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. 2015 Mar 17:10:6.
doi: 10.1186/s13000-015-0233-0.

Clinico-pathologic spectrum of C3 glomerulopathy-an Indian experience

Ganesh Kumar Viswanathan  1 , Ritambhra Nada  2 , Ashwani Kumar  3 , Raja Ramachandran  4 , Charan Singh Rayat  5 , Vivekanand Jha  6 , Vinay Sakhuja  7 , Kusum Joshi  8
Affiliations

Clinico-pathologic spectrum of C3 glomerulopathy-an Indian experience

Ganesh Kumar Viswanathan et al. Diagn Pathol. .

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.

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.

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Figures

Figure 1
Figure 1
Photomicrograph shows histomorphological patterns of DDD. (a) Mild mesangial proliferation. (b) Membranoproliferative glomerulonephritis with mesangial refractile material (Arrow). (c) Mesangial expansive pattern with mesangial nodules and basement membrane duplication. (d) Diffuse proliferative lesion with florid exudation. (e) mesangiocapillary pattern with crescent. (a,c,d,e Periodic acid-Schiff and b H&E X40 original).
Figure 2
Figure 2
Photomicrographs showing immunofluorescence pattern and EM of DDD and C3GN. (a) DDD-IF with C3, coarse staining of glomerular capillary loops and Bowmans capsule. (arrows) (b) Predominant mesangial rings with focal glomerular capillaries. (c) DDD - EM is showing glomerular capillary intramembranous dense osmiophilic material of variable thickness. (d) Osmiophilic material in the mesangium (star), subendothelial (red arrow), subepithelial humps (broad white arrows) (Uranyl acetate, b-2800, c-X36,00). (e) C3GN - IF Intense granular positivity in the mesangium and glomerular membranes. (f) EM - Subendothelial (red arrow) and mesangial (black arrow) (Uranyl acetate,X10,000).
Figure 3
Figure 3
Photomicrograph shows Histomorphological patterns of C3GN. (a) Mild mesangial proliferation. (b) Membranoproliferative pattern with basement membrane splitting (Arrow). (c) Mesangial expansive pattern with mesangial nodules. (d) Diffuse proliferative lesion with florid exudation (e) Mesangiocapillary pattern with crescent (Periodic acid Schiff H&E, a-d, X40 original, e-X20 original).
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