title: Clinico-pathologic spectrum of C3 glomerulopathy-an Indian experience.
abstract: 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 2(nd) to 4(th) 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.
  
  
  CONCLUSIONS
  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.
  The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1730070964135632.
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. ganeshpgi@gmail.com.
authors.forename: Ganesh Kumar
authors.initials: GK
authors.lastname: Viswanathan
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. ritamduseja@yahoo.com.
authors.forename: Ritambhra
authors.initials: R
authors.lastname: Nada
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. ashumicrobio@gmail.com.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. drraja_1980@yahoo.co.in.
authors.forename: Raja
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. csrayat@hotmail.com.
authors.forename: Charan Singh
authors.initials: CS
authors.lastname: Rayat
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. vjha@pginephro.org.
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Jha
authors.affiliation: Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. drvsakhuja@glide.net.in.
authors.forename: Vinay
authors.initials: V
authors.lastname: Sakhuja
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India. kus_joshi@yahoo.com.
authors.forename: Kusum
authors.initials: K
authors.lastname: Joshi
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002648:Child; D003176:Complement C3 / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015432:Glomerulonephritis, Membranoproliferative / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007194:India / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D010865:Pilot Projects; D011237:Predictive Value of Tests; D015995:Prevalence; D012189:Retrospective Studies; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C038245:C3 protein, human; D003176:Complement C3