C3 glomerulopathy in children: a European longitudinal study evaluating outcome.

BACKGROUND

C3 glomerulopathy is a rare clinical entity characterized by dysregulation of the alternative complement pathway in glomerular disease. Studies defining the natural history of C3G in the pediatric population are scarce.

METHODS

Patients included in this retrospective study were diagnosed between 2011 and 2020 in 12 European pediatric nephrology units. Data were collected from baseline, 6 months, 12 months and at the last follow-up. Complete remission (CR) was defined as a urinary protein creatinine ratio (UPCR) < 0.3 mg/mg with normal estimated glomerular filtration rate (eGFR). Partial remission was defined as a decrease in UPCR to 0.3 and 3 mg/mg with normal eGFR. Lack of remission was defined as non-response.

RESULTS

A total of 108 pediatric patients were included. Complete remission was achieved in 71/108 patients (65.7%), with probability of CR of 50% at 1.8 years and of 78% at 7 years. At presentation by univariate analysis the predictive factors at presentation associated with CR included eGFR (p = 0.028), UPCR (p = 0.004), serum C3 levels (p = 0.018), elevated plasma sC5b9 levels, defined as > 400 ng/ml, (p = 0.037), the presence of endocapillary proliferation (p = 0.017), and the absence of dense deposits on electron microscopy (p = 0.032). By multivariate analysis a low UPCR at presentation (p < 0.001) and the presence of endocapillary proliferation (p < 0.01) remained positively associated with CR.

CONCLUSIONS

Our data confirm that C3G has a more benign outcome in children compared to previous reports in adults, and suggest that endocapillary proliferation and the degree of proteinuria at onset are the most relevant prognostic factors.