The clinical spectrum of hemolytic uremic syndrome secondary to complement factor H autoantibodies

Atypical hemolytic uremic syndrome (aHUS) is associated with significant mortality, progression to end-stage renal disease and recurrence post transplantation. The deficiency of CFHR plasma proteins and autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) has a more favorable outcome. Guidelines suggest plasma therapy be initiated within 24 hours of presentation of aHUS. Presentation of aHUS, particularly, DEAP-HUS is associated with a diarrheal prodrome in up to 53% of patients and initiation of appropriate therapies is frequently delayed.

We report on 3 patients with DEAP-HUS, who presented with a diarrheal prodrome that delayed diagnosis and initiation of plasma therapy past the 24-hour window recommended. C3 was low in 2 cases at presentation. All patients had positive complement factor H (CFH) autoantibodies. Despite delay in initiating plasma therapy, all 3 cases remitted with restoration of normal renal function following initial presentation. One patient had a relapse but responded to further plasma exchange and immunosuppression. The remaining 2 patients were relapse-free without maintenance immunosuppression.

Our cases highlight the complexity of diagnosing DEAP-HUS due to the common occurrence of diarrhea in the prodromal phase and the subsequent delay in initiating of plasma therapy. We therefore advocate a low threshold for testing CFH autoantibodies in ambiguous cases where there is no history of bloody diarrhea or Shiga-toxin exposure.