C3 glomerulopathy in children: experience at a resource-limited center

Clin Exp Pediatr. 2024 Nov 28. doi: 10.3345/cep.2024.01256. Online ahead of print.

Abstract

Background: In children, C3 glomerulopathy (C3G) is a heterogeneous disease characterized by diverse clinicopathological profiles and kidney outcomes. However, diagnostic work-up in resource-limited settings is challenging because of the unavailability of complement assays and limited access to electron microscopy or genetic testing.

Purpose: This study aimed to describe the clinicopathological features and response to immunosuppression and evaluate renal outcomes among children with C3G in a resource-limited setting.

Methods: This retrospective cohort study involved a review of the hospital records of 46 children (2013-2021) diagnosed with C3G on kidney biopsy. Their clinical, laboratory, treatment, and outcome details at onset and follow-up were noted.

Results: The mean (SD) age was 9 (4) years. The common presentation was acute nephritis (27 [58.6%]), while one in five (19.5%) presented with rapidly progressive glomerulonephritis. Focal-crescentic glomerulonephritis (14 [30.4%]) was the common histological pattern. Electron microscopy was performed in 22 (47.8%), of which 17 were C3 glomerulonephritis (C3GN) and four were dense deposit disease (DDD). None of the patients underwent complement assay or genetic testing. Almost two-thirds (63%) received empirical immunosuppressive therapy, most commonly steroids. Of the 31/46 who completed follow-up (median [IQR] duration, 11.5 [6-24] months), six (19.4%) demonstrated complete kidney recovery, while the other 25 (80.7%) had kidney sequelae; of them, five (16.1%) progressed to end-stage kidney disease and two (4.3%) died by the last follow-up.

Conclusion: Pediatric C3G has a variable clinicopathological spectrum, while DDD is less common. Most patients present with glomerulonephritis and significant morbidities. The lack of genetic and C3Nephritic factor testing is a barrier to the comprehensive phenotyping and management of C3G in resource-limited settings.

Keywords: Alternate complement pathway; C3 glomerulopathy; Dense deposit disease; Glomerulonephritis in India children.