Paired Kidney Exchange Title presentation Update Subtitle ... 2011/… · Match ID Current DSA Peak...
Transcript of Paired Kidney Exchange Title presentation Update Subtitle ... 2011/… · Match ID Current DSA Peak...
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Title of presentationSubtitle if needed
Our National Launch
Paired Kidney Exchange Update
Professor Paolo FerrariDirector, National Paired Kidney Donation ProgramDepartment of Nephrology Fremantle Hospital
D
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Num
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Aug Sep Match Run
14/10/10
Oct Nov Dec Jan Match Run
07/02/11
FebMonth
Enrolled Unmatched Matches Transplants
AKX recruitment and match runs
Match run Feb 2011
Enrolled N=39NSW 15VIC 13QLD 4SA 0WA 7
Active N=26NSW 9VIC 11QLD 0SA 0WA 6
Cumulative(enrolled +
left program)
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1. High proportion of O recipients.
1
2
B
10AB
B
24A
105O
Recipients
ABAOBlood groups
Donors
69%
36%
2nd Match Run: issues with active pairs
cPRA Class 1 Class 2 Any Class 1 or 2
>75% 47% 27% 50%
>50% 57% 40% 63%
2. All pairs were sensitised, most pairs had high level of sensitisation (avg cPRA: 65% Class 1 and 46% class 2).
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February 2011 Match Run Results
Match run 2(b), excluding matching if DSA >8000MFI
• Several combinations with 2‐way and 3‐way chains and AD chains.
• In total 12 recipients matched in 6 acceptable combinations.
• The combination with the maximum number of possible transplants matched 9 recipients (5 blood group O, 4 blood group A) and included 1 AD.
• Presence of low‐level DSAs (all <2600MFI, except 1x 4900MFI) in 7/12 matched recipients, 4/12 single DSA and 3/12 double DSAs.
• No DSA associated with a previous antigen mismatch.
Match run 2(a), excluding matching if DSA >2000MFI NO MATCHES.
A second match run was performed using a higher antibody threshold (>8000MFI) to identify further matches.
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Rank 1, MP 0.23 Rank 2, MP 0.37 Rank 3, MP 0.41
Rank 4, MP 0.55 Rank 5, MP 0.78 Rank 6, MP 0.85
Pairs required for crossmatch:
Ranking of combinations
1 2 3 4 5 6 7 8 9 10
1
3
2 1
3
27
3
8
5
4
6 5
4
6
5 6
5 6
1
9
2
4 7 4 7
10 6 10 5
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MatchID
Current DSA Peak DSA Crossmatch current serum
Released for transplant
Number Class Σ MFI Number Class Σ MFI1 0 n/a n/a 0 n/a n/a Neg No (broken AD chain)2 0 n/a n/a 0 n/a n/a Neg No (broken AD chain)3 0 n/a n/a 0 n/a n/a Neg* Yes4 0 I (1951) 4 I 20958 POS B cell No5 1 I 2331 1 I 2331 Neg Yes6 1 II 3296 1 II 3296 Neg Yes7 1 I 3373 1 I 3373 Neg Yes8 1 II 4937 1 II 4937 Neg Same recipient as 39 2 I 4942 2 I 4942 Neg Yes
10 2 I 5688 2 I 5688 POS B cell No11 2 I 9641 3 I 16394 POS B cell No
12AD 0 n/a n/a 0 n/a n/a Neg Yes
Σ MFI = cumulative MFI, *required DTT treatment for autoantibody
DSA and crossmatch results of pairs matched in the second AKX match run
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HLA typingRecipient: A11,68; B35,51: DR4,15
Donor #1 (Tx 1994): A11,33; B35,56; DR4,-Matched AKX donor: A*2402,3001; B*0801,1302; DR*0301,0701
HLA antibodies:Current: A*3303 (6230), A*2901 (5649), A*2902 (3360), A*3101 (2834)Peak: A*3002 (7221), A*3001 (2036)
Antibodies to A1C CREG include A29, A30, A31, A33.
Match ID #4No DSA >2000MFI, but POS B CELL CROSSMATCH
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PKD transplants following match run #2Combination 866
Chain 117 Chain 115
PKD pair Altruistic donor TWL recipient
10 March 2011 6 April 2011
3x O O 2x O O1x A A
NSW VIC
NSW
MP= 1.00
MP= 0.22MP= 0.08
cPRA 88%
cPRA 92%
cPRA 34%
WAWA
WA
MP= 0.34
MP= 0.46
MP= 0.11
WA
cPRA 73%
cPRA 76%
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0
2000
4000
6000
8000
10000
12000
MFI
P=0.005
CL. I CXM negative
P=0.002
CL. I CXM positiv
e
CL. II CXM negative
CL. II CXM positiv
e
Strength of Luminex DSA and crossmatch positivity
Single DSA strength
Morris GP, et al. Hum Immunol 2010; 71:268-273. Gloor JM, et al. AJT 2010; 10:582-589.
Cumulative DSA strength
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Lefaucheur C, et al. JASN 2010; 21:1398-1406.
Impact of pre‐formed DSA in patients with negative CDC crossmatch at the time of transplantation
MFI≤460 (N=325) 460<MFI≤3000 (N=27)
3000<MFI≤6000 (N=11) MFI>6000 (N=39)
Irish A, et al. unpublished
Hazard Ratio : Class 1 = 2.0 (0.3-15.6) Class 2 = 12.5 (3.2-48) Class 1&2 = 13.2 (4.4-40)
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Strength of individual DSA
Patients with graft lossMFI Median 2144 (IQR 1577-3463)
Patients without graft lossMFI Median 3933 (IQR 2676-5905)
Transplantation 2011; epub
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Luminex detects:- non-complement binding IgG2/IgG4 antibodies- mixture of antibodies against intact and denatured HLA
Exclusion based on Luminex alone may reduce the patient’schance of receiving a donor kidney with acceptable outcome.
Pitfalls of Luminex SAB testing
A small proportion of patients display alloantibodies specificities to public cross reactive epitope group (CREG) antigens.- Luminex identifies most, but not all Ab specific for CREG
CREG reactivity should be considered to define unacceptablemismatches.
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Low match rate in conventional 2-way and 3-way PKD due to:• High level of sensitisation of enrolled pairs.• Failure to enrol unsensitised ABOi pairs. • Excessively stringent HLA antibody allocation.
AKX outlook
Solutions to increase match rates:• Increase DSA threshold for the exclusion of unacceptable antigens?• Consider ABOi paired exchanges?• Include unsensitised ABOi pairs?• Include all altruistic donors?
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Bingaman C et al., NEJM 2010; 363:1091-1092
Single‐centre 2½‐years experience, San Antonio Texas1. All incompatible donor-recipient pairs2. Compatible pairs with donors >45 years of age
64% cross-match incompatibility, 36% ABO incompatibility83 PKD procedures (22 x 2-way and 13 x 3-way exchanges)
Enrolled AKX pairs AKX transplants
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Acknowledgements1. NCC coordinator: Claudia Woodroffe
2. HLA laboratories: Narelle Watson, Linda Cantwell, Alycia Thornton, Samantha Fidler
3. NOMS: Jenni Wright, Paul Slater
4. Transplant teams at:Westmead: Lincoln Dealtry, Howard Lau, Henry PleassRMH: Belinda Bennett, Robert MillarRNSH: Jason Chan, Justin Vass, Vik PuttaswamyRPAH:Melanie Farrer, Richard Allen, Arthur VasilarasSCGH: Linda Colefax, Bulang He, Andrew MitchellMMC: Orla Maney, Al Saunder, John Gribbin and nephrologists, anaesthetists, theatre nurses, ...
5. Hospitals recruiting pairs in AKX
6. PKE advisory committee: Scott Campbell (RTAC), Richard Allen (FRACS), Wendy Rogers (Medical Ethics), Rhonda Holdsworth (ARCBS), Frank Christiansen (ASEATTA)
7. Australia Air Express: Renee Norgrove
8. Transplant Authority: Gerry O’Callaghan, Catherine Ellis, Eva Mehakovic