Comparison of dominant and nondominant C3 deposition in primary glomerulonephritis

Background: Alternative complement pathway dysregulation plays a key role in glomerulonephritis (GN) and is associated with C3 deposition. Herein, we examined pathological and clinical differences between cases of primary GN with C3-dominant (C3D-GN) and nondominant (C3ND-GN) deposition.Methods: We extracted primary GN data from the Korean GlomeruloNEphritis sTudy (KoGNET). C3D-GN was defined as C3 staining two grades greater than C1q, C4, and immunoglobulin via immunofluorescence analysis. To overcome a large difference in the num-ber of patients between the C3D-GN and C3ND-GN groups (31 vs. 9,689), permutation testing was used for analysis.Results: The C3D-GN group exhibited higher serum creatinine (p 5 0.001), a greater prevalence of estimated glomerular filtration rate of <60 mL/min/1.72 m2 (p 5 0.001), higher (but not significantly so) C-reactive protein level, and lower serum C3 level (p 5 0.001). Serum albumin, urine protein/creatinine ratio, number of patients who progressed to end-stage renal disease, and all-cause mortality were comparable between groups. Interstitial fibrosis and mesangial cellularity were greater in the C3D-GN group (p = 0.04 and p = 0.01, respectively) than in the C3ND-GN group. C3 deposition was dominant in the former group (p < 0.001), in parallel with in-creased subendothelial deposition (p 5 0.001).Conclusion: Greater progression of renal injury and higher mortality occurred in patients with C3D-GN than with C3ND-GN, along with pathologic differences in interstitial and mesangial changes.