#2442 Ten years of C3 glomerulopathy: a nationwide cohort study

Abstract Background and Aims C3 glomerulopathy (C3G) is a rare but potentially devastating disease affecting both children and adults. It frequently leads to kidney failure within ten years after diagnosis 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 post-infectious settings (C3-PIGN). The diagnosis is made by combining clinical data with light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM) findings. Currently, little is known about the incidence and subtype distribution throughout the population. We constructed a large cohort of C3G patients in the Netherlands of the past ten years. With this cohort we were able to identify incidence and potential variances between subtypes across different regions of the country. We also correlated disease subtypes with certain histopathological findings and analyzed these histopathological findings throughout the years. Method A search in the national Dutch pathology database (PALGA) was performed. Patients diagnosed with C3G from January 2014 until December 2023 were identified by two independent observers. Cross tabulations were used to assess the correlation of disease subtypes and glomerular patterns, and the geographical distribution of C3G subtypes and histological disease patterns. Non-parametric analysis was used to evaluate the age distribution at diagnosis. Results The selection resulted in a cohort of 280 patients, consisting of: C3GN (n = 101), DDD (n = 39), unspecified C3G (i.e. either DDD or C3GN, n = 106), C3-PIGN (n = 29) and 5 others. The median age of biopsy at the time of diagnosis was 19 for DDD (range 4 to 75) and 58 for C3GN (range 2 to 86), showing that age distribution depends on C3G subtype (P < 0.001). C3G subtypes were associated with specific glomerulonephritis patterns (P < 0.001), namely that DDD and C3GN were associated with membranoproliferative glomerulonephritis, and C3-PIGN was associated with endocapillary or exudative pattern. There were no statistically significant variations found in C3G subtype distribution between different provinces or province clusters (P = 0.142). Conclusion We present the largest C3G cohort known today, consisting of biopsy proven C3G patients in the Netherlands over a ten year period. We investigated the incidence of C3G in different regions and its disease presentation in kidney biopsies. Results show that C3G incidence is evenly distributed across different regions of The Netherlands. The variability in histological presentation was substantial, therefore we conclude that diagnosing and subtyping C3G cannot be done confidently based on histological pattern alone. This emphasizes the need for optimal and well-defined IF and EM evaluation. This cohort will be an important tool for testing subsequent hypotheses, and inspire future research.