Atypical hemolytic uremic syndrome treated with anti-C5 antibody agent eculizumab, without genetic complement abnormalities.

Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening disease often complicated by end-stage renal disease. Anti-C5 antibody agents have been developed for the treatment of aHUS: these are highly effective but limited in use owing to the difficulty of diagnosing aHUS in the acute clinical phase. The pathophysiology of aHUS is a thrombotic microangiopathy (TMA) caused by complement dysregulation triggered by environmental factors in susceptible individuals with genetic factors. Although several germline variants associated with aHUS have been identified, approximately half of patients with aHUS lack known pathogenic variants. It is essential to recognize the characteristic clinical features of aHUS. These include the triad of hemolytic anemia, thrombocytopenia, and renal impairment, without the presence of Shiga toxin-producing Escherichia coli infection, thrombotic thrombocytopenic purpura associated with ADAMTS13 deficiency, or TMA from secondary cause. In this case, plasma exchange could not be continued owing to allergy. Early diagnosis allowed for prompt administration of eculizumab at the time of relapse, with favorable outcomes. Based on the finding of no genetic abnormalities, eculizumab was discontinued after 12 months, with no recurrence for 3 years. On day 27 of hospitalization, renal biopsy revealed endothelial damage. Since a definitive diagnosis cannot be made with genetic testing in the acute stage and approximately half of patients have no genetic abnormalities, it is suggested to diagnose the condition as per the clinical definition and commence treatment with plasma exchange. If thrombotic thrombocytopenic purpura is excluded, switching to eculizumab is another treatment option according to clinical conditions.