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C1q nephropathy in the pediatric population: pathology and pathogenesis

Pediatric Nephrology volume 25, pages 1385–1396 (2010)Cite this article

Abstract

C1q nephropathy was originally described nearly 25 years ago by Jennette and Hipp. Since that time there have been a limited number of publications on C1q nephropathy, most of them in the pediatric literature. Despite reported incidences as high as 16% in some pediatric biopsy series, a consensus definition on the diagnosis of C1q nephropathy is lacking and its existence as a distinct clinical disease entity remains controversial. The purpose of this review is to discuss the biology of C1q in the context of mechanisms of C1q deposition, and to provide a detailed analysis of the published pediatric case series with a focus on the pathological criteria used to establish the diagnosis of C1q nephropathy as well as long-term outcomes in children.

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Fig. 1

References

  1. Peters DK, Williams DG (1972) Complement and the kidney. Proc R Soc Med 65:1095–1098

    CAS  PubMed  Google Scholar 

  2. Neilson EG, Couser WG (2001) Immunologic renal diseases. Lippincott Williams & Wilkins, Nashville, p 1311

    Google Scholar 

  3. Turnberg D, Cook HT (2005) Complement and glomerulonephritis: new insights. Curr Opin Nephrol Hypertens 14:223–228

    Article  CAS  PubMed  Google Scholar 

  4. Quigg RJ (2003) Complement and the kidney. J Immunol 171:3319–3324

    CAS  PubMed  Google Scholar 

  5. Seelen MA, Daha MR (2006) The role of complement in autoimmune renal disease. Autoimmunity 39:411–415

    Article  CAS  PubMed  Google Scholar 

  6. Fogo AB, Kashgarian M (2005) Diagnostic atlas of renal pathology. Saunders, Philadelphia, p 480

    Google Scholar 

  7. Jennette JC, Olson JL, Schwartz MM, Silva FG (2006) Heptinstall’s pathology of the kidney. Lippincott Williams & Wilkins, Baltimore

    Google Scholar 

  8. Smith RJ, Alexander J, Barlow PN, Botto M, Cassavant TL, Cook HT, de Cordoba SR, Hageman GS, Jokiranta TS, Kimberling WJ, Lambris JD, Lanning LD, Levidiotis V, Licht C, Lutz HU, Meri S, Pickering MC, Quigg RJ, Rops AL, Salant DJ, Sethi S, Thurman JM, Tully HF, Tully SP, van der Vlag J, Walker PD, Würzner R, Zipfel PF, Dense Deposit Disease Focus Group (2007) New approaches to the treatment of dense deposit disease. J Am Soc Nephrol 18:2447–2456

    Article  CAS  PubMed  Google Scholar 

  9. Servais A, Fremeaux-Bacchi V, Lequintrec M, Salomon R, Blouin J, Knebelmann B, Grunfeld JP, Lesavre P, Noel LH, Fakhouri F (2007) Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with hemolytic uremic syndrome. J Med Genet 44:193–199

    Article  CAS  PubMed  Google Scholar 

  10. 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

    Article  PubMed  Google Scholar 

  11. Mii A, Shimizu A, Masuda Y, Fujita E, Aki K, Ishizaki M, Sato S, Griesemer A, Fukuda Y (2009) Current status and issues of C1q nephropathy. Clin Exp Nephrol 13:263–274

    Article  CAS  PubMed  Google Scholar 

  12. Vizjak A, Ferluga D, Rozic M, Hvala A, Lindic J, Levart TK, Jurcic V, Jennette JC (2008) Pathology, clinical presentations, and outcomes of C1q nephropathy. J Am Soc Nephrol 19:2237–2244

    Article  PubMed  Google Scholar 

  13. Arlaud GJ, Gaboriaud C, Thielens NM, Rossi V (2002) Structural biology of C1. Biochem Soc Trans 30:1001–1006

    Article  CAS  PubMed  Google Scholar 

  14. Petry F, Hauptmann G, Goetz J, Grosshans E, Loos M (1997) Molecular basis of a new type of C1q-deficiency associated with a non-functional low molecular weight (LMW) C1q: parallels and differences to other known genetic C1q-defects. Immunopharmacology 38:189–201

    Article  CAS  PubMed  Google Scholar 

  15. Loos M, Martin H, Petry F (1989) The biosynthesis of C1q, the collagen-like and Fc recognizing molecule of the complement system. Behring Inst Mitt (84):32–41

  16. Hoekzema R, Swaak AJ, Brouwer MC, van Rooijen A, Nieuwenhuys EJ, Hack CE (1990) Significance of low molecular weight C1q in systemic lupus erythematosus. Ann Rheum Dis 49:698–704

    Article  CAS  PubMed  Google Scholar 

  17. Muller W, Hanauske-Abel H, Loos M (1978) Biosynthesis of the first component of complement by human and guinea pig peritoneal macrophages: evidence for an independent production of the C1 subunits. J Immunol 121:1578–1584

    CAS  PubMed  Google Scholar 

  18. Lu JH, Teh BK, Wang L, Wang YN, Tan YS, Lai MC, Reid KB (2008) The classical and regulatory functions of C1q in immunity and autoimmunity. Cell Mol Immunol 5:9–21

    Article  CAS  PubMed  Google Scholar 

  19. Ziccardi RJ, Tschopp J (1982) The dissociation properties of native C1. Biochem Biophys Res Commun 107:618–623

    Article  CAS  PubMed  Google Scholar 

  20. Villiers CL, Arlaud GJ, Painter RH, Colomb MG (1980) Calcium binding properties of the C1 subcomponents C1q, C1r and C1s. FEBS Lett 117:289–294

    Article  CAS  PubMed  Google Scholar 

  21. Augener W, Grey HM, Cooper NR, Muller-Eberhard HJ (1971) The reaction of monomeric and aggregated immunoglobulins with C1. Immunochemistry 8:1011–1020

    Article  CAS  PubMed  Google Scholar 

  22. Duncan AR, Winter G (1988) The binding site for C1q on IgG. Nature 332:738–740

    Article  CAS  PubMed  Google Scholar 

  23. Ziccardi RJ (1983) The first component of human complement (C1): activation and control. Springer Semin Immunopathol 6:213–230

    Article  CAS  PubMed  Google Scholar 

  24. Mevorach D, Mascarenhas JO, Gershov D, Elkon KB (1998) Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 188:2313–2320

    Article  CAS  PubMed  Google Scholar 

  25. Van den Dobbelsteen ME, van der Woude FJ, Schroeijers WE, Klar-Mohamad N, van Es LA, Daha MR (1993) C1Q, a subunit of the first component of complement, enhances the binding of aggregated IgG to rat renal mesangial cells. J Immunol 151:4315–4324

    PubMed  Google Scholar 

  26. Sato T, van Dixhoorn MG, Heemskerk E, van Es LA, Daha MR (1997) C1q, a subunit of the first component of complement, enhances antibody-mediated apoptosis of cultured rat glomerular mesangial cells. Clin Exp Immunol 109:510–517

    Article  CAS  PubMed  Google Scholar 

  27. Cortes-Hernandez J, Fossati-Jimack L, Carugati A, Potter PK, Walport MJ, Cook HT, Botto M (2002) Murine glomerular mesangial cell uptake of apoptotic cells is inefficient and involves serum-mediated but complement-independent mechanisms. Clin Exp Immunol 130:459–466

    Article  CAS  PubMed  Google Scholar 

  28. Van den Dobbelsteen ME, van der Woude FJ, Schroeijers WE, Klar-Mohamad N, van Es LA, Daha MR (1996) Both IgG-and C1q-receptors play a role in the enhanced binding of IgG complexes to human mesangial cells. J Am Soc Nephrol 7:573–581

    PubMed  Google Scholar 

  29. Trendelenburg M (2005) Antibodies against C1q in patients with systemic lupus erythematosus. Springer Semin Immunopathol 27:276–285

    Article  CAS  PubMed  Google Scholar 

  30. Ghai R, Waters P, Roumenina LT, Gadjeva M, Kojouharova MS, Reid KB, Sim RB, Kishore U (2007) C1q and its growing family. Immunobiology 212:253–266

    Article  CAS  PubMed  Google Scholar 

  31. Jennette JC, Hipp CG (1985) Immunohistopathologic evaluation of C1q in 800 renal biopsy specimens. Am J Clin Pathol 83:415–420

    CAS  PubMed  Google Scholar 

  32. Jennette JC, Hipp CG (1985) C1q nephropathy: a distinct pathologic entity usually causing nephrotic syndrome. Am J Kidney Dis 6:103–110

    CAS  PubMed  Google Scholar 

  33. Iskandar SS, Browning MC, Lorentz WB (1991) C1q nephropathy: a pediatric clinicopathologic study. Am J Kidney Dis 18:459–465

    CAS  PubMed  Google Scholar 

  34. Lau KK, Gaber LW, Delos Santos NM, Wyatt RJ (2005) C1q nephropathy: features at presentation and outcome. Pediatr Nephrol 20:744–749

    Article  PubMed  Google Scholar 

  35. Kersnik Levart T, Kenda RB, Avgustin Cavic M, Ferluga D, Hvala A, Vizjak A (2005) C1Q nephropathy in children. Pediatr Nephrol 20:1756–1761

    Article  PubMed  Google Scholar 

  36. Fukuma Y, Hisano S, Segawa Y, Niimi K, Tsuru N, Kaku Y, Hatae K, Kiyoshi Y, Mitsudome A, Iwasaki H (2006) Clinicopathologic correlation of C1q nephropathy in children. Am J Kidney Dis 47:412–418

    Article  PubMed  Google Scholar 

  37. Wong CS, Fink CA, Baechle J, Harris AA, Staples AO, Brandt JR (2009) C1q nephropathy and minimal change nephrotic syndrome. Pediatr Nephrol 24:761–767

    Article  PubMed  Google Scholar 

  38. Roberti I, Baqi N, Vyas S, Kim DU (2009) A single-center study of C1q nephropathy in children. Pediatr Nephrol 24:77–82

    Article  PubMed  Google Scholar 

  39. Nishida M, Kawakatsu H, Okumura Y, Hamaoka K (2005) C1q nephropathy with asymptomatic urine abnormalities. Pediatr Nephrol 20:1669–1670

    Article  PubMed  Google Scholar 

  40. Kuwano M, Ito Y, Amamoto Y, Aida K (1993) A case of congenital nephrotic syndrome associated with positive C1q immunofluorescence. Pediatr Nephrol 7:452–454

    Article  CAS  PubMed  Google Scholar 

  41. Shappell SB, Myrthil G, Fogo A (1997) An adolescent with relapsing nephrotic syndrome: minimal-change disease versus focal-segmental glomerulosclerosis versus C1q nephropathy. Am J Kidney Dis 29:966–970

    Article  CAS  PubMed  Google Scholar 

  42. Nishida M, Kawakatsu H, Komatsu H, Ishiwari K, Tamai M, Sawada T (2000) Spontaneous improvement in a case of C1q nephropathy. Am J Kidney Dis 35:E22

    Article  CAS  PubMed  Google Scholar 

  43. Srivastava T, Chadha V, Taboada EM, Alon US (2000) C1q nephropathy presenting as rapidly progressive crescentic glomerulonephritis. Pediatr Nephrol 14:976–979

    Article  CAS  PubMed  Google Scholar 

  44. Ekim M, Ikinciogullari A, Berberoglu M, Tulunay O, Sencer H, Ozkaya N, Reisli I, Tumer N (2002) C1q nephropathy: a case with severe atopic dermatitis. Pediatr Nephrol 17:547–549

    Article  PubMed  Google Scholar 

  45. Roberti I, Sachdev S, Aronsky A, Kim DU (2006) C1q nephropathy in a child with a chromosome 13 deletion. Pediatr Nephrol 21:737–739

    Article  PubMed  Google Scholar 

  46. Krinsky CS, Harris A (2006) An 18-year-old woman with proteinuria and renal insufficiency. C1q nephropathy. Arch Pathol Lab Med 130:e53–e55

    PubMed  Google Scholar 

  47. Hanevold C, Mian A, Dalton R (2006) C1q nephropathy in association with Gitelman syndrome: a case report. Pediatr Nephrol 21:1904–1908

    Article  PubMed  Google Scholar 

  48. Lim IS, Yun KW, Moon KC, Cheong HI (2007) Proteinuria in a boy with infectious mononucleosis, C1q nephropathy, and Dent’s disease. J Korean Med Sci 22:928–931

    Article  PubMed  Google Scholar 

  49. Kari JA, Jalalah SM (2008) C1q nephropathy in two young sisters. Pediatr Nephrol 23:487–490

    Article  PubMed  Google Scholar 

  50. Bitzan M, Ouahed JD, Krishnamoorthy P, Bernard C (2008) Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution. Pediatr Nephrol 23:1355–1361

    Article  PubMed  Google Scholar 

  51. Taggart L, Harris A, El-Dahr S, Iorember F (2010) C1q nephropathy in a child presenting with recurrent gross hematuria. Pediatr Nephrol 25:165–168

    Article  Google Scholar 

  52. Jennette JC (2004) C1q nephropathy. In: Massry SG, Glassock RJ (eds) Textbook of nephrology. Lippincott, Williams & Wilkins, Philadelphia, pp 730–733

    Google Scholar 

  53. Davenport A, Maciver AG, Mackenzie JC (1992) C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome? Nephrol Dial Transplant 7:391–396

    CAS  PubMed  Google Scholar 

  54. International Study of Kidney Diseases in Children (1978) Nephrotic syndrome in children: prediction of histology from clinical and laboratory characteristics at the time of diagnosis. Kidney Int 13:159–165

    Article  Google Scholar 

  55. Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (1997) Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. J Am Soc Nephrol 8:769–776

    CAS  PubMed  Google Scholar 

  56. Hodson EM, Craig JC, Willis NS (2005) Evidence-based management of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 20:1523–1530

    Article  PubMed  Google Scholar 

  57. Hodson EM, Knight JF, Willis NS, Craig JC (2005) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev (1):CD001533

  58. Colquitt JL, Kirby J, Green C, Cooper K, Trompeter RS (2007) The clinical effectiveness and cost-effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review. Health Technol Assess 11:1–93

    Google Scholar 

  59. Allen WR, Travis LB, Cavallo T, Brouhard BH, Cunningham RJ 3rd (1982) Immune deposits and mesangial hypercellularity in minimal change nephrotic syndrome: clinical relevance. J Pediatr 100:188–191

    Article  CAS  PubMed  Google Scholar 

  60. Southwest Pediatric Nephrology Study Group (1983) Childhood nephrotic syndrome associated with diffuse mesangial hypercellularity. A report of the Southwest Pediatric Nephrology Study Group. Kidney Int 24:87–94

    Article  Google Scholar 

  61. Silverstein DM, Craver RD (2008) Mesangial hypercellularity in children: presenting features and outcomes. Pediatr Nephrol 23:921–928

    Article  PubMed  Google Scholar 

  62. Schnaper HW (2003) Idiopathic focal segmental glomerulosclerosis. Semin Nephrol 23:183–193

    Article  PubMed  Google Scholar 

  63. Gipson DS, Gibson K, Gipson PE, Watkins S, Moxey-Mims M (2007) Therapeutic approach to FSGS in children. Pediatr Nephrol 22:28–36

    Article  PubMed  Google Scholar 

  64. Hodson EM, Habashy D, Craig JC (2006) Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev (2):CD003594

  65. Wehrmann M, Bohle A, Held H, Schumm G, Kendziorra H, Pressler H (1990) Longterm prognosis of focal sclerosing glomerulonephritis. An analysis of 250 cases with particular regard to tubulointerstitial changes. Clin Nephrol 33:115–122

    CAS  PubMed  Google Scholar 

  66. Paik KH, Lee BH, Cho HY, Kang HG, Ha IS, Cheong HI, Jin DK, Moon KC, Choi Y (2007) Primary focal segmental glomerular sclerosis in children: clinical course and prognosis. Pediatr Nephrol 22:389–395

    Article  PubMed  Google Scholar 

  67. Abeyagunawardena AS, Sebire NJ, Risdon RA, Dillon MJ, Rees L, Van’t Hoff W, Kumarasiri PV, Trompeter RS (2007) Predictors of long-term outcome of children with idiopathic focal segmental glomerulosclerosis. Pediatr Nephrol 22:215–221

    Article  PubMed  Google Scholar 

  68. Rifai A, Mannik M (1983) Clearance kinetics and fate of mouse IgA immune complexes prepared with monomeric or dimeric IgA. J Immunol 130:1826–1832

    CAS  PubMed  Google Scholar 

  69. Rifai A, Millard K (1985) Glomerular deposition of immune complexes prepared with monomeric or polymeric IgA. Clin Exp Immunol 60:363–368

    CAS  PubMed  Google Scholar 

  70. Emancipator SN (1988) Experimental models of IgA nephropathy. Am J Kidney Dis 12:415–419

    CAS  PubMed  Google Scholar 

  71. Gomez-Guerrero C, Lopez-Armada MJ, Gonzalez E, Egido J (1994) Soluble IgA and IgG aggregates are catabolized by cultured rat mesangial cells and induce production of TNF-alpha and IL-6, and proliferation. J Immunol 153:5247–5255

    CAS  PubMed  Google Scholar 

  72. Chao TK, Rifai A, Ka SM, Yang SM, Shui HA, Lin YF, Sytwu HK, Lee WH, Kung JT, Chen A (2006) The endogenous immune response modulates the course of IgA-immune complex mediated nephropathy. Kidney Int 70:283–297

    Article  CAS  PubMed  Google Scholar 

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Affiliations

  1. Division of Pediatric Nephrology and Hypertension, Department of Pediatrics, University of Texas School of Medicine, Houston, USA

    Scott E. Wenderfer, Rita D. Swinford & Michael C. Braun

  2. Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, USA

    Scott E. Wenderfer & Michael C. Braun

  3. IMM/UTHSC-H, 1825 Pressler Street, Room 630C, Houston, TX, 77030, USA

    Michael C. Braun

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  1. Scott E. Wenderfer
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Correspondence to Michael C. Braun.

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Wenderfer, S.E., Swinford, R.D. & Braun, M.C. C1q nephropathy in the pediatric population: pathology and pathogenesis. Pediatr Nephrol 25, 1385–1396 (2010). https://doi.org/10.1007/s00467-009-1429-x

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  • DOI: https://doi.org/10.1007/s00467-009-1429-x

Keywords

  • C1q
  • C1q nephropathy
  • Complement
  • Focal segmental glomerular sclerosis
  • Nephrotic syndrome
  • Mesangial proliferation