Complement gene mutations in children with C3 glomerulopathy: Do they affect clinical outcome?

Abstract Background C3 glomerulopathy(C3G) is a complement-mediated disease caused by abnormalities in the alternative complement pathway. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to MMF treatment in pediatric C3G patients with and without mutations in complement related genes. Methods Sixty pediatric C3G patients were included, divided into two groups based on complement related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. Results Out of the 60 patients, 17 had mutations, with the most common mutation in the CH gene (47%). The mean age at diagnosis was significantly higher in the group with mutation (12.9 ± 3.6 vs 11.2 ± 4.1 years p = 0.039). While the patients without mutation were most frequently presented with the nephritic syndrome (44.2%), patients with the mutation were most likely to have asymptomatic urinary abnormalities (%47.1, p = 0.043). Serum parameters and histopathological characteristics were similar between the groups, but hypoalbuminemia was more common in patients without mutation. During a 45-month follow-up,10 patients progressed to CKD5, with four having a genetic mutation. The time to develop CKD5 was longer in the mutation group but not significantly different. MMF treatment had no effect on C3G progression in either group. Conclusions This study is the largest pediatric study examining the relationship between genotype and phenotype in C3G. We showed that in the mutation group often presented with asymptomatic urinary abnormalities, were diagnosed relatively late, but were not different from the mutation group in terms of MMF treatment response and kidney survival.