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 Proteinuria relapsed when eculizumab was withdrawn, but the re-introduction of eculizumab normalized proteinuria.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 Eculizumab was withdrawn due to multiple viral reactivations, but the re-introduction of the drug a few months later enabled a moderate decrease in proteinuria.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.
Similar content being viewed by others
References
Sethi S, Fervenza FC (2012) Membranoproliferative glomerulonephritis—a new look at an old entity. N Engl J Med 366:1119–1131
Bomback AS, Appel GB (2012) Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol 8:634–642
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–e348
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 63:40–48
Bomback AS (2014) Eculizumab in the treatment of membranoproliferative glomerulonephritis. Nephron Clin Pract 128:270–276
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 82:454–464
Bacchetta J, Cochat P (2015) Primary disease recurrence-effects on paediatric renal transplantation outcomes. Nat Rev Nephrol 11:371–384
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 28:1031–1038
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 29:85–94
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 20:286–292
Vivarelli M, Pasini A, Emma F (2012) ECULIZUMAB for the treatment of dense deposit disease. N Engl J Med 366:1163–1165
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 24:597–600
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 88:1153–1160
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 29:1107–1111
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 44:2690–2694
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
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.
Rights and permissions
About this article
Cite this article
Lebreton, C., Bacchetta, J., Dijoud, F. et al. C3 glomerulopathy and eculizumab: a report on four paediatric cases. Pediatr Nephrol 32, 1023–1028 (2017). https://doi.org/10.1007/s00467-017-3619-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-017-3619-2