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C3 nephritic factor associated with C3 glomerulopathy in children

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Abstract

Background

C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF.

Methods

We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes.

Results

Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases.

Conclusions

C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable.

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References

  1. Fakhouri F, Fremeaux-Bacchi V, Noel LH, Cook HT, Pickering MC (2010) C3 glomerulopathy: a new classification. Nat Rev Nephrol 6(8):494–499

    Article  PubMed  CAS  Google Scholar 

  2. Sethi S, Fervenza F, Zhang Y, Nasr S, Leung N, Vrana J, Cramer C, Nester C, Smith R (2011) Proliferative Glomerulonephritis secondary to dysfunction of the alternative pathway of complement. Clin J Am Soc Nephrol 6:1009–1017

    Article  PubMed  Google Scholar 

  3. Smith R, Alexander J, Barlow P (2007) New approaches to the treatment of dense deposit disease. J Am Soc Nephrol 18:2447–2456

    Article  PubMed  CAS  Google Scholar 

  4. Gale D, De Jorge E, Cook H (2010) Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet 376:794–801

    Article  PubMed  CAS  Google Scholar 

  5. D’Agati VD, Bomback AS (2012) C3 glomerulopathy: what’s in a name ? Kidney Int 82(4):379–381

    Article  PubMed  Google Scholar 

  6. Sethi S, Fervenza F (2011) Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol 31(4):341–348

    Article  PubMed  CAS  Google Scholar 

  7. Appel G, Cook H, Hageman G, Jennette J, Kashgarian M, Kirschfink M, Lambris J, Lanning L, Lutz H, Meri S, Rose N, Salant D, Sethi S, Smith R, Smoyer W, Tully H, Tully S, Walker P, Welsh M, Würzner R, Zipfel P (2005) Membranoproliferative glomerulonephritis type II (Dense Deposit Disease): an update. J Am Soc Nephrol 16:1392–1404

    Article  PubMed  Google Scholar 

  8. Servais A, Fremeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B, Grünfeld JP, Lesavre P, Noël LH, Fakhouri F (2007) Primary gloemrulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. J Med Genet 44:193–199

    Article  PubMed  CAS  Google Scholar 

  9. Sethi S, Gamez J, Vrana J, Theis J, Ill H, Zipfel P, Dogan A, Smith R (2009) Glomeruli of dense deposit disease contain components of the alternative and terminal complement pathway. Kidney Int 75(9):952–960

    Article  PubMed  CAS  Google Scholar 

  10. Leroy V, Fremeaux-Bacchi V, Peuchmaur M, Baudouin V, Deschenes G, Macher MA, Loirat C (2011) Membranoproliferative glomerulonephritis with C3nef and genetic complement dysregulation. Pediatr Nephrol 26:419–424

    Article  PubMed  Google Scholar 

  11. Orth S, Ritz E (1998) The nephrotic syndrome. N Engl J Med 338(17):1202–1211

    Article  PubMed  CAS  Google Scholar 

  12. Warady B, Hebert D, Sullivan E, Alexander S, Tejani A (1997) Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 11(1):49–64

    Article  PubMed  CAS  Google Scholar 

  13. Rapport REIN Agence Biomedecine (2010) http://www.socnephrologie.org/REIN/documents.htm

  14. Servais A, Noël LH, Roumenina L, 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 82:454–464

    Article  PubMed  CAS  Google Scholar 

  15. Sethi S, Fervenza F, Zhang Y, Zand Y, Zand L, Vrana J, Nasr S, Theis J, Dogan A, Smith R (2012) C3 glomerulopnephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment and follow-up. Kidney Int 82:465–473

    Article  PubMed  CAS  Google Scholar 

  16. Nasr S, Valeri A, Appel G, Sherwinter J, Stokes M, Said S, Markowitz G, D’Agati V (2009) Dense deposit disease: clinicopathologic study of 32 pediatric and adult patients. Clin J Am Soc Nephrol 4:22–32

    Article  PubMed  Google Scholar 

  17. Roumenina L, Loirat C, Dragon-Durey M (2011) Alternative complement pathway assessment in patients with atypical HUS. J Immunol Methods 365:8–26

    Article  PubMed  CAS  Google Scholar 

  18. Fremeaux-Bacchi, Weiss L, Brun P (1994) Selective disappearance of C3NeF IgG autoantibody in the plasma of patient with membranoproliferative glomerulonephritis following renal transplantation. Nephrol Dial Transplant 9:811–814

    PubMed  CAS  Google Scholar 

  19. Rougier N, Kazatchkine MD, Rougier JP, Fremeaux-Bacchi V, Blouin J, Deschenes G, Soto B, Baudouin V, Pautard B, Proesmans W, Weiss E, Weiss L (1998) Human complement factor H deficiency associated with hemolytic uremic syndrome. J Am Soc Nephrol 9(12):2318–2326

    PubMed  CAS  Google Scholar 

  20. Alchi B, Jayne D (2009) Membranoproliferative glomerulonephritis. Pediatr Nephrol 25(8):1409–1418

    Article  PubMed  Google Scholar 

  21. Sethi S, Fervenza F (2012) Membranoproliferative glomerulonephritis—A new look at an old entity. N Engl J Med 366:1119–1131

    Article  PubMed  CAS  Google Scholar 

  22. Cameron J, Turner D, Heaton J, Williams D, Ogg C, Chantler C, Haycock G, Hicks J (1983) Idiopathic mesangiocapillary glomerulonephritis. Comparison of types I and II in children and adults and long-term prognosis. Am J Med 74(2):175–192

    Article  PubMed  CAS  Google Scholar 

  23. Bennett W, Fassett R, Walker R, Fairley K, D’Apice A, Kincaid-Smith P (1989) Mesangiocapillary glomerulonephritis type II (dense deposit disease): clinical features of progressive disease. Am J Kidney Dis 13(6):469–476

    PubMed  CAS  Google Scholar 

  24. Little M, Dupont P, Campbell E, Dorman A, Walshe J (2006) Severity of primary MPGN, rather than MPGN type, determines renal survival and post-transplantation recurrence risk. Kidney Int 69(3):504–511

    Article  PubMed  CAS  Google Scholar 

  25. Fremeaux-Bacchi V, Weiss L, Demouchy C, May A, Palomera S, Kazatchkine M (1994) Hypocomplementaemia of poststreptococcal acute glomerulonephritis is associated with C3 nephritic (C3NeF) IgG autoantibody activity. Nephrol Dial Transplant 9(12):1747–1750

    PubMed  CAS  Google Scholar 

  26. Sethi S, Fervenza F, Zhang Y, Zand L, Meyer N, Borsa N, Nasr S, Smith R (2013) Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int 83(2):293–299

    Article  PubMed  CAS  Google Scholar 

  27. Vernon K, Goicoechea de Jorge E, Hall AE, Fremeaux-Bacchi V, Aitman TJ, Cook HT, Hangartner R, Koziell A, Pickering MC (2012) Acute presentation and persistent glomerulonephritis following streptococcal infection in a patient with heterozygous complement factor H-related protein 5 deficiency. Am J Kidney Dis 60(1):121–125

    Article  PubMed  Google Scholar 

  28. Zhang Y, Meyer N, Wang K, Nishimura C, Frees K, Jones M, Katz L, Sethi S, Smith R (2012) Causes of alternative pathway dysregulation in dense deposit disease. Clin J Am Soc Nephrol 7(22):265–274

    Article  PubMed  CAS  Google Scholar 

  29. Ram S, Lewis L, Rice P (2010) Infections of people with complement deficiencies and patients who have undergone splenectomy. Clin Microbiol Rev 23(4):740–780

    Article  PubMed  CAS  Google Scholar 

  30. Levin A (1999) Management of membranoproliferative glomerulonephritis: evidence-based recommendations. Kidney Int 70:S41–S46

    Article  CAS  Google Scholar 

  31. Glassock RJ (2009) Membranoproliferative glomerulonephritis. In: Ponticelli C, Glassock RJ (eds) Treatment of primary glomerulonephritis, 2nd edn. Oxford University Press, Oxford, England, pp 375–398

    Chapter  Google Scholar 

  32. Lu D, Moon M, Lanning LD, McCarthy A, Smith R (2012) Clinical features and outcomes of 98 children and adults with dense deposit disease. Pediatr Nephrol 27:773–781

    Article  PubMed  Google Scholar 

  33. McEnery (1990) Membranoproliferative glomerulonephritis: the Cincinnati experience-cumulative renal survival from 1957–1989. J Pediatr 116:S109–S114

    Article  PubMed  CAS  Google Scholar 

  34. Ford D, Briscoe D, Shanley P, Lum G (1992) Childhood membranoproliferative glomerulonephritis type I: limited steroid therapy. Kidney Int 41:1606–1612

    Article  PubMed  CAS  Google Scholar 

  35. Tarashish P, Bernstain J, Tobin J, Edelmann C (1992) Treatment of mesangiocapillary glomerulonephritis with alternate-day prednisone-a report of the International Study of Kidney Disease in Children. Pediatr Nephrol 6:123–130

    Article  Google Scholar 

  36. Emre S, Sirin A, Alpay H, Tanman F, Uvsal V, Navir A, Bilge I (1995) Pulse methylprednisolone therapy in children with membranoproliferative glomerulonephritis. Acta Paediatr Jpn 37:626–629

    Article  PubMed  CAS  Google Scholar 

  37. Bahat E, Akkava BKS, Karpuzoglu G, Guven AG (2007) Comparison of pulse and oral steroid in childhood membranoproliferative glomerulonephritis. J Nephrol 20:234–245

    PubMed  Google Scholar 

  38. Chapman S, Cameron J, Chantler C, Turner D (1980) Treatment of mesangiocapillary glomerulonephritis in children with combined immunosuppression and anticoagulation. Arch Dis Child 55:446–451

    Article  PubMed  CAS  Google Scholar 

  39. Faedda R, Satta A, Tanda F, Pirisi M, Bartoli E (1994) Immunosuppressive treatment of membranoproliferative glomerulonephritis. Nephron 67:59–65

    Article  PubMed  CAS  Google Scholar 

  40. Choi M, Eustace J, Gimenez L, Atta M, Scheel P, Sothinathan R, Briggs W (2002) Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int 61:1098–1114

    Article  PubMed  CAS  Google Scholar 

  41. Jones G, Juazczak M, Kingdon E, Harber M, Sweny P, Burns A (2004) Treatment of idiopathic membranoproliferative glomerulonephritis with mycophenolate mofetil an steroids. Nephrol Dial Transplant 19:3160–3164

    Article  PubMed  Google Scholar 

  42. D’Amico G, Ferrario F (1992) Mesangiocapillary glomerulonephritis. J Am Soc Nephrol 2:S159–S166

    PubMed  Google Scholar 

  43. Sethi S, Nester C, Smith R (2012) Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int 81:434–441

    Article  PubMed  Google Scholar 

  44. Smith R, Harris C, Pickering M (2011) Dense deposit disease. Mol Immunol 48:1604–1610

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. LH Noël (Assistance Publique-Hopitaux de Paris, Department of Pathology, Hôpital Necker, France) and Dr. F. Dijoud (CHU Lyon Groupement hospitalier Est, Department of Pathology) for iconography.

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Authors and Affiliations

  1. Department of Pediatrics, Nephrology unit, CHU de Reims, Reims, France

    Camille Nicolas & Christine Pietrement

  2. Department of Pathology, Department of Nephrology, CHU de Reims, Reims, France

    Vincent Vuiblet

  3. Assistance Publique-Hopitaux de Paris, Department of Immunology, Hôpital Européen Georges Pompidou, Paris, France

    Stéphanie Ngo & Véronique Frémeaux-Bacchi

  4. Assistance Publique-Hopitaux de Paris, Department of Pediatric Nephrology, Hôpital Robert Debré, Paris, France

    Veronique Baudouin & Marie-Alice Macher

  5. Department of Pediatrics, Nephrology Unit, CHU Nancy, Nancy, France

    Isabele Vrillon

  6. Assistance Publique-Hôpitaux de Paris, Department of Pediatric Nephrology, Hôpital Necker Enfants-Malades, Paris, France

    Nathalie Biebuyck-Gouge

  7. Department of Pediatrics, Nephrology Unit, CHRU Lille Jeanne de Flandre, Lille, France

    Maud Dehennault

  8. Department of Pediatrics, Nephrology Unit, CHU Rennes, Rennes, France

    Sophie Gié

  9. Department of Pediatrics, Nephrology Unit, CHU Montpellier, Montpellier, France

    Denis Morin

  10. Department of Pediatrics, Nephrology Unit, CHU Tours, Tours, France

    Hubert Nivet

  11. Department of Pediatrics, Nephrology Unit, CHU Besançon, Besançon, France

    François Nobili

  12. Department of Pediatric Nephrology, Hôpital Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France

    Tim Ulinski

  13. Department of Pediatric Nephrology, Hôpital Femme Mère-Enfant, Bron, France

    Bruno Ranchin

  14. INSERM Umrs872, CRC Paris, Paris, France

    Maria Chiarra Marinozzi

  15. Pédiatrie A, CHU de Reims, 45 rue Cognacq Jay, 51092, Reims cedex, France

    Christine Pietrement

  16. Service d’Immunologie Biologique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908, Paris cedex 15, France

    Véronique Frémeaux-Bacchi

Authors
  1. Camille Nicolas
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  2. Vincent Vuiblet
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Correspondence to Véronique Frémeaux-Bacchi or Christine Pietrement.

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Nicolas, C., Vuiblet, V., Baudouin, V. et al. C3 nephritic factor associated with C3 glomerulopathy in children. Pediatr Nephrol 29, 85–94 (2014). https://doi.org/10.1007/s00467-013-2605-6

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  • DOI: https://doi.org/10.1007/s00467-013-2605-6

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