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Abstract: SA-PO0114

Diagnostic Complexities and Challenging Therapeutics in Patients with Systemic Lupus Erythematosus and Thrombotic Microangiopathy

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Paredes, William Mauricio, Cleveland Clinic, Cleveland, Ohio, United States
  • Chaudhry, Iman Waseem, Cleveland Clinic, Cleveland, Ohio, United States
  • Ferreira Provenzano, Laura, Cleveland Clinic, Cleveland, Ohio, United States
Introduction

Factor I deficiency is a rare genetic disorder that affects the regulation of the alternative complement pathway, leading to uncontrolled complement activation. This dysregulation can precipitate thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury with endothelial damage. Renal involvement can result in acute kidney injury or progression to chronic kidney disease. Mutations in Factor I have been implicated in atypical hemolytic uremic syndrome (aHUS).

Case Description

We describe a 43-year-old Caucasian woman with a history of systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), class I lupus nephritis with prior TMA, and stage IV chronic kidney disease. She presented with acute kidney injury (Cr 6.1 mg/dL), anemia, thrombocytopenia, anasarca, and oliguria. Her baseline creatinine ranged from 2–3 mg/dL. First biopsy done 6 months before admission revealed class I lupus nephritis with TMA, and she was treated with rituximab, mycophenolate, voclosporin, corticosteroids, and hydroxychloroquine. Due to the patient's choice, given she had an episode of upper gastrointestinal bleeding, she decided to stop warfarin and was on apixaban.
Due to worsening renal function and proteinuria (protein-creatinine ratio of 12.3 g/g), a repeat kidney biopsy was performed, which showed negative immunofluorescence and acute and chronic TMA. Post-biopsy, she developed a large subcapsular perinephric hematoma requiring embolization and transfusion. Laboratory workup revealed low Factor I (1.2 mg/dL; normal 1.6–3.7). Factor H autoantibodies were negative, and rare schistocytes on peripheral smear. She remained off dialysis, despite her creatinine rose to 5.05 mg/dL post-bleed.

Discussion

This case illustrates the diagnostic complexity in patients with SLE and suspected complement-mediated TMA. The progression of renal dysfunction and proteinuria despite immunosuppressive therapy suggests a superimposed or evolving aHUS. Her APS further compounds the prothrombotic state, complicating anticoagulation management. This case underscores the importance of high clinical suspicion, early complement testing, and potential consideration of complement inhibition (e.g., eculizumab). Genetic analysis may help confirm the diagnosis and guide therapy.

Digital Object Identifier (DOI)