14th Congress of the Asian Society of TransplantationKidneyProgress in Desensitization of the Highly HLA Sensitized Patient

- Sensitization to HLAs is a major barrier to successful organ transplantation. Despite recent efforts to amend this problem by using revisions of the United Network for Organ Sharing allocation system, most sensitized patients continue to wait extensive periods of time for a life-saving allograft.
- Current desensitization protocols include the use of high-dose intravenous immunoglobulin, intravenous immunoglobulin + plasma exchange, and rituximab.
- Acceptable results have been achieved with these protocols, but significant challenges remain.
- Newer agents are emerging, which include complement inhibitors, newer B-cell-depleting agents, anticytokine therapies, and immunoglobulin endopeptidase treatments.

The presence of HLA antibodies remains a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality for patients remaining on long-term dialysis. In recent years, a number of new approaches have been developed to overcome these barriers. Intravenous immunoglobulin (IVIG) remains the lynchpin of HLA desensitization therapy and has been shown in a prospective, randomized, placebo-controlled trial to improve transplantation rates. In addition, IVIG used in low doses with plasma exchange is a reliable protocol for desensitization. Another significant advancement was the addition of rituximab (anti-B-cell therapy) to IVIG and plasma exchange-based desensitization. This approach has significantly improved rates of transplantation and outcomes. There is limited experience with bortezomib (anti-plasma cell therapy) and eculizumab (complement inhibition) for desensitization. However, recent data from a completed trial of eculizumab failed to show a significant benefit for prevention of antibody-mediated rejection compared with standard therapy plus placebo, and bortezomib produced inconsistent results. There is a growing interest in developing new therapeutic agents for desensitization. Newer approaches that address antibody reduction with B-cell depletion are discussed.