The Long-Term Impact of B-Cell Depletion in Highly Sensitized Renal Recipients.

Abstract

More evidence now shows that B cells play a significant role in short and long-term outcomes of renal transplant. B cells can produce not only antibodies (Ab) against the donor cells, but also can serve as an antigen presenting cells and play a central role in the formation of tertiary lymphoid organs and the modulation of chronic rejection. We explored the effects of adding a B cell depleting agent, rituximab (RTX), to a standard rabbit anti-thymocyte globulin (rATG) induction regimen for renal transplant recipients (RTRs) with PRA>50% and received a compatible cross match renal transplant. Following induction therapy, 15 RTRs were given 2 doses of RTX (375 mg/M2) within the first month post-transplant. Their long-term outcomes were compared to a historical control group of 23 RTRs who received rATG alone. Donor and recipient demographics were similar in both groups. Maintenance immunosuppression included tacrolimus, mycophenolic acid and prednisone. Patient survivals were not different between groups, Figure 1. Graft survival was superior with combination therapy compared to rATG induction alone (Figure 2). While 30% of the rATG alone group experienced cellular rejection and 26% humoral rejection, none of the rATG plus RTX group had rejection (p<0.001). In the rATG alone group, 8 (34%) RTRs developed donor specific antibodies compared to none in the rATG plus RTX group (p=0.01). The rate of infections and other complications was similar in both groups. Thus, in the highly sensitized patient receiving a cross match negative kidney transplant, the addition of RTX to rATG provided superior outcomes to rATG alone without incurring additional risk. This combination induction therapy should be considered for a high risk population.Figure: No Caption available.Figure: No Caption available.