The role of anti-HLA antibodies in the prevention, diagnosis, and management of antibody-mediated rejection after kidney transplant

Abstract

Background . The available literature contains relatively few studies investigating the role of anti-human leukocyte antigen (anti-HLA) antibodies – including pre-existing antibodies, de novo synthesized antibodies, and donor-specific antibodies (DSAs) – in the prevention, diagnosis, and treatment of acute kidney transplant (KT) rejection. Materials and methods . We evaluated the prevalence and specificity of pre-existing anti-HLA antibodies, the incidence and specificity of de novo anti-HLA antibody synthesis (including DSAs), and their impact on treatment outcomes at a major national transplant center. A total of 1,663 KTs performed over an 8-year period (2016–2024) were analyzed. The study cohort comprised 962 men (57.8%) and 701 women (42.2%), with a median age of 46 years (interquartile range: 37–55 years). Prior to transplantation, 90.3% of recipients received dialysis-based renal replacement therapy, while 161 patients underwent pre-emptive KT. Results . The presence of pre-existing anti-HLA antibodies was significantly associated with a higher incidence of acute rejection episodes (p < 0.001), increased need for treatment with polyclonal antibodies (p < 0.001), a greater frequency of nonfunctioning kidney grafts (p < 0.001), and higher in-hospital mortality rates (p < 0.001). Similarly, the de novo synthesis of anti-HLA antibodies was significantly associated with an increased incidence of acute rejection (p = 0.004), a greater need for plasmapheresis as part of rejection management (p < 0.001), and a lower likelihood of a functioning kidney graft at the time of hospital discharge (p = 0.037). Conclusion. Despite the high efficacy of modern immunosuppressive regimens, acute rejection remains a major factor compromising kidney graft survival. Assessing the impact of anti-HLA antibodies on KT outcomes therefore remains a pressing issue in modern KT.