Abstract
Background
Post-infectious glomerulonephritis (PIGN) usually follows a benign course, but few children have an atypical, severe presentation, and these exceptional cases have been linked to the dysregulation of the complement alternative pathway (CAP). There is a considerable overlap in the histopathological features of PIGN and C3 glomerulopathy (C3G), which is also associated with CAP dysregulation but has a poorer outcome. We hypothesized that PIGN and C3G define a disease spectrum, and that in the past there may be some children with C3G who were misclassified with PIGN before C3G was described as a separate disease entity.
Methods
Children with PIGN (n = 33) diagnosed between 1985 and 2010 who underwent a renal biopsy due to their unusual course were reviewed and of them, 8 were reclassified into C3G based on the current classification criteria. Outcome was based on the degree of proteinuria, C3 level, and renal function at follow-up.
Results
Sixteen (72.7%) children with typical PIGN recovered completely as compared to only 2 (25%) with C3G. Of note, children with “typical” PIGN had a more severe disease course at onset; however, the outcome at last follow up was favorable.
Conclusions
Our results support the hypothesis that PIGN and C3G form a disease spectrum and have different long-term clinical implications and management strategies.
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References
Eison TM, Ault BH, Jones DP, Chesney RW, Wyatt RJ (2011) Post-streptococcal acute glomerulonephritis in children: clinical features and pathogenesis. Pediatr Nephrol 26:165–180
Nadasdy T, Hebert LA (2011) Infection-related glomerulonephritis: understanding mechanisms. Semin Nephrol 31:369–375
Montseny JJ, Meyrier A, Kleinknecht D, Callard P (1995) The current spectrum of infectious glomerulonephritis. Experience with 76 patients and review of the literature. Medicine (Baltimore) 74:63–73
Fakhouri F, Fremeaux-Bacchi V, Noel LH, Cook HT, Pickering MC (2010) C3 glomerulopathy: a new classification. Nat Rev Nephrol 6:494–499
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 LH, Peters DK, Rodriguez de Cordoba S, Servais A, Sethi S, Song WC, Tamburini P, Thurman JM, Zavros M, Cook HT (2013) C3 glomerulopathy: consensus report. Kidney Int 84:1079–1089
Servais A, Noel LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, Macher MA, Zuber J, Karras A, Provot F, Moulin B, Grunfeld JP, Niaudet P, Lesavre P, Fremeaux-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
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
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 7:748–756
Sethi S, Fervenza FC, Zhang Y, Zand L, Meyer NC, Borsa N, Nasr SH, Smith RJ (2013) Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int 83:293–299
Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263
Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637
Rodriguez-Iturbe B, Musser JM (2008) The current state of poststreptococcal glomerulonephritis. J Am Soc Nephrol 19:1855–1864
Fremeaux-Bacchi V, Weiss L, Demouchy C, May A, Palomera S, Kazatchkine MD (1994) Hypocomplementaemia of poststreptococcal acute glomerulonephritis is associated with C3 nephritic factor (C3NeF) IgG autoantibody activity. Nephrol Dial Transplant 9:1747–1750
Meri S (1985) Complement activation by circulating serum factors in human glomerulonephritis. Clin Exp Immunol 59:276–284
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
Radhakrishnan S, Lunn A, Kirschfink M, Thorner P, Hebert D, Langlois V, Pluthero F, Licht C (2012) Eculizumab and refractory membranoproliferative glomerulonephritis. N Engl J Med 366:1165–1166
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Badria Al-Ghaithi and Rahul Chanchlani contributed equally to this work.
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Al-Ghaithi, B., Chanchlani, R., Riedl, M. et al. C3 Glomerulopathy and post-infectious glomerulonephritis define a disease spectrum. Pediatr Nephrol 31, 2079–2086 (2016). https://doi.org/10.1007/s00467-015-3311-3
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DOI: https://doi.org/10.1007/s00467-015-3311-3