Desensitization Protocols and Their Outcome

• Published in: Clinical journal of the American Society of Nephrology 2011-04, Vol.6 (4), p.922-936
• Main Authors: Marfo, Kwaku, Lu, Amy, Ling, Min, Akalin, Enver
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Murine-Derived - therapeutic use; Biopsy; Desensitization, Immunologic - adverse effects; Desensitization, Immunologic - methods; Graft Rejection - etiology; Graft Survival; HLA Antigens - immunology; Humans; Immunoglobulins, Intravenous - therapeutic use; Immunosorbent Techniques; Isoantibodies - blood; Kidney Transplantation - immunology; Risk Assessment; Rituximab; Waiting Lists
• ISSN: 1555-9041; 1555-905X
• DOI: 10.2215/CJN.08140910

In the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients.