A decade of C3 glomerulopathy-A nationwide cohort study

Abstract

Introduction C3 glomerulopathy (C3G) is a rare but devastating disease affecting children and adults. It frequently leads to end-stage kidney failure, and currently no specific treatment exists. C3G is used as a collective term for dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) and is thought to sometimes occur in postinfectious settings (C3-PIGN). Currently, little is known about the incidence and distribution of subtypes in the population. We analyzed a large cohort of patients with C3G in the Netherlands regarding incidence and disease subtype distribution in relation to geographical factors and histopathological findings. Methods A search in the Dutch Nationwide Pathology Databank (Palga) was performed to identify patients diagnosed with C3G from January 2014 until December 2023, subsequently ascertained by 2 independent observers. We assessed the correlation of disease subtypes with glomerular patterns, and the geographical distribution was charted. Results The selection resulted in a cohort of 280 patients consisting of C3GN (n = 101), DDD (n = 39), unspecified C3G (n = 106), C3-PIGN (n = 29), and others (n = 5). The median age at biopsy diagnosis was 19 (range: 4-75) years for DDD and 54 (range: 2-86) years for C3GN, showing age distribution depends on C3G subtype (P < 0.001). DDD and C3G were associated with membranoproliferative pattern and C3-PIGN with endocapillary or exudative pattern. Conclusion Our results show consistent assessment of kidney biopsies across the country and absence of geographical factors influencing disease development.