Clinical Profile and Outcome of C3-Dominant Glomerulonephritis: Retrospective Study

Abstract – Background: Complement 3 (C3)-dominant glomerulonephritis (GN) are rare diseases resulting from alternative complement pathway dysregulation; they include C3 glomerulopathy (C3G), paraprotein-associated GN, and C3-dominant infection-related GN (IRGN). To our knowledge, long-term follow-up studies of clinical profile and outcomes of this rare disorder are sparse. We studied kidney histopathology baseline findings, outcomes, treatment, and its complications of C3-dominant GN in our setting. Objectives: We studied the clinical, pathological profiles, and outcomes of patients with C3-dominant GN. Methods: This study was a single centre, retrospective, case record based observational study at a tertiary care hospital in Southern India. Consecutive patients of C3-dominant GN on kidney biopsy from 2013 to 2023 were included. Demography, laboratory and histopathological data, treatment and outcomes were studied. Results: Of 2, 175 kidney biopsies, 141 (6.48%) showed C3-dominant GN; 74 (52.5%) C3G, 67 (47.5%) IRGN. Median age was 43 years (IQR 29–59.5), males 90 (63.8%). Preceding skin/throat infections were seen in 32/141 (22.7%). At presentation, median serum creatinine was 1.7 mg/dL (IQR: 1.2–3.6), eGFR <60 mL/min/1.73 m ² in 91/141 (64.5%), 111/141 (78.7%) had low serum C3 levels. Nephrotic proteinuria was seen in 65/141 (46%), Crescents in 45 (31.9%). Remission was partial in 38/141 (27%), complete in 45/141 (31.9%) and 31/141 (22%) progressed to end-stage kidney disease (ESKD). On immunosuppression, commonest infection was pneumonia in 15/70 (21.4%) and 27/141 (19.1%) died at an average follow-up of 25.7 months. Diabetes mellitus, percentage sclerosis, and presence of crescents predicted development of CKD stage 5. Conclusion: Over 10 years, C3-dominant GN represented 6.48% of kidney biopsies. Nephrotic proteinuria and kidney failure are common at presentation with 58% achieving some remission, 22% going on to ESKD and mortality of 19%.