title: 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.
authors.affiliation: Department of Medicine, Jersey Shore University Medical Center, Hackensack-Meridian Health, Seton Hall-Hackensack-Meridian School of Medicine, 1945 NJ Route 33, Neptune, NJ, 07753, USA. Arif.Asif@hackensackmeridian.org.
authors.forename: Arif
authors.initials: A
authors.lastname: Asif
authors.affiliation: Division of Nephrology and Hypertension, Miller School of Medicine, University of Miami, Batchelor Research Institute (R762), 1580 N.W. 10th Avenue, Miami, FL, 33136, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Nayer
authors.affiliation: Division of Nephrology, Dialysis and Transplantation, Department of Medicine I, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Haas
mesh_terms: D000328:Adult; D000465:Algorithms; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D000066491:Clinical Decision-Making; D015897:Comorbidity; D003167:Complement Activation / Q000187:drug effects*; D051056:Complement Inactivating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000276:immunology*; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D011237:Predictive Value of Tests; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000276:immunology; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; D003165:Complement System Proteins; C481642:eculizumab
keywords: Complement; Hypertension; Kidney transplantation; Pregnancy; Thrombotic microangiopathy