From Dialysis to Recovery: Atypical Hemolytic Uremic Syndrome Unmasked by Complement Factor I Mutation

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) driven by dysregulation of the alternative complement pathway. Genetic mutations in complement regulatory proteins, including complement factor I (CFI), are common contributors to disease pathogenesis. Early recognition and targeted treatment are crucial to prevent irreversible organ damage. Case Description: We report a case of a 38-year-old male with no PMHx who presented with acute encephalopathy and severe kidney injury (BUN>112/creat 16.3 mg/dl). Laboratory findings also revealed microangiopathic hemolytic anemia(Hb: 5 g/dl, LDH: 1649 U/l, haptoglobin <30 mg/dl & peripheral smear with schistocytes), thrombocytopenia(Plt: 32k). He was initially treated with plasma exchange until ADAMTS13 level resulted. ADAMTS13 activity was preserved, ruling out TTP. He required hemodialysis for uremic encephalopathy and anuria. Kidney biopsy confirmed TMA, and a complement genetic panel revealed a pathogenic CFI gene mutation (c.772G>A, p.Ala258Thr) in exon 5. He then received complement inhibition therapy with eculizumab, subsequently transitioned to ravulizumab. He demonstrated significant clinical recovery and remains off dialysis to date that is 2 years post presentation. Discussion: Atypical HUS represents a diagnostic and therapeutic challenge due to its overlap with other thrombotic microangiopathies. This case exemplifies the need for a high index of suspicion in patients presenting with TMA, particularly when ADAMTS13 levels are normal and Shiga toxin is absent. The identification of a pathogenic CFI mutation (c.772G>A, p.Ala258Thr) supports a complement-mediated mechanism of disease. CFI plays a critical role in regulating the alternative complement pathway by inactivating C3b and C4b, thereby preventing excessive complement activation. Mutations in CFI can result in inadequate inactivation of the complement cascade, leading to endothelial damage and microvascular thrombosis. The patient responded well to complement inhibition. His renal recovery, marked by the cessation of hemodialysis, underscores the potential for reversibility of kidney injury when treatment is initiated promptly. In summary, this case reinforces the critical role of early diagnosis, comprehensive complement genetic evaluation, and targeted complement inhibition in the successful management of aHUS.