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Assessing risk in kidney transplantation: Back to Complement ?

This study investigates the impact of anti-HLA antibodies on graft outcomes in kidney transplantation. It highlights the risk associated with negative and positive crossmatches, presenting data from 225 patients that shows a stark contrast in failure rates: 8 failed out of 195 negative crossmatches (4.1%) versus 24 failures from 30 positive crossmatches (80%). The utilization of Luminex solid-phase assays and ELISA/CDC techniques to analyze donor-specific antibodies (DSA) reveals significant correlations with rejection rates. Long-term prognosis and clinical characteristics are also discussed, emphasizing the need for careful risk assessment pre- and post-transplant.

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Assessing risk in kidney transplantation: Back to Complement ?

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  1. Assessing risk in kidney transplantation: Back to Complement ? D. Glotz 2013

  2. TOTAL ANTI-HLA

  3. 195 negative crossmatch: 8 failed (4,1%) 225 patients 30 positive crossmatch: 24 failed (80%)

  4. Luminex

  5. Solid phase assays (CXM neg) ELISA/CDC in pregraft sera Ac + 100 100 Ac + 80 80 60 60 Ac - 40 40 Ac - 20 20 0 0 0 10 20 30 0 10 20 30 ELISA (P < 0,05) CDC (ns) Anti-HLA Abs and prevalence of rejection Dalla Vecchia, Transpl 97

  6. 12 3 5 13 5 2 88 13 3 73 28 3 p=0,2 p<0,0009 Solid phase assays ELISA CDC <10% 10-50% >50% <10% 10-50% >50% Graft loss No graft loss 124 Tx 1991-1994 Monteiro Transpl. 97

  7. TOTAL DSA ANTI-HLA

  8. Distribution of donor specific anti-HLA activity depending of the DSA detection technique Lefaucheur JASN 2010

  9. Incidence ofHumoral Rejection General population :8,9% Patients DSA+ :34,9%(p<0,00001) Patients DSA- :3,1% Lefaucheur AJT 2007/2008

  10. Low positive predictive value….

  11. Limits of SAFB techniques Low PPV

  12. TOTAL DSA C-binding subclass DSA ANTI-HLA

  13. C1q-binding antibodies Prediction of AMR on peri-Tx serum 18 pediatric heart Tx Chin, JHLT 2011

  14. C1q binding DSA study • Observational study • Necker and Saint-Louis • 1016 patients Tx 2005-2009

  15. Study design Tx 01/2005-06/2009 1016 pts 01/2012 1 year Rejection Clinical characteristics GFR Bx DSA DSA-C1q GFR Bx DSA DSA-C1q Follow-up 4.4±09yr Pts/graft survival GFR Loupy, NEJM 2013

  16. Study demographics Loupy, NEJM 2013

  17. POST-TX DSA: OUTCOME DSA+/C1q+ = Higher risk of graft loss Loupy, NEJM 2013

  18. POST-TX DSA: OUTCOME Loupy, NEJM 2013

  19. Multivariate analysis

  20. Clinical value of the C1q assay For graft loss For ABMR Loupy, NEJM 2013

  21. Assessing risk in kidney transplantation: Back to Complement ! D. Glotz 2013

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