C3 glomerulopathy associated with monoclonal gammopathy: impact of chronic histologic lesions and beneficial effects of clone-targeted therapies.

Abstract

INTRODUCTION\nC3 glomerulopathy associated with monoclonal gammopathy (C3G-MIg) is a rare entity. Herein, we analyzed the clinical and histologic features of a cohort of C3G-MIg patients.\n\n\nMETHODS\nRetrospective, multicenter, observational study. Patients diagnosed with C3G-MIg between 1995-2021 were enrolled. All had genetic studies of the alternative complement pathway. The degree of disease activity and chronicity was analyzed using the C3G histologic index. Descriptive statistics and propensity-score matching (PSM) analysis were used to evaluate the main outcome of the study (kidney failure [KF]).\n\n\nRESULTS\nThe study group included 23 patients: median age 63 years (IQR 48-70), 57% males. IgG kappa was the most frequent MIg (65%). The diagnosis of C3G-MIg was made in transplanted kidneys in 7 patients (30%). Five (22%) had C3 nephritic factor and 5 (22%) anti-factor H antibodies. One patient carried a pathogenic variant in CFH gene.During a follow-up of 40 months (IQR 14-69), 9 patients (39%) reached KF, and these patients had a significant higher total chronicity score in kidney biopsy. Patients who received clone-targeted therapy had a significant higher survival compared to other management. Those who achieved hematological response had a significant higher kidney survival. Outcome was remarkably poor in kidney transplant recipients, 5 of them (71%) reaching KF.By PSM (adjusting for age, kidney function, proteinuria and chronicity score), no significant differences were observed in kidney survival between C3G patients with/without MIg.\n\n\nCONCLUSIONS\nThe C3G histologic index can be used in patients with C3G-MIg to predict kidney prognosis, with higher chronicity scores being associated with worse outcomes. Clone-targeted therapies and the development of hematological response, are associated with better kidney prognosis.