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Rituximab fails where eculizumab restores renal function in C3nef-related DDD

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Dense deposit disease (DDD), a C3 glomerulopathy (C3G), is a rare disease with unfavorable progression towards end-stage kidney disease. The pathogenesis of DDD is due to cytotoxic effects related to acquired or genetic dysregulation of the complement alternative pathway, which is at times accompanied by the production of C3 nephritic factor (C3NeF), an auto-antibody directed against the alternative C3 convertase. Available treatments include plasma exchange, CD20-targeted antibodies, and a terminal complement blockade via the anti-C5 monoclonal antibody eculizumab.


We report here the case of an 8-year-old child with C3NeF and refractory DDD who presented with a nephritic syndrome. She tested positive for C3NeF activity; C3 was undetectable. Genetic analyses of the alternative complement pathway were normal. Methylprednisolone pulses and mycophenolate mofetil treatment resulted in complete recovery of renal function and a reduction in proteinuria. Corticosteroids were tapered and then withdrawn. Four months after corticosteroid discontinuation, hematuria and proteinuria recurred, and a renal biopsy confirmed an active DDD with a majority of extracapillary crescents. Despite an increase in immunosuppressive drugs, including methylprednisolone pulses and rituximab therapy, the patient suffered acute renal failure within 3 weeks, requiring dialysis. Eculizumab treatment resulted in a quick and impressive response. Hematuria very quickly resolved, kidney function improved, and no further dialysis was required. The patient received bimonthly eculizumab injections of 600 mg, allowing for normalization of renal function and reduction of proteinuria to <0.5 g per day. Since then, she continues to receive eculizumab.


Complement regulation pathway-targeted therapy may be a specific and useful treatment for rapidly progressing DDD prior to the development of glomerulosclerosis. Our data provide evidence supporting the pivotal role of complement alternative pathway abnormalities in C3G with DDD.

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  1. Angelo JR, Bell CS, Braun MC (2011) Allograft failure in kidney transplant recipients with membranoproliferative glomerulonephritis. Am J Kidney Dis 57(2):291–299

    Article  PubMed  Google Scholar 

  2. Braun MC, Stablein DM, Hamiwka LA, Bell L, Bartosh SM, Strife CF (2005) Recurrence of membranoproliferative glomerulonephritis type II in renal allografts: The North American Pediatric Renal Transplant Cooperative Study experience. J Am Soc Nephrol 16(7):2225–2233

    Article  PubMed  Google Scholar 

  3. Licht C, Fremeaux-Bacchi V (2009) Hereditary and acquired complement dysregulation in membranoproliferative glomerulonephritis. Thromb Haemost 101:271–278

    PubMed  CAS  Google Scholar 

  4. Fakhouri F, Fremeaux-Bacchi V, Noel LH, Cook HT, Pickering MC (2010) C3 glomerulopathy: a new classification. Nat Rev Nephrol 6:494–499

    Article  PubMed  CAS  Google Scholar 

  5. Sethi S, Fervenza FC, Zhang Y, Nasr SH, Leung N, Vrana J, Cramer C, Nester CM, Smith RJ (2011) Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement. Clin J Am Soc Nephrol 6:1009–1017

    Article  PubMed Central  PubMed  Google Scholar 

  6. Skerka C, Licht C, Mengel M, Uzonyi B, Strobel S, Zipfel PF, Józsi M (2009) Autoimmune forms of thrombotic microangiopathy and membranoproliferative glomerulonephritis: indications for a disease spectrum and common pathogenic principles. Mol Immunol 46:2801–2807

    Article  PubMed  CAS  Google Scholar 

  7. Goodship TH, Pappworth IY, Toth T, Denton M, Houlberg K, McCormick F, Warland D, Moore I, Hunze EM, Staniforth SJ, Hayes C, Cavalcante DP, Kavanagh D, Strain L, Herbert AP, Schmidt CQ, Barlow PN, Harris CL, Marchbank KJ (2012) Factor H autoantibodies in membranoproliferative glomerulonephritis. Mol Immunol 52(3–4):200–206

    Article  PubMed  CAS  Google Scholar 

  8. Leroy V, Fremeaux-Bacchi V, Peuchmaur M, Baudouin V, Deschênes G, Macher MA, Loirat C (2011) Membranoproliferative glomerulonephritis with C3NeF and genetic complement dysregulation. Pediatr Nephrol 26(3):419–424

    Article  PubMed  Google Scholar 

  9. Habbig S, Mihatsch MJ, Heinen S, Beck B, Emmel M, Skerka C, Kirschfink M, Hoppe B, Zipfel PF, Licht C (2009) C3 deposition glomerulopathy due to a functional factor H defect. Kidney Int 75:1230–1234

    Article  PubMed  Google Scholar 

  10. Servais A, Noel LH, Roumenina LT, LeQuintrec M, Ngo S, Dragon 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 abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 82(4):454–464

    Article  PubMed  CAS  Google Scholar 

  11. Lu DF, Moon M, Lanning LD, McCarthy AM, Smith RJ (2012) Clinical features and outcomes of 98 children and adults with dense deposit disease. Pediatr Nephrol 27(5):773–781

    Article  PubMed  Google Scholar 

  12. Nester CM, Smith RJ (2013) Treatment options for C3 glomerulopathy. Curr Opin Nephrol Hypertens 22(2):231–237

    Article  PubMed  Google Scholar 

  13. McCaughan JA, O’Rourke DM, Courtney AE (2012) Recurrent dense deposit disease after renal transplantation: an emerging role for complementary therapies. Am J Transplant 12:1046–1051

    Article  PubMed  CAS  Google Scholar 

  14. Gurkan S, Fyfe B, Weiss L, Xiao X, Zhang Y, Smith RJ (2013) Eculizumab and recurrent C3 glomerulonephritis. Pediatr Nephrol 28:1975–1981

    Article  PubMed  Google Scholar 

  15. Dillon JJ, Hladunewich M, Haley WE, Reich HN, Cattran DC, Fervenza FC (2012) Rituximab therapy for Type I membranoproliferative glomerulonephritis. Clin Nephrol 77(4):290–295

    Article  PubMed  CAS  Google Scholar 

  16. Zuber J, Fakhouri F, Roumenina Lubka T, Loirat C, Fremeaux-Bacchi V (2012) Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8(11):643–657

    Article  PubMed  CAS  Google Scholar 

  17. Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, Röth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L (2006) The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 355(12):1233–1243

    Article  PubMed  CAS  Google Scholar 

  18. Gruppo RA, Rother RP (2009) Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med 360(5):544–546

    Article  PubMed  CAS  Google Scholar 

  19. Vivarelli M, Pasini A, Emma F (2012) Eculizumab for the treatment of Dense-Deposit disease. N Engl J Med 366(12):1163–1165

    Article  PubMed  CAS  Google Scholar 

  20. Daina E, Noris M, Remuzzi G (2012) Eculizumab in a patient with dense-deposit disease. N Engl J Med 366:1161–1163

    Article  PubMed  CAS  Google Scholar 

  21. Radhakrishnan S, Lunn A, Kirschfink M, Thorner P, Hebert D, Langlois V, Pluthero F, Licht C (2012) Eculizimab and refractory Membranoproliferative Glomerulonephritis. N Engl J Med 366(12):1165–1167

    Article  PubMed  CAS  Google Scholar 

  22. Cravedi P (2012) Role of monoclonal antibodies in the treatment of immune-mediated kidney disease: the state of the art. G Ital Nefrol 29(3):274–282

    PubMed  Google Scholar 

  23. Herlitz LC, Bomback AS, Markowitz GS, Stokes MB, Smith RN, Colvin RB, Appel GB, D’Agati VD (2012) Pathology after eculizumab in dense deposit disease and C3 GN. J Am Soc Nephrol 23(7):1229–1237

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Bomback AS, Smith RJ, Barile GR, Zhang Y, Heher EC, Herlitz L, Stokes MB, Markowitz GS, D’Agati VD, Canetta PA, Radhakrishnan J, Appel GB (2012) Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol 7(5):748–756

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Correspondence to Caroline Rousset-Rouvière.

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Rousset-Rouvière, C., Cailliez, M., Garaix, F. et al. Rituximab fails where eculizumab restores renal function in C3nef-related DDD. Pediatr Nephrol 29, 1107–1111 (2014).

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