TY - JOUR
T1 - Long-term follow-up including extensive complement analysis of a pediatric C3 glomerulopathy cohort
AU - Michels, Marloes A.H.M.
AU - Wijnsma, Kioa L.
AU - Kurvers, Roel A.J.
AU - Westra, Dineke
AU - Schreuder, Michiel F.
AU - van Wijk, Joanna A.E.
AU - Bouts, Antonia H.M.
AU - Gracchi, Valentina
AU - Engels, Flore A.P.T.
AU - Keijzer-Veen, Mandy G.
AU - Dorresteijn, Eiske M.
AU - Volokhina, Elena B.
AU - van den Heuvel, Lambertus P.W.J.
AU - van de Kar, Nicole C.A.J.
N1 - Funding Information:
R. K. was supported by Sengers Stipendium, Amalia Children’s Hospital, Radboudumc, Nijmegen. This work was supported by a grant from the Dutch Kidney Foundation (13OCA27 COMBAT Consortium).
Publisher Copyright:
© 2021, The Author(s).
PY - 2022/3
Y1 - 2022/3
N2 - 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. Graphical abstract: [Figure not available: see fulltext.]
AB - 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. Graphical abstract: [Figure not available: see fulltext.]
KW - C3 glomerulonephritis
KW - C3 glomerulopathy
KW - C3 nephritic factor
KW - Children
KW - Complement system
KW - Dense deposit disease
U2 - 10.1007/s00467-021-05221-6
DO - 10.1007/s00467-021-05221-6
M3 - Article
AN - SCOPUS:85114087644
SN - 0931-041X
VL - 37
SP - 601
EP - 612
JO - Pediatric Nephrology
JF - Pediatric Nephrology
ER -