Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Pediatric Nephrology
Published in: Pediatric Nephrology 8/2010

01-08-2010 | Review

C1q nephropathy in the pediatric population: pathology and pathogenesis

Authors: Scott E. Wenderfer, Rita D. Swinford, Michael C. Braun

Published in: Pediatric Nephrology | Issue 8/2010

Login to get access

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.
Literature
1.
Peters DK, Williams DG (1972) Complement and the kidney. Proc R Soc Med 65:1095–1098PubMed
2.
Neilson EG, Couser WG (2001) Immunologic renal diseases. Lippincott Williams & Wilkins, Nashville, p 1311
3.
Turnberg D, Cook HT (2005) Complement and glomerulonephritis: new insights. Curr Opin Nephrol Hypertens 14:223–228CrossRefPubMed
4.
Quigg RJ (2003) Complement and the kidney. J Immunol 171:3319–3324PubMed
5.
Seelen MA, Daha MR (2006) The role of complement in autoimmune renal disease. Autoimmunity 39:411–415CrossRefPubMed
6.
Fogo AB, Kashgarian M (2005) Diagnostic atlas of renal pathology. Saunders, Philadelphia, p 480
7.
Jennette JC, Olson JL, Schwartz MM, Silva FG (2006) Heptinstall’s pathology of the kidney. Lippincott Williams & Wilkins, Baltimore
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 18:2447–2456CrossRefPubMed
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 44:193–199CrossRefPubMed
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 75:1230–1234CrossRefPubMed
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 13:263–274CrossRefPubMed
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 19:2237–2244CrossRefPubMed
13.
Arlaud GJ, Gaboriaud C, Thielens NM, Rossi V (2002) Structural biology of C1. Biochem Soc Trans 30:1001–1006CrossRefPubMed
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 38:189–201CrossRefPubMed
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 49:698–704CrossRefPubMed
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 121:1578–1584PubMed
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 5:9–21CrossRefPubMed
19.
Ziccardi RJ, Tschopp J (1982) The dissociation properties of native C1. Biochem Biophys Res Commun 107:618–623CrossRefPubMed
20.
Villiers CL, Arlaud GJ, Painter RH, Colomb MG (1980) Calcium binding properties of the C1 subcomponents C1q, C1r and C1s. FEBS Lett 117:289–294CrossRefPubMed
21.
Augener W, Grey HM, Cooper NR, Muller-Eberhard HJ (1971) The reaction of monomeric and aggregated immunoglobulins with C1. Immunochemistry 8:1011–1020CrossRefPubMed
22.
23.
Ziccardi RJ (1983) The first component of human complement (C1): activation and control. Springer Semin Immunopathol 6:213–230CrossRefPubMed
24.
Mevorach D, Mascarenhas JO, Gershov D, Elkon KB (1998) Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med 188:2313–2320CrossRefPubMed
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 151:4315–4324PubMed
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 109:510–517CrossRefPubMed
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 130:459–466CrossRefPubMed
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 7:573–581PubMed
29.
Trendelenburg M (2005) Antibodies against C1q in patients with systemic lupus erythematosus. Springer Semin Immunopathol 27:276–285CrossRefPubMed
30.
Ghai R, Waters P, Roumenina LT, Gadjeva M, Kojouharova MS, Reid KB, Sim RB, Kishore U (2007) C1q and its growing family. Immunobiology 212:253–266CrossRefPubMed
31.
Jennette JC, Hipp CG (1985) Immunohistopathologic evaluation of C1q in 800 renal biopsy specimens. Am J Clin Pathol 83:415–420PubMed
32.
Jennette JC, Hipp CG (1985) C1q nephropathy: a distinct pathologic entity usually causing nephrotic syndrome. Am J Kidney Dis 6:103–110PubMed
33.
Iskandar SS, Browning MC, Lorentz WB (1991) C1q nephropathy: a pediatric clinicopathologic study. Am J Kidney Dis 18:459–465PubMed
34.
Lau KK, Gaber LW, Delos Santos NM, Wyatt RJ (2005) C1q nephropathy: features at presentation and outcome. Pediatr Nephrol 20:744–749CrossRefPubMed
35.
Kersnik Levart T, Kenda RB, Avgustin Cavic M, Ferluga D, Hvala A, Vizjak A (2005) C1Q nephropathy in children. Pediatr Nephrol 20:1756–1761CrossRefPubMed
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 47:412–418CrossRefPubMed
37.
Wong CS, Fink CA, Baechle J, Harris AA, Staples AO, Brandt JR (2009) C1q nephropathy and minimal change nephrotic syndrome. Pediatr Nephrol 24:761–767CrossRefPubMed
38.
Roberti I, Baqi N, Vyas S, Kim DU (2009) A single-center study of C1q nephropathy in children. Pediatr Nephrol 24:77–82CrossRefPubMed
39.
Nishida M, Kawakatsu H, Okumura Y, Hamaoka K (2005) C1q nephropathy with asymptomatic urine abnormalities. Pediatr Nephrol 20:1669–1670CrossRefPubMed
40.
Kuwano M, Ito Y, Amamoto Y, Aida K (1993) A case of congenital nephrotic syndrome associated with positive C1q immunofluorescence. Pediatr Nephrol 7:452–454CrossRefPubMed
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 29:966–970CrossRefPubMed
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:E22CrossRefPubMed
43.
Srivastava T, Chadha V, Taboada EM, Alon US (2000) C1q nephropathy presenting as rapidly progressive crescentic glomerulonephritis. Pediatr Nephrol 14:976–979CrossRefPubMed
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 17:547–549CrossRefPubMed
45.
Roberti I, Sachdev S, Aronsky A, Kim DU (2006) C1q nephropathy in a child with a chromosome 13 deletion. Pediatr Nephrol 21:737–739CrossRefPubMed
46.
Krinsky CS, Harris A (2006) An 18-year-old woman with proteinuria and renal insufficiency. C1q nephropathy. Arch Pathol Lab Med 130:e53–e55PubMed
47.
Hanevold C, Mian A, Dalton R (2006) C1q nephropathy in association with Gitelman syndrome: a case report. Pediatr Nephrol 21:1904–1908CrossRefPubMed
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 22:928–931CrossRefPubMed
49.
50.
Bitzan M, Ouahed JD, Krishnamoorthy P, Bernard C (2008) Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution. Pediatr Nephrol 23:1355–1361CrossRefPubMed
51.
Taggart L, Harris A, El-Dahr S, Iorember F (2010) C1q nephropathy in a child presenting with recurrent gross hematuria. Pediatr Nephrol 25:165–168CrossRef
52.
Jennette JC (2004) C1q nephropathy. In: Massry SG, Glassock RJ (eds) Textbook of nephrology. Lippincott, Williams & Wilkins, Philadelphia, pp 730–733
53.
Davenport A, Maciver AG, Mackenzie JC (1992) C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome? Nephrol Dial Transplant 7:391–396PubMed
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 13:159–165CrossRef
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 8:769–776PubMed
56.
Hodson EM, Craig JC, Willis NS (2005) Evidence-based management of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 20:1523–1530CrossRefPubMed
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
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 100:188–191CrossRefPubMed
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 24:87–94CrossRef
61.
Silverstein DM, Craver RD (2008) Mesangial hypercellularity in children: presenting features and outcomes. Pediatr Nephrol 23:921–928CrossRefPubMed
62.
63.
Gipson DS, Gibson K, Gipson PE, Watkins S, Moxey-Mims M (2007) Therapeutic approach to FSGS in children. Pediatr Nephrol 22:28–36CrossRefPubMed
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 33:115–122PubMed
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 22:389–395CrossRefPubMed
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 22:215–221CrossRefPubMed
68.
Rifai A, Mannik M (1983) Clearance kinetics and fate of mouse IgA immune complexes prepared with monomeric or dimeric IgA. J Immunol 130:1826–1832PubMed
69.
Rifai A, Millard K (1985) Glomerular deposition of immune complexes prepared with monomeric or polymeric IgA. Clin Exp Immunol 60:363–368PubMed
70.
Emancipator SN (1988) Experimental models of IgA nephropathy. Am J Kidney Dis 12:415–419PubMed
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 153:5247–5255PubMed
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 70:283–297CrossRefPubMed
Metadata
Title
C1q nephropathy in the pediatric population: pathology and pathogenesis
Authors
Scott E. Wenderfer
Rita D. Swinford
Michael C. Braun
Publication date
01-08-2010
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 8/2010
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-009-1429-x

Other articles of this Issue 8/2010

Pediatric Nephrology 8/2010 Go to the issue

Original Article

Smell and taste function in children with chronic kidney disease

Letter to the Editors

Neurofibromatosis type 1 with idiopathic hypercalciuria, nephrolithiasis and horseshoe kidney

Erratum

Erratum to: Normal-range albuminuria does not exclude nephropathy in diabetic children

Letter to the Editors

Elevated FGF-23 and parathormone in linear nevus sebaceous syndrome with resistant rickets

Letter to the Editors

Primary Sjögren syndrome that developed after IgA nephropathy

Brief Report

Vascular involvement in tuberous sclerosis