Clinical and Experimental Nephrology

, Volume 13, Issue 4, pp 263–274 | Cite as

Current status and issues of C1q nephropathy

  • Akiko Mii
  • Akira Shimizu
  • Yukinari Masuda
  • Emiko Fujita
  • Kaoru Aki
  • Masamichi Ishizaki
  • Shigeru Sato
  • Adam Griesemer
  • Yuh Fukuda
Review Article


C1q nephropathy, first proposed by Jennette and Hipp [Am J Clin Pathol 83:415-420, 1985; Am J Kidney Dis 6:103-110, 1985], was described as a distinct glomerular disease entity characterized by extensive mesangial deposition of C1q, with associated mesangial immune complexes, and the absence of any clinical and laboratory evidence of systemic lupus erythematosus. Now, 20 years since the first report, the disease entity is gradually attaining recognition, particularly in the field of pediatrics. C1q is the subcomponent of C1 in the classical pathway of complement activation. Generally, C1q deposition is caused by the activation of C1 by immunoglobulin G (IgG) and IgM; therefore, C1q nephropathy is considered as an immune complex glomerulonephritis. However, in C1q nephropathy, it remains unclear whether the deposition of C1q in the glomeruli is in response to the deposition of immunoglobulin or immune complex, or whether deposition is non-specific trapping that accompanies increased glomerular protein trafficking associated with proteinuria. Since not only the pathogenesis of C1q deposition in glomeruli but also its significance are still uncertain, it has not yet been established as an independent disease. From recent publications of the clinical and pathological characterizations, C1q nephropathy has been thought to be a subgroup of primary focal segmental glomerular sclerosis. However, many reports describe different symptoms, histopathologies, therapeutic responses and prognoses, suggesting that C1q nephropathy is not a single disease entity, but that it may be a combination of several disease groups. There are many uncertain areas requiring further investigation, though it is hoped that a detailed examination of future cases will clarify the subgroups making up C1q nephropathy and their clinicopathological characteristics, and will lead to the establishment of C1q nephropathy as an independent disease entity.


C1q nephropathy Complement C1q 


  1. 1.
    Jennette JC, Hipp CG. Immunohistopathologic evaluation of C1q in 800 renal biopsy specimens. Am J Clin Pathol. 1985;83:415–20.PubMedGoogle Scholar
  2. 2.
    Jennette JC, Hipp CG. C1q nephropathy: a distinct pathologic entity usually causing nephrotic syndrome. Am J Kidney Dis. 1985;6:103–10.PubMedGoogle Scholar
  3. 3.
    Prodinger WM, Würzner R, Stoiber H, Dierich MP. Complement. In: Paul WE, editor. Fundamental immunology. 5th ed. Philadelphia: Lippincott Williams Wilkins; 2003. p. 1077–103.Google Scholar
  4. 4.
    Walport MJ, Lachmann PJ. Complement. In: Lachmann PJ, Peters SK, Rosen FS, Walport MJ, editors. Clinical aspects of immunology. 5th ed. Boston: Blackwell Scientific Publications; 1993. p. 347–70.Google Scholar
  5. 5.
    Berger SP, Roos A, Daha MR. Complement and the kidney: what the nephrologists needs to know in 2006? Nephrol Dial Transplant. 2005;20:2613–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Brown KM, Sachs SH, Sheerin NS. Mechanisms of disease: the complement system in renal injury—New ways of looking at an old foe. Nat Clin Pract Nephrol. 2007;3:277–86.CrossRefPubMedGoogle Scholar
  7. 7.
    Kishore U, Gaboriaud C, Waters P, Shrive AK, Greenhough TJ, Reid KBM, et al. C1q and tumor necrosis factor superfamily: modularity and versatility. Trends Immunol. 2004;25:551–61.CrossRefPubMedGoogle Scholar
  8. 8.
    Eggleton P, Tenner AJ, Reid KB. C1q receptors. Clin Exp Immunol. 2000;120:406–12.CrossRefPubMedGoogle Scholar
  9. 9.
    van den Dobbelsteen ME, van der Woude FJ, Schroeijers WE, Klar-Mohamad N, van Es LA, Daha MR. Both IgG- and C1q-receptors play a role in the enhanced binding of IgG complexes to human mesangial cells. J Am Soc Nephrol.. 1996;7:573–81.PubMedGoogle Scholar
  10. 10.
    Davenport A, Maciver AG, Mackenzie JC. C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome? Nephrol Dial Transplant. 1992;7:391–6.PubMedGoogle Scholar
  11. 11.
    Jones E, Magil A. Nonsystemic mesangiopathic glomerulonephritis with “full house”immunofluorescence. Pathological and clinical observation in five patients. Am J Clin Pathol. 1982;78:29–34.PubMedGoogle Scholar
  12. 12.
    Sharman A, Furness P, Feehally J. Distinguishing C1q nephropathy from lupus nephritis. Nephrol Dial Transplant. 2004;19:1420–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Iskandar SS, Browning MC, Lorentz WB. C1q Nephropathy: a pediatric clinicopathologic study. Am J Kidney Dis. 1991;18:459–65.PubMedGoogle Scholar
  14. 14.
    Markowitz GS, Shwimmer JA, Stokes MB, Nasr S, Seigle RL, Valeri AM, et al. C1q nephropathy: a variant of focal segmental glomerulosclerosis. Kidney Int. 2003;64:1232–40.CrossRefPubMedGoogle Scholar
  15. 15.
    Lau KK, Gaber LW, Santos NMD, Wyatt RJ. C1q nephropathy: features at presentation and outcome. Pediatr Nephrol. 2005;20:744–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Levart TK, Kenda RB, Cavic MA, Ferluga D, Hvala A, Vizjak A. C1q nephropathy in children. Pediatr Nephrol. 2005;20:1756–61.CrossRefGoogle Scholar
  17. 17.
    Nishida M, Kawakatsu H, Okumura Y, Hamaoka K. C1q nephropathy with asymptomatic urine abnormalities. Pediatr Nephrol. 2005;20:1669–70.CrossRefPubMedGoogle Scholar
  18. 18.
    Fukuma Y, Hisano S, Segawa Y, Niimi K, Tsuru N, Kaku Y, et al. Clinicopathologic correlation of C1q nephropathy in children. Am J Kidney Dis. 2006;47:412–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Hisano S, Fukuma Y, Segawa Y, Niimi K, Kaku Y, Hatae K, Saitoh T, Takeshita M, Iwasaki H. Clinicopathologic Correlation and Outcome of C1q Nephropathy. Clin J Am Soc Nephrol. 2008;3:1637–43.CrossRefPubMedGoogle Scholar
  20. 20.
    Kari JA, Jalalah SM. C1q nephropathy in two young sisters. Pediatr Nephrol. 2008;23:487–90.CrossRefPubMedGoogle Scholar
  21. 21.
    Kuwano M, Ito Y, Amamoto Y, Aida K. A case of congenital nephrotic syndrome associated with positive C1q immunofluorescence. Pediatr Nephrol. 1993;7:452–4.CrossRefPubMedGoogle Scholar
  22. 22.
    Imai H, Yasuda T, Satoh K, Miura AB, Sugawara T, Nakamoto Y. Pan-nephritis (glomerulonephritis, arteriolitis, and tubulointerstitial nephritis) associated with predominant mesangial C1q deposition and hypocomplementemia: a variant type of C1q nephropathy? Am J Kidney Dis. 1996;27:583–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Shappell SB, Myrthil G, Fogo A. An adolescent with relapsing nephrotic syndrome: minimal-change disease versus focal-segmental glomerulosclerosis versus C1q nephropathy. Am J Kidney Dis. 1997;29:966–70.CrossRefPubMedGoogle Scholar
  24. 24.
    Sato K, Kudo K, Sakurada T, Yuda F, Sato H, Saito T. Case of glomerular nephritis with C1q uniquely deposited in the mesangial region. Nippon Naika Gakkai Zasshi. 1999;88:1518–20.PubMedGoogle Scholar
  25. 25.
    Srivastava T, Chadha V, Taboada EM, Alon US. C1q nephropathy presenting as rapidly progressive crescentic glomerulonephritis. Pediatr Nephrol. 2000;14:976–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Isaac J, Shihab FS. De novo C1q nephropathy in the renal allograft of a kidney pancreas transplant recipient: BK virus-induced nephropathy? Nephron. 2002;92:431–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Sardani Y, Qin K, Haas M, Aronson AJ, Rosenfield RL. Bartter syndrome complicated by immune complex nephropathy. Case report and literature review. Pediatr Nephrol. 2003;18:913–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Hashimoto S, Ogawa Y, Ishida T, Mochizuki T, Koike T, Sato H, et al. Steroid-sensitive nephrotic syndrome associated with positive C1q immunofluorescence. Clin Exp Nephrol. 2004;8:266–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Krinsky CS, Harris A. An 18-year-old woman with proteinuria and renal insufficiency. C1q nephropathy. Arch Pathol Lab Med. 2006;130:e53–5.PubMedGoogle Scholar
  30. 30.
    Roberti I, Sachdev S, Aronsky A, Kim DU. C1q nephropathy in a child with a chromosome 13 deletion. Pediatr Nephrol. 2006;21:737–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Hanevold C, Mian A, Dalton R. C1q nephropathy in association with Gitelman syndrome: a case report. Pediatr Nephrol. 2006;21:1904–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Lim IS, Yun KW, Moon KC, Cheong HI. Proteinuria in a boy with infectious mononucleosis, C1q nephropathy, and Dent’s disease. J Korean Med Sci. 2007;22:928–31.CrossRefPubMedGoogle Scholar
  33. 33.
    Bitzan M, Ouahed JD, Krishnamoorthy P, Bernard C. Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution. Pediatr Nephrol. 2008;23:1355–61.CrossRefPubMedGoogle Scholar
  34. 34.
    Hisano S, Matsushita M, Fujita T, Uesugi N, Iwasaki H. Activation of the lectin complement pathway in C1q nephropathy. J Am Soc Nephrol. 2006;17:256A. (Abstract).Google Scholar
  35. 35.
    Lu JH, Teh BK, Wang L, Wang YN, Tan YS, Lai MC, et al. The classical and regulatory functions of C1q in immunity and autoimmunity. Cell Mol Immunol. 2008;5:9–21.PubMedCrossRefGoogle Scholar
  36. 36.
    Trendelenburg M. Antibodies against C1q in patients with systemic lupus erythematosus. Springer Semin Immunopathol. 2005;27:276–85.CrossRefPubMedGoogle Scholar
  37. 37.
    Flierman R, Daha MR. Pathogenic role of anti-C1q autoantibodies in the development of lupus nephritis-a hypothesis. Mol Immunol. 2007;44:133–8.CrossRefPubMedGoogle Scholar
  38. 38.
    Churg J, Bernstein J, Glassock RJ. Focal semental glomerulosclerosis. In: Churg J, Bernstein J, Glassock RJ, editors. Renal disease: classification and atlas of glomerular disease. New York: Igaku-Shoin Medical Publishers Inc; 1995. p. 45–65.Google Scholar
  39. 39.
    Andresdottir MB, Assmann KJ, Hilbrands LB, Wetzels JF. Type I Membranoproliferative glomerulonephritis in a renal allograft: a recurrence induced by a cytomegalovirus infection? Am J Kidney Dis. 2000;35:E6.CrossRefPubMedGoogle Scholar
  40. 40.
    Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990;37:663–76.CrossRefPubMedGoogle Scholar
  41. 41.
    Bhimma R, Coovadia HM. Hepatitis B virus-associated nephropathy. Am J Nephrol. 2004;24:198–211.CrossRefPubMedGoogle Scholar
  42. 42.
    Lai AS, Lai KN. Viral nephropathy. Nat Clin Pract Nephrol. 2006;2:254–62.CrossRefPubMedGoogle Scholar
  43. 43.
    Alpers CE, Kowalewska J. Emerging paradigms in the renal pathology of viral diseases. Clin J Am Soc Nephrol. 2007;2(Suppl 1):S6–12.CrossRefPubMedGoogle Scholar
  44. 44.
    Yamabe H. Hepatitis C virus-associated glomerulonephritis. Nippon Rinsho. 2004;62(Suppl 7):550–3.PubMedGoogle Scholar
  45. 45.
    Johnson RJ, Willson R, Yamabe H, Couser W, Alpers CE, Wener MH, et al. Renal manifestations of hepatitis C virus infection. Kidney Int. 1994;46:1255–63.CrossRefPubMedGoogle Scholar
  46. 46.
    Haas M, Kaul S, Eustace JA. HIV-associated immune complex glomerulonephritis with “lupus-like” features: a clinicopathologic study of 14 cases. Kidney Int. 2005;67:1381–90.CrossRefPubMedGoogle Scholar
  47. 47.
    Obana M, Nakanishi K, Sako M, Yata N, Nozu K, Tanaka R, et al. Segmental membranous glomerulonephritis in children: comparison with global membranous glomerulonephritis. Clin J Am Soc Nephrol. 2006;1:723–9.CrossRefPubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2009

Authors and Affiliations

  • Akiko Mii
    • 1
  • Akira Shimizu
    • 1
  • Yukinari Masuda
    • 1
  • Emiko Fujita
    • 1
  • Kaoru Aki
    • 1
  • Masamichi Ishizaki
    • 1
  • Shigeru Sato
    • 2
  • Adam Griesemer
    • 3
  • Yuh Fukuda
    • 1
  1. 1.Department of Analytic Human PathologyNippon Medical SchoolTokyoJapan
  2. 2.Central Institute for Electron Microscopic ResearchesNippon Medical SchoolTokyoJapan
  3. 3.Transplantation Biology Research CenterMassachusetts General Hospital/Harvard Medical SchoolBostonUSA

Personalised recommendations