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Paediatric Renal Transplantation

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Paediatric Renal Transplantation Dr Heather Maxwell ... all patients 5-year transplant survival by recipient age UK PAEDIATRIC KIDNEY TRANSPLANTATION: ... – PowerPoint PPT presentation

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Title: 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
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 1990s
  • 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) 99 (97-100)
Graft Survival 1yr 94 (90-96) 97 (94-98)

Jan 2001 Dec 2005
Patient Survival 5yrs 99 (97-100) 97 (94-99)
Graft Survival 5yrs 81 (77-85) 91 (86-94)
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 Renal Failure
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
  • MM reviews
  • Small number of transplants
  • High risk patients

15
RHSC Audit Surgical Complications
1998-2003 N52 2003-2007 N28 2008-2011 N29
Haematoma 4 (8) 2 (7) 1 (3)
Lymphocoele 3 (6) 1 (2) 0
Ureteric Problems 3 (6) 2 (7) 4 (14)
AV Fistula 1 (2) 1 (2) 0
Thrombosis 0 1 (2) 4 (14)
Kinked Renal vein 1 (2) 0
Re-exploration 6 (12) 6 (21) 8 (28)
3 grafts lost
16
RHSC Audit Medical Complications
1998-2003 N52 2003-2007 N28 2008-2011 N29
Rejection Episodes 18 (35) 8 (29) 3 (10)
Infections 14 (27) 3 (11) 5 (17)
PTLD 6 (12) 0 0
Diabetes 5 (10) 0 1
CAN 1 (4) 0
Recurrence of FSGS 1 (4) 0
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 97
BPAR 10 7
Growth 0.17SD 0.04SD
Adverse Glucose Metabolism 3 16
Grenda et al, 2010
18
Rejection Rate
Probability of First Rejection at 12 Months Probability of First Rejection at 12 Months Probability of First Rejection at 12 Months Probability of First Rejection at 12 Months Probability of First Rejection at 12 Months
Transplant Year LIVING DONOR LIVING DONOR DECEASED DONOR DECEASED DONOR
Transplant Year SE SE
1987-90 54.1 1.7 69.3 1.4
1991-94 45.8 1.5 61.0 1.5
1995-98 33.6 1.3 42.5 1.6
1999-02 22.9 1.3 26.9 1.7
2003-06 13.7 1.5 17.9 1.7
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
  • MM 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

Donor factors Recipient factors Other factors
Age Age Age match
Cause of death Primary renal disease HLA
Ethnicity Registration waiting time Shipping
Gender Ethnicity Kidney damage
CMV Gender Graft year
CMV
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 Age match
Cause of death Primary renal disease HLA
Ethnicity Registration waiting time Shipping
Gender Ethnicity Kidney damage
CMV Gender Graft year
CMV
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 (lt20hours)
  • 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

37
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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
51
Cold ischaemia time (hours) of DBD paediatric
kidney only transplants
52
Reported immunosuppression following deceased
paediatric kidney only transplant (3mth)
SSteroid AAzathioprine MMycophenolate CCyclosp
orin TTacrolimus
Proportion of transplants
Year of graft
53
Graft survival following first DBD paediatric
kidney only transplant
2006-2010 1yr survival 95 (92-97) N308
2001-2005 5yr survival 81 (77-85) N360
1996-2000 10yr survival 63 (58-68) N411
1991-1995 15yr survival 45 (41-50) N488
1986-1990 20yr survival 27 (23-31) N442
plt0.0001
54
Graft survival following first DBD paediatric
kidney only transplant excluding failures within
the first year
2001-2005 5yr survival 88 (84-91) N328
1996-2000 10yr survival 73 (68-78) N345
1991-1995 15yr survival 55 (50-60) N392
1986-1990 20yr survival 38 (32-44) N310
plt0.01
p0.5 (1991 2005)
55
Graft survival following first living paediatric
kidney only transplant
2006-2010 1yr survival 97 (94-98) N286
2001-2005 5yr survival 91 (86-95) N198
1996-2000 10yr survival 74 (64-81) N116
1991-1995 15yr survival 45 (32-58) N67
1986-1990 20yr survival 35 (20-50) N47
p0.008
56
Graft survival following first living paediatric
kidney only transplant excluding failures within
the first year
2001-2005 5yr survival 95 (90-97) N173
1996-2000 10yr survival 78.0 (68-85) N107
1991-1995 15yr survival 49 (34-62) N60
1986-1990 20yr survival 37 (22-53) N42
p0.009
57
Graft survival following first paediatric kidney
only transplant
5 yr survival 10 yr survival 20 yr
survival Living 88 (85 - 91) 71 (65 -
76) 48 (38 - 58) (n714) plt0.0001
plt0.0001 plt0.0001 DBD 72 (70 - 74)
59 (57 - 61) 37 (33 - 40) (n2009)
58
Graft survival following first paediatric kidney
only transplant
5 yr survival 10 yr survival 20 yr
survival Living 88 (85 - 91) 71 (65 -
76) 48 (38 - 58) (n714) plt0.0001
plt0.0001 plt0.0001 DBD 72 (70 - 74)
59 (57 - 61) 37 (33 - 40) (n2009)
59
Graft survival following first DBD paediatric
kidney only transplant
lt6 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 lt16s in
2009
UK Renal Registry Report 2010
63
Pre-emptive Transplantation
NHSBT
Transplant Activity in the UK, 2010-11
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 1999-2009
with receiving rhGH
UK Renal Registry Report 2010
66
UK Paediatric Renal Registry
Hb standard by MMF use 1999-2009
Patients achieving the haemoglobin standard in
2009
Hb standard by GFR 1999-2009
UK Renal Registry Report 2010
67
Transplant Work Up

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

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

71
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72
Current Immunosuppression
  • Tacrolimus
  • Mycophenolate Mofitil
  • Treatment Arm
  • Daclizumab
  • Prednisolone for 5 days
  • Control Arm
  • Standard prednisolone

Treatment Arm Control
Graft Survival 97 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
donors
UK Transplant 09/03
77
ABOi Transplants
  • Group A consists of 2 types A1 and A2
  • A2 is less antigenic than A1
  • A1gtBgtA2
  • 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
Recipient
Recipient
O A B AB
O Yes Yes Yes Yes
A - Yes - Yes
B - - Yes Yes
AB - - - Yes
O A B AB
O Yes Yes Yes Yes
A ? Yes ? Yes
B ? ? Yes Yes
AB No ? ? Yes
Donor
Donor
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