Impact of Donor HLA Mismatch Grade on Recipient HLA Locus-Specific Sensitisation in Patients Returning to the Kidney Transplant Waiting List Following a Failed Primary Kidney Allograft
Department of Surgery and Tissue Typing Laboratory, University of Cambridge, Cambridge, United Kingdom
Meeting: 2013 American Transplant Congress
Abstract number: 407
Background: The impact of Human Leukocyte Antigen (HLA) matching algorithms on kidney allocation policies in the modern era of immunosuppression is controversial. This study investigated the relationship between HLA mismatch grade and alloantibody development following primary renal transplant failure.
Methods: A total of 131 of 1,411 patients with a failed primary kidney transplant who were re-listed for transplantation from 1995 to 2010 were studied. Multiple sera obtained before transplantation, on re-listing and 3-monthly thereafter were screened using a combination of lymphocyte panel screening (PRA), Luminex HLA class I and II antibody detection and Single Antigen Beads. The effect of donor HLA mismatches at individual loci (HLA-A, -B, -C, -DRB1, -DRB3-5 and -DQ) on the calculated reaction frequency (cRF) against a panel of 10,000 HLA typed UK donors was determined.
Results: HLA mismatch grade correlated strongly with the overall incidence and magnitude of post-transplant allosensitisation defined by PRA, Luminex and SAB-defined cRF (p<0.001). The risk and level of sensitisation against individual HLA-A, -B, -DR and -DQ loci increased with increasing number of donor HLA mismatches within each locus; this relationship was stronger for HLA-A and -DR loci [odds ratios of 3.0 (CI: 1.8-4.4) and 2.9 (CI: 2.1-4.2) respectively, p<0.001] which also best predicted overall post-transplant HLA class I and II sensitisation respectively. Incidence and mean cRF of post-transplant HLA-DR specific sensitisation increased by 12% and 5% respectively following failure of HLA-DR matched grafts, but 62% and 57% respectively for 2 HLA-DR mismatched grafts. Of patients with 2 HLA-DR mismatched grafts, 70% became highly sensitised (≥85% cRF) against class II alloantigens and 80% developed donor specific antibody. On multivariate analysis, HLA mismatch grade and immunosuppression weaning were independent predictors of HLA sensitisation whereas transplant nephrectomy was not.
Conclusion: This analysis is the most comprehensive to date showing that HLA matching, particularly for HLA-DR, is important in first-time renal allograft recipients to avoid allosensitisation if it is likely they will require future listing for repeat transplantation following graft failure.
To cite this abstract in AMA style:
Gjorgjimajkoska O, Taylor C, Sharples L, Chatzizacharias N, Peacock S, Morgan C, Bolton E, Bradley J, Kosmoliaptsis V. Impact of Donor HLA Mismatch Grade on Recipient HLA Locus-Specific Sensitisation in Patients Returning to the Kidney Transplant Waiting List Following a Failed Primary Kidney Allograft [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/impact-of-donor-hla-mismatch-grade-on-recipient-hla-locus-specific-sensitisation-in-patients-returning-to-the-kidney-transplant-waiting-list-following-a-failed-primary-kidney-allograft/. Accessed May 17, 2025.« Back to 2013 American Transplant Congress