Chantal Loirat 1 , Fadi Fakhouri 2 , Gema Ariceta 3 , Nesrin Besbas 4 , Martin Bitzan 5 , Anna Bjerre 6 , Rosanna Coppo 7 , Francesco Emma 8 , Sally Johnson 9 , Diana Karpman 10 , Daniel Landau 11 , Craig B Langman 12 , Anne-Laure Lapeyraque 13 , Christoph Licht 14 , Carla Nester 15 , Carmine Pecoraro 16 , Magdalena Riedl 17 , Nicole C A J van de Kar 18 , Johan Van de Walle 19 , Marina Vivarelli 8 , Véronique Frémeaux-Bacchi 20
Anti-factor H antibody, Atypical hemolytic uremic syndrome, Children, Combined liver–kidney transplantation, Complement, Eculizumab, Hemolytic uremic syndrome, Kidney transplantation, Plasma exchange, Plasma infusion, Thrombotic microangiopathy
Atypical hemolytic uremic syndrome (aHUS) emerged during the last decade as a disease largely of complement dysregulation. This advance facilitated the development of novel, rational treatment options targeting terminal complement activation, e.g., using an anti-C5 antibody (eculizumab). We review treatment and patient management issues related to this therapeutic approach. We present consensus clinical practice recommendations generated by HUS International, an international expert group of clinicians and basic scientists with a focused interest in HUS. We aim to address the following questions of high relevance to daily clinical practice: Which complement investigations should be done and when? What is the importance of anti-factor H antibody detection? Who should be treated with eculizumab? Is plasma exchange therapy still needed? When should eculizumab therapy be initiated? How and when should complement blockade be monitored? Can the approved treatment schedule be modified? What approach should be taken to kidney and/or combined liver-kidney transplantation? How should we limit the risk of meningococcal infection under complement blockade therapy? A pressing question today regards the treatment duration. We discuss the need for prospective studies to establish evidence-based criteria for the continuation or cessation of anticomplement therapy in patients with and without identified complement mutations.