Pediatric Nephrology

, Volume 32, Issue 6, pp 1081–1087 | Cite as

Successful discontinuation of eculizumab under immunosuppressive therapy in DEAP-HUS

  • Agnes Hackl
  • Rasmus Ehren
  • Michael Kirschfink
  • Peter F. Zipfel
  • Bodo B. Beck
  • Lutz T. Weber
  • Sandra HabbigEmail author
Brief Report



Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome (DEAP-HUS), which is characterized by the deficiency of complement-factor H-related (CFHR) plasma proteins and the subsequent formation of autoantibodies against complement factor H (CFH), has been reported to have an adverse outcome in one third of patients. Therapy options include prompt removal of antibodies by plasma exchange and immunosuppressive therapy. Recently, restoration of complement control using the monoclonal antibody eculizumab has been shown to be effective as first- and as second-line therapy in cases of therapy resistance or severe side effects of the applied therapy.


Here, we report a 6-year-old girl with DEAP-HUS and first-line therapy with eculizumab under immunosuppressive therapy with glucocorticoids and mycophenolate mofetil (MMF). This therapy led to a prompt and sustained clinical recovery, to a stable reduction of complement activation, and to a rapid decline in autoantibody titer. A second increase in the autoantibody titer was successfully treated with methylprednisolone and the child remained in remission. After 8.3 months of sustained complement control and 4.5 months of stable antibody suppression, eculizumab was successfully discontinued without any sign of relapse.


To our knowledge, this is the first reported case of a child with DEAP-HUS treated with the combination of eculizumab and immunosuppression as first-line therapy avoiding any HUS- or therapy-related complications and resulting in prompt clinical recovery. Importantly, clinical remission is maintained after discontinuation of eculizumab under stable immunosuppression.


Complement activation Thrombotic microangiopathy Renal failure Child 



A disintegrin and metalloproteinase with thrombospondin-1 motifs (13th member of the family)


Atypical hemolytic uremic syndrome


Anti-nuclear antibodies


Anti-neutrophil cytoplasmic antibodies


Area under the curve


Body surface area


Complement factor H/I/B


Complement factor H-related


Chronic kidney disease


Deficiency of complement factor H-related plasma proteins and complement factor H autoantibody-positive hemolytic uremic syndrome


Diacylglycerol kinase epsilon




Lactate dehydrogenase


Methylmalonic aciduria and homocystinuria type C protein


Mycophenolate mofetil


Mycophenolic acid


Plasma infusions


Renal replacement therapy


Soluble C5b-9




Therapeutic plasma exchange


Compliance with ethical standards


There was no financial support or funding for this study

Conflicts of interest

AH and BBB received fees for invited lectures from Alexion. MK received fees for invited lectures and advisory board meetings from Alexion and for lectures from Euro Diagnostica. PFZ received lecture fees from Alexion. LTW is a member of the Scientific Advisory Board of Alexion. RE and SH declare that they have no conflicts of interest.


  1. 1.
    Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, Coppo R, Emma F, Johnson S, Karpman D, Landau D, Langman CB, Lapeyraque AL, Licht C, Nester C, Pecoraro C, Riedl M, van de Kar NC, Van de Walle J, Vivarelli M, Frémeaux-Bacchi V, HUS International (2016) An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 31:15–39CrossRefPubMedGoogle Scholar
  2. 2.
    Kavanagh D, Goodship T (2010) Genetics and complement in atypical HUS. Pediatr Nephrol 25:2431–2442CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Zipfel PF, Mache C, Müller D, Licht C, Wigger M, Skerka C, European DEAP-HUS Study Group (2010) DEAP-HUS: deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome. Pediatr Nephrol 25:2009–2019CrossRefPubMedGoogle Scholar
  4. 4.
    Józsi M, Licht C, Strobel S, Zipfel SL, Richter H, Heinen S, Zipfel PF, Skerka C (2008) Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood 111:1512–1514CrossRefPubMedGoogle Scholar
  5. 5.
    Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D, Nester CM, Noris M, Pickering MC, Rodríguez de Córdoba S, Roumenina LT, Sethi S, Smith RJ, Participants C (2016) Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. doi: 10.1016/j.kint.2016.10.005 PubMedGoogle Scholar
  6. 6.
    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 368:2169–2181CrossRefPubMedGoogle Scholar
  7. 7.
    Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, Lieberman KV, Maringhini S, Pape L, Rees L, van de Kar NC, Vande Walle J, Ogawa M, Bedrosian CL, Licht C (2016) Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 89:701–711CrossRefPubMedGoogle Scholar
  8. 8.
    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, Indian HUS Registry (2014) Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children. Kidney Int 85:1151–1160CrossRefPubMedGoogle Scholar
  9. 9.
    Khandelwal P, Gupta A, Sinha A, Saini S, Hari P, Dragon Durey MA, Bagga A (2015) Effect of plasma exchange and immunosuppressive medications on antibody titers and outcome in anti-complement factor H antibody-associated hemolytic uremic syndrome. Pediatr Nephrol 30:451–457CrossRefPubMedGoogle Scholar
  10. 10.
    Noone D, Waters A, Pluthero FG, Geary DF, Kirschfink M, Zipfel PF, Licht C (2014) Successful treatment of DEAP-HUS with eculizumab. Pediatr Nephrol 29:841–851CrossRefPubMedGoogle Scholar
  11. 11.
    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 64:633–637CrossRefPubMedGoogle Scholar
  12. 12.
    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–e1768CrossRefPubMedGoogle Scholar
  13. 13.
    Hisano M, Ashida A, Nakano E, Suehiro M, Yoshida Y, Matsumoto M, Miyata T, Fujimura Y, Hattori M (2015) Autoimmune-type atypical hemolytic uremic syndrome treated with eculizumab as first-line therapy. Pediatr Int 57:313–317CrossRefPubMedGoogle Scholar
  14. 14.
    Ardissino G, Possenti I, Tel F, Testa S, Salardi S, Ladisa V (2015) Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update. Am J Kidney Dis 66:172–173CrossRefPubMedGoogle Scholar
  15. 15.
    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 63:40–48CrossRefPubMedGoogle Scholar
  16. 16.
    Fakhouri F, Fila M, Provôt F, Delmas Y, Barbet C, Châtelet V, Rafat C, Cailliez M, Hogan J, Servais A, Karras A, Makdassi R, Louillet F, Coindre JP, Rondeau E, Loirat C, Frémeaux-Bacchi V (2017) Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol 12:50–59CrossRefPubMedGoogle Scholar
  17. 17.
    Johnson S, Stojanovic J, Ariceta G, Bitzan M, Besbas N, Frieling M, Karpman D, 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 29:1967–1978CrossRefPubMedGoogle Scholar
  18. 18.
    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 36:1119–1121CrossRefPubMedGoogle Scholar
  19. 19.
    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 8:407–415CrossRefPubMedGoogle Scholar
  20. 20.
    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 21:2180–2187CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Licht C, Noone D (2014) Treatment of DEAP-HUS—seeking the best strategy. Pediatr Nephrol 29:941–942CrossRefPubMedGoogle Scholar
  22. 22.
    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 219:9–16CrossRefPubMedGoogle Scholar
  23. 23.
    Weber LT (2015) Therapeutic drug monitoring in pediatric renal transplantation. Pediatr Nephrol 30:253–265CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Pediatric Nephrology, Children’s and Adolescents’ HospitalUniversity Hospital of CologneCologneGermany
  2. 2.Institute of ImmunologyUniversity of HeidelbergHeidelbergGermany
  3. 3.Department of Infection BiologyLeibniz Institute for Natural Product Research and Infection BiologyJenaGermany
  4. 4.Friedrich Schiller UniversityJenaGermany
  5. 5.Institute of Human GeneticsUniversity Hospital of CologneCologneGermany
  6. 6.Center for Molecular MedicineUniversity Hospital of CologneCologneGermany

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