Clinico-pathologic spectrum of C3 glomerulopathy-an Indian experience

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• 作者：Ganesh Kumar Viswanathan (1)
  Ritambhra Nada (1)
  Ashwani Kumar (1)
  Raja Ramachandran (2)
  Charan Singh Rayat (1)
  Vivekanand Jha (2)
  Vinay Sakhuja (2)
  Kusum Joshi (1)
  
  1. Department of Histopathology ; Post Graduate Institute of Medical Education and Research ; Chandigarh ; 160012 ; India
  2. Department of Nephrology ; Post Graduate Institute of Medical Education and Research ; Chandigarh ; 160012 ; India
  
• 关键词：Alternate complement pathway ; C3 glomerulopathy ; Complement ; Dense deposit disease ; Nephrotic ; Nephritic
• 刊名：Diagnostic Pathology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：10
• 期：1
• 全文大小：1,721 KB
• 参考文献：1. Fakhouri, F, Fr茅meaux-Bacchi, V, No毛l, L-H, Cook, HT, Pickering, MC (2010) C3 glomerulopathy: a new classification. Nat Rev Nephrol 6: pp. 494-9 CrossRef
  2. Sethi, S, Fervenza, FC (2012) Membranoproliferative glomerulonephritis鈥攁 new look at an old entity. N Engl J Med 366: pp. 1119-31 CrossRef
  3. Jackson, E, McAdams, A, Strife, C, Forristal, J, Welch, T, West, C (1987) Differences between membranoproliferative glomerulonephritis types I and III in clinical presentation, glomerular morphology, and complement perturbation. Am J Kidney Dis 9: pp. 115-20 CrossRef
  4. Athanasiou, Y, Voskarides, K, Gale, DP, Damianou, L, Patsias, C, Zavros, M (2011) Familial C3 glomerulopathy associated with CFHR5 mutations: clinical characteristics of 91 patients in 16 pedigrees. Clin J Am Soc Nephrol 6: pp. 1436-46 CrossRef
  5. Sethi, S, Gamez, JD, Vrana, JA, Theis, JD, Bergen, HR, Zipfel, PF (2009) Glomeruli of dense deposit disease contain components of the alternative and terminal complement pathway. Kidney Int 75: pp. 952-60 CrossRef
  6. Sethi, S, Nester, CM, Smith, RJH (2012) Membranoproliferative glomerulonephritis and C3 glomerulopathy: resolving the confusion. Kidney Int 81: pp. 434-41 CrossRef
  7. Sethi, S, Fervenza, FC, Zhang, Y, Nasr, SH, Leung, N, Vrana, J (2011) Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement. Clin J Am Soc Nephrol 6: pp. 1009-17 CrossRef
  8. Sethi, S, Fervenza, FC, Zhang, Y, Zand, L, Vrana, JA, Nasr, SH (2012) C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up. Kidney Int 82: pp. 465-73 CrossRef
  9. Servais, A, No毛l, LH, Roumenina, LT, Quintrec, M, Ngo, S, Dragon-Durey, MA (2012) Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 82: pp. 454-64 CrossRef
  10. Barbour, TD, Pickering, MC, Cook, HT (2013) Recent insights into C3 glomerulopathy. Nephrol Dialys Transplant 28: pp. 1685-93 CrossRef
  11. Smith, RJH, Harris, CL, Pickering, MC (2011) Dense deposit disease. Mol Immunol 48: pp. 1604-10 CrossRef
  12. Nasr, SH, Valeri, AM, Appel, GB, Sherwinter, J, Stokes, MB, Said, SM (2009) Dense deposit disease: clinicopathologic study of 32 pediatric and adult patients. Clin J Am Soc Nephrol 4: pp. 22-32 CrossRef
  13. Bomback, AS, Smith, RJ, Barile, GR, Zhang, Y, Heher, EC, Herlitz, L (2012) Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol 7: pp. 748-56 CrossRef
  14. Gurkan, S, Fyfe, B, Weiss, L, Xiao, X, Zhang, Y, Smith, RJ (2013) Eculizumab and recurrent C3 glomerulonephritis. Pediatr Nephrol 28: pp. 1975-81 CrossRef
  15. Gale, DP, Jorge, EG, Cook, HT, Martinez-Barricarte, R, Hadjisavvas, A, McLean, AG (2010) Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis. Lancet 376: pp. 794-801 CrossRef
  16. Pickering MC, D, D'Agati, V, Nester, CM, Smith, RJ, Haas, M, Appel, GB (2013) C3 glomerulopathy: consensus report. Kidney Int 84: pp. 1079-89 CrossRef
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• 刊物主题：Pathology;
• 出版者：BioMed Central
• ISSN：1746-1596

文摘

Background C3 glomerulopathy (C3GP) is characterized by deposition of complement C3 with absence/traces of immunoglobulins in the glomeruli and categorized into dense deposit disease (DDD), C3 glomerulonephritis (C3GN), complement factor H related protein 5(CFHR5) nephropathy etc. Collaborative efforts of pathologists, complement biologists and nephrologists worldwide are expanding the histomorphological pattern and laboratory findings related to C3GP. Hence, we studied point prevalence and morphological spectrum of C3GP in Indian patients to correlate morphological patterns with standard therapies and outcome of the patients. Methods Retrospective analysis of renal biopsies (2007-2012,n-4565), which on immunofluorescence (IF) had C3 dominant deposits with absence or trace amount of immunoglobulin was carried out. Histopathology and electronmicroscopy (EM) were reviewed; cases were re-classified as DDD and C3GN. Histomorphological patterns of both groups were compared and correlated with treatment. Clinical details and follow up of patients were retrieved from the department of nephrology. Results There were 31 cases (0.7%) of C3GP sub-classified as DDD (n-13) and C3GN (n-14). It was difficult to sub-classify 4 cases since EM showed overlapping features. C3GN and DDD had distinct clinical characteristics and disease outcome, though pathological features were overlapping. Majority of C3GP patients were males and were in 2nd to 4th decade of life. Nephrotic syndrome in DDD and nephritic-nephrotic presentation in C3GN patients was more common. Hypertension and oliguria were more often observed in C3GN than DDD. Membranoproliferative pattern (MPGN) was commonest pattern in DDD; other patterns seen were mesangial proliferative, mesangial expansive/nodular, exudative and crescentic. C3GN also had all the above patterns, the predominant ones being MPGN and mesangial proliferative. Limited follow-up revealed response to therapy only in C3GN (33%). Progression to ESRD was 33% in DDD and 10% cases in C3GN. Conclusion C3GP comprise 0.7% of all renal biopsies. MPGN pattern was the commonest morphological pattern in DDD whereas MPGN and mesangial proliferative pattern were equally dominant patterns in C3GN. EM of 4 cases (13%) showed intermediate features. Evaluation of alternate complement pathway must be done in all cases to identify the point of dysregulated alternate complement pathway and to confirm the diagnosis in ambiguous cases. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1730070964135632