2015 Kidney Allocation - PowerPoint Presentation

Slide1

2015

Kidney Allocation

Task

Force

HLA

Working Group

Slide2

HLA Working Group

Membership

Co-Chairs

Susan Fuggle, David Turner

H&I Members

Richard

B

attle,

M

artin Barnardo,

D

avid Briggs, Derek Middleton, Tracey Rees, Craig Taylor, Bob Vaughan

Clinical Members

Sian Griffin, Vasilis

Kosmoliaptsis

, Nizam Mamode,

C

armelo

Puliatti

, Nick

Torpey

, Chris Watson

NHSBT Statistics and Scientific Support

Lisa Bradbury, Chloe Brown,

Rachel

Johnson, Laura Pankhurst, Linda

Shelper

Slide3

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?

Slide4

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?

Slide5

Repertoire and Resolution of HLA typing

Required repertoire agreed for 2006 NKAS

Currently includes:

HLA-A,B,C,DR,DQ

Intermediate level of resolution

Clinical requirement for donor HLA-DP typing to ensure efficient organ allocation

Patients have registered unacceptable HLA-DP specificities

Agreed

by KAG, but not currently funded

Slide6

Positive crossmatches:

2010-15

Year

Kidneys Allocated

Positive crossmatch

n=

%

2010

976

36

3.7

2011

938

26

2.7

2012

956

23

2.4

2013

1138

25

2.2

2014

1180

24

2.0

2015

1112

16

1.4

Total

6300

150

2.4

Slide7

Reasons for

a Positive Crossmatch:

2010-15

n=150

5%

5%

1%

2%

3%

54/150 (36%)

+

ve

crossmatches caused by

specificities, DP, DQA and some DR alleles,

outside the required minimum

resolution

Slide8

Repertoire and Resolution of HLA typing

Living Donor Kidney Sharing Scheme

Donors HLA-DP typed, taken into account in the algorithm

Laboratories are typing deceased donors for HLA-DP, because of the recognised clinical need

about 80% donors routinely typed

Not currently used in allocation

Slide9

Repertoire and Resolution of HLA typing

Working group recommend repertoire

and resolution

of donor HLA typing should

be

extended

Details of resolution to be

agreed

Resource implications to be discussed

Slide10

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?

Slide11

Current HLA matching criteria

Working group exploring:I

nfluence of HLA matching on transplant outcome

Broad matching as current algorithm e.g. DR1-DR9

Matching at the HLA split level

e.g

HLA-DR1-18

I

ncorporation of additional loci- HLA-C and DQ

Matching for HLA epitopes

Immunogenicity of epitopes

Vasilis

Kosmoliaptsis

, Craig TaylorConsidering defaulting of rare HLA specificities

Slide12

Cohort

1 year graft survival: 1 April 2009 – 31 March 2014

5 year graft survival: 1 April 2006

– 31 March 2010

Includes

DBD & DCD transplants

Includes

1

st

graft and re-graft kidney only transplants

Excludes incompatible transplants

Adult only transplants

Transplants in the UK

Slide13

Cox Regression Modelling

Are the mismatched variables significant when added into a statistical model which allows for other known important factors in graft survival?

A Cox proportional hazards regression model was fitted, adjusting for

Recipient unit Dialysis status at registration

Primary renal disease (grouped) Financial year of transplant

Recipient gender CRF at transplant (grouped)

Recipient age CIT

hrs

(grouped)

Recipient blood group Donor age

Recipient ethnicity Donor type

The outcome variable was graft survival at 1 or 5

years.

Slide14

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)

5 year (06-10)

HR

P

HR

P

HR

P

HR

P

Number of mismatches to

A

0

1.00

1.00

1.00

1.00

1 or 2

1.32

0.02

1.19

0.07

1.19

0.3

1.19

0.1

  Number of mismatches to B01.001.001.001.001 or 21.730.00011.360.0021.790.0041.470.001  Number of mismatches to DR01.001.001.001.001 or 21.230.031.250.0081.030.81.240.03  Number of mismatches to DR/DQ0/01.001.001.001.000/1,21.110.61.130.51.310.31.080.71,2/01.070.61.130.30.900.61.060.71,2/1,21.360.0061.340.0021.180.31.350.007Number of mismatches to B/Cw0/01.001.001.001.000/1,21.860.021.320.11.100.81.110.61,2/02.360.00021.360.071.790.081.460.051,2/1,22.200.00011.560.00041.840.021.550.003

Cox Regression Modelling (1)

Slide15

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)

5 year (06-10)

HR

P

HR

P

HR

P

HR

P

HLA Level

1

1.00

1.00

1.00

1.00

2

1.73

0.003

1.17

0.2

1.60

0.08

1.28

0.1

3

2.060.00011.490.0011.720.041.600.00241.890.011.450.081.750.11.640.04  Total mismatches01.001.001.001.001-31.730.011.370.031.410.31.350.084-62.250.00021.620.00081.640.11.590.0057-102.320.0021.940.0012.060.052.010.004Total mismatcheslinear1.110.00011.090.00011.100.011.100.0001Cox Regression Modelling (2)

Slide16

Slide17

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?

Slide18

Role for

epitope matching (

to minimise antibody formation)

A

ntibody

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

MMnumber of eplet MM (

Kosmoliaptsis et al, AJT 2016)electrostatic MM

Questions:

analyses required to

inform

use in

allocation

f

easibility in

the near future

Slide19

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?

Slide20

Calculated Reaction Frequency

Number of patients

registered

Waiting time (days)

Median 95% CI

 

0-84%

7917

963

942 - 984

85-94%

344

1577

1487 - 1667

95-99%

377

2138

1870 – 2406

100%

164

2424

2072 – 2776

TOTAL

8802

1016

995 - 1037

 

Median wait to transplant for

adult patients

2½ years

6½ years

Slide21

Sensitisation of long waiting

patients (>7yrs)

Transplanted: 1 Sep 14 – 31 Jan 2016

Waiting list: as at 1 Sep 2014 and 1 Feb 2016

Sensitisation

N= 147

N= 260

N= 319

95-98%

99%

100%

85-94%

0-84%

Slide22

Median waiting time to transplant

Apr 06 - Mar 10

Slide23

Initial Considerations

Current policy - level 4 mismatched kidneys [2DR or 2B, 1DR] are not allocated, limits access for HSP

Remove

HLA matching criteria for these

patients

Consider

cRF

% at which patients receive priority in the algorithm

Time from listing when patients receive priority

Scale of priority

Ensure suitable offers are accepted

Slide24

2015

Kidney Allocation Task

Force

HLA

Working

Group

work ongoing……