Fernando Mos

Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients with De Novo Drug-Induced Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA), a severe complication of renal transplantation, is a pathological process involving microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. It generally appears within the first weeks after transplantation, when immunosuppressive drugs are used at high doses. De novo TMA may also be drug-induced when calcineurin inhibitors or proliferation signal inhibitors are used. We report three cases of de novo drug-induced TMA in renal transplant patients who were managed by replacing calcineurin inhibitors or proliferation signal inhibitors with belatacept, a primary maintenance immunosuppressive drug, which blocks the CD28 costimulation pathway, preventing the activation of T lymphocytes. To identify the cause of TMA, we ruled out HUS, hepatitis C serology, HIV serology, parvovirus B19, cytomegalovirus, anti-HLA antibodies, and prolonged activated partial thromboplastin time. We suspect that the TMA was caused by the calcineurin inhibitors or proliferation signal inhibitors. Belatacept treatment was initiated at a dose of 10 mg/kg on days 1, 5, 14, 28, 60, and 90; maintenance treatment was 5 mg/kg once a month for 1 year. Belatacept, in combination with other agents, prevented graft rejection in three patients.

Use of bortezomib to treat anti-HLA antibodies in renal transplant patients: A single-center experience

Donor-specific human leukocyte antigen (HLA) antibodies (DSA) are associated with decreased graft survival and may cause graft rejection. Bortezomib, a selective inhibitor of the 26S proteasome developed to treat multiple myeloma, has been used for its anti-plasma cell activity in patients undergoing transplantation. We describe our experience with bortezomib used to reduce anti-HLA antibodies in eight renal transplant patients. Patients received bortezomib (1.3mg/m(2)) on days 1, 4, 8, and 11 beginning when antibodies were detected. It was used alone in one patient and was complemented with plasmapheresis in five patients, with IVIG in one patient, and with IVIG and plasmapheresis in another patient. De novo DSA class II were detected in all eight patients and two also had DSA class I. Antibodies were entirely eliminated in five (62.5%) patients 90 days after treatment but only reduced in the other three (62.5%). Notably, they later increased in one patient. Five (62.5%) patients had AMR, two (25%) had mixed rejection, and one had no rejection. our results suggest that bortezomib is effective for reducing DSA avoiding chronic graft injury.

Belatacept-based, ATG-Fresenius-induction regimen for kidney transplant recipients: A proof-of-concept study

Belatacept provides effective immunosuppression while avoiding the nephrotoxicities associated with calcineurin inhibitors (CNIs). However, existing belatacept-based regimens still have high rates of acute rejection. We hypothesized that therapy with belatacept, mycophenolic acid (MMA), steroids and induction therapy with rabbit anti-thymocyte globulin Fresenius (ATGF), rejection rate could be reduced. Prospective, single center, proof-of-concept study including males and females aged ≥18years, Epstein-Barr virus (EBV)-seropositive recipients of a first, HLA non-identical, live or deceased donor kidney allograft. Only patients with a calculated panel reactive antibody score of 0% were included. Three donors were positive for Chagas disease. Six of twelve patients had at least one infection and five were readmitted to the hospital for treatment. One patient had a Trypanosoma cruzi infection via the graft treated successfully. Median cold ischemia time for the transplant patients with a deceased donor was 21.5h. Mean serum creatinine levels at 1, 3 and 6months were 1.76±0.59, 1.55±0.60 and 1.49±0.60mg/dl, respectively. Two of twelve patients experienced clinical, biopsy-proven rejection, successfully treated with methylprednisolone. No patient developed post-transplant lymphoproliferative disorder (PTLD) or any other malignancy and no patient lost their graft or died during follow-up. The potential of this approach makes it worthy of further investigation.