Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: case reports and a review of the evidence for treatment with eculizumab

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 % of cases of aHUS. CACs activate the alternative pathway of complement and may be comorbid with aHUS or may unmask a previously undiagnosed case. In this review, three case reports are presented illustrating the onset and diagnosis of aHUS in the setting of different CACs (pregnancy complications, malignant hypertension, renal transplantation). The report also reviews the evidence for a variety of CACs, including those mentioned above as well as infections and drug-induced TMA, and the overlap with aHUS. Finally, we introduce an algorithm for diagnosis and treatment of aHUS in the setting of CACs. If TMA persists despite initial management for the specific CAC, aHUS should be considered. The terminal complement inhibitor eculizumab should be initiated for all patients with confirmed diagnosis of aHUS, with or without a comorbid CAC.

Keywords: Complement; Hypertension; Kidney transplantation; Pregnancy; Thrombotic microangiopathy.

Fig. 1

Management algorithm for patients with CACs and TMA. ADAMTS13 a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, aHUS atypical hemolytic uremic syndrome, CAC complement-amplifying condition, STEC Shiga-like toxin-producing Escherichia coli, TMA thrombotic microangiopathy, TTP thrombotic thrombocytopenic purpura. ^aThe differential diagnosis section of the algorithm has been adapted from [5]