Abstract
Background
C3 glomerulopathy (C3G) is rare type of glomerulonephritis resulting from the glomerular deposition of C3 due to dysregulation of the alternative pathway of complement. It is further subdivided into C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), depending on the ultrastructural features. C3GN usually presents with a membranoproliferative pattern of injury. Crescents may or may not be present. However, we have noted a severe necrotizing and crescentic glomerulonephritis in a small subset of C3GN patients.
Case diagnosis/treatment
We present the clinical features, kidney biopsy findings, complement evaluation, treatment, and follow-up of four C3GN patients. We also compare the findings with four DDD patients with a severe necrotizing and crescentic glomerulonephritis. The patients were young and presented with hematuria and proteinuria. The biopsy was remarkable for the large number of crescents, in association with bright glomerular staining for C3. The patients were treated with steroids/immunosuppressive drugs. Three of the 4 C3GN patients and 2 of the 4 DDD patients showed stable renal function at follow-up. We find remarkable similarities between our C3GN patients with crescents and the previously described entity of juvenile acute nonproliferative glomerulonephritis.
Conclusions
To summarize, C3G with a severe crescentic phenotype is rare, affects children and young adults, and has a variable response to steroid and immunosuppressive treatment. It is important to recognize this rare cause of crescentic glomerulonephritis so that appropriate evaluation and treatment can be carried out.
Similar content being viewed by others
References
Pickering MC, D'Agati VD, Nester CM, Smith RJ, Haas M, Appel GB, Alpers CE, Bajema IM, Bedrosian C, Braun M, Doyle M, Fakhouri F, Fervenza FC, Fogo AB, Fremeaux-Bacchi V, Gale DP, Goicoechea de Jorge E, Griffin G, Harris CL, Holers VM, Johnson S, Lavin PJ, Medjeral-Thomas N, Paul Morgan B, Nast CC, Noel L-H, Peters DK, Rodriguez de Cordoba S, Servais A, Sethi S, Song W-C, Tamburini P, Thurman JM, Zavros M, Cook HT (2013) C3 glomerulopathy: consensus report. Kidney Int 84:1079–1089
Hou J, Markowitz GS, Bomback AS, Appel GB, Herlitz LC, Barry Stokes M, D'Agati VD (2014) Toward a working definition of C3 glomerulopathy by immunofluorescence. Kidney Int 85:450–456
Sethi S, Nester CM, Smith RJH (2012) Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int 81:434–441
Fakhouri F, Fremeaux-Bacchi V, Noel L-H, Cook HT, Pickering MC (2010) C3 glomerulopathy: a new classification. Nat Rev Nephrol 6:494–499
Sethi S, Fervenza FC, Zhang Y, Nasr SH, Leung N, Vrana J, Cramer C, Nester CM, Smith RJH (2011) Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement. Clin J Am Soc Nephrol 6:1009–1017
Servais A, Fremeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B, Grunfeld J-P, Lesavre P, Noel L, Fakhouri F (2007) Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. J Med Genet 44:193–199
Sethi S, Fervenza FC, Zhang Y, Zand L, Vrana JA, Nasr SH, Theis JD, Dogan A, Smith RJH (2012) C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int 82:465–473
Sethi S, Fervenza FC (2012) Membranoproliferative glomerulonephritis: a new look at an old entity. N Engl J Med 366:1119–1131
Cook HT, Pickering MC (2015) Histopathology of MPGN and C3 glomerulopathies. Nat Rev Nephrol 11:14–22
Sethi S, Fervenza FC, Zhang Y, Smith RJH (2012) Secondary focal and segmental glomerulosclerosis associated with single-nucleotide polymorphisms in the genes encoding complement factor H and C3. Am J Kidney Dis 60:316–321
West CD, McAdams AJ, Witte DP (2000) Acute non-proliferative glomerulitis: a cause of renal failure unique to children. Pediatr Nephrol 14:786–793
Fervenza FC, Smith RJH, Sethi S (2012) Association of a novel complement Factor H mutation with severe crescentic and necrotizing glomerulonephritis. Am J Kidney Dis 60:126–132
Jennette JC, Falk RJ (2014) Pathogenesis of antineutrophil cytoplasmic autoantibody-mediated disease. Nat Rev Rheumatol 10:463–473
Kambham N (2012) Crescentic glomerulonephritis: an update on pauci-immune and anti-GBM diseases. Adv Anat Pathol 19:111–124
Abrera-Abeleda MA, Nishimura C, Frees K, Jones M, Maga T, Katz LM, Zhang Y, Smith RJH (2011) Allelic variants of complement genes associated with dense deposit disease. J Am Soc Nephrol 22:1551–1559
Abrera-Abeleda MA, Nishimura C, Smith JLH, Sethi S, McRae JL, Murphy BF, Silvestri G, Skerka C, Jozsi M, Zipfel PF, Hageman GS, Smith RJH (2006) Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease). J Med Genet 43:582–589
Sethi S, Fervenza FC, Zhang Y, Zand L, Meyer NC, Borsa N, Nasr SH, Smith RJH (2013) Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int 83:293–299
Acknowledgements
We thank Dr Anthony Chang, University of Chicago, for providing the light microscopy picture of patient 3.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Disclosure
None.
Conflicts of interest
None.
Rights and permissions
About this article
Cite this article
Ravindran, A., Fervenza, F.C., Smith, R.J.H. et al. C3 glomerulonephritis with a severe crescentic phenotype. Pediatr Nephrol 32, 1625–1633 (2017). https://doi.org/10.1007/s00467-017-3702-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-017-3702-8