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Long-term follow-up including extensive complement analysis of a pediatric C3 glomerulopathy cohort
Marloes A H M Michels1, Kioa L Wijnsma2, Roel A J Kurvers3
1Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands. marloes.michels@radboudumc.nl.
Insights
This study followed 29 children with C3 glomerulopathy (C3G), finding a generally benign outcome. Persistent low complement C3 levels correlated with C3 nephritic factors, and C3 glomerulonephritis showed distinct complement profiles.
Area of Science:
- Nephrology
- Immunology
- Pediatric Medicine
Background:
- C3 glomerulopathy (C3G) is a rare kidney disease defined by C3 deposition in glomeruli.
- C3G encompasses dense deposit disease (DDD) and C3 glomerulonephritis (C3GN).
- This study focuses on the long-term complement analysis of pediatric C3G patients.
Purpose of the Study:
- To describe the clinical and laboratory findings in a cohort of Dutch children with C3G.
- To analyze complement system abnormalities in pediatric C3G.
- To evaluate the long-term outcomes of C3G in children.
Main Methods:
- Included 29 pediatric C3G patients (19 DDD, 10 C3GN) diagnosed between 1992-2014.
- Collected clinical, laboratory, and specialized complement assays (rare variants, autoantibodies, biomarkers).
- Assessed complement C3 levels, C3 nephritic factors (C3NeFs), and soluble C5b-9 (sC5b-9).
Main Results:
- DDD patients had lower initial estimated glomerular filtration rate (eGFR).
- C3NeFs were detected in 20 patients and persisted despite treatment.
- C3GN patients showed higher sC5b-9 and lower properdin levels compared to DDD patients.
Conclusions:
- Pediatric C3G cohort extensively characterized with complement features.
- Benign long-term outcome observed in most patients.
- Persistent low C3 linked to C3NeF; C3GN associated with specific complement markers, suggesting targeted therapies.
Background:
C3 glomerulopathy (C3G) is a rare kidney disorder characterized by predominant glomerular depositions of complement C3. C3G can be subdivided into dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). This study describes the long-term follow-up with extensive complement analysis of 29 Dutch children with C3G.
Methods:
Twenty-nine C3G patients (19 DDD, 10 C3GN) diagnosed between 1992 and 2014 were included. Clinical and laboratory findings were collected at presentation and during follow-up. Specialized assays were used to detect rare variants in complement genes and measure complement-directed autoantibodies and biomarkers in blood.
Results:
DDD patients presented with lower estimated glomerular filtration rate (eGFR). C3 nephritic factors (C3NeFs) were detected in 20 patients and remained detectable over time despite immunosuppressive treatment. At presentation, low serum C3 levels were detected in 84% of all patients. During follow-up, in about 50% of patients, all of them C3NeF-positive, C3 levels remained low. Linear mixed model analysis showed that C3GN patients had higher soluble C5b-9 (sC5b-9) and lower properdin levels compared to DDD patients. With a median follow-up of 52 months, an overall benign outcome was observed with only six patients with eGFR below 90 ml/min/1.73 m2 at last follow-up.
Conclusions:
We extensively described clinical and laboratory findings including complement features of an exclusively pediatric C3G cohort. Outcome was relatively benign, persistent low C3 correlated with C3NeF presence, and C3GN was associated with higher sC5b-9 and lower properdin levels. Prospective studies are needed to further elucidate the pathogenic mechanisms underlying C3G and guide personalized medicine with complement therapeutics.
