Advertisement

Pediatric Nephrology

, Volume 32, Issue 6, pp 1023–1028 | Cite as

C3 glomerulopathy and eculizumab: a report on four paediatric cases

  • Célia Lebreton
  • Justine Bacchetta
  • Frédérique Dijoud
  • Lucie Bessenay
  • Véronique Fremeaux-Bacchi
  • Anne Laure Sellier-Leclerc
Original Article

Abstract

Background

Eculizumab may be used to treat C3-glomerulopathy (C3G), a rare but severe glomerular disease.

Diagnosis and Treatment

Patients 1, 2 and 3 were diagnosed with nephritic syndrome with alternative complement pathway activation (low C3, C3Nef-positive) and C3G at the age of 9, 13 and 12 years, respectively. Treatment with eculizumab normalized proteinuria within 1, 2 and 7 months, respectively. Proteinuria relapsed when eculizumab was withdrawn, but the re-introduction of eculizumab normalized proteinuria. Patient 4 was diagnosed with C3G at 9 years of age, with progression to end-stage renal disease within 2 years, followed by a first renal transplantation (R-Tx) with early disease recurrence and graft loss within 39 months. After a second R-Tx, she rapidly presented with biological and histological recurrence: therapy with eculizumab was started, with no effect on proteinuria after 5 months, in a complex clinical setting (i.e. association of C3G recurrence, humoral rejection and BK nephritis). Eculizumab was withdrawn due to multiple viral reactivations, but the re-introduction of the drug a few months later enabled a moderate decrease in proteinuria.

Conclusion

These cases illustrate the efficacy of eculizumab, at least on native kidneys, in paediatric C3G. However, larger international studies are warranted to confirm the benefit and safety of eculizumab therapy.

Keywords

C3 glomerulonephritis Paediatrics Eculizumab Recurrence post-transplantation Children 

Notes

Acknowledgements

The authors would like to thank Dr Marie-Nathalie Sarda (Department of Biology, Hospices Civils de Lyon) for her help in local complement assessment, and also Dr Moglie Le Quintrec, Pr Eric Rondeau, Pr Chantal Loirat, Pr Fadi Fakhouri and Dr Sophie Chauvet for their expertise during the French multidisciplinary review of the first two cases.

Compliance with ethical standards

Ethics

The local ethical committee (CPP Lyon Sud Est II) approved this retrospective review of cases (IRB 00009118, session 1/27/2016).

Disclosure of interest

JB received travel grants from Alexion. ALL received travel grants from Alexion and honararia from Alexion (2013, 2014). VFB acts as a scientific advisor for Alexion.

References

  1. 1.
    Sethi S, Fervenza FC (2012) Membranoproliferative glomerulonephritis—a new look at an old entity. N Engl J Med 366:1119–1131CrossRefPubMedGoogle Scholar
  2. 2.
    Bomback AS, Appel GB (2012) Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol 8:634–642CrossRefPubMedGoogle Scholar
  3. 3.
    Bauters T, Bordon V, Robays H, Benoit Y, Dhooge C (2012) Successful use of eculizumab in a pediatric patient treated for paroxysmal nocturnal hemoglobinuria. J Pediatr Hematol Oncol 34:e346–e348CrossRefPubMedGoogle Scholar
  4. 4.
    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
  5. 5.
    Bomback AS (2014) Eculizumab in the treatment of membranoproliferative glomerulonephritis. Nephron Clin Pract 128:270–276CrossRefPubMedGoogle Scholar
  6. 6.
    Servais A, Noël LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grünfeld JP, Niaudet P, Lesavre P, Frémeaux-Bacchi V (2012) Acquired and genetic complement abdnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 82:454–464CrossRefPubMedGoogle Scholar
  7. 7.
    Bacchetta J, Cochat P (2015) Primary disease recurrence-effects on paediatric renal transplantation outcomes. Nat Rev Nephrol 11:371–384CrossRefPubMedGoogle Scholar
  8. 8.
    Van Stralen KJ, Verrina E, Belingheri M, Dudley J, Dusek J, Grenda R, Macher MA, Puretic Z, Rubic J, Rudaitis S, Rudin C, Schaefer F, Jager KJ (2013) Impact of graft loss among kidney diseases with a high risk of post-transplant recurrence in the paediatric population. Nephrol Dial Transplant 28:1031–1038CrossRefPubMedGoogle Scholar
  9. 9.
    Nicolas C, Vuiblet V, Baudouin V, Macher MA, Vrillon I, Biebuyck-Gouge N, Dehennault M, Gie S, Morin D, Nivet H, Nobili F, Ulinski T, Ranchin B, Marinozzi MC, Ngo S, Fremeaux-Bacchi V, Pietrement C (2014) C3 nephritic factor associated with C3 glomerulopathy in children. Pediatr Nephrol 29:85–94CrossRefPubMedGoogle Scholar
  10. 10.
    Okuda Y, Ishikura K, Hamada R, Harada R, Sakai T, Hamasaki Y, Hataya H, Fukuzawa R, Ogata K, Honda M (2015) Membranoproliferative glomerulonephritis and C3 glomerulonephritis : frequency, clinical features, and outcome in children. Nephrology 20:286–292CrossRefPubMedGoogle Scholar
  11. 11.
    Vivarelli M, Pasini A, Emma F (2012) ECULIZUMAB for the treatment of dense deposit disease. N Engl J Med 366:1163–1165CrossRefPubMedGoogle Scholar
  12. 12.
    De S, Al-Nabhani D, Thorner P, Cattran D, Piscione TD, Licht C (2009) Remission of resistant MPGN type I with mycophenolate mofetil and steroids. Pediatr Nephrol 24:597–600CrossRefPubMedGoogle Scholar
  13. 13.
    Rabasco C, Cavero T, Román E, Rojas-Rivera J, Olea T, Espinosa M, Cabello V, Fernández-Juarez G, González F, Ávila A, Baltar JM, Díaz M, Alegre R, Elías S, Antón M, Frutos MA, Pobes A, Blasco M, Martín F, Bernis C, Macías M, Barroso S, de Lorenzo A, Ariceta G, López-Mendoza M, Rivas B, López-Revuelta K, Campistol JM, Mendizábal S, de Córdoba SR, Praga M, Spanish Group for the Study of Glomerular Diseases (GLOSEN) (2015) Effectiveness of mycophenolate mofetil in C3 glomerulonephritis. Kidney Int 88:1153–1160CrossRefPubMedGoogle Scholar
  14. 14.
    Rousset-Rouvière C, Cailliez M, Garaix F, Bruno D, Laurent D, Tsimaratos M (2014) Rituximab fails where eculizumab restores renal function in C3nef related DDD. Pediatr Nephrol 29:1107–1111CrossRefPubMedGoogle Scholar
  15. 15.
    González-Roncero F, Suñer M, Bernal G, Cabello V, Toro M, Pereira P, Angel Gentil M (2012) Eculizumab treatment of acute antibody-mediated rejection in renal transplantation: case reports. Transplant Proc 44:2690–2694CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Service de Néphrologie Rhumatologie Dermatologie Pédiatriques, Centre de Référence des Maladies Rénales Rares Hôpital Femme Mère EnfantHospices Civils de LyonBronFrance
  2. 2.Faculté de Médecine Lyon EstLyonFrance
  3. 3.Laboratoire d’Anatomopathologie, Groupe Hospitalier EstHospices Civils de LyonBronFrance
  4. 4.Service de PédiatrieCHU Clermont FerrandClermont FerrandFrance
  5. 5.Laboratoire d’Immunologie, Hôpital Georges PompidouAssistance publique–Hôpitaux de Paris (AP-HP)ParisFrance

Personalised recommendations