Clinicopathological features of C3 glomerulopathy in children: a single-center experience

• Published in: Pediatric nephrology (Berlin, West) Vol. 35; no. 1; pp. 153 - 162
• Main Authors: Drake, Keri A., Ellington, Natalie, Gattineni, Jyothsna, Torrealba, Jose R., Hendricks, Allen R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2020; Springer Nature B.V
• Subjects: Adolescent; Autoantibodies; Biopsy; Child; Children; Complement C3 - genetics; Complement C3 - immunology; Complement component C3; Complement factor H; Complement Inactivator Proteins - analysis; Complement Inactivator Proteins - immunology; Disease Progression; Electron microscopy; Female; Follow-Up Studies; Genetic screening; Genetic Testing; Glomerulonephritis; Glomerulonephritis, Membranoproliferative - blood; Glomerulonephritis, Membranoproliferative - complications; Glomerulonephritis, Membranoproliferative - genetics; Glomerulonephritis, Membranoproliferative - immunology; Humans; Kidney Failure, Chronic - epidemiology; Kidney Failure, Chronic - immunology; Kidney Glomerulus - immunology; Kidney Glomerulus - pathology; Kidney Glomerulus - ultrastructure; Male; Medicine; Medicine & Public Health; Microscopy, Electron; Mutation; Nephrology; Original Article; Pathophysiology; Patients; Pediatrics; Rare diseases; Renal function; Retrospective Studies; Urology; dense deposit disease; nephritic factor; children; C3 glomerulopathy; C3 glomerulonephritis
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-019-04388-3

Background C3 glomerulopathy (C3G) is defined by dominant glomerular deposition of C3 and minimal or no immunoglobulin, with two subtypes—dense deposit disease (DDD) and C3 glomerulonephritis (C3GN)—distinguished by features on electron microscopy (EM). Given that this rare disease has generally unfavorable yet highly variable outcomes, we sought out to review the histopathology, complement/genetic studies, and renal outcomes of pediatric patients with C3G at our institution. Methods All native kidney biopsies performed in a single pediatric hospital over a 10-year period were reviewed for features of C3G. Of 589 biopsy reports, we identified 9 patients fulfilling the diagnostic criteria for C3G and retrospectively reviewed their clinical chart and renal biopsy findings. Results We identified 4 patients with DDD, 4 with C3GN, and 1 indeterminate case, with features of both C3GN and DDD. Five patients were positive for one or more nephritic factors (C3NeF, C4NeF, C5NeF) with 1 patient additionally positive for complement factor H (CFH) autoantibody. Genetic testing done in 5 of the 9 patients failed to identify any causative mutations. Three patients showed progressive renal dysfunction over a mean follow-up period of 33 months. Conclusions Complement and genetic studies are now routinely recommended for patients with a histopathological diagnosis of C3G. Careful interpretation of these studies and their prognostic and therapeutic implications in conjunction with biopsy findings is needed to further understand the pathophysiology of this rare disease in children.