Severe Acute-Hybrid Rejection Occurring Nine Months After Kidney Transplantation: A Report Of Rescue By Orchestration Of Antirejection Therapies

Although a majority of acute rejection (AR) in non-sensitized recipients is T-cell-mediated by primed T cells, recent studies have shown that antibody-mediated acute rejection occurs in 20-30% of AR, and that it is often refractory to conventional antirejection therapy; possibly leading to graft loss. We report a case of severe acute-hybrid rejection consisting of both features in a non-sensitized kidney recipient, which was rescued by the orchestration of antirejection therapies. A 33-yr-old Japanese male, with advanced-stage chronic kidney disease with an unknown etiology, underwent a HLA 3/6 mismatch and ABO-compatible living-related kidney transplantation preemptively. He had an excellent clinical course, except for initial cytomegalovirus infection, with good graft function [serum creatinine (sCr) 1.1 mg/dL]. Nine months later, his creatinine abruptly increased to 2.1 mg/dL, when graft biopsy revealed acute T cell-mediated rejection (ATMR) grade IA, and simultaneous acute antibody-mediated rejection (AAMR) grade I. Antirejeciton therapy, comprising methyl-prednisolone pulse and 15-deoxyspergualin, and second line rituximab and plasmapheresis, was ineffective. Moreover, histologically and clinically, the rejection status deteriorated (ATMR grade III and AAMR grade III, max sCr 4.0 mg/dL). Next, we administered muromonab CD3 and basiliximab, which could eradicate the complicated severe AR without opportunistic infection, even under the strong immunosuppression. The present case implies that high-grade combined rejection can respond to anti-CD 20 and anti-CD25 mAbs, without serious complication; however, post-operative, thorough appropriate monitoring of immunosuppression is important because its effects are limited.