Transplanting highly sensitized patients

Abstract

Immunological barrier posed by preformed antibodies against donor's human leukocyte antigen (HLA) antigens compounds the situation of global shortage of kidney donors. Pretransplantation sensitization carries a high risk of acute rejection and allograft loss. Therefore, there is a need for careful evaluation of potential recipients, based on HLA typing, HLA match, and comprehensive screening of antibodies (is conceptual). Sensitization events include previous transplantations, blood transfusions, or pregnancies. Despite advances in molecular techniques and solid-phase assays used to identify at-risk patients, kidney transplantation continues to be challenging in patients with calculated panel reactive antibodies greater than 85%. The development of desensitization protocols has been used to overcome acute rejection risk; however, the associated further increase in the risk of infection and malignancy is of significant concern owing to enhanced immunosuppression. The introduction of rituximab, bortezomib, plasmapheresis, and intravenous immunoglobulins has improved the success rate of desensitization protocols. On the contrary, paired (pooled) exchange kidney program has been instrumental in widening access to allografts to highly sensitized patients by offering lesser HLA mismatches. Moreover, desensitization protocols are rather expensive, leading to a high economic burden in the pretransplantation and posttransplantation period. This review aims to discuss the scientific basis and practical issues of managing highly sensitized patients.