Overcoming the Barriers of Immunological Incompatibility via Desensitization Protocols in ABO-Compatible Living-Donor Kidney Transplant: Long-Term Follow-Up from a Tertiary Care Centre

Background: Human Leukocyte Antigen (HLA) incompatibility remains a significant challenge in kidney transplantation especially in the background of paucity of available kidneys for donation with exponentially rising incidence of ESKD. This immunological obstacle is difficult to bridge and often leads to early or late graft rejection and reduced long-term graft survival. This study aims to evaluate the long-term outcomes of kidney transplant recipients who underwent desensitization protocols to overcome Immunological incompatibility at a tertiary care center. Methods: A retrospective cohort study was conducted in KFSHRC Jeddah between June 2015 till December 2023 involving 41 ABO compatible renal transplant recipients with positive flow cross match; preformed DSA and high HLA mismatch. Patients received desensitization therapy, including plasmapheresis, intravenous immunoglobulin (IVIg), and rituximab, prior to transplantation. The primary outcomes measured were graft survival, graft failure, incidence of acute rejection, all-cause mortality over a 10-year follow-up period. Results: The age was between 20 to 73 years with 90% of patients females with a followup duration 1to 9 years. We observed a graft survival of 85% with 15% (n=5) incidence of graft failure. Reason of graft failure was CAN (n=2); chronic AMR(n=2); Bk Nephropathy(n=1). We did not experience graft failure in first 6 months of follow-up. There were 20 incidences of graft rejection in 16 patients; 18 ABMR and 2 TCMR who responded to therapy. Most of rejections ( n=17) were observed in first 1 year of transplant. Mean creatinine at 6 months, 2 years, 5 years and plus 5 years followup was 86, 95, 98, 106 umol/l . We did not observe any incidence of all-cause mortality in our patient population. Conclusion: We conclude by saying that desensitization therapy can overcome the immunological incompatibility with favorable short and long term patient and graft associated outcomes. Future research should focus on optimizing and individualizing desensitization protocols and exploring novel therapies to further improve outcomes for HLA-incompatible kidney transplant recipients