Paired Donation Andrew Bradley Rachel Johnson Joanne Allen Susan V Fuggle Cambridge University NHS Hospitals NHS Foundation trust
Showing a preference 1860 John Calcott Horsley
UK Living Donor kidney transplant 1000 800 Altruistic donor (non-directed) Paired exchange donor Unrelated donor (directed) Related donor Number 600 400 200 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Year
Analysis of UK living donor transplants (2000-2007, n= 3142) Graft survival Unrelated Related p 1 year 96% 95% ns 5 year 93% 89% 0.0002 No influence of HLA matching on graft survival
UK paired donation scheme Human Tissue Act made paired (and nondirected altruistic) living kidney donation possible from September 2006 BTS & NHSBT developed arrangements for paired donation in the UK
UK paired donation scheme Human Tissue Act made paired (and nondirected altruistic) living kidney donation possible from September 2006 BTS & NHSBT developed arrangements for paired donation in the UK NEWS BBC July 2007 : Couples swap kidneys in UK first Peter Horrell, from Cambridgeshire, donated a kidney to a man from Lothian, while the man's wife gave a kidney to Mr Horrell's wife Roma.
Arrangements for KPD Donor and patient assessments Registration with ODT Quarterly matching runs' to identify possible transplants and optimise transplants according to scoring scheme (working with experts in matching algorithms from Glasgow University) Crossmatch tests for suitability of transplants Independent Assessor review & HTA panel approvals Operations arranged and carried out simultaneously Anonymity Donor kidney travels
Simulations Having identified relevant factors, simulations used to inform decision-making about appropriate weights and other issues Simulations based on real data from 20 centres 400 transplants that could not proceed over 2-year period due to ABO or HLA incompatibility
How many couples are needed? Maximum % transplanted No. of couples on list
How many points for Local exchange (based on 5 areas of the UK) HLA match (4 levels) Prioritisation factors Sensitisation (% of blood group identical donors having antigens which are declared unacceptable for the recipient pool of 10,000) Age difference between the 2 donors Blood group match consider restricting use of O donors Identify combination of transplants with highest sum of point scores for individual transplants
Cold ischaemia time and Allograft Outcomes in Live Donor Renal Transplantation: Is Live Donor Organ Transplantation Feasible? C.E. Simpkins et al John Hopkins University 2007; 7: 99-107 Analysed 38 463 LD kidney transplants reported to OPTN in USA Impact of CIT on: delayed graft function acute rejection 1-year creatinine allograft survival
CIT 0-2h 2-4h 4-6h 6-8h (32 719) (4 663) (692) (393) DGF 4.7% 4.9% 8.3% 9.2% Simpkins et al AJT 2007; 7: 99-107
Matching runs 2-way matching runs quarterly since April 2007 3-way exchanges also considered since April 2008 Donor 1 Recip 1 Donor Recip 3 3 Donor 5 Recip 5 Donor 2 Recip 2 Donor 4 Recip 4 2-way exchange 3-way exchange (paired exchange (pooled exchange)
Paired donation - national matching scheme Points score for each possible transplant to prioritise possible exchanges Local exchange (based on 5 areas of UK): 20 points Sensitised patient: 0-50 points for 0-100% sensitised HLA matched transplant: Small donor-donor age difference: max 15 points for 000 mismatch 3 points if <=20 years Blood group O donor kidneys only used in group O recipients HLA match and maximum donor age can be specified at registration
Paired donation programme Jan 2007 April 2010 Total of 335 patients (364 pairs) enrolled All 23 UK adult kidney transplant centres involved 53% spouse/partner pairs 40% ABO incompatible, 44% HLA incompatible, 16% ABOi + HLAi 144 transplants identified 64 (19%) of enrolled patients transplanted by end June 2010 max 22% if all remaining possible transplants proceed
Paired donation matching run summary Run no. Run date No. of pairs No. of exchanges identified 2-way 3-way No. of transplants possible No. of transplants achieved 1 Apr 07 9 1 2 2 2 Jul 07 26 1 2 2 3 Oct 07 32 0 0 4 Jan 08 66 3 6 2 5 Apr 08 76 2 4 16 2 6 Jul 08 85 1 2 2 7 Oct 08 123 6 3 21 8 8 Jan 09 126 5 1 13 10 9 Apr 09 128 5 2 16 4 10 Jul 09 141 4 7 29 12 11 Oct 09 147 2 6 6 12 Jan 10 150 3 1 9 4 13 Apr 10 158 2 6 22 10+? 64 transplants to date including six 3-way exchanges
Blood group composition of pool: Jan 2010 150 pairs listed (141 patients); 83 (55%) blood group incompatible Recipient Blood Group O A B AB Total Donor Blood Group O 32 5 2 0 39 A 55 19 4 1 79 B 14 6 8 0 28 AB 3 0 1 0 4 Total 104 30 15 1 150 55 (37%) are A to O incompatible pairs
HLA sensitisation of pool:jan 2010 Calculated sensitisation (%)* 0-9 10-29 30-49 50-64 65-84 85-94 95-99 100 Total No. of patients 31 2 3 11 13 14 37 30 141 % of patients 22 1 2 8 9 10 26 21 100 * Calculated based on comparing each patient s unacceptable antigens with HLA types of blood group identical donors in pool of 10,000 actual donors
Transplant summary Jan 07 April 2010 64 transplants in total 46 (72%) from two-way, 18 (28%) from three-way exchanges 31 ABOi pairs, 31 HLAi and 2 ABOi & HLAi pairs 45 (70%) spouse/partner pairs Median CIT 5 hrs (range 1-9 hrs) DGF in 8/49 (16%) transplants 3 failed transplants (day 54, 97, 177) 71/144 (49%) identified transplants confirmed as not proceeding 37% +ve XM 23% alternative transplant 20% donor or recipient unfit 21% other reasons
Transplant rates by ABO Recipient ABO O A B AB Donor ABO O A 5/74 (7%) 12/116 (10%) 12/24 (50%) 9/40 (23%) 4/11 (36%) 9/24 (38%) 0/0 (0%) 0/3 (0%) B 4/30 (13%) 8/21 (38%) 0/8 (0%) 1/2 (50%) AB 0/5 (0%) 0/2 (0%) 0/4 (0%) 0/0 (0%) Number transplanted / number enrolled (%)
HLA sensitisation issue April 2010 pool Calculated sensitisation (%) 0-9 10-84 85-94 95-99 100 Total No. of patients 28 27 15 40 34 144 % of patients 19 19 10 28 24 100 Sensitisation calculated based on comparing each patient s unacceptable antigens with HLA types of blood group identical donors in pool of 10,000 actual donors No. of patients enrolled 140 120 100 80 60 40 20 0 23 68 Transplant rates Tx. rates: 25% 33% 23% 3% No PD tx. 27 56 PD tx. 10 33 4 114 0-9 10-84 85-94 95-100 Sensitisation level
Summary 335 patients enrolled; 144 transplants identified 64 (19%) of enrolled patients transplanted (inc 18 in 3-way exchanges) Most success for A/B, B/A ABOi and moderately sensitised patients (esp A/O combination) 49% identified transplants did not proceed 3.1% of live donor transplants in UK in 2009 Implement domino (chain) paired donation in 2011
Improvements made following recent workshop Suspension of patients from DD list immediately they are matched Suspension of patients from paired list after unsuccessful run so they are properly reviewed for next run Review of crossmatching logistics / materials
N Engl J Med 2009, 360;11
NEAD Chain
Domino (chain) paired donation
Domino (chain) paired donation
Domino (chain) paired donation
Altruistic, non-directed donors 32 altruistic donor transplants (July 2007-Dec 2009) Mean donor age 51 years (range 24-69); 15 F, 17 M Mean recipient age 49 years (range 24-71 years) Average recipient waiting time 4 years Median CIT 6 hrs (range 1-20 hrs) 1 PNF, 3 DGF in 24 transplants with follow-up
Further plans (2010) Altruistic donor chains (domino paired donation) agreed in principle Simultaneous transplants and short chains in first instance Prioritise paired donation patients who have had most unsuccessful matching runs
Desensitisation vs Paired donation Desensitisation Advantages (1) Donor known to recipient (2) Timing predictable (3) HLA match may be better Disadvantages (1) Complex and expensive (2) May not be available locally (3) Risks of desensitisation procedure (4) Transplant outcome may be inferior
Desensitisation vs Paired donation Paired donation Advantages (1) No added risk to recipient (2) Good outcome after transplantation (3) Listing for PD increases effectiveness of pool Disadvantages (1) Unpredictable wait (2-5% annual mortality on dialysis) (2) Donor & recipient not known to each other (3) Likely to be poor HLA match
Making the choice Desensitsation Nature of incompatibility: ABOi vs HLAi Ease of desensitisation Likely outcome after desensitisation Paired donation Likelihood of finding a matched pair HLA match Patient s views Number of matching runs
Treatment options ABOi and or HLA Abi LD Paired exchange Desensitisation Offering neither is not acceptable
Treatment options ABOi and or HLA Abi LD Paired exchange No match Desensitisation No match Match found Remain on DD list LD Transplant
Treatment options ABOi and or HLA Abi LD Paired exchange No match Desensitisation Paired exchange plus desensitisation No match Match found Remain on DD list LD Transplant
Making the choice ABOi Outcome after Ab depletion equivalent to ABO compatible? Morbidity from antibody depletion protocol Donor Recipient Ab titre Chance of match A B often low 50% B A often low 50% A2 O usually low 10% A or B O often high 10%
Bingham AW et al NEJM 2010 San Antonio Tx centre Initiated KPD scheme in March 2008 Enrolled Ab incompatible donors Also enrolled compatible pairs with donor aged >45 yrs All recipients negative Flow XM Matching daily
Expansion of Kidney Paired Donation (KPD) San Antonio Bingaman AW et al. N Engl J Med 2010;363:1091-1092.
Showing a preference Paired exchange Desensitisation