1. Kidney allocation in the UK
David Turner
PhD, FRCPath,
Lead for H&I Services, Scottish National Blood Transfusion Service,
Edinburgh, UK

3. 34%
32%
26%
12%
40%
55%

4. Allocation of deceased donor organs
HLA type
performed (~4 hours)
Recipient identified by ODT,
vXM / crossmatch performed
(~5 hours);
if NEGATIVE transplant
goes ahead (if positive risk management / or veto?)
~7000 patients awaiting an organ tx, inc kidney, pancreas, heart, liver. ODT matching algorithm produces a matching run and organs are offered out across the UK
cadaveric
donor

6. National Kidney Allocation Scheme (2006 NKAS)
All kidneys from DBD allocated by national rules -:
Tier A: 000 mismatched paediatric patients, HSP or DR homozygous
Tier B: 000 mismatched paediatric patients
Tier C: 000 mismatched adult patients, HSP or DR homozygous
Tier D: 000 mismatched adult patients + paediatric patients – favourably matched [100,010,110]
Tier E: All other eligible patients
Within Tiers, patients prioritised by point score:
Waiting time points: point for each day on list
HLA match & age points combined: max 3500
Age difference points: *(donor-recipient age diff)2
Location points: same centre, 750 local area
HLA homozygous points: HLA-B 100, HLA-DR 500
Blood group points: for B patients when donor is O
PHASING IN 6

7. HSP & the 2006 NKAS HLA-A,B,DR Mismatches HSP Level 1 000
HSP prioritised in Tiers A and C
Level 2
0 DR & 0/1 B mm
HSP considered if: local to donor or antibody profile completely defined
Level 3
0 DR & 2 B mm or
1 DR & 0/1 B mm
HSP considered
Level 4
1 DR & 2 B mm or
2 DR mm
Kidneys not offered through 2006 NKAS

8. Revised Specificities used for HLA matching
HLA-A: 1, 2, 3, 9, 10, 11, 19, 28, 29, 36, 43, 80 (n=12)
HLA-B: 5, 7, 8, 12, 13, 14, 15, 16, 17, 18, 21, 22, , 35, 37, 40, 41, 42, 46, 47, 48, 53, 59,
67, 70, 73, 78, 81, 82, (n=30)
HLA-DR: 1, 103, 2, 3, 4, 5, 6, 7, 8, 9, 10 (n=11)
<2% frequency in donor pool, with close counterparts
based on serological reactivity/sequence data

9. HLA defaults used for matching in national allocation

10. 2006 National Kidney Allocation Scheme
Results of 8 years of the
2006 National Kidney Allocation Scheme

11. Waiting times of adult transplant patients
% transplants
1998 scheme scheme

12. HLA mismatch levels of adult transplant patients
HLA mm level
% transplants
1998 scheme scheme

13. Transplant HLA mismatch by age
Transplants
(2006 scheme, years 1-8)
000 mm
0 DR & 0/1 B mm
0 DR & 2 B mm or
1 DR & 0/1 B mm
HLA level
Due to points system in allocation, younger patients
get better matches (Levels 1,2)

14. Ethnicity of adult transplant patients
% transplants
1998 scheme scheme

15. Transplants achieved through antigen defaulting
Transplant due to defaulting
% transplants
Ethnicity

17. Change to the kidney allocation scheme
Agreed by UK KAG that patients waiting >7yrs would get absolute priority in the deceased donor allocation scheme
Applies to both DBD and DCD allocation schemes
Introduced 3rd Sept 2014

19. Summary
HLA matching important in 2006 UK National Kidney Allocation Scheme
Poorly matched grafts avoided: [1 DR+ 2 B mm] [2 DR mm]
Points score gives HLA match a greater weight for younger patients than older patients:
Younger patients are receiving well-matched transplants
Fully national scheme & more flexible approach to HLA matching
More transplants for:
Long waiting patients
Homozygous patients
Young adults
Difficult to match patients, including HSP and ethnic minority patients
Excellent one year graft survival, no increase in cold ischemia time

20. DCD Kidney Allocation- 3rd September 2014

21. Background >40% kidneys are from DCD
Organs donated for transplantation are a national resource
Kidney allocation should be open, objective and transparent
DBD kidneys -Formalised national allocation scheme for both kidneys
DCD kidneys - Non-standardised local arrangements
Some centres already sharing DCD kidneys
e.g: North Thames area, Edinburgh and Glasgow
Local sharing arrangements may reflect difficulty in performing two same centre concurrent kidney transplants

22. 2014 DCD kidney sharing scheme
One kidney retained locally, second kidney shared regionally
Both kidneys prioritised according to the 2006 NKAS principles
To avoid significant changes to centre activity, donor age criteria will apply to manage the ‘phasing-in’ process

23. DCD donor kidney sharing regions
Region Patients listed North (30%) Midlands (25%) London (27%) South West (17%)
Gla
Edi
New
Bel
Lee
Liv Man
Shef
Not
Lei
Cam
Bir Cov
Car
Oxf
Bri NT ST
Por
Ply

25. Recent discussion on allocation changes
In 2015 the UK KAG chair requested a review of the current allocation scheme
Various workstreams, including H&I

26. Terms of Reference
Is the current HLA typing repertoire and resolution appropriate?
What would be the consequences of a change in typing repertoire in terms of complexity and cost of donor/recipient HLA typing?
Are the current HLA matching criteria appropriate?
Is there a role for epitope matching (to minimise antibody formation)?
How should unacceptable specificities be listed and used in allocation?

27. Reasons for a Positive Crossmatch: 2010-15 n=1505% 5% 1% 2% 3%
54/150 (36%) +ve crossmatches caused by specificities, DP, DQA and some DR alleles, outside the required minimum resolution

28. Working group exploring....
Influence of HLA matching on outcome
Broad matching as current algorithm e.g. DR1-DR9
Matching at the HLA split level e.g HLA-DR1-18
Defaulting of rare HLA specificities
Incorporation of additional loci- HLA-C and DQ
Matching for HLA epitopes
Influence of HLA matching on Ab production
Via analysis of UK data looking at AgMM, aaMM, EpMM, EMM

29. Cox Regression Modelling (1)
Including failures in first 30 days
Excluding failures in first 30 days
Description
Level
1 year (09-14)
5 year (06-10)
1 year (09-14) HR P
Number of mismatches to A
1.00
1 or 2
1.32
0.02
1.19
0.07
0.3
0.1
Number of mismatches to B
1.73
0.0001
1.36
0.002
1.79
0.004
1.47
0.001
Number of mismatches to DR
1.23
0.03
1.25
0.008
1.03
0.8
1.24
Number of mismatches to DR/DQ
0/0
0/1,2
1.11
0.6
1.13
0.5
1.31
1.08
0.7
1,2/0
1.07
0.90
1.06
1,2/1,2
0.006
1.34
1.18
1.35
0.007
Number of mismatches to B/Cw
1.86
1.10
2.36
0.0002
0.08
1.46
0.05
2.20
1.56
0.0004
1.84
1.55
0.003

30. Cox Regression Modelling (2)
Including failures in first 30 days
Excluding failures in first 30 days
Description
Level
1 year (09-14)
5 year (06-10)
1 year (09-14) HR P
HLA Level 1
1.00 2
1.73
0.003
1.17
0.2
1.60
0.08
1.28
0.1 3
2.06
0.0001
1.49
0.001
1.72
0.04
0.002 4
1.89
0.01
1.45
1.75
1.64
Total mismatches
1-3
1.37
0.03
1.41
0.3
1.35
4-6
2.25
0.0002
1.62
0.0008
1.59
0.005
7-10
2.32
1.94
0.05
2.01
0.004
linear
1.11
1.09
1.10

31. Role for epitope matching (to minimise antibody formation)
Antibody formation post Tx is related to HLA Ag mismatch/epitope load
Recent papers show HLA Ab production associated with
number of HLA Ag MM (Kosmoliaptsis et al, Kidney Int 2014; 86:1039)
number of aa MM
number of eplet MM (Kosmoliaptsis et al, AJT 2016)
electrostatic MM
Questions:
analyses required to inform use in allocation
feasibility in the near future

32. Conclusions of H&I Working Group
Require extended typing of donors to include DPB1,DQA to reduce pos XM
Maintain HLA matching in future allocation scheme, but perhaps based on number of MM across A,B,C,DR,DQ
Remove HLA matching criteria for HSP
For HSP consider
cRF% at which patients receive priority in the algorithm
Time from listing when patients receive priority
Scale of priority