Diagnostic utility of C4d immunohistochemistry in membranous nephropathy.

Objectives: Membranous nephropathy (MN), also called membranous glomerulopathy, is one of the leading causes of nephrotic syndrome in adults which is defined by the presence of subepithelial immune complex deposits with a spectrum of changes in the glomerular basement membrane (GBM). It is known that C4d is a byproduct of the classic and lectin pathway. There is deposition of C4d noted in the cases of immune complex-mediated glomerulonephritis involving the classical/lectin pathway including MN. The main objective of this study is to assess the utility C4d as an immunohistochemical (IHC) stain in MN.

Materials: A total of 43 cases of MN (primary & secondary) were taken, and 39 cases of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) were used as the control group. All the relevant data were retrieved from the hospital database. C4d immunohistochemistry was performed in the cases as well as the control group.

Results: A diffuse continuous staining pattern in the glomeruli was observed in cases of primary MN whereas a discontinuous staining in the glomerulI favors a secondary MN. 26/29 cases of MCD showed positivity in the podocytes. Among the cases of FSGS, 7/10 cases showed positivity in the podocytes with 3 cases showing an associated mesangial blush pattern of staining.

Conclusion: Very few studies are available demonstrating the importance of C4d IHC in MN. C4d IHC can be a useful adjunct for immunofluorescence, especially in cases of early MN.