A Rare and Complex Case of Multifactorial Thrombotic Microangiopathy in A Kidney Transplant Recipient: Interplay Between Antibody Mediated Rejection, Tacrolimus Toxicity, Cytomegalovirus Disease and BNT162b2mRNA Vaccine

Abstract

Thrombotic microangiopathy (TMA) in kidney transplant recipients is uncommon and difficult to manage, often with poor graft outcomes [1]. This is a complex and interesting case of an older, highly sensitised kidney transplant recipient who presented with <em>de novo</em> post-transplant TMA in the setting of antibody mediated rejection (ABMR), with other drivers being tacrolimus toxicity, cytomegalovirus (CMV) infection and anti-SARS-CoV-2 BNT162b2 mRNA vaccination. This led to rapid, irrecoverable graft loss. 76-year-old female presenting three years post deceased donor renal transplant with ABMR. Her three-year course post-transplant was complicated with further opportunities for sensitisation. Firstly, with two discrete episodes of CMV disease requiring alteration in immunosuppression regimen. Secondly, she had a biopsy-confirmed episode of cell mediated rejection after switching from tacrolimus to everolimus due to tacrolimus toxicity. Finally, her admission with fulminant rejection was preceded by almost 6 months of sub-therapeutic tacrolimus levels. 4 weeks prior to this admission, the patient also had her second dose of BNT162b2 mRNA vaccine. Her graft function deteriorated rapidly, with final transplant biopsy showing severe TMA with graft infarct. This case illustrates a complex case of a highly sensitised patient with a difficult post-transplant course who unfortunately suffered a very severe episode of ABMR-associated TMA after further sensitisation during her post-transplant course, with other drivers including CNI toxicity and CMV disease as well as potential further immune stimulation from BNT162b2 mRNA vaccine.