Belatacept provides immunosuppression via costimulation blockade and has been associated with improved renal function compared to calcineurin inhibitor based therapies. We developed the Maryland Aggregate Pathology Index (MAPI) to identify kidneys with pre-existing pathology (MAPI ≥ 8) that predicted grafts with poorer outcomes. We investigated the use of belatacept with these kidneys to determine outcomes.

Methods:

Investigator initiated trial was developed to prospectively study patients with MAPI ≥ 8 to receive belatacept immunosuppression for 12 months. Patients received alemtuzumab induction therapy (30 mg), mycophenolate mofetil (MMF), and steroid withdrawal over 21 days. Biopsies were performed pre-transplant, and at 3 and 12 months, and renal function and infectious complications were monitored.

Results:

17 eligible patients underwent renal transplantation with MAPI ≥ 8 kidneys. Four patients discontinued the study secondary to surgical complication aborting transplant, primary non-function, non-compliance, and rejection. Patients were average 55.1 y/o, 76 % African-American, and 68% male. Delayed graft function was observed in 67% patients. No cases of post-transplant lymphoproliferative disorder (PTLD) or progressive multifocal leukoencephalopathy (PML)were observed. Average pre-implant MAPI score was 9, which was observed to decrease to a score of 3 at 3 months (p<0.01), and a score of 4 at 12 months (p<0.01) post-transplant. All patients were weaned off steroids. Rejection was observed in 3 patients on therapy (19%), one of whom had multiple episodes and was converted to tacrolimus. Average creatinine level was 1.75 mg/dL at 3 months and 1.89 mg/dL at 12 months. Average glomerular filtration rate was 62 mL/min at 3 months and 54 mL/min at 12 months. Most common adverse events were gastrointestinal intolerability and urinary tract infection.

Conclusion:

Belatacept/MMF therapy combined with alemtuzumab induction and steroid withdrawal provided good outcomes in kidneys with significant pre-transplant pathology. Despite high delayed graft function rates, rejection rates were low and kidney function was good at 3 and 12 months. MAPI pathology scores significantly improved post-transplant with belatacept therapy suggesting reversibility of pre-transplant pathologic findings.

« Back to 2015 American Transplant Congress