome

20. Audit
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
To investigate the influence of a variety of factors on five-year renal transplant survival in a more recent cohort of paediatric recipients
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:
Donor factors
Recipient factors
Other factors
Age
Age match
Cause of death
Primary renal disease
HLA
Ethnicity
Registration waiting time
Shipping
Gender
Kidney damage
CMV
Graft year
Sensitisation
Residual sensitisation

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:
Donor factors
Recipient factors
Other factors
Age
Age match
Cause of death
Primary renal disease
HLA
Ethnicity
Registration waiting time
Shipping
Gender
Kidney damage
CMV
Graft year
Sensitisation
Residual sensitisation

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
Some of these are evidence based others are more difficult to prove

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
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: )
2003 – 2005 median 264 days (95% CI: ) 2006 – 2008 median 374 days (95% CI: )
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. 2010 34% ethnic minority patients registered on transplant list
Recipient ethnicity of deceased paediatric kidney only transplant patients
Proportion of transplants
% ethnic minority patients registered on transplant list
Year of graft

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

51. Cold ischaemia time (hours) of DBD paediatric kidney only transplants

52. Reported immunosuppression following deceased paediatric kidney only transplant (3mth)
S=Steroid
A=Azathioprine
M=Mycophenolate
C=Cyclosporin
T=Tacrolimus
Proportion of transplants
Year of graft

53. Graft survival following first DBD paediatric kidney only transplant
yr survival 95% (92-97) N=308
yr survival 81% (77-85) N=360
yr survival 63% (58-68) N=411
yr survival 45% (41-50) N=488
yr survival 27% (23-31) N=442
p<0.0001

54. Graft survival following first DBD paediatric kidney only transplant
excluding failures within the first year
yr survival 88% (84-91) N=328
yr survival 73% (68-78) N=345
yr survival 55% (50-60) N=392
yr survival 38% (32-44) N=310
p<0.01
p=0.5 (1991 – 2005)

55. Graft survival following first living paediatric kidney only transplant
yr survival 97% (94-98) N=286
yr survival 91% (86-95) N=198
yr survival 74% (64-81) N=116
yr survival 45% (32-58) N=67
yr survival 35% (20-50) N=47
p=0.008

56. excluding failures within the first year
Graft survival following first living paediatric kidney only transplant
excluding failures within the first year
yr survival 95% (90-97) N=173
yr survival 78.0% (68-85) N=107
yr survival 49% (34-62) N=60
yr survival 37% (22-53) N=42
p=0.009

57. Graft survival following first paediatric kidney only transplant
5 yr survival 10 yr survival 20 yr survival
Living ( ) ( ) ( )
(n=714) p< p< p<0.0001
DBD ( ) ( ) ( )
(n=2009)

58. Graft survival following first paediatric kidney only transplant
5 yr survival 10 yr survival 20 yr survival
Living ( ) ( ) ( )
(n=714) p< p< p<0.0001
DBD ( ) ( ) ( )
(n=2009)

59. Graft survival following first DBD paediatric kidney only transplant
<6 years
6-11 years
12-17 years

60. UK Renal Registry
Paediatric Data

61. UK Paediatric Renal Registry
UK Renal Registry Report 2010

62. UK Paediatric Renal Registry
Treatment modality at 90 days after
start of RRT by 5 year time period
Current RRT treatment used by prevalent
<16s in 2009
UK Renal Registry Report 2010

63. Pre-emptive Transplantation
NHSBT
Transplant Activity in the UK,

64. UK Paediatric Renal Registry
UK Renal Registry Report 2010

65. UK Paediatric Renal Registry
Median systolic BP SDS in transplant pts in 2009
Median HtSDS in pts receiving RRT from
with % receiving rhGH
UK Renal Registry Report 2010

66. UK Paediatric Renal Registry
Hb standard by MMF use
% Patients achieving the
haemoglobin standard in 2009
Hb standard by GFR
UK Renal Registry Report 2010

67. Transplant Work Up

68. The Transplant Team Radiologist Psychologists Transplant Co-ordinator
Nephrologist
Surgeon
Specialist renal
nurses
Tissue Typing
Dietitian
Social worker
Teacher

69. Pre-Transplant Management
Attention to nutrition, growth, BP, proteinuria
Pre-transplant work-up
Blood vessels
Echocardiogram
Virology (CMV, EBV, Varicella)
Bladder
Psychology, education
HLA antibodies
Plan for operation
There are two main aspects to the management pre-transplant. One is to have the child as well as possible to be able to deal with the rigours of the operation and immunosuppression and the other is to gather as much information as possible so as to be able to plan the operation and treatment without any nasty surprises. We need to know if the child is prone to viral infections EBV CMV etc, if the vessels are normal, if the bladder is safe.

70. Transplant Procedure Transplant surgeon and paediatric urologist
Anaesthetist
Paediatric nephrologist
Patient data easily accessible to all staff
Patient well hydrated
Early doppler USS if concerns re thrombosis
Close monitoring in ITU

72. Current Immunosuppression
Tacrolimus
Mycophenolate Mofitil
Treatment Arm
Daclizumab
Prednisolone for 5 days
Control Arm
Standard prednisolone
Treatment Arm
Control
Graft Survival
97%
BPAR
10% 7%
Growth
0.17SD
0.04SD
Adverse Glucose Metabolism 3%
16%
Grenda et al, 2010

73. Access to Transplantation

74. Access to transplantation
Criteria for suitable recipient
Age / size
Sensitisation
Pre-emptive transplantation
Virtual cross-match
ABO Incompatibility
Paired donation

75. HLA Match

76. HLA-A phenotype frequencies in 10 000 UK cadaver kidney donors
UK Transplant 09/03

77. ABOi Transplants Group A consists of 2 types – A1 and A2
A2 is less antigenic than A1
A1>B>A2
Group O patients have higher titres of antibodies
Anti-A titres are higher than anti-B titres
Titres of 1 in 8 or 1 in 16 are low
No additional treatment necessary for low titre antibodies which do not appear to pose an additional risk

78. ABOi Transplants

79. ABOi Transplants O A B AB O A B AB Recipient Recipient Yes Yes* - Yes No
Donor
Donor