Immunological Dynamics and Outcomes of ABO-Incompatible Kidney Transplants: Insights From a 5+-Year Follow-Up at a Transplant-Heavy Tertiary Center in Saudi Arabia.

BACKGROUND

ABO-incompatible (ABOi) kidney transplantation is an essential strategy to expand the donor pool for patients with end-stage kidney disease (ESKD). However, it poses significant immunological challenges because of the risk of graft rejection. In Saudi Arabia, where ABOi transplants are limited, there is a paucity of long-term locoregional data on the impact of immunological factors on graft outcomes. This study evaluated ABOi transplant outcomes in patients with more than 5 years of follow-up, with a primary focus on immunological factors and their role in graft survival and rejection.

METHODS

We analyzed data from 24 adult patients who underwent ABOi kidney transplantation between October 31, 2015, and December 30, 2019, with follow-up until December 31, 2024. Key immunological factors assessed included donor-recipient blood group mismatch, human leukocyte antigen (HLA) mismatches, preformed donor-specific antibodies (DSAs) and non-DSA anti-HLA antibodies, flow cross-match results, and anti-ABO titers before and after transplantation. Posttransplant infections were also evaluated for their potential immunological impact. The desensitization protocol comprised rituximab, plasma exchange, and intravenous immunoglobulin (IVIg), with pretransplant anti-ABO titers required to be ≤ 8. Exclusion criteria included pediatric ABOi kidney transplants and patients experiencing major vascular or surgical complications necessitating re-exploration within 7 days posttransplant. Immunosuppressive therapy included methylprednisolone and ATG induction, with prednisolone, tacrolimus, and mycophenolate mofetil for maintenance. The studied outcomes were graft survival, rejection episodes, graft failure, and all-cause mortality.

RESULTS

Over a mean follow-up of 68 ± 12.6 months, graft survival was 91.7% (n = 22). Graft rejection occurred in 16.7% (n = 4) of the patients, with two cases (8.3%) of graft failure attributed to severe antibody-mediated rejection (ABMR). Key immunological risk factors for rejection included the presence of non-DSA anti-HLA antibodies, low-titer positive cross-match, > 8 HLA mismatches, and unrelated donors. A total of 49 infectious episodes occurred in 19 recipients, of which 29 (59%) occurred within the first posttransplant year and were not associated with graft dysfunction or rejection. Posttransplant serum creatinine remained stable during follow-up, with median values of 89.0, 88.0, 85.0, and 88.0 μmol/L at 1, 12, 36, and 60 months, respectively, and 77.0 μmol/L at last follow-up (minimum follow-up, 64 months). No mortality was observed.

CONCLUSION

ABOi kidney transplantation demonstrates excellent long-term outcomes; however, immunological factors play a pivotal role in determining the risk of rejection. Careful patient selection is warranted, as even seemingly minor immunological factors can provoke graft rejection in the context of ABO incompatibility. Posttransplant infections were not significantly associated with graft dysfunction or rejection. A small sample size allows us to report these findings; however, to review their significance, a larger cohort of patients, incorporating protocol biopsies, in a prospective multicenter study is needed to validate these findings.