Posttransplant Thrombotic Microangiopathy: Unraveling a Mystery

Abstract

A 24 year old lady who was diagnosed with chronic kidney disease stage 5 in 2016 underwent a pre-emptive live related renal transplant in the same year. She had kidney allograft dysfunction and eventually lost the transplant kidney in 2019 requiring hemodialysis. She underwent a deceased donor renal transplant in February 2022. She developed allograft dysfunction with a creatinine of 2.5 mg/dl in October 2022, and a renal allograft biopsy subsequently showed Thrombotic microangiopathy, arteriolar form. There were no features of rejection in the biopsy and Donor specific antibody done by Luminex lysate method was negative. Her Single antigen bead done subsequently was also negative. CMV DNA PCR was not detectable. Tacrolimus was switched to Cyclosporine, however her allograft function continued to worsen. Complement mutation analysis was negative and acquired complement defects were also not detected. Subsequently, Single antigen bead for non HLA antibodies showed positivity for MICA antibodies. She underwent 7 sessions of plasmapheresis and her renal functions did not improve and her creatinine continued to increase to 4.2 mg/dl. Complement activating assay for these MICA antibodies was positive. She was treated with two doses of 300 mg Eculizumab in December 2022, her allograft functions in February 2023 have improved to 2 mg/dl. This case highlights the extensive evaluation for post transplant TMA, the use of non HLA antibody assays and complement activating assays of these antibodies to decide on appropriate use of Eculizumab for salvaging transplant allograft.