Eculizumab Therapy and Kidney Recovery in SARS-CoV-2-Induced Complement-Mediated Thrombotic Microangiopathy (CM-TMA)

Introduction: Thrombotic Microangiopathies (TMA) have a diverse pathogenesis, featuring microangiopathic hemolytic anemia, thrombocytopenia, end-organ injury, affecting renal microvasculature via microthrombi formation. Advancements in complement biology have introduced targeted therapies like Eculizumab, interrupting the terminal complement pathway mitigating microvascular thrombotic endothelial damage. Case Description: 60-year-old male, hospitalized for chest pain secondary to uncontrolled hypertension with a negative cardiac workup, and incidental SARS-CoV-2 infection, returned three weeks later with a two-week history of malaise and reduced urine output. He denied infectious, or gastrointestinal symptoms. Investigation revealed a creatinine of 4.09 mg/dL (baseline 0.9 mg/dL). UA with proteinuria and 50 RBC/HPF. Paraproteinemia and autoimmune workup including anti-GBM, ANCA, Lupus serology, Lupus Anticoagulant, Antiphospholipid antibody, C3/C4/CH50 complement, Factor H level and Factor H autoantibody were unremarkable. ADAMSTS-13 activity was not supportive of TTP, Coombs Test was negative. Given a negative stool culture and deteriorating renal function (peak creatinine 5.32 mg/dL), suspicion for CM-TMA increased, prompting pursuit of a renal biopsy to guide management. Light microscopy revealed acute to subacute TMA with secondary acute tubular injury confirming our suspicion of CM-TMA. He was established with an outpatient dialysis center and hematology for Eculizumab infusions. The patient suffered cardiac arrest during a dialysis session requiring hospitalization delaying his Eculizumab infusions. The cardiac arrest was attributed to an anaphylactic reaction to intradialytic iron infusion. He eventually began his Eculizumab regimen; clinical course is highlighted by discontinuation of dialysis four months after renal insult. He maintains routine follow-up with nephrology and hematology clinic for maintenance Eculizumab infusions. Discussion: Although genetic analysis was inconclusive, a 'first-hit' mutation predisposing to complement dysregulation coupled with SARS-CoV-2 as a 'second-hit' remains a likely pathogenesis. There are no current guidelines describing the length of Eculizumab therapy in this particular case. Our aim is to emphasize the importance of standardizing the duration of Eculizumab therapy, particularly in the absence of autoantibodies or familial history.