Systemic Thrombotic Microangiopathy Induced by Antibody-Mediated Rejection in a Highly Sensitized Kidney Transplant Recipient

Introduction: Atypical HUS (aHUS) is a form of thrombotic microangiopathy (TMA), which is defined by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury. aHUS is caused by uncontrolled activation of the alternative pathway of the complement cascade, and can be due to a variety of causes, such as genetic defects in complement related factors or acquired autoantibodies to complement regulators. Here we present a unique case of aHUS post kidney transplant in a highly sensitized recipient. Case Description: A 38 year old female with history of ESRD secondary to bilateral ureteral reflux disease, presented for deceased donor kidney transplantation. The patient was highly sensitized with panel reactive antibody of 100% due to history of blood transfusions and pregnancy. She underwent desensitization while on the waiting list with eight sessions of plasmapheresis and replacement IVIG. This resulted in a flow negative T and B cell crossmatch kidney transplant offer with pre-existing class I and II donor specific HLA antibodies (DSAs). On post-operative day 1, she developed acute kidney injury, acute anemia, thrombocytopenia, and schistocytes were found on the blood smear. Additional labs showed low C3, elevated LDH, and undetectable haptoglobin level. ADAMTS13 functional assay was 54%. aHUS was suspected, and patient was immediately started on eculizumab. Subsequent kidney biopsy showed evidence of microangiopathy with focal C4d positivity. Hematologic markers improved within 24-48 hours after initiation of eculizumab, as did renal function. Follow up genetic testing revealed homozygous CFHR1 deletion. Discussion: This case illustrates an early development of acute antibody mediated rejection manifested as systemic TMA post kidney transplantation. This process was likely triggered by the presence of DSAs in the setting of homozygous CFHR1 deletion, and promptly responded to eculizumab. This case supports the use of pre-transplant genetic testing to stratify patients who are at high risk for developing post-transplant TMA, and such can help guide the decision-making process of peri-operative use of eculizumab.