Skip to main content
SpringerLink
Log in

Membranoproliferative Glomerulonephritis and C3 Glomerulopathy in Children

  • Living reference work entry
  • Latest version View entry history
  • First Online:
Pediatric Nephrology

  • 92 Accesses

Abstract

Membranoproliferative glomerulonephritis (MPGN) and C3 glomerulopathy (C3G) define a disease pattern characterized by proteinuria, hypertension, and impaired kidney function with a significant risk of disease progression to end-stage kidney disease (ESKD) despite all current treatment efforts. While historically morphological criteria were applied to classify MPGN, recent advances in the understanding of disease pathogenesis with the appreciation of predominant glomerular C3 deposition and the identification of a key role for the complement alternative pathway (AP) resulted in disease reclassification. Today, C3G characterizes a glomerulopathy with predominant C3 deposition. It can be subdivided by electron microscopy into dense deposit disease (DDD) with electron-dense deposits located in the lamina densa of the glomerular basement membrane (GBM), and C3 glomerulonephritis (C3GN) with deposits in subendothelial, subepithelial, and/or mesangial localization. By contrast, cases with coappearance of C3 and immunoglobulins are classified as idiopathic immune-complex MPGN (IC-MPGN). Interestingly, complement mutations and C3 nephritic factor (C3NeF) – an IgG antibody binding to and stabilizing the AP C3 convertase – are found in about 20 and 80% of C3G cases, respectively, but can also be found in IC-MPGN patients. Current treatment recommendations include conservative measures in all cases, and in some immunosuppression with corticosteroids and mycophenolate mofetil (MMF). While milder in children compared to adults, overall prognosis is poor, with roughly 20% of children reaching end-stage kidney disease (ESKD) within 10–15 years. Future treatment strategies are expected to include therapies that block the AP and thereby reduce glomerular C3 accumulation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ACEi:

Angiotensin-converting enzyme inhibitor

aHUS:

Atypical hemolytic uremic syndrome

AMD:

Age-related macular degeneration

AP:

Alternative pathway (of complement)

aPL:

Acquired partial lipodystrophy

ARB:

Angiotensin II receptor antagonist

ASO titer:

Antistreptolysin O titer

C:

Complement

C3G:

C3 glomerulopathy

C3GN:

C3 glomerulonephritis

C3NeF:

C3 nephritic factor

C4NeF:

C4 nephritic factor

C5NeF:

C5 nephritic factor

CFB:

Complement factor B

CFH:

Complement factor H

CFHR1-5:

Complement-factor-H-related protein 1-5

CFI:

Complement factor I

CFP:

Properdin

CP:

Classical pathway (of complement)

DDD:

Dense deposit disease

DEAP-HUS:

Deficiency of FHR plasma proteins and FH autoantibody positive HUS

DGKE:

Diacylglycerol kinase epsilon

ESKD:

End-stage kidney disease

FFP:

Fresh frozen plasma

GBM:

Glomerular basement membrane

GN:

Glomerulonephritis

IC:

Immune complex

iC3b:

Inactivated C3b

Ig:

Immunoglobulin

IRGN:

Infection-related glomerulonephritis

LP:

Lectin pathway (of complement)

MCP:

Membrane-cofactor protein

MLPA:

Multiplex ligation-dependent probe amplification

MMF:

Mycophenolate mofetil

MPGN:

Membranoproliferative glomerulonephritis

NeF:

Nephritic factor

NGS:

Next-generation sequencing

PMN:

Polymorphonuclear leukocytes

RAAS:

Renin-angiotensin-aldosterone system

SCR:

Short consensus repeat

SNP:

Single-nucleotide polymorphism

TMA:

Thrombotic microangiopathy

References

  1. Volheard F, Fahr T. Die Brightsche Nierenkrankheit. Berlin: Springer; 1914.

    Google Scholar 

  2. MacCallum WG. Glomerular changes in nephritis. Bull Johns Hopkins Hosp. 1934;55:416.

    Google Scholar 

  3. Bell ET. A clinical and pathological study of subacute and chronic glomerulonephritis, including lipoid nephrosis. Am J Pathol. 1938;14(6):691–736.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Ellis A. Natural history of Bright’s disease: clinical, histological and experimental observations. Lancet. 1942;1(1):1–7.

    Article  Google Scholar 

  5. Allen AC. The kidney: medical and surgical disease. Scranton: Grune & Stratton; 1951.

    Google Scholar 

  6. Jones DB. Nephrotic glomerulonephritis. Am J Pathol. 1957;33(2):313–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. West CD, McAdams AJ, McConville JM, Davis NC, Holland NH. Hypocomplementemic and normocomplementemic persistent (chronic) glomerulonephritis; clinical and pathologic characteristics. J Pediatr. 1965;67(6):1089–112.

    Article  Google Scholar 

  8. Anders D, Agricola B, Sippel M, Thoenes W. Basement membrane changes in membranoproliferative glomerulonephritis. Virchows Arch. 1977;376:1–19.

    Article  CAS  Google Scholar 

  9. Burkholder PM, Marchand A, Krueger RP. Mixed membranous and proliferative glomerulonephritis. A correlative light, immunofluorescence, and electron microscopic study. Lab Investig. 1970;23:459–79.

    CAS  PubMed  Google Scholar 

  10. Habib R, Gubler M-C, Loirat C, Maiz HB, Levy M. Dense deposit disease: a variant of membranoproliferative glomerulonephritis. Kidney Int. 1975;7:204–15.

    Article  CAS  PubMed  Google Scholar 

  11. Strife CF, McEnery PT, McAdams AJ, West CD. Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane. Clin Nephrol. 1977;7(2):65–72.

    CAS  PubMed  Google Scholar 

  12. Nachman PH, Glassock RJ. Membranoproliferative glomerulonephritis. Nephrol Self Assess Program. 2010;9(3):138–40.

    Google Scholar 

  13. Bomback AS, Appel GB. Pathogenesis of the C3 glomerulopathies and reclassification of MPGN. Nat Rev Nephrol. 2012;8(11):634–42.

    Article  CAS  PubMed  Google Scholar 

  14. Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. Semin Nephrol. 2011;31(4):341–8.

    Article  CAS  PubMed  Google Scholar 

  15. Fervenza FC, Sethi S, Glassock RJ. Idiopathic membranoproliferative glomerulonephritis: does it exist? Nephrol Dial Transplant. 2012;0:1–7.

    Google Scholar 

  16. Sethi S, Gamez JD, Vrana JA, Theis JD, Bergen HR 3rd, Zipfel PF, et al. Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway. Kidney Int. 2009;75(9):952–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sethi S, Vrana JA, Theis JD, Dogan A. Mass spectrometry based proteomics in the diagnosis of kidney disease. Curr Opin Nephrol Hypertens. 2013;22(3):273–80.

    Article  CAS  PubMed  Google Scholar 

  18. Walker PD, Ferrario F, Joh K, Bonsib SM. Dense deposit disease is not a membranoproliferative glomerulonephritis. Mod Pathol. 2007;20:605–16.

    Article  PubMed  Google Scholar 

  19. Sibley RK, Kim Y. Dense intramembranous deposit disease: new pathologic features. Kidney Int. 1984;25:660–70.

    Article  CAS  PubMed  Google Scholar 

  20. Joh K, Aizawa S, Matsuyama N, Yamaguchi Y, Kitajima T, Sakai O, et al. Morphologic variations of dense deposit disease: light and electron microscopic, immunohistochemical and clinical findings in 10 patients. Acta Pathol Japonica. 1993;43:552–65.

    CAS  Google Scholar 

  21. Nasr SH, Valeri AM, Appel GB, Sherwinter J, Stokes MB, Said SM, et al. Dense deposit disease: clinicopathologic study of 32 pediatric and adult patients. Clin J Am Soc Nephrol. 2009;4:22–32.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Davis AE, Schneeberger EE, Grupe WE, McCluskey RT. Membranoproliferative glomerulonephritis (MPGN type I) and dense deposit disease (DDD) in children. Clin Nephrol. 1978;9:184–93.

    CAS  PubMed  Google Scholar 

  23. Vargas R, Thompson KJ, Wilson D, Cameron JS, Turner DR, Gill D, et al. Mesangiocapillary glomerulonephritis with dense “deposits” in the basement membranes of the kidney. Clin Nephrol. 1976;5:73–82.

    CAS  PubMed  Google Scholar 

  24. Kim Y, Vernier RL, Fish AJ, Michael AF. Immunofluorescence studies of dense deposit disease. The presence of railroad tracks and mesangial rings. Lab Investig. 1979;40(4):474–80.

    CAS  PubMed  Google Scholar 

  25. Jones DB. Membranoproliferative glomerulonephritis. One or many diseases? Arch Pathol Lab Med. 1977;101:457–61.

    CAS  PubMed  Google Scholar 

  26. Zollinger HU, Mihatsch MJ. Focally accentuated glomerulonephritis. In: Zollinger HU, Mihatsch MJ, editors. Renal pathology in biopsy: light, electron, and immunofluorescent microscopy and clinical aspects. New York: Springer; 1978. p. 282.

    Chapter  Google Scholar 

  27. Cook HT. C3 glomerulopathy. F1000Res. 2017;6:248.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Berger J, Galle P. Altération singulière des membranes basales du rein. J Urol Nephrol. 1962;68:116–22.

    CAS  Google Scholar 

  29. Galle P, Mahieu P. Electron dense alteration of kidney basement membranes: a renal lesion specific of a systemic disease. Am J Med. 1975;58:749–64.

    Article  CAS  PubMed  Google Scholar 

  30. Hogg RJ, Silva FG, Walker PD, Cavallo T. Dense deposit disease in children: prognostic value of clinical and pathologic indicators. The Southwest Pediatric Nephrology Study Group. Am J Kidney Dis. 1985;6(3):161–9.

    Article  Google Scholar 

  31. Jenis EH, Sandler P, Hill GS, Knieser MR, Jensen GE, Roskes SD. Glomerulonephritis with basement membrane dense deposits. Arch Pathol. 1974;97:84–91.

    CAS  PubMed  Google Scholar 

  32. Sethi S, Fervenza FC, Zhang Y, Zand L, Vrana JA, Nasr SH, et al. C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int. 2012;82(4):465–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Nast CC. Infection-related glomerulonephritis: changing demographics and outcomes. Adv Chronic Kidney Dis. 2012;19(2):68–75.

    Article  PubMed  Google Scholar 

  34. Boils CL, Nasr SH, Walker PD, Couser WG, Larsen CP. Update on endocarditis-associated glomerulonephritis. Kidney Int. 2015;87(6):1241–9.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Khalighi MA, Wang S, Henriksen KJ, Bock M, Keswani M, Meehan SM, et al. Revisiting post-infectious glomerulonephritis in the emerging era of C3 glomerulopathy. Clin Kidney J. 2016;9(3):397–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Messias NC, Walker PD, Larsen CP. Paraffin immunofluorescence in the renal pathology laboratory: more than a salvage technique. Mod Pathol. 2015;28(6):854–60.

    Article  CAS  PubMed  Google Scholar 

  37. Nasr SH, Galgano SJ, Markowitz GS, Stokes MB, D’Agati VD. Immunofluorescence on pronase-digested paraffin sections: a valuable salvage technique for renal biopsies. Kidney Int. 2006;70(12):2148–51.

    Article  CAS  PubMed  Google Scholar 

  38. Aita K, Ito S, Tanabe K, Toma H, Yamaguchi Y, Nagata M. Early recurrence of dense deposit disease with marked endocapillary proliferation after renal transplantation. Pathol Int. 2006;56:101–9.

    Article  PubMed  Google Scholar 

  39. Shahidi-Asl M, Ananth M, Boineau F, Meleg-Smith S. Apparent progression of acute glomerulonephritis to dense deposit disease. Ultrastruct Pathol. 2000;24:273–7.

    Article  CAS  PubMed  Google Scholar 

  40. Sato H, Saito T, Seino J, Ootaka T, Kyogoku Y, Furuyama T, et al. Dense deposit disease: its possible pathogenesis suggested by an observation of a patient. Clin Nephrol. 1987;27(1):41–5.

    CAS  PubMed  Google Scholar 

  41. Sawanobori E, Umino A, Kanai H, Matsushita K, Iwasa S, Kitamura H, et al. A prolonged course of group A streptococcus-associated nephritis: a mile case of dense deposit disease? Clin Nephrol. 2009;71(6):703–7.

    Article  CAS  PubMed  Google Scholar 

  42. Suzuki K, Tsugawa K, Oki E, Aita K, Endo M, Waga S, et al. Dense deposit disease presenting as endocapillary proliferative nephritis. Pediatr Int. 2009;51(5):739–41.

    Article  PubMed  Google Scholar 

  43. Kerns E, Rozansky D, Troxell ML. Evolution of immunoglobulin deposition in C3-dominant membranoproliferative glomerulopathy. Pediatr Nephrol. 2013;28:2227–31.

    Article  PubMed  Google Scholar 

  44. Pickering MC, Cook HT, Warren J, Bygrave AE, Moss J, Walport MJ, et al. Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat Genet. 2002;31(4):424–8.

    Article  CAS  PubMed  Google Scholar 

  45. Hegasy GA, Manuelian T, Hogasen K, Jansen JH, Zipfel PF. The molecular basis for hereditary porcine membranoproliferative glomerulonephritis type II: point mutations in the factor H coding sequence block protein secretion. Am J Pathol. 2002;161(6):2027–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jansen JH, Hogasen K, Harboe M, Hovig T. In situ complement activation in porcine membranoproliferative glomerulonephritis type II. Kidney Int. 1998;53(2):331–49.

    Article  CAS  PubMed  Google Scholar 

  47. Hogasen K, Jansen JH, Mollnes TE, Hovdenes J, Harboe M. Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency. J Clin Invest. 1995;95(3):1054–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pickering MC, de Jorge EG, Martinez-Barricarte R, Recalde S, Garcia-Layana A, Rose KL, et al. Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains. J Exp Med. 2007;204(6):1249–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Michelfelder S, Parsons J, Bohlender LL, Hoernstein SNW, Niederkruger H, Busch A, et al. Moss-produced, glycosylation-optimized human factor H for therapeutic application in complement disorders. J Am Soc Nephrol. 2017;28(5):1462–74.

    Article  CAS  PubMed  Google Scholar 

  50. Fakhouri F, de Jorge EG, Brune F, Azam P, Cook HT, Pickering MC. Treatment with human complement factor H rapidly reverses renal complement deposition in factor H-deficient mice. Kidney Int. 2010;78(3):279–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Paixao-Cavalcante D, Hanson S, Botto M, Cook HT, Pickering MC. Factor H facilitates the clearance of GBM bound iC3b by controlling C3 activation in fluid phase. Mol Immunol. 2009;46(10):1942–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nichols EM, Barbour TD, Pappworth IY, Wong EK, Palmer JM, Sheerin NS, et al. An extended mini-complement factor H molecule ameliorates experimental C3 glomerulopathy. Kidney Int. 2015;88(6):1314–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ruseva MM, Peng T, Lasaro MA, Bouchard K, Liu-Chen S, Sun F, et al. Efficacy of targeted complement inhibition in experimental C3 glomerulopathy. J Am Soc Nephrol. 2016;27(2):405–16.

    Article  CAS  PubMed  Google Scholar 

  54. Yang Y, Denton H, Davies OR, Smith-Jackson K, Kerr H, Herbert AP, et al. An engineered complement factor H construct for treatment of C3 glomerulopathy. J Am Soc Nephrol. 2018;29(6):1649–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhang Y, Keenan A, Dai DF, May KS, Anderson EE, Lindorfer MA, et al. C3(H2O) prevents rescue of complement-mediated C3 glomerulopathy in Cfh−/− Cfd−/− mice. JCI Insight. 2020;5(9):e135758.

    Article  PubMed Central  Google Scholar 

  56. Lesher AM, Zhou L, Kimura Y, Sato S, Gullipalli D, Herbert AP, et al. Combination of factor H mutation and properdin deficiency causes severe C3 glomerulonephritis. J Am Soc Nephrol. 2013;24(1):53–65.

    Article  CAS  PubMed  Google Scholar 

  57. Ruseva MM, Vernon KA, Lesher AM, Schwaeble WJ, Ali YM, Botto M, et al. Loss of properdin exacerbates C3 glomerulopathy resulting from factor H deficiency. J Am Soc Nephrol. 2013;24(1):43–52.

    Article  CAS  PubMed  Google Scholar 

  58. Rose KL, Paixao-Cavalcante D, Fish J, Manderson AP, Malik TH, Bygrave AE, et al. Factor I is required for the development of membranoproliferative glomerulonephritis in factor H-deficient mice. J Clin Invest. 2008;118(2):608–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Schulze M, Pruchno CJ, Burns M, Baker PJ, Johnson RJ, Couser WG. Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis. Am J Pathol. 1993;142(1):179–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. de Jorge EG, Macor P, Paixao-Cavalcante D, Rose KL, Tedesco F, Cook HT, et al. The development of atypical hemolytic uremic syndrome depends on complement C5. J Am Soc Nephrol. 2011;22(1):137–45.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Verroust PJ, Wilson CB, Dixon FJ. Lack of nephritogenicity of systemic activation of the alternate complement pathway. Kidney Int. 1974;6(3):157–69.

    Article  CAS  PubMed  Google Scholar 

  62. Simpson IJ, Moran J, Evans DJ, Peters DK. Prolonged complement activation in mice. Kidney Int. 1978;13(6):467–71.

    Article  CAS  PubMed  Google Scholar 

  63. Devalaraja-Narashimha K, Meagher K, Luo Y, Huang C, Kaplan T, Muthuswamy A, et al. Humanized C3 mouse: a novel accelerated model of C3 glomerulopathy. J Am Soc Nephrol: JASN. 2021;32(1):99–114.

    Google Scholar 

  64. Goicoechea de Jorge E, Caesar JJ, Malik TH, Patel M, Colledge M, Johnson S, et al. Dimerization of complement factor H-related proteins modulates complement activation in vivo. Proc Natl Acad Sci U S A. 2013;110(12):4685–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Xiao X, Ghossein C, Tortajada A, Zhang Y, Meyer N, Jones M, et al. Familial C3 glomerulonephritis caused by a novel CFHR5-CFHR2 fusion gene. Mol Immunol. 2016;77:89–96.

    Article  CAS  PubMed  Google Scholar 

  66. Corvillo F, Okroj M, Nozal P, Melgosa M, Sanchez-Corral P, Lopez-Trascasa M. Nephritic factors: an overview of classification, diagnostic tools and clinical associations. Front Immunol. 2019;10:886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Jozsi M, Reuter S, Nozal P, Lopez-Trascasa M, Sanchez-Corral P, Prohaszka Z, et al. Autoantibodies to complement components in C3 glomerulopathy and atypical hemolytic uremic syndrome. Immunol Lett. 2014;160(2):163–71.

    Article  CAS  PubMed  Google Scholar 

  68. Servais A, Noel L-H, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey M-A, et al. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. 2012;82(4):454–64.

    Article  CAS  PubMed  Google Scholar 

  69. Tanuma Y, Ohi H, Hatano M. Two types of C3 nephritic factor: properdin-dependent C3NeF and properdin-independent C3NeF. Clin Immunol Immunopathol. 1990;56(2):226–38.

    Article  CAS  PubMed  Google Scholar 

  70. Spitzer RE, Stitzel AE. On the origin and control of C3NeF. In Vivo. 1988;2(1):79–81.

    CAS  PubMed  Google Scholar 

  71. Berthoux FC, Carpenter CB, Traeger J, Merrill JP. C3 nephritic factor and heat labile complement inactivator in chronic hypocomplementemic mesangioproliferative glomerulonephritis. [French] Le Facteur Nephritique (C3 Nephritic Factor) Et L’inactivateur Thermolabile Du Complement (Heat Labile Complement Inactivator) Dans Les Glomerulonephrites Mesangioproliferatives Hypocomplementaires Chroniques. Actualites Nephrologiques de l’Hopital Necker. 1974;1974:141–56.

    Google Scholar 

  72. Waldo FB, Forristal J, Beischel L, West CD. A circulating inhibitor of fluid-phase amplification. C3 convertase formation in systemic lupus erythematosus. J Clin Invest. 1985;75(6):1786–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Arroyave CM, Wilson MR, Tan EM. Serum factors activating the alternative complement pathway in autoimmune disease: description of two different factors from patients with systemic lupus erythematosus. J Immunol. 1976;116(3):821–6.

    Article  CAS  PubMed  Google Scholar 

  74. Wilson MR, Arroyave CM, Nakamura RM, Vaughan JH, Tan EM. Activation of the alternative complement pathway in systemic lupus erythematosus. Clin Exp Immunol. 1976;26(1):11–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Sethi S, Fervenza FC, Zhang Y, Zand L, Meyer NC, Borsa N, et al. Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int. 2013;83(2):293–9.

    Article  CAS  PubMed  Google Scholar 

  76. Lewis LA, Ram S. Meningococcal disease and the complement system. Virulence. 2014;5(1):98–126.

    Article  PubMed  Google Scholar 

  77. Paixao-Cavalcante D, Lopez-Trascasa M, Skattum L, Giclas PC, Goodship TH, de Cordoba SR, et al. Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation. Kidney Int. 2012;82(10):1084–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Iatropoulos P, Noris M, Mele C, Piras R, Valoti E, Bresin E, et al. Complement gene variants determine the risk of immunoglobulin-associated MPGN and C3 glomerulopathy and predict long-term renal outcome. Mol Immunol. 2016;71:131–42.

    Article  CAS  PubMed  Google Scholar 

  79. Nicolas C, Vuiblet V, Baudouin V, Macher M-A, Vrillon I, Biebuyck-Gouge N, et al. C3 nephritic factor associated with C3 glomerulopathy in children. Pediatr Nephrol. 2014;29(1):85–94.

    Article  PubMed  Google Scholar 

  80. Leroy V, Fremeaux-Bacchi V, Peuchmaur M, Baudouin V, Deschenes G, Macher M-A, et al. Membranoproliferative glomerulonephritis with C3NeF and genetic complement dysregulation. Pediatr Nephrol. 2011;26(3):419–24.

    Article  PubMed  Google Scholar 

  81. Marinozzi MC, Roumenina LT, Chauvet S, Hertig A, Bertrand D, Olagne J, et al. Anti-factor B and anti-C3b autoantibodies in C3 glomerulopathy and Ig-associated membranoproliferative GN. J Am Soc Nephrol. 2017;28(5):1603–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Strobel S, Zimmering M, Papp K, Prechl J, Jozsi M. Anti-factor B autoantibody in dense deposit disease. Mol Immunol. 2010;47(7–8):1476–83.

    Article  CAS  PubMed  Google Scholar 

  83. Chen Q, Muller D, Rudolph B, Hartmann A, Kuwertz-Broking E, Wu K, et al. Combined C3b and factor B autoantibodies and MPGN type II. N Engl J Med. 2011;365(24):2340–2.

    Article  CAS  PubMed  Google Scholar 

  84. Hofer J, Janecke AR, Zimmerhackl LB, Riedl M, Rosales A, Giner T, et al. Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol. 2013;8(3):407–15.

    Article  CAS  PubMed  Google Scholar 

  85. Jokiranta TS, Solomon A, Pangburn MK, Zipfel PF, Meri S. Nephritogenic lambda light chain dimer: a unique human miniautoantibody against complement factor H. J Immunol. 1999;163(8):4590–6.

    Article  CAS  PubMed  Google Scholar 

  86. Meri S, Koistinen V, Miettinen A, Tornroth T, Seppala IJ. Activation of the alternative pathway of complement by monoclonal lambda light chains in membranoproliferative glomerulonephritis. J Exp Med. 1992;175(4):939–50.

    Article  CAS  PubMed  Google Scholar 

  87. Blanc C, Togarsimalemath SK, Chauvet S, Le Quintrec M, Moulin B, Buchler M, et al. Anti-factor H autoantibodies in C3 glomerulopathies and in atypical hemolytic uremic syndrome: one target, two diseases. J Immunol. 2015;194(11):5129–38.

    Article  CAS  PubMed  Google Scholar 

  88. Garam N, Prohaszka Z, Szilagyi A, Aigner C, Schmidt A, Gaggl M, et al. C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy. Orphanet J Rare Dis. 2019;14(1):247.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Zhang Y, Meyer NC, Fervenza FC, Lau W, Keenan A, Cara-Fuentes G, et al. C4 nephritic factors in C3 glomerulopathy: a case series. Am J Kidney Dis. 2017;70(6):834–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Blom AM, Corvillo F, Magda M, Stasilojc G, Nozal P, Perez-Valdivia MA, et al. Testing the activity of complement convertases in serum/plasma for diagnosis of C4NeF-mediated C3 glomerulonephritis. J Clin Immunol. 2016;36(5):517–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Marinozzi MC, Chauvet S, Le Quintrec M, Mignotet M, Petitprez F, Legendre C, et al. C5 nephritic factors drive the biological phenotype of C3 glomerulopathies. Kidney Int. 2017;92(5):1232–41.

    Article  CAS  PubMed  Google Scholar 

  92. Smith RJH, Appel GB, Blom AM, Cook HT, D’Agati VD, Fakhouri F, et al. C3 glomerulopathy – understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019;15(3):129–43.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Bu F, Borsa NG, Jones MB, Takanami E, Nishimura C, Hauer JJ, et al. High-throughput genetic testing for thrombotic microangiopathies and C3 glomerulopathies. J Am Soc Nephrol. 2016;27(4):1245–53.

    Article  CAS  PubMed  Google Scholar 

  94. Iatropoulos P, Daina E, Curreri M, Piras R, Valoti E, Mele C, et al. Cluster analysis identifies distinct pathogenetic patterns in C3 glomerulopathies/immune complex-mediated membranoproliferative GN. J Am Soc Nephrol. 2018;29(1):283–94.

    Article  CAS  PubMed  Google Scholar 

  95. Abrera-Abeleda MA, Nishimura C, Frees K, Jones M, Maga T, Katz LM, et al. Allelic variants of complement genes associated with dense deposit disease. J Am Soc Nephrol. 2011;22(8):1551–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ault BH, Schmidt BZ, Fowler NL, Kashtan CE, Ahmed AE, Vogt BA, et al. Human factor H deficiency. Mutations in framework cysteine residues and block in H protein secretion and intracellular catabolism. J Biol Chem. 1997;272(40):25168–75.

    Article  CAS  PubMed  Google Scholar 

  97. Chen Q, Wiesener M, Eberhardt HU, Hartmann A, Uzonyi B, Kirschfink M, et al. Complement factor H-related hybrid protein deregulates complement in dense deposit disease. J Clin Invest. 2014;124(1):145–55.

    Article  CAS  PubMed  Google Scholar 

  98. Dragon-Durey MA, Fremeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G, et al. Heterozygous and homozygous factor h deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: report and genetic analysis of 16 cases. J Am Soc Nephrol. 2004;15(3):787–95.

    Article  CAS  PubMed  Google Scholar 

  99. Gale DP, de Jorge EG, Cook HT, Martinez-Barricarte R, Hadjisavvas A, McLean AG, et al. Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet. 2010;376(9743):794–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Habbig S, Mihatsch MJ, Heinen S, Beck B, Emmel M, Skerka C, et al. C3 deposition glomerulopathy due to a functional factor H defect. Kidney Int. 2009;75(11):1230–4.

    Article  PubMed  Google Scholar 

  101. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI, et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A. 2005;102(20):7227–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tortajada A, Yebenes H, Abarrategui-Garrido C, Anter J, Garcia-Fernandez JM, Martinez-Barricarte R, et al. C3 glomerulopathy-associated CFHR1 mutation alters FHR oligomerization and complement regulation. J Clin Invest. 2013;123(6):2434–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Vogt BA, Wyatt RJ, Burke BA, Simonton SC, Kashtan CE. Inherited factor H deficiency and collagen type III glomerulopathy. Pediatr Nephrol. 1995;9(1):11–5.

    Article  CAS  PubMed  Google Scholar 

  104. Licht C, Heinen S, Jozsi M, Loschmann I, Saunders RE, Perkins SJ, et al. Deletion of Lys224 in regulatory domain 4 of factor H reveals a novel pathomechanism for dense deposit disease (MPGN II). Kidney Int. 2006;70(1):42–50.

    Article  CAS  PubMed  Google Scholar 

  105. Martinez-Barricarte R, Heurich M, Valdes-Canedo F, Vazquez-Martul E, Torreira E, Montes T, et al. Human C3 mutation reveals a mechanism of dense deposit disease pathogenesis and provides insights into complement activation and regulation. J Clin Invest. 2010;120(10):3702–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Levy M, Halbwachs-Mecarelli L, Gubler MC. H deficiency in two brothers with atypical dense intramembranous deposit disease. Kidney Int. 1986;30(6):949–56.

    Article  CAS  PubMed  Google Scholar 

  107. Abrera-Abeleda MA, Nishimura C, Smith JLH, Sethi S, McRae JL, Murphy BF, et al. 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. 2006;43(7):582–9.

    Article  CAS  PubMed  Google Scholar 

  108. Smith RJH, Alexander J, Barlow PN, Botto M, Cassavant TL, Cook HT, et al. New approaches to the treatment of dense deposit disease. J Am Soc Nephrol. 2007;18(9):2447–56.

    Article  CAS  PubMed  Google Scholar 

  109. Xiao X, Pickering MC, Smith RJ. C3 glomerulopathy: the genetic and clinical findings in dense deposit disease and c3 glomerulonephritis. Semin Thromb Hemost. 2014;40(4):465–71.

    Article  CAS  PubMed  Google Scholar 

  110. Malik TH, Lavin PJ, De Jorge EG, Vernon KA, Rose KL, Patel MP, et al. A hybrid CFHR3-1 gene causes familial C3 glomerulopathy. J Am Soc Nephrol. 2012;23(7):1155–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon-Durey MA, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide french series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Ozaltin F, Li B, Rauhauser A, An SW, Soylemezoglu O, Gonul II, et al. DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN. J Am Soc Nephrol. 2013;24(3):377–84.

    Article  CAS  PubMed  Google Scholar 

  113. Mele C, Lemaire M, Iatropoulos P, Piras R, Bresin E, Bettoni S, et al. Characterization of a new DGKE intronic mutation in genetically unsolved cases of familial atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol. 2015;10(6):1011–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lemaire M, Fremeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet. 2013;45(5):531–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Levine AP, Chan MMY, Sadeghi-Alavijeh O, Wong EKS, Cook HT, Ashford S, et al. Large-scale whole-genome sequencing reveals the genetic architecture of primary membranoproliferative GN and C3 glomerulopathy. J Am Soc Nephrol. 2020;31(2):365–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Medjeral-Thomas NR, O’Shaughnessy MM, O’Regan JA, Traynor C, Flanagan M, Wong L, et al. C3 glomerulopathy: clinicopathologic features and predictors of outcome. Clin J Am Soc Nephrol. 2014;9(1):46–53.

    Article  CAS  PubMed  Google Scholar 

  117. Coppo R, Gianoglio B, Porcellini MG, Maringhini S. Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian National Registry of Renal Biopsies in Children). Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal Immunopathology of the Italian Society of Nephrology. Nephrol Dial Transplant. 1998;13(2):293–7.

    Article  CAS  PubMed  Google Scholar 

  118. Lu D-F, Moon M, Lanning LD, McCarthy AM, Smith RJH. Clinical features and outcomes of 98 children and adults with dense deposit disease. Pediatr Nephrol. 2012;27(5):773–81.

    Article  PubMed  Google Scholar 

  119. Athanasiou Y, Voskarides K, Gale DP, Damianou L, Patsias C, Zavros M, et al. Familial C3 glomerulopathy associated with CFHR5 mutations: clinical characteristics of 91 patients in 16 pedigrees. Clin J Am Soc Nephrol. 2011;6(6):1436–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Besbas N, Gulhan B, Gucer S, Korkmaz E, Ozaltin F. A novel CFHR5 mutation associated with C3 glomerulonephritis in a Turkish girl. J Nephrol. 2014;27(4):457–60.

    Article  CAS  PubMed  Google Scholar 

  121. Medjeral-Thomas N, Malik TH, Patel MP, Toth T, Cook HT, Tomson C, et al. A novel CFHR5 fusion protein causes C3 glomerulopathy in a family without Cypriot ancestry. Kidney Int. 2014;85(4):933–7.

    Article  CAS  PubMed  Google Scholar 

  122. Jackson EC, McAdams AJ, Strife CF. Differences between membranoproliferative glomerulonephritis types I and III in clinical presentation, glomerular morphology, and complement perturbation. Am J Kidney Dis. 1987;9(2):115–20.

    Article  CAS  PubMed  Google Scholar 

  123. Deltas C, Gale D, Cook T, Voskarides K, Athanasiou Y, Pierides A. C3 glomerulonephritis/CFHR5 nephropathy is an endemic disease in Cyprus: clinical and molecular findings in 21 families. Adv Exp Med Biol. 2013;735:189–96.

    Article  CAS  PubMed  Google Scholar 

  124. Zhan X, Larson DE, Wang C, Koboldt DC, Sergeev YV, Fulton RS, et al. Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. Nat Genet. 2013;45(11):1375–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Mullins RF, Aptsiauri N, Hageman GS. Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis. Eye. 2001;15(Pt 3):390–5.

    Article  CAS  PubMed  Google Scholar 

  126. Mullins RF, Russell SR, Anderson DH, Hageman GS. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J. 2000;14(7):835–46.

    Article  CAS  PubMed  Google Scholar 

  127. Appel GB, Cook HT, Hageman G, Jennette JC, Kashgarian M, Kirschfink M, et al. Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. J Am Soc Nephrol. 2005;16(5):1392–403.

    Article  PubMed  Google Scholar 

  128. Mathieson PW, Wurzner R, Oliveria DB, Lachmann PJ, Peters DK. Complement-mediated adipocyte lysis by nephritic factor sera. J Exp Med. 1993;177(6):1827–31.

    Article  CAS  PubMed  Google Scholar 

  129. Misra A, Peethambaram A, Garg A. Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature. Medicine. 2004;83(1):18–34.

    Article  CAS  PubMed  Google Scholar 

  130. Alchi B, Jayne D. Membranoproliferative glomerulonephritis. Pediatr Nephrol. 2010;25(8):1409–18.

    Article  PubMed  Google Scholar 

  131. Chauvet S, Berthaud R, Devriese M, Mignotet M, Vieira Martins P, Robe-Rybkine T, et al. Anti-factor B antibodies and acute postinfectious GN in children. J Am Soc Nephrol. 2020;31(4):829–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Fremeaux-Bacchi V, Kavanagh D, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539–51.

    Article  CAS  PubMed  Google Scholar 

  133. Yuan M, Zou J, Zhang X, Liu H, Teng J, Zhong Y, et al. Combination therapy with mycophenolate mofetil and prednisone in steroid-resistant idiopathic membranoproliferative glomerulonephritis. Clin Nephrol. 2010;73(5):354–9.

    Article  CAS  PubMed  Google Scholar 

  134. Dimkovic N, Jovanovic D, Kovacevic Z, Rabrenovic V, Nesic V, Savin M, et al. Mycophenolate mofetil in high-risk patients with primary glomerulonephritis: results of a 1-year prospective study. Nephron Clin Pract. 2009;111(3):c189–c96.

    Article  CAS  PubMed  Google Scholar 

  135. Mazo A, Margieva T, Vashurina T, Zrobok O, Tsygin A. The treatment of membranoproliferative glomerulonephritis in children with mycophenolate mofetil. Pediatr Nephrol. 2013;28(8):1607–8.

    Google Scholar 

  136. Caravaca-Fontan F, Diaz-Encarnacion MM, Lucientes L, Cavero T, Cabello V, Ariceta G, et al. Mycophenolate mofetil in C3 glomerulopathy and pathogenic drivers of the disease. Clin J Am Soc Nephrol. 2020;15(9):1287–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Avasare RS, Canetta PA, Bomback AS, Marasa M, Caliskan Y, Ozluk Y, et al. Mycophenolate mofetil in combination with steroids for treatment of C3 glomerulopathy: a case series. Clin J Am Soc Nephrol. 2018;13(3):406–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Bagheri N, Nemati E, Rahbar K, Nobakht A, Einollahi B, Taheri S. Cyclosporine in the treatment of membranoproliferative glomerulonephritis. Arch Iran Med. 2008;11(1):26–9.

    CAS  PubMed  Google Scholar 

  139. Fan L, Liu Q, Liao Y, Li Z, Ji Y, Yang Z, et al. Tacrolimus is an alternative therapy option for the treatment of adult steroid-resistant nephrotic syndrome: a prospective, multicenter clinical trial. Int Urol Nephrol. 2013;45(2):459–68.

    Article  CAS  PubMed  Google Scholar 

  140. Li X, Li H, Ye H, Li Q, He X, Zhang X, et al. Tacrolimus therapy in adults with steroid- and cyclophosphamide-resistant nephrotic syndrome and normal or mildly reduced GFR. Am J Kidney Dis. 2009;54(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  141. Rabasco C, Cavero T, Roman E, Rojas-Rivera J, Olea T, Espinosa M, et al. Effectiveness of mycophenolate mofetil in C3 glomerulonephritis. Kidney Int. 2015;88(5):1153–60.

    Article  CAS  PubMed  Google Scholar 

  142. Haddad M, Lau K, Butani L. Remission of membranoproliferative glomerulonephritis type I with the use of tacrolimus. Pediatr Nephrol. 2007;22(10):1787–91.

    Article  PubMed  Google Scholar 

  143. Kiyomasu T, Shibata M, Kurosu H, Shiraishi K, Hashimoto H, Hayashidera T, et al. Cyclosporin A treatment for membranoproliferative glomerulonephritis type II. Nephron. 2002;91(3):509–11.

    Article  PubMed  Google Scholar 

  144. Hiramatsu M. Cyclosporin a treatment for dense deposit disease with steroid resistant nephrotic syndrome. Pediatr Nephrol. 2010;25(9):1804.

    Google Scholar 

  145. Dillon JJ, Hladunewich M, Haley WE, Reich HN, Cattran DC, Fervenza FC. Rituximab therapy for Type I membranoproliferative glomerulonephritis. Clin Nephrol. 2012;77(4):290–5.

    Article  CAS  PubMed  Google Scholar 

  146. Kong WY, Swaminathan R, Irish A. Our experience with rituximab therapy for adult-onset primary glomerulonephritis and review of literature. Int Urol Nephrol. 2013;45(3):795–802.

    Article  CAS  PubMed  Google Scholar 

  147. Perez-Saez MJ, Toledo K, Navarro MD, Lopez-Andreu M, Redondo MD, Ortega R, et al. Recurrent membranoproliferative glomerulonephritis after second renal graft treated with plasmapheresis and rituximab. Transplant Proc. 2011;43(10):4005–9.

    Article  CAS  PubMed  Google Scholar 

  148. Sugiura H, Takei T, Itabashi M, Tsukada M, Moriyama T, Kojima C, et al. Effect of single-dose rituximab on primary glomerular diseases. Nephron Clin Pract. 2011;117(2):c98–c105.

    Article  CAS  PubMed  Google Scholar 

  149. Guiard E, Karras A, Plaisier E, Duong Van Huyen J-P, Fakhouri F, Rougier J-P, et al. Patterns of noncryoglobulinemic glomerulonephritis with monoclonal Ig deposits: correlation with IgG subclass and response to rituximab. Clin J Am Soc Nephrol. 2011;6(7):1609–16.

    Article  CAS  PubMed  Google Scholar 

  150. McCaughan JA, O’Rourke DM, Courtney AE. Recurrent dense deposit disease after renal transplantation: an emerging role for complementary therapies. Am J Transplant. 2012;12(4):1046–51.

    Article  CAS  PubMed  Google Scholar 

  151. Daina E, Noris M, Remuzzi G. Eculizumab in a patient with dense-deposit disease. N Engl J Med. 2012;366(12):1161–3.

    Article  CAS  PubMed  Google Scholar 

  152. Nord AT, Nord BL, Schmidt AE, Smith DS. Management of dense deposit disease with plasmapheresis and eculizumab. J Clin Apher. 2014;29(1):28–9.

    Google Scholar 

  153. McGinley E, Watkins R, McLay A, Boulton-Jones JM. Plasma exchange in the treatment of mesangiocapillary glomerulonephritis. Nephron. 1985;40(4):385–90.

    Article  CAS  PubMed  Google Scholar 

  154. Radhakrishnan S, Lunn A, Kirschfink M, Thorner P, Hebert D, Langlois V, et al. Eculizumab and refractory membranoproliferative glomerulonephritis. N Engl J Med. 2012;366(12):1165–6.

    Article  CAS  PubMed  Google Scholar 

  155. Oberkircher OR, Enama M, West JC, Campbell P, Moran J. Regression of recurrent membranoproliferative glomerulonephritis type II in a transplanted kidney after plasmapheresis therapy. Transplant Proc. 1988;20(1 Suppl 1):418–23.

    CAS  PubMed  Google Scholar 

  156. Kurtz KA, Schlueter AJ. Management of membranoproliferative glomerulonephritis type II with plasmapheresis. J Clin Apher. 2002;17(3):135–7.

    Article  PubMed  Google Scholar 

  157. Banks RA, May S, Wallington T. Acute renal failure in dense deposit disease: recovery after plasmapheresis. Br Med J (Clin Res Ed). 1982;284(6332):1874–5.

    Article  CAS  Google Scholar 

  158. Masutani K, Katafuchi R, Ikeda H, Yamamoto H, Motoyama K, Sugitani A, et al. Recurrent nephrotic syndrome after living-related renal transplantation resistant to plasma exchange: report of two cases. Clin Transpl. 2005;19(Suppl 14):59–64.

    Article  Google Scholar 

  159. Montoliu J, Bergada E, Botey A, Torras A, Darnell A, Arrizabalaga P, et al. Plasmapheresis induced recovery from renal failure in mesangiocapillary glomerulonephritis of acute onset. Proc Eur Dial Transplant Assoc. 1983;19:794–9.

    CAS  PubMed  Google Scholar 

  160. Muczynski KA. Plasmapheresis maintained renal function in an allograft with recurrent membranoproliferative glomerulonephritis type I. Am J Nephrol. 1995;15(5):446–9.

    Article  CAS  PubMed  Google Scholar 

  161. Pipeleers L, Sennesael J, Massart A, Geers C, Goodship T, Stordeur P, et al. Successful use of plasma exchange to prevent recurrence of C3 glomerulonephritis after kidney transplantation: a case report. Transplantation. 2012;94:1050.

    Article  Google Scholar 

  162. Saxena R, Frankel WL, Sedmak DD, Falkenhain ME, Cosio FG. Recurrent type I membranoproliferative glomerulonephritis in a renal allograft: successful treatment with plasmapheresis. Am J Kidney Dis. 2000;35(4):749–52.

    Article  CAS  PubMed  Google Scholar 

  163. Yadav P, Ognjanovic M, Coulthard M, Moghal N, Lambert H, Tse Y. Recurrent (MPGN) membranoproliferative glomerulonephritis type 1 successfully treated with plasma exchange (PE). Pediatr Nephrol. 2011;26(9):1665–6.

    Google Scholar 

  164. Morton MR, Bannister KM. Renal failure due to mesangiocapillary glomerulonephritis in pregnancy: use of plasma exchange therapy. Clin Nephrol. 1993;40(2):74–8.

    CAS  PubMed  Google Scholar 

  165. Roord JJ, van Diemen-van Steenvoorde RA, Schuurman HJ, Rijkers GT, Zegers BJ, Gmelig Meyling FH, et al. Membranoproliferative glomerulonephritis in a patient with congenital deficiency of the third component of complement: effect of treatment with plasma. Am J Kidney Dis. 1989;13(5):413–7.

    Article  CAS  PubMed  Google Scholar 

  166. Bomback AS, Smith RJ, Barile GR, Zhang Y, Heher EC, Herlitz L, et al. Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol. 2012;7(5):748–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Daina E, Noris M, Remuzzi G. Eculizumab in a patient with dense-deposit disease. [Erratum appears in N Engl J Med. 2012;366(15):1454]. N Engl J Med. 2012;366(12):1161–1163.

    Google Scholar 

  168. Vivarelli M, Pasini A, Emma F. Eculizumab for the treatment of dense-deposit disease. N Engl J Med. 2012;366(12):1163–5.

    Article  CAS  PubMed  Google Scholar 

  169. Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25(11):1256–64.

    Article  CAS  PubMed  Google Scholar 

  170. Pickering MC, Warren J, Rose KL, Carlucci F, Wang Y, Walport MJ, et al. Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice. Proc Natl Acad Sci U S A. 2006;103(25):9649–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Gurkan S, Fyfe B, Weiss L, Xiao X, Zhang Y, Smith RJ. Eculizumab and recurrent C3 glomerulonephritis. Pediatr Nephrol. 2013;28(10):1975–81.

    Article  PubMed  PubMed Central  Google Scholar 

  172. Ozkaya O, Nalcacioglu H, Tekcan D, Genc G, Meydan BC, Ozdemir BH, et al. Eculizumab therapy in a patient with dense-deposit disease associated with partial lipodystropy. Pediatr Nephrol. 2014;29(7):1283–7.

    Article  PubMed  Google Scholar 

  173. Rousset-Rouviere C, Cailliez M, Garaix F, Bruno D, Laurent D, Tsimaratos M. Rituximab fails where eculizumab restores renal function in C3nef-related DDD. Pediatr Nephrol. 2014;29(6):1107–11.

    Article  PubMed  Google Scholar 

  174. Vivarelli M, Emma F. Treatment of C3G with complement blockers. Semin Thromb Hemost. 2014;40(4):472–7.

    Google Scholar 

  175. Le Quintrec M, Lapeyraque AL, Lionet A, Sellier-Leclerc AL, Delmas Y, Baudouin V, et al. Patterns of clinical response to eculizumab in patients with C3 glomerulopathy. Am J Kidney Dis. 2018;72(1):84–92.

    Article  PubMed  CAS  Google Scholar 

  176. Ruggenenti P, Daina E, Gennarini A, Carrara C, Gamba S, Noris M, et al. C5 convertase blockade in membranoproliferative glomerulonephritis: a single-arm clinical trial. Am J Kidney Dis. 2019;74(2):224–38.

    Article  CAS  PubMed  Google Scholar 

  177. Kirpalani A, Jawa N, Smoyer WE, Licht C. Midwest pediatric nephrology C. long-term outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis in children. Kidney Int Rep. 2020;5(12):2313–24.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Van Stralen KJ, Verrina E, Belingheri M, Dudley J, Dusek J, Grenda R, et al. Impact of graft loss among kidney diseases with a high risk of post-transplant recurrence in the paediatric population. Nephrol Dial Transplant. 2013;28(4):1031–8.

    Article  PubMed  CAS  Google Scholar 

  179. Braun MC, Stablein DM, Hamiwka LA, Bell L, Bartosh SM, Strife CF. Recurrence of membranoproliferative glomerulonephritis type II in renal allografts: the North American Pediatric Renal Transplant Cooperative Study experience. J Am Soc Nephrol. 2005;16(7):2225–33.

    Article  PubMed  Google Scholar 

  180. Zand L, Lorenz EC, Cosio FG, Fervenza FC, Nasr SH, Gandhi MJ, et al. Clinical findings, pathology, and outcomes of C3GN after kidney transplantation. J Am Soc Nephrol. 2014;25(5):1110–7.

    Article  CAS  PubMed  Google Scholar 

  181. Vernon KA, Gale DP, De Jorge EG, McLean AG, Maxwell PH, Pickering MC, et al. Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant. Mol Immunol. 2010;47:2202.

    Article  Google Scholar 

  182. Gupta A, Quigg RJ. Glomerular diseases associated with hepatitis B and C. Adv Chronic Kidney Dis. 2015;22(5):343–51.

    Article  PubMed  Google Scholar 

  183. Johnson RJ, Gretch DR, Yamabe H, Hart J, Bacchi CE, Hartwell P, et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N Engl J Med. 1993;328(7):465–70.

    Article  CAS  PubMed  Google Scholar 

  184. Kamar N, Marion O, Abravanel F, Izopet J, Dalton HR. Extrahepatic manifestations of hepatitis E virus. Liver Int. 2016;36(4):467–72.

    Article  PubMed  Google Scholar 

  185. Karamadoukis L, Toth T, Tomson C. Membranoproliferative glomerulonephritis associated with an Epstein-Barr virus infection. NDT Plus. 2008;1(5):319–21.

    PubMed  PubMed Central  Google Scholar 

  186. D’Agati VD, Appel GB. Renal pathology of human immunodeficiency virus infection. Semin Nephrol. 1998;18(4):406–21.

    PubMed  Google Scholar 

  187. Haffner D, Schindera F, Aschoff A, Matthias S, Waldherr R, Schärer K. The clinical spectrum of shunt nephritis. Nephrol Dial Transplant. 1997;12(6):1143–8.

    Article  CAS  PubMed  Google Scholar 

  188. Elmaci I, Senday D, Silav G, Ekenel F, Balak N, Ayan E, et al. Nocardial cerebral abscess associated with mycetoma, pneumonia, and membranoproliferative glomerulonephritis. J Clin Microbiol. 2007;45(6):2072–4.

    Article  PubMed  PubMed Central  Google Scholar 

  189. Frew AJ, Higgins RM. Empyema and mesangiocapillary glomerulonephritis with nephrotic syndrome. Br J Dis Chest. 1988;82(1):93–6.

    Article  CAS  PubMed  Google Scholar 

  190. Ram R, Sandeep P, Sridhar AV, Rukumangadha N, Sivakumar V. Membranoproliferative glomerulonephritis and Pott’s disease. Clin Kidney J. 2014;7(4):391–3.

    Article  PubMed  PubMed Central  Google Scholar 

  191. Silva Junior GB, Daher Ede F, Pires Neto Rda J, Pereira ED, Meneses GC, Araújo SM, et al. Leprosy nephropathy: a review of clinical and histopathological features. Rev Inst Med Trop Sao Paulo. 2015;57(1):15–20.

    Article  PubMed  Google Scholar 

  192. Provatopoulou S, Papasotiriou M, Papachristou E, Gakiopoulou H, Marangos M, Goumenos DS. Membranoproliferative glomerulonephritis in a patient with chronic brucellosis. Kidney Res Clin Pract. 2018;37(3):298–303.

    Article  PubMed  PubMed Central  Google Scholar 

  193. Leclerc S, Royal V, Dufresne SF, Mondésert B, Laurin LP. Membranoproliferative glomerulonephritis in a patient with chronic Q fever. Kidney Int Rep. 2020;5(12):2393–8.

    Article  PubMed  PubMed Central  Google Scholar 

  194. Silva GBDJ, Pinto JR, Barros EJG, Farias GMN, Daher EF. Kidney involvement in malaria: an update. Rev Inst Med Trop Sao Paulo. 2017;59:e53–e8.

    Google Scholar 

  195. Neves PDMM, Jorge LB, Cavalcante LB, Malheiros D, Woronik V, Dias CB. Schistosomiasis-associated glomerulopathy: clinical aspects, pathological characteristics, and renal outcomes. Clin Nephrol. 2020;93(5):251–61.

    Article  PubMed  Google Scholar 

  196. Seedat YK. Glomerular disease in the tropics. Semin Nephrol. 2003;23(1):12–20.

    Article  PubMed  Google Scholar 

  197. Spatola L, Generali E, Angelini C, Badalamenti S, Selmi C. HCV-negative mixed cryoglobulinemia and kidney involvement: in-depth review on physiopathological and histological bases. Clin Exp Med. 2018;18(4):465–71.

    Article  PubMed  Google Scholar 

  198. Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018;93(4):789–96.

    Article  PubMed  Google Scholar 

  199. Jelusic M, Sestan M, Cimaz R, Ozen S. Different histological classifications for Henoch-Schönlein purpura nephritis: which one should be used? Pediatr Rheumatol Online J. 2019;17(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  200. François H, Mariette X. Renal involvement in primary Sjögren syndrome. Nat Rev Nephrol. 2016;12(2):82–93.

    Google Scholar 

  201. Ion O, Obrișcă B, Ismail G, Sorohan B, Bălănică S, Mircescu G, et al. Kidney involvement in hypocomplementemic urticarial vasculitis syndrome-A case-based review. J Clin Med. 2020;9(7):2131.

    Google Scholar 

  202. Zand L, Fervenza FC, Nasr SH, Sethi S. Membranoproliferative glomerulonephritis associated with autoimmune diseases. J Nephrol. 2014;27(2):165–71.

    Article  CAS  PubMed  Google Scholar 

  203. Yoshino A, Honda M, Kanegane H, Obata K, Matsukura H, Sakazume S, et al. Membranoproliferative glomerulonephritis in a patient with X-linked agammaglobulinemia. Pediatr Nephrol. 2006;21(1):36–8.

    Article  PubMed  Google Scholar 

  204. Motwani SS, Herlitz L, Monga D, Jhaveri KD, Lam AQ, Forum ASoNO-N. Paraprotein–related kidney disease: glomerular diseases associated with paraproteinemias. Clin J Am Soc Nephrol. 2016;11(12):2260–2272.

    Google Scholar 

  205. Sethi S, Zand L, Leung N, Smith RJH, Jevremonic D, Herrmann SS, et al. Membranoproliferative glomerulonephritis secondary to monoclonal gammopathy. Clin J Am Soc Nephrol. 2010;5(5):770–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Karafin MS, Humphrey RL, Detrick B. Evaluation of monoclonal and oligoclonal gammopathies in a pediatric population in a major urban center. Am J Clin Pathol. 2014;141(4):482–7.

    Article  PubMed  Google Scholar 

  207. Nasr SH, Valeri AM, Cornell LD, Fidler ME, Sethi S, Leung N, et al. Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. 2011;6(4):775–84.

    Article  PubMed  PubMed Central  Google Scholar 

  208. Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, Appel GB, D’Agati V. Fibrillary and immunotactoid glomerulonephritis: distinct entities with different clinical and pathologic features. Kidney Int. 2003;63:1450–61.

    Article  PubMed  Google Scholar 

  209. Nasr SH, Satoskar A, Markowitz G, Valeri A, Appel GB, Stokes MB, et al. Proliferative glomerulonephritis with monoclonal IgG deposits. J Am Soc Nephrol. 2009;20(9):2055–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Miller P, Xiao AY, Kung VL, Sibley RK, Higgins JP, Kambham N, et al. Progression of proliferative glomerulonephritis with monoclonal IgG deposits in pediatric patients. Pediatr Nephrol. 2021;36(4):927–937.

    Google Scholar 

  211. Nasr SH, Larsen CP, Sirac C, Theis JD, Domenger C, Chauvet S, et al. Light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits is associated with a high detection rate of the pathogenic plasma cell clone. Kidney Int. 2020;97(3):589–601.

    Article  CAS  PubMed  Google Scholar 

  212. Larsen CP, Messias NC, Walker PD, Fidler ME, Cornell LD, Hernandez LH, et al. Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits. Kidney Int. 2015;88(4):867–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Nasr SH, Valeri AM, Cornell LD, Fidler ME, Sethi S, D’Agati VD, et al. Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution. Clin J Am Soc Nephrol. 2012;7(2):231–9.

    Article  PubMed  Google Scholar 

  214. Kowalewska J, Nicosia RF, Smith KD, Kats A, Alpers CE. Patterns of glomerular injury in kidneys infiltrated by lymphoplasmacytic neoplasms. Hum Pathol. 2011;42(6):896–903.

    Article  PubMed  Google Scholar 

  215. Li SJ, Chen HP, Chen YH, Zhang LH, Tu YM, Liu ZH. Renal involvement in non-Hodgkin lymphoma: proven by renal biopsy. PLoS One. 2014;9(4):e95190.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  216. Kim JY, Lee MY, Kim B, Park CW, Chang YS, Chung S. Membranoproliferative glomerulonephritis following allogeneic hematopoietic stem cell transplantation. Clin Exp Nephrol. 2010;14(6):630–2.

    Article  PubMed  Google Scholar 

  217. Jhaveri KD, Shah HH, Calderon K, Campenot ES, Radhakrishnan J. Glomerular diseases seen with cancer and chemotherapy: a narrative review. Kidney Int. 2013;84(1):34–44.

    Article  CAS  PubMed  Google Scholar 

  218. Zhou Q, Zhang Y, Zhou G, Zhu J. Kidney biopsy findings in two patients with TAFRO syndrome: case presentations and review of the literature. BMC Nephrol. 2020;21(1):499–509.

    Article  PubMed  PubMed Central  Google Scholar 

  219. Kurose N, Mizutani KI, Kumagai M, Shioya A, Guo X, Nakada S, et al. An extranodal histopathological analysis of idiopathic multicentric Castleman disease with and without TAFRO syndrome. Pathol Res Pract. 2019;215(3):410–3.

    Article  PubMed  Google Scholar 

  220. Sugimoto K, Ueda S, Okada M, Takemura T. Membranoproliferative glomerulonephritis associated with Rosai-Dorfman disease. Clin Nephrol Case Stud. 2017;5:54–9.

    Article  PubMed  PubMed Central  Google Scholar 

  221. Strife CF, Hug G, Chuck G, McAdams AJ, Davis CA, Kline JJ. Membranoproliferative glomerulonephritis and alpha 1-antitrypsin deficiency in children. Pediatrics. 1983;71(1):88–92.

    Article  CAS  PubMed  Google Scholar 

  222. Jhaveri KD, D’Agati VD, Pursell R, Serur D. Coeliac sprue-associated membranoproliferative glomerulonephritis (MPGN). Nephrol Dial Transplant. 2009;24:3545–8.

    Article  CAS  PubMed  Google Scholar 

  223. Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol. 2018;13(2):300–17.

    Article  CAS  PubMed  Google Scholar 

  224. Zahr RS, Yee ME, Weaver J, Twombley K, Matar RB, Aviles D, et al. Kidney biopsy findings in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol. 2019;34(8):1435–45.

    Article  PubMed  Google Scholar 

  225. Roufosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen KJ, Horsfield C, et al. A 2018 reference guide to the Banff classification of renal allograft pathology. Transplantation. 2018;102(11):1795–814.

    Article  PubMed  PubMed Central  Google Scholar 

  226. Kim EJ, Shin DH, Jeon HJ, Rhee SY, Nam ES, Park JY, et al. A rare case of polyneuropathy and monoclonalgammopathy with recurrent acute kidney injury. Electrolyte Blood Press. 2016;14(1):5–10.

    Article  PubMed  PubMed Central  Google Scholar 

  227. Noris M, Remuzzi G. Glomerular diseases dependent on complement activation, including atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and C3 glomerulopathy: core curriculum 2015. Am J Kidney Dis. 2015;66(2):359–75.

    Article  PubMed  PubMed Central  Google Scholar 

  228. Togarsimalemath SK, Sethi SK, Duggal R, Le Quintrec M, Jha P, Daniel R, et al. A novel CFHR1-CFHR5 hybrid leads to a familial dominant C3 glomerulopathy. Kidney Int. 2017;92(4):876–87.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada

    Christoph Licht & Magdalena Riedl Khursigara

  2. Division of Nephrology and Dialysis, Department of Pediatric Subspecialties, Bambino Gesù Pediatric Hospital – IRCCS, Rome, Italy

    Marina Vivarelli

  3. Centre for Inflammatory Disease, Imperial College, London, UK

    Matthew C. Pickering

  4. Arkana Laboratories, Little Rock, AR, USA

    Patrick D. Walker

Authors
  1. Christoph Licht
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina Vivarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Magdalena Riedl Khursigara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthew C. Pickering
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Patrick D. Walker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christoph Licht .

Editor information

Editors and Affiliations

  1. Division of Nephrology, Bambino Gesù Children’s Hospital –, ROMA, Roma, Italy

    Francesco Emma

  2. Division of Nephrology and Hypertension The Heart Institute, University of Cincinnati Cincinnati Children’s Hospital Medical C, Cincinnati, OH, USA

    Stuart Goldstein

  3. Division of Nephrology, All India Institute of Medical Sciences, Ansari Nagar East, Delhi, India

    Arvind Bagga

  4. Division of Pediatric Nephrology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Carlton M. Bates

  5. Renal Unit, Graet Ormond Street Hospital, London, UK

    Rukshana Shroff

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer-Verlag GmbH Germany, part of Springer Nature

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Licht, C., Vivarelli, M., Riedl Khursigara, M., Pickering, M.C., Walker, P.D. (2021). Membranoproliferative Glomerulonephritis and C3 Glomerulopathy in Children. In: Emma, F., Goldstein, S., Bagga, A., Bates, C.M., Shroff, R. (eds) Pediatric Nephrology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27843-3_29-2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-27843-3_29-2

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-27843-3

  • Online ISBN: 978-3-642-27843-3

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Chapter history

  1. Latest

    Membranoproliferative Glomerulonephritis and C3 Glomerulopathy in Children
    Published:
    08 June 2021

    DOI: https://doi.org/10.1007/978-3-642-27843-3_29-2

  2. Original

    Membranoproliferative and C3-Mediated GN in Children
    Published:
    11 February 2015

    DOI: https://doi.org/10.1007/978-3-642-27843-3_29-1

Search

Navigation