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Abstract: PO1483

Post-Transplant Thrombotic Microangiopathy due to a Pathogenic Mutation in Complement Factor I

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation


  • Shaikh, Sana J., Washington University in St Louis, St Louis, Missouri, United States
  • Saleem, Maryam, Washington University in St Louis, St Louis, Missouri, United States
  • Java, Anuja, Washington University in St Louis, St Louis, Missouri, United States

Thrombotic microangiopathy (TMA) is characterized by hemolytic anemia, thrombocytopenia, and AKI. Atypical hemolytic uremic syndrome (aHUS) is a classic complement-mediated TMA that occurs when genetic variants in complement proteins result in a dysregulated complement system. Genetic variants in complement Factor I (CFI) have been reported in 5–15% of patients with aHUS.

Case Description

28-year-old African American man with ESKD secondary to biopsy-proven PLA2R-positive membranous nephropathy underwent a 2/2/1 mismatch ABO incompatible living-unrelated kidney transplantation. Induction immunosuppression included methylprednisolone and Thymoglobulin. Post-op course was complicated by bleeding and he was taken back to the OR on POD 1. Labs showed anemia (Hgb 7.7 g/dL), thrombocytopenia (PLT 25 k/µl), low haptoglobin (< 10 mg/dL), high LDH (580 Units/L), low C3 and normal C4. ADAMTS-13 activity and coagulation profile were normal. Graft function was delayed. This raised concern for a TMA. Tacrolimus was not initiated. Allograft biopsy performed on POD 4 confirmed the diagnosis. Eculizumab was administered, resulting in resolution of thrombocytopenia and hemolysis, and gradual renal recovery.

Genetic testing for complement revealed a ‘variant of uncertain significance’ in CFI (Iso357Met). This variant is located in the serine protease domain of Factor I which contains the catalytic site. Functional analysis of the variant using recombinant proteins revealed that it had defective complement regulatory activity. This work established that the CFI variant was deleterious and thus defined the etiopathogenesis of TMA in the patient.


This is a case of de novo post-transplant aHUS due to a pathogenic complement mutation, likely triggered by transplant surgery. Our strategy of recombinant protein production followed by detailed functional assessment defined the functional repertoire of the variant protein and provided critical guidance relative to the underlying pathophysiology and appropriate therapeutic regimen.