Pediatric Nephrology

, Volume 31, Issue 1, pp 15–39 | Cite as

An international consensus approach to the management of atypical hemolytic uremic syndrome in children

  • Chantal LoiratEmail author
  • Fadi Fakhouri
  • Gema Ariceta
  • Nesrin Besbas
  • Martin Bitzan
  • Anna Bjerre
  • Rosanna Coppo
  • Francesco Emma
  • Sally Johnson
  • Diana Karpman
  • Daniel Landau
  • Craig B Langman
  • Anne-Laure Lapeyraque
  • Christoph Licht
  • Carla Nester
  • Carmine Pecoraro
  • Magdalena Riedl
  • Nicole C. A. J. van de Kar
  • Johan Van de Walle
  • Marina Vivarelli
  • Véronique Frémeaux-Bacchi
  • for HUS International


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.


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 



The authors wish to thank DR MK Taha, Institute Pasteur, Invasive Bacterial Infections Unit and National Reference Centre for Meningococci, Paris, France, for his helpful insights on the debate of meningococcal infection prophylaxis

Authors contribution

C. Loirat, F. Fakhouri and V. Fremeaux-Bacchi participated in the concept, design and writing of the article. C. Loirat, V. Fremeaux-Bacchi, G. Ariceta, S. Johnson, AL. Lapeyraque, and C. Nester participated to a meeting in Paris on February 26, 2014, to define the domains requiring discussion and consensus.

Four critical revisions of the article and consensus approval of the final version was given by the authors indicated above and by M. Bitzan, R. Coppo, F. Emma, D. Karpman, D. Landau, C.B. Langman, C. Licht, M. Riedl, N. van de Kar and M. Vivarelli. N. Besbas, A. Bjerre, C. Pecoraro and J. van de Walle gave approval of the revisions and final version. All authors except F. Fakhouri and V. Fremeaux-Bacchi are members of HUS International.

Declaration of interests

The following authors declare interests. G. Ariceta, F. Fakhouri, V. Fremeaux-Bacchi, S. Johnson, D. Landau, AL. Lapeyraque, C. Licht, C. Loirat and N. van de Kar have served on Advisory Boards and/or teaching courses for Alexion Pharmaceuticals. C. Licht received research grants from Alexion Pharmaceuticals. D. Karpman, C. Licht and C. Loirat were the national coordinators of the multi-center Eculizumab trials in aHUS in Sweden, Canada and France, respectively. G. Ariceta, F. Fakhouri, V. Fremeaux-Bacchi, S. Johnson, C. Licht and J. van de Valle are members of the Scientific Advisory Board of the International aHUS Registry of Alexion Pharmaceuticals. M. Bitzan and C. Loirat were scientific advisers for Thallion Pharmaceuticals. C. Licht served on Advisory Board of Achillon Pharmaceuticals.


  1. 1.
    Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G (2010) Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5:1844–1859PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Maga TK, Nishimura CJ, Weaver AE, Frees KL, Smith RJ (2010) Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome. Hum Mutat 31:E1445–E1460PubMedCrossRefGoogle Scholar
  3. 3.
    Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschênes G, Lebranchu Y, Zuber J, Loirat C (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Kavanagh D, Goodship TH, Richards A (2013) Atypical hemolytic uremic syndrome. Semin Nephrol 33:508–530PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Nester CM, Thomas CP (2012) Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated? Hematology 2012:617–625PubMedGoogle Scholar
  6. 6.
    Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa M, Grinyó JM, Praga M, Torra R, Vilalta R, Rodríguez de Córdoba S (2013) An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia 33:27–45PubMedGoogle Scholar
  7. 7.
    Cataland SR, Wu HM (2014) How I treat: the clinical differentiation and initial treatment of adult patients with atypical hemolytic uremic syndrome. Blood 123:2478–2484PubMedCrossRefGoogle Scholar
  8. 8.
    Scully M, Goodship T (2014) How I treat thrombotic thrombocytopenic purpura and atypical haemolytic uraemic syndrome. Br J Haematol 164:759–766PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Lemaire M, Frémeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili F, Martinez F, Ji W, Overton JD, Mane SM, Nürnberg G, Altmüller J, Thiele H, Morin D, Deschenes G, Baudouin V, Llanas B, Collard L, Majid MA, Simkova E, Nürnberg P, Rioux-Leclerc N, Moeckel GW, Gubler MC, Hwa J, Loirat C, Lifton RP (2013) Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 45:531–536PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, Loirat C, Pecoraro C, Taylor CM, Van de Kar N, Vandewalle J, Zimmerhackl LB, European Paediatric Study Group for HUS (2009) Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 24:687–696PubMedCrossRefGoogle Scholar
  11. 11.
    Johnson S, Stojanovic J, Ariceta G, Bitzan M, Besbas N, Karpman D, Frieling M, Landau D, Langman C, Licht C, Pecoraro C, Riedl M, Siomou E, Van de Kar N, Walle JV, Loirat C, Taylor CM (2014) An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome. Pediatr Nephrol 29:1967–1978PubMedCrossRefGoogle Scholar
  12. 12.
    Zuber J, Fakhouri F, Roumenina LT, Loirat C, Frémeaux-Bacchi V, French Study Group for aHUS/C3G (2012) Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8:643–657PubMedCrossRefGoogle Scholar
  13. 13.
    Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2169–2181PubMedCrossRefGoogle Scholar
  14. 14.
    Wong EK, Goodship TH, Kavanagh D (2013) Complement therapy in atypical haemolytic uraemic syndrome (aHUS). Mol Immunol 56:199–212PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Besbas N, Karpman D, Landau D, Loirat C, Proesmans W, Remuzzi G, Rizzoni G, Taylor CM, Van de Kar N, Zimmerhackl LB, Besbas N, Karpman D, Landau D, Loirat C, Proesmans W, Remuzzi G, Rizzoni G, Taylor CM, Van de Kar N, Zimmerhackl LB, European Paediatric Research Group for HUS (2006) A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int 70:423–431PubMedGoogle Scholar
  16. 16.
    Loirat C, Frémeaux-Bacchi V (2011) Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 6:60PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Fakhouri F, Jablonski M, Lepercq J, Blouin J, Benachi A, Hourmant M, Pirson Y, Dürrbach A, Grünfeld JP, Knebelmann B, Frémeaux-Bacchi V (2008) Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome. Blood 112:4542–4545PubMedCrossRefGoogle Scholar
  18. 18.
    Le Quintrec M, Lionet A, Kamar N, Karras A, Barbier S, Buchler M, Fakhouri F, Provost F, Fridman WH, Thervet E, Legendre C, Zuber J, Frémeaux-Bacchi V (2008) Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation. Am J Transplant 8:1694–1701PubMedCrossRefGoogle Scholar
  19. 19.
    Fakhouri F, Roumenina L, Provot F, Sallée M, Caillard S, Couzi L, Essig M, Ribes D, Dragon-Durey MA, Bridoux F, Rondeau E, Frémeaux-Bacchi V (2010) Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol 21:859–867PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Spinale JM, Ruebner RL, Kaplan BS, Copelovitch L (2013) Update on Streptococcus pneumoniae associated hemolytic uremic syndrome. Curr Opin Pediatr 25:203–208PubMedCrossRefGoogle Scholar
  21. 21.
    Yagi H, Matsumoto M, Fujimura Y (2012) Paradigm shift of childhood thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency. Presse Med 41:e137–e155PubMedCrossRefGoogle Scholar
  22. 22.
    Loirat C, Coppo P, Veyradier A (2013) Thrombotic thrombocytopenic purpura in children. Curr Opin Pediatr 25:216–224PubMedCrossRefGoogle Scholar
  23. 23.
    Hassenpflug WA, Budde U, Schneppenheim S, Schneppenheim R (2014) Inherited thrombotic thrombocytopenic purpura in children. Semin Thromb Hemost 40:487–492PubMedCrossRefGoogle Scholar
  24. 24.
    Reese JA, Muthurajah DS, Kremer Hovinga JA, Vesely SK, Terrell DR, George JN (2013) Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer 60:1676–1682PubMedCrossRefGoogle Scholar
  25. 25.
    Hie M, Gay J, Galicier L, Provôt F, Presne C, Poullin P, Bonmarchand G, Wynckel A, Benhamou Y, Vanhille P, Servais A, Bordessoule D, Coindre JP, Hamidou M, Vernant JP, Veyradier A, Coppo P, French Thrombotic Microangiopathies Reference Centre (2014) Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood 124:204–210PubMedCrossRefGoogle Scholar
  26. 26.
    Espié E, Grimont F, Mariani-Kurkdjian P, Bouvet P, Haeghebaert S, Filliol I, Loirat C, Decludt B, Minh NN, Vaillant V, de Valk H (2008) Surveillance of hemolytic uremic syndrome in children less than 15 years of age, a system to monitor O157 and non-O157 Shiga toxin-producing Escherichia coli infections in France, 1996–2006. Pediatr Infect Dis J 27:595–601PubMedCrossRefGoogle Scholar
  27. 27.
    Rosales A, Hofer J, Zimmerhackl LB, Jungraithmayr TC, Riedl M, Giner T, Strasak A, Orth-Höller D, Würzner R, Karch H, German-Austrian HUS Study Group (2012) Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis 54:1413–1421PubMedCrossRefGoogle Scholar
  28. 28.
    Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS (2013) Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol 28:2097–2105PubMedCrossRefGoogle Scholar
  29. 29.
    Sharma AP, Greenberg CR, Prasad AN, Prasad C (2007) Hemolytic uremic syndrome (HUS) secondary to cobalamin C (cblC) disorder. Pediatr Nephrol 22:2097–2103PubMedCrossRefGoogle Scholar
  30. 30.
    Menni F, Testa S, Guez S, Chiarelli G, Alberti L, Esposito S (2012) Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria. Pediatr Nephrol 27:1401–1405PubMedCrossRefGoogle Scholar
  31. 31.
    Cornec-Le Gall E, Delmas Y, De Parscau L, Doucet L, Ogier H, Benoist JF, Fremeaux-Bacchi V, Le Meur Y (2013) Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency. Am J Kidney Dis 63:119–123PubMedCrossRefGoogle Scholar
  32. 32.
    Kömhoff M, Roofthooft MT, Westra D, Teertstra TK, Losito A, van de Kar NC, Berger RM (2013) Combined pulmonary hypertension and renal thrombotic microangiopathy in cobalamin C deficiency. Pediatrics 132:e540–e544PubMedCrossRefGoogle Scholar
  33. 33.
    Fischer S, Huemer M, Baumgartner M, Deodato F, Ballhausen D, Boneh A, Burlina AB, Cerone R, Garcia P, Gökçay G, Grünewald S, Häberle J, Jaeken J, Ketteridge D, Lindner M, Mandel H, Martinelli D, Martins EG, Schwab KO, Gruenert SC, Schwahn BC, Sztriha L, Tomaske M, Trefz F, Vilarinho L, Rosenblatt DS, Fowler B, Dionisi-Vici C (2014) Clinical presentation and outcome in a series of 88 patients with the cblC defect. J Inherit Metab Dis 37:831–840PubMedCrossRefGoogle Scholar
  34. 34.
    Huemer M, Scholl-Bürgi S, Hadaya K, Kern I, Beer R, Seppi K, Fowler B, Baumgartner MR, Karall D (2014) Three new cases of late-onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy. Orphanet J Rare Dis 9:161PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Peffault de Latour R, Xhaard A, Fremeaux-Bacchi V, Coppo P, Fischer AM, Helley D, Socié G (2013) Successful use of eculizumab in a patient with post-transplant thrombotic microangiopathy. Br J Haematol 161:279–280PubMedCrossRefGoogle Scholar
  36. 36.
    Jodele S, Licht C, Goebel J, Dixon BP, Zhang K, Sivakumaran TA, Davies SM, Pluthero FG, Lu L, Laskin BL (2013) Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Blood 122:2003–2007PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Jodele S, Fukuda T, Vinks A, Mizuno K, Laskin BL, Goebel J, Dixon BP, Teusink A, Pluthero FG, Lu L, Licht C, Davies SM (2014) Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Biol Blood Marrow Transplant 20:518–525PubMedCrossRefGoogle Scholar
  38. 38.
    Szilágyi A, Kiss N, Bereczki C, Tálosi G, Rácz K, Túri S, Györke Z, Simon E, Horváth E, Kelen K, Reusz GS, Szabó AJ, Tulassay T, Prohászka Z (2013) The role of complement in Streptococcus pneumoniae-associated haemolytic uraemic syndrome. Nephrol Dial Transplant 28:2237–2245PubMedCrossRefGoogle Scholar
  39. 39.
    Gilbert RD, Nagra A, Haq MR (2013) Does dysregulated complement activation contribute to haemolytic uraemic syndrome secondary to Streptococcus pneumoniae? Med Hypotheses 81:400–403PubMedCrossRefGoogle Scholar
  40. 40.
    Kokame K, Nobe Y, Kokubo Y, Okayama A, Miyata T (2005) FRETS-VWF73, a first fluorogenic substrate for ADAMTS13 assay. Br J Haematol 129:93–100PubMedCrossRefGoogle Scholar
  41. 41.
    Mackie I, Langley K, Chitolie A, Liesner R, Scully M, Machin S, Peyvandi F (2013) Discrepancies between ADAMTS13 activity assays in patients with thrombotic microangiopathies. Thromb Haemost 109:488–496PubMedCrossRefGoogle Scholar
  42. 42.
    Thouzeau S, Capdenat S, Stépanian A, Coppo P, Veyradier A (2013) Evaluation of a commercial assay for ADAMTS13 activity measurement. Thromb Haemost 110:852–853PubMedCrossRefGoogle Scholar
  43. 43.
    Noris M, Bucchioni S, Galbusera M, Donadelli R, Bresin E, Castelletti F, Caprioli J, Brioschi S, Scheiflinger F, Remuzzi G, Noris M, Bucchioni S, Galbusera M, Donadelli R, Bresin E, Castelletti F, Caprioli J, Brioschi S, Scheiflinger F, Remuzzi G, International Registry of Recurrent and Familial HUS/TTP (2005) Complement factor H mutation in familial thrombotic thrombocytopenic purpura with ADAMTS13 deficiency and renal involvement. J Am Soc Nephrol 16:1177–1183PubMedCrossRefGoogle Scholar
  44. 44.
    Keir LS, Saleem MA (2014) Current evidence for the role of complement in the pathogenesis of Shiga toxin haemolytic uraemic syndrome. Pediatr Nephrol 29:1895–1902PubMedCrossRefGoogle Scholar
  45. 45.
    Poolpol K, Orth-Höller D, Speth C, Zipfel PF, Skerka C, de Córdoba SR, Brockmeyer J, Bielaszewska M, Würzner R (2014) Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. Mol Immunol 58:77–84PubMedCrossRefGoogle Scholar
  46. 46.
    Guigonis V, Frémeaux-Bacchi V, Giraudier S, Favier R, Borderie D, Massy Z, Mougenot B, Rosenblatt DS, Deschênes G (2005) Late-onset thrombocytic microangiopathy caused by cblC disease: association with a factor H mutation. Am J Kidney Dis 45:588–595PubMedCrossRefGoogle Scholar
  47. 47.
    Bouts AH, Roofthooft MT, Salomons GS (2010) CD46-associated atypical hemolytic uremic syndrome with uncommon course caused by cblC deficiency. Pediatr Nephrol 25:2547–2548PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Loirat C, Saland J, Bitzan M (2012) Management of hemolytic uremic syndrome. Presse Med 41:e115–e135PubMedCrossRefGoogle Scholar
  49. 49.
    Ståhl AL, Vaziri-Sani F, Heinen S, Kristoffersson AC, Gydell KH, Raafat R, Gutierrez A, Beringer O, Zipfel PF, Karpman D (2008) Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation. Blood 111:5307–5315PubMedCrossRefGoogle Scholar
  50. 50.
    Dragon-Durey MA, Sethi SK, Bagga A, Blanc C, Blouin J, Ranchin B, André JL, Takagi N, Cheong HI, Hari P, Le Quintrec M, Niaudet P, Loirat C, Fridman WH, Frémeaux-Bacchi V (2010) Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol 21:2180–2187PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Hofer J, Janecke AR, Zimmerhackl LB, Riedl M, Rosales A, Giner T, Cortina G, Haindl CJ, Petzelberger B, Pawlik M, Jeller V, Vester U, Gadner B, van Husen M, Moritz ML, Würzner R, Jungraithmayr T, German-Austrian HUS Study Group (2013) Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 8:407–415PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS, Saini H, Kotresh ST, Ali U, Bhatia D, Ohri A, Kumar M, Agarwal I, Gulati S, Anand K, Vijayakumar M, Sinha R, Sethi S, Salmona M, George A, Bal V, Singh G, Dinda AK, Hari P, Rath S, Dragon-Durey MA, Bagga A (2014) Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 85:1151–1160PubMedCrossRefGoogle Scholar
  53. 53.
    Loirat C, Fremeaux-Bacchi V (2014) Anti-factor H autoantibody-associated haemolytic uremic syndrome: the earlier diagnosed and treated, the better. Kidney Int 85:1019–1022PubMedCrossRefGoogle Scholar
  54. 54.
    Hofer J, Giner T, Józsi M (2014) Complement factor h-antibody-associated hemolytic uremic syndrome: pathogenesis, clinical presentation, and treatment. Semin Thromb Hemost 40:431–443PubMedCrossRefGoogle Scholar
  55. 55.
    Malina M, Gulati A, Bagga A, Majid MA, Simkova E, Schaefer F (2013) Peripheral gangrene in children with atypical hemolytic uremic syndrome. Pediatrics 131:e331–e335PubMedCrossRefGoogle Scholar
  56. 56.
    Westland R, Bodria M, Carrea A, Lata S, Scolari F, Fremeaux-Bacchi V, D'Agati VD, Lifton RP, Gharavi AG, Ghiggeri GM, Sanna-Cherchi S (2014) Phenotypic expansion of DGKE-associated diseases. J Am Soc Nephrol 25:1408–1414PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Sánchez Chinchilla D, Pinto S, Hoppe B, Adragna M, Lopez L, Justa Roldan ML, Peña A, Lopez Trascasa M, Sánchez-Corral P, Rodríguez de Córdoba S (2014) Complement mutations in diacylglycerol kinase-ε-associated atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 9:1611–1619PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Fremeaux-Bacchi V, Moulton EA, Kavanagh D, Dragon-Durey MA, Blouin J, Caudy A, Arzouk N, Cleper R, Francois M, Guest G, Pourrat J, Seligman R, Fridman WH, Loirat C, Atkinson JP (2006) Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome. J Am Soc Nephrol 17:2017–2025PubMedCrossRefGoogle Scholar
  59. 59.
    Bresin E, Rurali E, Caprioli J, Sanchez-Corral P, Fremeaux-Bacchi V, Rodriguez de Cordoba S, Pinto S, Goodship TH, Alberti M, Ribes D, Valoti E, Remuzzi G, Noris M, European Working Party on Complement Genetics in Renal Diseases (2013) Combined complement gene mutations in atypical hemolytic uremic syndrome influence clinical phenotype. J Am Soc Nephrol 24:475–486PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Bu F, Maga T, Meyer NC, Wang K, Thomas CP, Nester CM, Smith RJ (2014) Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome. J Am Soc Nephrol 25:55–64PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Feng S, Eyler SJ, Zhang Y, Maga T, Nester CM, Kroll MH, Smith RJ, Afshar-Kharghan V (2013) Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome. Blood 22:1487–1493CrossRefGoogle Scholar
  62. 62.
    Moore I, Strain L, Pappworth I, Kavanagh D, Barlow PN, Herbert AP, Schmidt CQ, Staniforth SJ, Holmes LV, Ward R, Morgan L, Goodship TH, Marchbank KJ (2010) Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. Blood 115:379–387PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Holmes LV, Strain L, Staniforth SJ, Moore I, Marchbank K, Kavanagh D, Goodship JA, Cordell HJ, Goodship TH (2013) Determining the population frequency of the CFHR3/CFHR1 deletion at 1q32. PLoS One 8:e60352PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Quaggin SE (2013) DGKE and atypical HUS. Nat Genet 45:475–476PubMedCrossRefGoogle Scholar
  65. 65.
    Geerdink LM, Westra D, van Wijk JA, Dorresteijn EM, Lilien MR, Davin JC, Kömhoff M, Van Hoeck K, van der Vlugt A, van den Heuvel LP, van de Kar NC (2012) Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol 27:1283–1291PubMedCentralPubMedCrossRefGoogle Scholar
  66. 66.
    Cataland SR, Holers VM, Geyer S, Yang S, Wu HM (2014) Biomarkers of the alternative pathway and terminal complement activity at presentation confirms the clinical diagnosis of aHUS and differentiates aHUS from TTP. Blood 123:3733–3738PubMedCrossRefGoogle Scholar
  67. 67.
    Noris M, Galbusera M, Gastoldi S, Macor P, Banterla F, Bresin E, Tripodo C, Bettoni S, Donadelli R, Valoti E, Tedesco F, Amore A, Coppo R, Ruggenenti P, Gotti E, Remuzzi G (2014) Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood 124:1715–1726PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Volokhina EB, Westra D, van der Velden TJ, van de Kar NC, Mollnes TE, van den Heuvel LP (2014) Complement activation patterns in atypical hemolytic uremic syndrome during acute phase and in remission. Clin Exp Immunol. doi: 10.1111/cei.12426 PubMedCentralPubMedGoogle Scholar
  69. 69.
    Watson R, Lindner S, Bordereau P, Hunze EM, Tak F, Ngo S, Zipfel PF, Skerka C, Dragon-Durey MA, Marchbank KJ (2014) Standardisation of the factor H autoantibody assay. Immunobiology 219:9–16PubMedCrossRefGoogle Scholar
  70. 70.
    Le Quintrec M, Zuber J, Moulin B, Kamar N, Jablonski M, Lionet A, Chatelet V, Mousson C, Mourad G, Bridoux F, Cassuto E, Loirat C, Rondeau E, Delahousse M, Frémeaux-Bacchi V (2013) Complement genes strongly predict recurrence and graft outcome in adult renal transplant recipients with atypical hemolytic and uremic syndrome. Am J Transplant 13:663–675PubMedCrossRefGoogle Scholar
  71. 71.
    Zuber J, Le Quintrec M, Krid S, Bertoye C, Gueutin V, Lahoche A, Heyne N, Ardissino G, Chatelet V, Noël LH, Hourmant M, Niaudet P, Frémeaux-Bacchi V, Rondeau E, Legendre C, Loirat C, French Study Group for Atypical HUS (2012) Eculizumab for atypical hemolytic uremic syndrome recurrence in renal transplantation. Am J Transplant 12:3337–3354PubMedCrossRefGoogle Scholar
  72. 72.
    Khandelwal P, Sinha A, Hari P, Bansal VK, Dinda AK, Bagga A (2014) Outcomes of renal transplant in patients with anti-complement factor H antibody-associated hemolytic uremic syndrome. Pediatr Transplant 18:E134–E139PubMedCrossRefGoogle Scholar
  73. 73.
    Sinibaldi S, Guzzo I, Piras R, Bresin E, Emma F, Dello Strologo L (2013) Post-transplant recurrence of atypical hemolytic uremic syndrome in a patient with thrombomodulin mutation. Pediatr Transplant 17:E177–E181PubMedCrossRefGoogle Scholar
  74. 74.
    Saland JM, Ruggenenti P, Remuzzi G, Consensus Study Group (2009) Liver–kidney transplantation to cure atypical hemolytic uremic syndrome. J Am Soc Nephrol 20:940–949PubMedCrossRefGoogle Scholar
  75. 75.
    European Medicines Agency. Soliris (eculizumab): EU summary of product characteristics.Mar14 human/000791/WC500054208.pdf
  76. 76.
    Alexion Pharmaceuticals Inc. Soliris_ (eculizumab): US prescribing information.4/2014. docs/label/2014/125166s368s380lbl.pdf
  77. 77.
    Licht C, Greenbaum LA, Muus P, Babu S, Bedrosian CL, Cohen D, Delmas Y, Douglas K, Furman R, Gaber O, Goodship T, Herthelius M, Hourmant M, Legendre C, Remuzzi G, Sheerin N, Trivelli A, Loirat C (2015) Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome: 2-year results from extensions of phase 2 studies. Kidney Int. doi: 10.1038/ki.2014.423 PubMedCentralPubMedGoogle Scholar
  78. 78.
    Legendre C, Greenbaum L, Sheerin N, Cohen D, Gaber A, Eitner F, Delmas Y, Furman R, Feldkamp T, Fouque D, Bedrosian C, Loirat C (2013) Eculizumab efficacy in aHUS patients with progressing TMA, with or without prior renal transplant [Abstract]. Am J Transplant 13:278–279Google Scholar
  79. 79.
    Greenbaum LA, Fila M, Tsimaratos M, Ardissino G, Al-Akash SI, Evans J, Henning P, Lieberman KV, Maringhini S, Pape L, Rees L, Van De Kar N, Van De Walle J, Ogawa M, Bedrosian CL, Licht C (2013) Eculizumab inhibits thrombotic microangiopathy and improves renal function in pediatric atypical hemolytic uremic syndrome patients [Abstract]. J Am Soc Nephrol 24:821A–822AGoogle Scholar
  80. 80.
    Fakhouri F, Hourmant M, Campistol Plana JM, Cataland SR, Espinosa M, Gaber AO, Menne J, Minetti EE, Provot F, Rondeau E, Ruggenenti PL, Weekers LE, Ogawa M, Bedrosian CL, Legendre CM (2014) Eculizumab inhibits thrombotic microangiopathy, and improves renal function in adult atypical hemolytic uremic syndrome patients: 1-Year Update [Abstract]. J Am Soc Nephrol 25:751AGoogle Scholar
  81. 81.
    Loirat C, Legendre CM, Ogawa M, Bedrosian CL, Kincaid J, Fakhouri F (2014) Safety and efficacy of eculizumab in adult aHUS patients, with or without a history of renal transplant [Abstract]. J Am Soc Nephrol 25:754Google Scholar
  82. 82.
    Rathbone J, Kaltenthaler E, Richards A, Tappenden P, Bessey A, Cantrell A (2013) A systematic review of eculizumab for atypical haemolytic uraemic syndrome (aHUS). BMJ Open 3:e003573PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Vilalta R, Lara E, Madrid A, Chocron S, Muñoz M, Casquero A, Nieto J (2012) Long-term eculizumab improves clinical outcomes in atypical hemolytic uremic syndrome. Pediatr Nephrol 27:2323–2326PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Cayci FS, Cakar N, Hancer VS, Uncu N, Acar B, Gur G (2012) Eculizumab therapy in a child with hemolytic uremic syndrome and CFI mutation. Pediatr Nephrol 27:2327–2331PubMedCrossRefGoogle Scholar
  85. 85.
    Giordano M, Castellano G, Messina G, Divella C, Bellantuono R, Puteo F, Colella V, Depalo T, Gesualdo L (2012) Preservation of renal function in atypical hemolytic uremic syndrome by eculizumab: a case report. Pediatrics 130:e1385–e1388PubMedCrossRefGoogle Scholar
  86. 86.
    Besbas N, Gulhan B, Karpman D, Topaloglu R, Duzova A, Korkmaz E, Ozaltin F (2013) Neonatal onset atypical hemolytic uremic syndrome successfully treated with eculizumab. Pediatr Nephrol 28:155–158PubMedCrossRefGoogle Scholar
  87. 87.
    Gulleroglu K, Fidan K, Hançer VS, Bayrakci U, Baskin E, Soylemezoglu O (2013) Neurologic involvement in atypical hemolytic uremic syndrome and successful treatment with eculizumab. Pediatr Nephrol 28:827–830PubMedCrossRefGoogle Scholar
  88. 88.
    Gilbert RD, Fowler DJ, Angus E, Hardy SA, Stanley L, Goodship TH (2013) Eculizumab therapy for atypical haemolytic uraemic syndrome due to a gain-of-function mutation of complement factor B. Pediatr Nephrol 28:1315–1318PubMedCrossRefGoogle Scholar
  89. 89.
    Vaisbich MH, Henriques Ldos S, Watanabe A, Pereira LM, Metran CC, Malheiros DA, Modanez F, Silva JD, Vieira S, Macedo AC, Massarope B, Furusawa EA, Schvartsman BG (2013) Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature. J Bras Nefrol 35:237–241PubMedCrossRefGoogle Scholar
  90. 90.
    Hu H, Nagra A, Haq MR, Gilbert RD (2013) Eculizumab in atypical haemolytic uraemic syndrome with severe cardiac and neurological involvement. Pediatr Nephrol 29:1103–1106PubMedCrossRefGoogle Scholar
  91. 91.
    Christmann M, Hansen M, Bergmann C, Schwabe D, Brand J, Schneider W (2014) Eculizumab as first-line therapy for atypical hemolytic uremic syndrome. Pediatrics 133:e1759–e1763PubMedCrossRefGoogle Scholar
  92. 92.
    Michaux K, Bacchetta J, Javouhey E, Cochat P, Frémaux-Bacchi V, Sellier-Leclerc AL (2014) Eculizumab in neonatal hemolytic uremic syndrome with homozygous factor H deficiency. Pediatr Nephrol 29:2415–2419PubMedCrossRefGoogle Scholar
  93. 93.
    Fakhouri F, Delmas Y, Provot F, Barbet C, Karras A, Makdassi R, Courivaud C, Rifard K, Servais A, Allard C, Besson V, Cousin M, Châtelet V, Goujon JM, Coindre JP, Laurent G, Loirat C, Frémeaux-Bacchi V (2014) Insights from the use in clinical practice of eculizumab in adult patients with atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of 19 cases. Am J Kidney Dis 63:40–48PubMedCrossRefGoogle Scholar
  94. 94.
    Hodgkins KS, Bobrowski AE, Lane JC, Langman CB (2012) Clinical grand rounds: atypical hemolytic uremic syndrome. Am J Nephrol 35:394–394PubMedCrossRefGoogle Scholar
  95. 95.
    Alachkar N, Bagnasco SM, Montgomery RA (2012) Eculizumab for the treatment of two recurrences of atypical hemolytic uremic syndrome in a kidney allograft. Transpl Int 25:e93–e95PubMedCrossRefGoogle Scholar
  96. 96.
    Reuter S, Heitplatz B, Pavenstädt H, Suwelack B (2013) Successful long-term treatment of TMA with eculizumab in a transplanted patient with atypical hemolytic uremic syndrome due to MCP mutation. Transplantation 96:e74–e76PubMedCrossRefGoogle Scholar
  97. 97.
    Zuber J, Le Quintrec M, Morris H, Frémeaux-Bacchi V, Loirat C, Legendre C (2013) Targeted strategies in the prevention and management of atypical HUS recurrence after kidney transplantation. Transplant Rev (Orlando) 27:117–125CrossRefGoogle Scholar
  98. 98.
    Xie L, Nester CM, Reed AI, Zhang Y, Smith RJ, Thomas CP (2012) Tailored eculizumab therapy in the management of complement factor H-mediated atypical hemolytic uremic syndrome in an adult kidney transplant recipient: a case report. Transplant Proc 44:3037–3040PubMedCrossRefGoogle Scholar
  99. 99.
    Pelicano MB, de Córdoba SR, Diekmann F, Saiz M, Herrero S, Oppenheimer F, Campistol JM (2013) Anti-C5 as prophylactic therapy in atypical hemolytic uremic syndrome in living-related kidney transplantation. Transplantation 96:e26–e29PubMedCrossRefGoogle Scholar
  100. 100.
    Román-Ortiz E, Mendizabal Oteiza S, Pinto S, López-Trascasa M, Sánchez-Corral P, Rodríguez de Cordoba S (2014) Eculizumab long-term therapy for pediatric renal transplant in aHUS with CFH/CFHR1 hybrid gene. Pediatr Nephrol 29:149–153PubMedCrossRefGoogle Scholar
  101. 101.
    Békássy ZD, Kristoffersson AC, Cronqvist M, Roumenina LT, Rybkine T, Vergoz L, Hue C, Fremeaux-Bacchi V, Karpman D (2013) Eculizumab in an anephric patient with atypical haemolytic uraemic syndrome and advanced vascular lesions. Nephrol Dial Transplant 28:2899–2907PubMedCrossRefGoogle Scholar
  102. 102.
    Walport MJ (2001) Complement. First of two parts. N Engl J Med 344:1058–1066PubMedCrossRefGoogle Scholar
  103. 103.
    Nolan TM, Nissen MD, Naz A, Shepard J, Bedell L, Hohenboken M, Odrljin T, Dull PM (2013) Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age. Hum Vaccin Immunother 10:280–289PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Abdelnour A, Silas PE, Lamas MR, Aragón CF, Chiu NC, Chiu CH, Acuña TH, Castrejón Tde L, Izu A, Odrljin T, Smolenov I, Hohenboken M, Dull PM (2014) Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants. Vaccine 32:965–972PubMedCrossRefGoogle Scholar
  105. 105.
    Zlamy M, Hofer J, Elias J, Vogel U, Frosch M, Jungraithmayr T, Zimmerhackl LB, Prelog M (2012) Immunogenicity of meningococcus C vaccination in a patient with atypical hemolytic uremic syndrome (aHUS) on eculizumab therapy. Pediatr Transplant 16:E246–E250PubMedCrossRefGoogle Scholar
  106. 106.
    Struijk GH, Bouts AH, Rijkers GT, Kuin EA, ten Berge IJ, Bemelman FJ (2013) Meningococcal sepsis complicating eculizumab treatment despite prior vaccination. Am J Transplant 13:819–820PubMedCrossRefGoogle Scholar
  107. 107.
    Hillmen P, Muus P, Röth A, Elebute MO, Risitano AM, Schrezenmeier H, Szer J, Browne P, Maciejewski JP, Schubert J, Urbano-Ispizua A, de Castro C, Socié G, Brodsky RA (2013) Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol 162:62–73PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.
    Sana G, Dragon-Durey MA, Charbit M, Bouchireb K, Rousset-Rouvière C, Bérard E, Salomon R, Frémeaux-Bacchi V, Niaudet P, Boyer O (2014) Long-term remission of atypical HUS with anti-factor H antibodies after cyclophosphamide pulses. Pediatr Nephrol 29:75–83PubMedCrossRefGoogle Scholar
  109. 109.
    Noone D, Waters A, Pluthero FG, Geary DF, Kirschfink M, Zipfel PF, Licht C (2014) Successful treatment of DEAP-HUS with eculizumab. Pediatr Nephrol 29:841–851PubMedCrossRefGoogle Scholar
  110. 110.
    Diamante Chiodini B, Davin JC, Corazza F, Khaldi K, Dahan K, Ismaili K, Adams B (2014) Eculizumab in anti-factor h antibodies associated with atypical hemolytic uremic syndrome. Pediatrics 133:e1764–e1768PubMedCrossRefGoogle Scholar
  111. 111.
    Green H, Harari E, Davidovits M, Blickstein D, Grossman A, Gafter U, Gafter-Gvili A (2014) Atypical HUS due to factor H antibodies in an adult patient successfully treated with eculizumab. Ren Fail 36:1119–1121PubMedCrossRefGoogle Scholar
  112. 112.
    Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, Macher MA, Niaudet P, Guest G, Boudailliez B, Bouissou F, Deschenes G, Gie S, Tsimaratos M, Fischbach M, Morin D, Nivet H, Alberti C, Loirat C, French Society of Pediatric Nephrology (2007) Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 18:2392–2400PubMedCrossRefGoogle Scholar
  113. 113.
    Réti M, Farkas P, Csuka D, Rázsó K, Schlammadinger Á, Udvardy ML, Madách K, Domján G, Bereczki C, Reusz GS, Szabó AJ, Prohászka Z (2012) Complement activation in thrombotic thrombocytopenic purpura. J Thromb Haemost 10:791–798PubMedCrossRefGoogle Scholar
  114. 114.
    Noris M, Mescia F, Remuzzi G (2012) STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 8:622–633PubMedCrossRefGoogle Scholar
  115. 115.
    Wu TC, Yang S, Haven S, Holers VM, Lundberg AS, Wu H, Cataland SR (2013) Complement activation and mortality during an acute episode of thrombotic thrombocytopenic purpura. J Thromb Haemost 11:1925–1927PubMedGoogle Scholar
  116. 116.
    Westwood JP, Langley K, Heelas E, Machin SJ, Scully M (2014) Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura. Br J Haematol 164:858–856PubMedCentralPubMedCrossRefGoogle Scholar
  117. 117.
    Tati R, Kristoffersson AC, Ståhl AL, Rebetz J, Wang L, Licht C, Motto D, Karpman D (2013) Complement activation associated with ADAMTS13 deficiency in human and murine thrombotic microangiopathy. J Immunol 191:2184–2193PubMedCentralPubMedCrossRefGoogle Scholar
  118. 118.
    Chapin J, Weksler B, Magro C, Laurence J (2012) Eculizumab in the treatment of refractory idiopathic thrombotic thrombocytopenic purpura. Br J Haematol 157:772–774PubMedCrossRefGoogle Scholar
  119. 119.
    Tsai E, Chapin J, Laurence JC, Tsai HM (2013) Use of eculizumab in the treatment of a case of refractory, ADAMTS13-deficient thrombotic thrombocytopenic purpura: additional data and clinical follow-up. Br J Haematol 162:558–559PubMedCentralPubMedCrossRefGoogle Scholar
  120. 120.
    Belingheri M, Possenti I, Tel F, Paglialonga F, Testa S, Salardi S, Ardissino G (2014) Cryptic activity of atypical hemolytic uremic syndrome and eculizumab treatment. Pediatrics 133:e1769–e1771PubMedCrossRefGoogle Scholar
  121. 121.
    Ariceta G, Arrizabalaga B, Aguirre M, Morteruel E, Lopez-Trascasa M (2012) Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants. Am J Kidney Dis 59:707–710PubMedCrossRefGoogle Scholar
  122. 122.
    Ardissino G, Tel F, Testa S, Marzano AV, Lazzari R, Salardi S, Edefonti A (2013) Skin involvement in atypical hemolytic uremic syndrome. Am J Kidney Dis 63:652–655PubMedCrossRefGoogle Scholar
  123. 123.
    Ohanian M, Cable C, Halka K (2011) Eculizumab safely reverses neurologic impairment and eliminates need for dialysis in severe atypical hemolytic uremic syndrome. Clin Pharmacol 3:5–12PubMedCentralPubMedGoogle Scholar
  124. 124.
    Salem G, Flynn JM, Cataland SR (2013) Profound neurological injury in a patient with atypical hemolytic uremic syndrome. Ann Hematol 92:557–558PubMedCrossRefGoogle Scholar
  125. 125.
    Beye F, Malbranche C, Tramecon D, Pernot C, Zanetta G, Mousson C, Guignard MH, Lazzarotti A (2013) Eculizumab: effectiveness of a shortened dosing schedule in the treatment of atypical haemolytic uremic syndrome of unknown origin. Therapie 68:119–122PubMedCrossRefGoogle Scholar
  126. 126.
    Pu JJ, Sido A (2014) Successful discontinuation of eculizumab therapy in a patient with aHUS. Ann Hematol 93:1423–1425PubMedCrossRefGoogle Scholar
  127. 127.
    Chaudhary P, Hepgur M, Sarkissian S, Smith RJ, Weitz IC (2014) Atypical haemolytic-uraemic syndrome due to heterozygous mutations of CFH/CFHR1-3 and complement factor H 479. Blood Transfus 12:111–113PubMedCentralPubMedGoogle Scholar
  128. 128.
    Loirat C, Macher MA, Elmaleh-Berges M, Kwon T, Deschênes G, Goodship TH, Majoie C, Davin JC, Blanc R, Savatovsky J, Moret J, Fremeaux-Bacchi V (2010) Non-atheromatous arterial stenoses in atypical haemolytic uraemic syndrome associated with complement dysregulation. Nephrol Dial Transplant 25:3421–3425PubMedCrossRefGoogle Scholar
  129. 129.
    Davin JC, Majoie C, Groothoff J, Gracchi V, Bouts A, Goodship TH, Loirat C (2011) Prevention of large-vessel stenoses in atypical hemolytic uremic syndrome associated with complement dysregulation. Pediatr Nephrol 26:155–157PubMedCentralPubMedCrossRefGoogle Scholar
  130. 130.
    Ažukaitis K, Loirat C, Malina M, Adomaitienė I, Jankauskienė A (2013) Macrovascular involvement in a child with atypical hemolytic uremic syndrome. Pediatr Nephrol 29:1273–1277PubMedCrossRefGoogle Scholar
  131. 131.
    Gargau M, Azancot M, Ramos R, Sanchez-Corral P, Montero MA, Seron D (2012) Early treatment with eculizumab may be beneficial in atypical haemolytic uraemic syndrome. Clin Kidney J 5:1–3CrossRefGoogle Scholar
  132. 132.
    Kim JJ, Simon CW, Reid CJ (2012) Eculizumab in atypical haemolytic-uraemic syndrome allows cessation of plasma exchange and dialysis. Clin Kidney J 0:1–3CrossRefGoogle Scholar
  133. 133.
    Povey H, Vundru R, Junglee N, Jibani M (2013) Renal recovery with eculizumab in atypical hemolytic uremic syndrome following prolonged dialysis. Clin Nephrol 82:326–331Google Scholar
  134. 134.
    Noris M, Remuzzi G (2014) Cardiovascular complications in atypical haemolytic uraemic syndrome. Nat Rev Nephrol 10:174–180PubMedCrossRefGoogle Scholar
  135. 135.
    Nishimura J, Yamamoto M, Hayashi S, Ohyashiki K, Ando K, Brodsky AL, Noji H, Kitamura K, Eto T, Takahashi T, Masuko M, Matsumoto T, Wano Y, Shichishima T, Shibayama H, Hase M, Li L, Johnson K, Lazarowski A, Tamburini P, Inazawa J, Kinoshita T, Kanakura Y (2014) Genetic variants in C5 and poor response to eculizumab. N Engl J Med 370:632–639PubMedCrossRefGoogle Scholar
  136. 136.
    Cugno M, Gualtierotti R, Possenti I, Testa S, Tel F, Griffini S, Grovetti E, Tedeschi S, Salardi S, Cresseri D, Messa P, Ardissino G (2014) Complement functional tests for monitoring eculizumab treatment in patients with atypical hemolytic uremic syndrome. J Thromb Haemost 12:1440–1448PubMedCrossRefGoogle Scholar
  137. 137.
    Mache CJ, Acham-Roschitz B, Frémeaux-Bacchi V, Kirschfink M, Zipfel PF, Roedl S, Vester U, Ring E (2009) Complement inhibitor eculizumab in atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 4:1312–1316PubMedCentralPubMedCrossRefGoogle Scholar
  138. 138.
    Köse O, Zimmerhackl LB, Jungraithmayr T, Mache C, Nürnberger J (2010) New treatment options for atypical hemolytic uremic syndrome with the complement inhibitor eculizumab. Semin Thromb Hemost 36:669–672PubMedCrossRefGoogle Scholar
  139. 139.
    Carr R, Cataland SR (2013) Relapse of aHUS after discontinuation of therapy with eculizumab in a patient with aHUS and factor H mutation. Ann Hematol 92:845–846PubMedCrossRefGoogle Scholar
  140. 140.
    Delmas Y, Bordes C, Loirat C, Fremeaux-Bacchi V, Combe C (2013) Post-partum atypical haemolytic uraemic syndrome treated with eculizumab: terminal complement activity assessment in clinical practice. Clin Kidney J 6:243–244PubMedCentralPubMedCrossRefGoogle Scholar
  141. 141.
    Cañigral C, Moscardó F, Castro C, Pajares A, Lancharro A, Solves P, de la Rubia J, Carpio N, Sanz MA (2014) Eculizumab for the treatment of pregnancy-related atypical hemolytic uremic syndrome. Ann Hematol 93:1421–1422PubMedGoogle Scholar
  142. 142.
    Ardissino G, Testa S, Possenti I, Tel F, Paglialonga F, Salardi S, Tedeschi S, Belingheri M, Cugno M (2014) Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am J Kidney Dis 64:633–637PubMedCrossRefGoogle Scholar
  143. 143.
    Verhave JC, Westra D, van Hamersvelt HW, van Helden M, van de Kar NC, Wetzels JF (2013) Living kidney transplantation in adult patients with atypical haemolytic uraemic syndrome. Neth J Med 71:342–347PubMedGoogle Scholar
  144. 144.
    Forbes TA, Bradbury MG, Goodship TH, McKiernan PJ, Milford DV (2013) Changing strategies for organ transplantation in atypical haemolytic uraemic syndrome: a tertiary case series. Pediatr Transplant 17:E93–E99PubMedCrossRefGoogle Scholar
  145. 145.
    Saland J (2014) Liver–kidney transplantation to cure atypical HUS: still an option post-eculizumab? Pediatr Nephrol 29:329–332PubMedCrossRefGoogle Scholar
  146. 146.
    Park SH, Kim GS (2014) Anesthetic management of living donor liver transplantation for complement factor H deficiency hemolytic uremic syndrome: a case report. Korean J Anesthesiol 66:481–485PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2015

Authors and Affiliations

  • Chantal Loirat
    • 1
    Email author
  • 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
  • for HUS International
  1. 1.Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Department of Pediatric NephrologyUniversité Paris Diderot Sorbonne Paris CitéParisFrance
  2. 2.Centre Hospitalier Universitaire de Nantes, Department of Nephrology and ImmunologyITUN and INSERM UMR S-1064NantesFrance
  3. 3.Pediatric Nephrology, Vall d’Hebron HospitalAutonoma University of BarcelonaBarcelonaSpain
  4. 4.Department of Pediatric NephrologyHacettepe University Faculty of MedicineAnkaraTurkey
  5. 5.Division of NephrologyMontreal Children’s Hospital and Mc Gill UniversityMontrealCanada
  6. 6.Department of PediatricsOslo University HospitalOsloNorway
  7. 7.City of the Health and the Science of Turin Health AgencyRegina Margherita Children’s HospitalTurinItaly
  8. 8.Bambino Gesù Children’s HospitalRomeItaly
  9. 9.Department of Paediatric NephrologyGreat North Children’s HospitalNewcastle Upon TyneUK
  10. 10.Department of Pediatrics, Clinical SciencesLund UniversityLundSweden
  11. 11.Soroka University Medical CenterBeer ShevaIsrael
  12. 12.The Ann and Robert H. Lurie Children’s Hospital of Chicago, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  13. 13.Service de Néphrologie, Département de Pédiatrie, CHU Sainte-JustineUniversité de MontréalMontréalCanada
  14. 14.The Hospital for Sick ChildrenTorontoCanada
  15. 15.Departments of Internal Medicine and the Stead Family Department of PediatricsUniversity of IowaIowa CityUSA
  16. 16.Santobono Children’s HospitalNaplesItaly
  17. 17.Department of PediatricsInnsbruck Medical UniversityInnsbruckAustria
  18. 18.Department of Pediatric Nephrology, Amalia Children’s HospitalRadboud University Medical CenterNijmegenThe Netherlands
  19. 19.University Hospital GhentGhentBelgium
  20. 20.Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Laboratory of ImmunologyINSERM UMRS 1138ParisFrance

Personalised recommendations