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E-Poster Submission Deadline
Please prepare and upload your E-Poster no later than March 14, 2026 11.59PM CET. After this date, you will no longer be able to prepare and upload your E-poster and it will not be displayed and accessible on the congress website.
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Abstract titles should be brief and reflect the content of the abstract.
C4d is a stable split product of complement activation through the classical and lectin pathways. While C4d staining is routinely used as a marker for antibody-mediated rejection in renal allografts, its diagnostic role in native kidney diseases is less established. Immune complex–mediated glomerulonephritides (GN) such as lupus nephritis, membranous nephropathy, and infection-related GN involve complement activation, often resulting in glomerular C4d deposition. Recent studies suggest that immunohistochemical (IHC) C4d staining on formalin-fixed paraffin-embedded (FFPE) tissue can mirror immunofluorescence (IF) findings, aiding in the diagnosis of immune complex–mediated GN and clarifying the complement activation pathway. However, there are no published data on the diagnostic utility of C4d in nephropathology practice from Africa. This cross-sectional study aimed to evaluate the correlation between C4d IHC and IF findings in native renal biopsies from a routine diagnostic practice in Kenya.
We retrospectively evaluated 68 consecutive native renal biopsies processed over a six-month period at a central referral nephropathology laboratory, all of which had both C4d IHC and IF performed as part of routine workup. C4d IHC was performed on FFPE sections using the Roche Ventana C4d antibody on a Ventana Benchmark Ultra autostainer. IF was done on frozen sections using standard antisera for IgG, IgA, IgM, C3, and C1q. Diagnostic categorization of biopsies was based on integrated light microscopy (LM), IF, and electron microscopy (EM) findings where available. Concordance between C4d staining patterns and IF results was assessed, focusing on the distribution (mesangial vs capillary wall) and intensity of deposits.
Among the 68 biopsies, diagnostic categories included: lupus nephritis (n=24), membranous nephropathy (n=7), infection-related GN (n=9), IgA nephropathy (n=5), minimal change disease (n=5), focal segmental glomerulosclerosis (n=4), diabetic nephropathy (n=4), HIV-associated nephropathy (n=2), and pauci-immune GN (n=2).
All immune complex–mediated GN (membranous nephropathy, lupus nephritis, IgA nephropathy, infection-related GN) demonstrated positive C4d staining with expected localization, closely mirroring the IF pattern and intensity of immune deposits (capillary wall and/or mesangial). Concordance between C4d and IF was high across these entities. In contrast, non–immune complex diseases—FSGS, MCD, diabetic nephropathy, and pauci-immune GN—were consistently negative for glomerular C4d, except for rare cases showing weak, non-specific staining.
Notably, membranous nephropathy exhibited strong, diffuse, continuous capillary wall C4d staining, paralleling the characteristic granular IgG and C3 IF pattern, reinforcing its diagnostic specificity.
C4d immunohistochemistry shows strong concordance with immunofluorescence in immune complex–mediated glomerular diseases and an excellent negative predictive value in excluding non–immune complex lesions. Routine incorporation of C4d IHC as a cost-efficient marker can enhance diagnostic accuracy in differentiating membranous nephropathy from minimal change disease, corroborate lupus nephritis classification, and support the identification of other immune complex–mediated GN in everyday nephropathology practice. Given its applicability to FFPE tissue and ease of correlation with light microscopy, C4d offers a practical, cost-effective adjunct diagnostic tool—particularly valuable in resource-limited settings where IF facilities may be unavailable or compromised such as in many parts of sub-Saharan Africa.
