Outcomes of belatacept-based quadruple immunosuppression therapy in kidney transplant recipients with persistent alloimmune response: a single-center observational study.

We conducted a retrospective review of adult kidney transplant recipients (KTRs) who received belatacept in addition to calcineurin inhibitors, antimetabolites, and corticosteroids for recurrent or refractory rejection or for persistent donor-specific antibodies (DSAs) unresponsive to standard therapy. Fifteen recipients were included. Kidney function remained stable on follow-up; median eGFR was 52 mL/min (R 23-91) at baseline and 54 mL/min (R 25-105) at 6 months (p = 0.15) after belatacept initiation. The DSA intensity declined significantly from a median of 4,990 mean fluorescence intensity (MFI) (R 0-23,305) at baseline to 1,644 MFI (R 0-6,903) at 3-6 months (p = 0.03). There was also a small reduction in biopsy-proven rejections from 85.7% to 63.6%. Infections occurred in most recipients (73.3%), with a majority arising more than 6 months after therapy initiation. Two patients developed post-transplant lymphoproliferative disorder (PTLD), each with either substantial prior exposure to lymphocyte-depleting agents or prolonged immunosuppression. Two deaths occurred, one related to PTLD and one to septic shock. These findings suggest that belatacept-based quadruple immunosuppression may reduce DSA and stabilize kidney function in patients with persistent alloimmunity, but without a statistically significant reduction in rejections. There is also a significant burden of infections and PTLD, highlighting the need for careful patient selection and caution before adopting this approach.