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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

Abstract

Background

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.

Diagnosis/treatment

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.

Conclusions

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.

Keywords

Complement activation Thrombotic microangiopathy Renal failure Child 

Abbreviations

ADAMTS13

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

aHUS

Atypical hemolytic uremic syndrome

ANAs

Anti-nuclear antibodies

ANCAs

Anti-neutrophil cytoplasmic antibodies

AUC

Area under the curve

BSA

Body surface area

CFH/CFI/CFB

Complement factor H/I/B

CFHR

Complement factor H-related

CKD

Chronic kidney disease

DEAP-HUS

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

DGKE

Diacylglycerol kinase epsilon

IS

Immunosuppression

LDH

Lactate dehydrogenase

MMACHC

Methylmalonic aciduria and homocystinuria type C protein

MMF

Mycophenolate mofetil

MPA

Mycophenolic acid

PI

Plasma infusions

RRT

Renal replacement therapy

sC5b-9

Soluble C5b-9

THBD

Thrombomodulin

TPE

Therapeutic plasma exchange

Notes

Compliance with ethical standards

Support/funding

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.

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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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