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1 Emory Transplant Center, Emory University, Atlanta, GA .

A Retrospective Analysis of 10 Years of Virtual Crossmatching for Deceased Donor Kidney Transplantation. Robert Bray, PhD 2 , Ravi Ruhil, MD 1 , Jonathan Beus 1 , Thomas Pearson, MD,dPhil 1 , Howard Gebel, PhD 2 and Nicole Turgeon, MD 1 . .

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1 Emory Transplant Center, Emory University, Atlanta, GA .

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  1. A Retrospective Analysis of 10 Years of Virtual Crossmatching for Deceased Donor Kidney Transplantation. • Robert Bray, PhD2, Ravi Ruhil, MD1, Jonathan Beus1, Thomas Pearson, MD,dPhil1, Howard Gebel, PhD2 and Nicole Turgeon, MD1. 1Emory Transplant Center, Emory University, Atlanta, GA. 2Department of Pathology, Emory University, Atlanta, GA. Emory Transplant Center

  2. Virtual Crossmatching: Predicting the Crossmatch Result based on: 1) Knowledge of the HLA antibody specificities present in the recipient. 2) The HLA phenotype of the potential donor.

  3. Virtual Crossmatch Assumptions • HLA Antibody testingis performed by solid-phase • methods and has EQUIVALENT SENSITIVITYas Final XM. • - Identification of ALL unacceptable (avoid) antigens • (A-, B-, Cw, DRB1, DRB3,4,5, DQB/A, DPB/A) • *** Requires accurate typing of deceased donors. • Negative PRA = ABSENCE of HLA antibody. • vXM Can be patient specific.

  4. “This approach to donor selection reduces unnecessary crossmatching and increases the likelihood of finding crossmatch-compatible donors for highly reactive patients.” Delmonico F, Fuller A, Cosimi A, Tolkoff-Rubin N, Russell P, Rodey G and Fuller TC. Transplantation 36:629. 1983. “We conclude that the approach of detailed antibody analysis can result in an improvement for successful transplantation of more dialysis patients who are highly sensitized to HLA allo-antigens.” Oldfather J, Anderson C, Phelan D, Cross D, Luger A and Rodey G. Transplantation 42:267, 1986.

  5. This is like deja vu all over again. - Yogi Berra

  6. Howard M. Gebel and Robert A. Bray 2014 C1q / IgG subclasses

  7. INTRODUCTION Sensitized patients represent a disadvantaged group with longer wait times and greater chance for death. Approaches for transplanting the highly sensitized patient include desensitization and acceptable mismatching of HLA antigens. Previously, we demonstrated that, via acceptable mismatching (ie; virtual crossmatching), highly sensitized patients not only have increased access to transplantation, they experience a low incidence of early antibody mediated rejection (AMR).

  8. Bray, Gebel. AJT (6):2307, 2006. Emory Algorithm for Evaluating the Sensitized Patient

  9. 5 Year Deceased-Donor Renal Allograft Survival in Unsensitized PRA Patients with Negative FCXM p> 0.05 % Graft Survival Months Post Tx Bray, et al. AJT 6:2307-2315, 2006

  10. METHODS We performed a retrospective analysis of two recipient groups: Evaluation of the longer-term graft and patient survival of the initial cohort of patients (2000-2003) published in 2006. (AJT 6:2307-2315, 2006.) Evaluation of long-term graft and patient survival among 1019 deceased donor transplant recipients from 2000 -2010.

  11. METHODS Transplanted patients were divided into 3 groups according to PRA level: - Low PRA = 0-19%, - Medium = 20-79% - High - 80-100% Patient survival and graft survival was analyzed via Kaplan-Meir survival curves. T cell mediated and antibody mediated rejection was analyzed by biopsy, clinical assessments and DSA analysis. Patients that were lost to follow up were excluded from the study

  12. Rejection Episodes p = N.S. Graft Survival 2000-2003 N=309 X Time to AMR (days) 1685 88 2101 p = N.S. Patient Survival

  13. p = N.S. 2000-2010 N=1019 Graft Survival % (N) % (N) X Time to AMR (days) 743 526 714 p = N.S. Patient Survival

  14. DISCUSSION High PRA groups showed graft and patient survival comparable to unsensitized recipients. Although a greater percentage of them experienced AMR (7% vs 3.2%) at 11 years post transplant, the time to AMR was long (~2yrs). However,this percentage is lower than historically published AMR data for the general population of transplant recipients and much lower than that observed after desensitization protocols. Our longer term experience with acceptable mismatching (vXM) continues to demonstrate that highly sensitized patients can be transplanted with a low incidence of ACR and AMR. Graft and patient survival is comparable to lower PRA recipients.

  15. CONCLUSIONS: • Allocation of deceased donor kidneys via a virtual • crossmatch/acceptable mismatch algorithm: • - Can increase allocation to sensitized patients. • - Is NOT associated with a significant increase • in early AMR. • - Will produce long-term graft and patient survival comparable to unsensitized recipients.

  16. CONCLUSIONS: • Allocation schemes that give priority to highly sensitized patients CAN result in a significant increase in the number of these patients receiving a transplant. • Such allocation schemes could result in durable long term graft survival for sensitized patients.

  17. Allocating Deceased Donor Kidneys to High cPRAPatients: A Simulation Howard M. Gebel, Bert Kasiske, Sally Gustafson, Eugene Shteyn Ajay Israni, Jon Snyder, John Friedewald, Dorry Segev

  18. ALLOCATION SIMULATION Using 2010 wait-list data for sensitized, kidney-alone transplants, a simulation was conducted to assess the relationship between cPRA and allocation priority. For this simulation, the allocation priority for the highly sensitized patients was realigned. Simulation priority was given to patients with cPRA=100%, then 99%, 98%, etc. to 80% CPRA and the assessments of “compatibility” were made using UNET patient data and unacceptable HLA antigens listed in UNET. ABO compatibility was part of the algorithm. H. Gebel, et al: 2013 SRTR

  19. METHODS Wait list data from 2010 was used for the simulation. 13,591 deceased donor kidneys were run through the simulation. ABO compatibility was used as the initial compatibility assessment. Subsequently, as each deceased donor was run against the list, a selected compatible recipient was identified and removed. A second match run was then executed with the next consecutive donor. Patients compatible with this donor were then removed from the subsequent match run. Iterations continued until all deceased donors had been evaluated through the match runs. In total, 13,118 (96.5%) kidneys were deemed compatible with a highly sensitized patient. This is in contrast to 1,517 actual transplants performed into highly sensitized patients in 2010.

  20. Actual vs Simulated Transplants* -- 2010 2562 659 860 1010 1455 2618 1929 5436 Percent of Transplants / CPRA Group 1700 80-84 85-89 90-94 95 96 97 98 99 100 CPRA Groups * HLA DP and DQA not evaluated. H. Gebel, et al: 2013 SRTR

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