Preoperative Management (Desensitization)

The identification of suitable donor kidneys for transplant candidates with high levels of circulating antibodies against human leukocyte antigen (HLA) is a major challenge and sensitized patients have a reduced chance of receiving a crossmatch-negative organ. For many highly sensitized renal transplant candidates, an acceptable donor is never identified, and the patient remains on dialysis indefinitely. In an attempt to improve the probability of transplant in the highly sensitized patients, several desensitization protocols have been developed that permit positive-crossmatch kidney transplantation. Alloantibodies are removed from the patient’s circulation by plasmapheresis or immunoadsorption in pretransplantation and their production is suppressed by T cell immunosuppression, intravenous immunoglobulins (IVIG), rituximab, or the proteasome inhibitor (bortezomib) based on the rationale that depletion of B lymphocytes or plasma cells may reduce anti-HLA antibodies production. Additional novel approaches are the blockage of complement activation by administration of the complement C5 inhibitor (eculizumab) or C1 esterase inhibitor, anti-IL-6 receptor blockers and the administration of immunoglobulin G (IgG)-degrading enzyme derived from Streptococcus pyogenes (IdeS) in highly sensitized patients. These new interventions aimed at the prevention of donor-specific antibodies (DSA)-mediated allograft injury and are somewhat promising therapeutic avenues currently still under investigation and much work remains to determine optimal protocols. Moreover, at present, there are no prospective and randomized trials comparing different desensitization protocols and no clear scientific data to recommend a certain protocol. In summary, although diverse desensitization protocols for positive-crossmatch kidney transplantations have improved access to transplantation for highly sensitized patients, more clinical experiences are clearly needed.