A Novel Glomerular C4d Scoring System: A Tool to Prognosticate Proliferative Exudative Pattern of Glomerular Injury

Proliferative exudative pattern of glomerular injury is usually a manifestation of an infection related or a post-infectious glomerulonephritis (PIGN). Rarely, it may represent a C3 glomerulopathy, which is a dysfunction of the alternative pathway of complement activation, and is then termed an atypical PIGN (aPIGN). C4d deposits in the glomerulus are footprints of the classical and/or lectin pathway of complement activation and hence is expected to be positive in immune-mediated glomerulonephritis (GN) like classical infection-related GN, and could be used to differentiate classical PIGN from atypical PIGN.

We report a novel C4d scoring system based on the intensity and the proportion of glomerular tuft staining, in a series of 104 biopsies with the proliferative exudative pattern of glomerular injury. Using a statistically derived cut-off score of 1.45, the cases were divided into C4d positive and C4d negative groups and compared to IF findings and the follow-up, available in 36 cases.

The C4d positive group had a significantly greater proportion of cases with immune complexes compared to the group with C3 deposits alone. In the follow-up, C4d negative group had also a greater number with partial/incomplete response compared to the C4d positive group.

We recommend that the C4d stain be done in all cases with a proliferative exudative pattern of glomerular injury to identify patients who would need a close follow up and further assays of complement function.