New treatments for acute humoral rejection of kidney allografts.

Acute antibody-mediated rejection (acute humoral rejection; AHR) of organ allografts usually presents as severe dysfunction with a high risk of allograft loss. Peritubular capillary complement C4d deposition with renal dysfunction, associated with circulating donor-specific anti-human leukocyte antigen alloantibodies, is diagnostic of AHR in kidney allografts. Removal of alloantibodies with suppression of antibody production and rejection reversal is now possible. Therapeutic strategies that include combinations of plasmapheresis (or immunoadsorption), tacrolimus, mycophenolate mofetil and/or intravenous immunoglobulins, as well as rituximab or splenectomy, have been recently used to successfully treat AHR. However, the optimal protocol to treat AHR still remains to be defined. Anti-CD20+ monoclonal antibody therapy (rituximab) aiming at depleting B cells and suppressing antibody production has been used as rescue therapy in some episodes of steroid- and antilymphocyte-resistant humoral rejection. Plasmapheresis and/or intravenous polyclonal immunoglobulin, as well as rituximab, have also been used to successfully desensitize selected high-immunological risk patients in anticipation of a previously cross-match positive (or ABO incompatible) kidney transplantation. In the near future, the possible role of new specific anti-B-cell approaches or, possibly, of new anti-T-cell activation approaches using selective agents such as belatacept should be assessed to further refine the present treatment of humoral rejection.