Fernando Caravaca-Fontán1,2, Laura Lucientes1,3, Núria Serra4, Teresa Cavero5, Raquel Rodado6, Natalia Ramos7, Fayna Gonzalez8, Amir Shabaka9, Virginia Cabello10, Ana Huerta11, Saúl Pampa-Saico12, Eduardo Gutiérrez5, Luis F Quintana13, Maria Esperanza López-Rubio14, Juliana Draibe15, Juana Alonso Titos16, Gema Fernández-Juárez9, Elena Goicoechea de Jorge1,3, Manuel Praga1,2. 1. Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain. 2. Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain. 3. Department of Immunology, Universidad Complutense de Madrid, Madrid, Spain. 4. Department of Nephrology, Fundación Puigvert, Barcelona, Spain. 5. Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain. 6. Department of Nephrology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain. 7. Department of Nephrology, Hospital Universitario Vall d'Hebron, Barcelona, Spain. 8. Department of Nephrology, Hospital Doctor Negrín, Gran Canaria, Spain. 9. Department of Nephrology, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain. 10. Department of Nephrology, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 11. Department of Nephrology, Hospital Universitario Puerta de Hierro, Madrid, Spain. 12. Department of Nephrology, Hospital Universitario Rey Juan Carlos, Móstoles, Madrid, Spain. 13. Complex Glomerular Disease Unit, Department of Nephrology, Hospital Clinic de Barcelona, University of Barcelona, Institut d'Investigacions Biomédiques August Pi i Sunyer, Barcelona, Spain. 14. Department of Nephrology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain. 15. Department of Nephrology, Hospital Universitario de Bellvitge, Barcelona, Spain. 16. Department of Nephrology, Hospital Regional Universitario Carlos Haya, Málaga, Spain.
Abstract
BACKGROUND: C3 glomerulopathy associated with monoclonal gammopathy (C3G-MIg) is a rare entity. Herein we analysed the clinical and histologic features of a cohort of C3G-MIg patients. METHODS: We conducted a retrospective, multicentre, observational study. Patients diagnosed with C3G-MIg between 1995 and 2021 were enrolled. All had genetic studies of the alternative complement pathway. The degree of disease activity and chronicity were analysed 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)]. RESULTS: The study group included 23 patients with a median age 63 of years [interquartile range (IQR) 48-70], and 57% were males. Immunoglobulin G kappa was the most frequent MIg (65%). The diagnosis of C3G-MIg was made in transplanted kidneys in seven patients (30%). Five (22%) patients had C3 nephritic factor and five (22%) had anti-factor H antibodies. One patient carried a pathogenic variant in the CFH gene. During a follow-up of 40 months (IQR 14-69), nine patients (39%) reached KF and these patients had a significantly higher total chronicity score on kidney biopsy. Patients who received clone-targeted therapy had a significantly higher survival compared with other management. Those who achieved haematological response had a significantly higher kidney survival. Outcome was remarkably poor in kidney transplant recipients, with five 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. CONCLUSIONS: The 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 a haematological response are associated with better kidney prognosis.
BACKGROUND: C3 glomerulopathy associated with monoclonal gammopathy (C3G-MIg) is a rare entity. Herein we analysed the clinical and histologic features of a cohort of C3G-MIg patients. METHODS: We conducted a retrospective, multicentre, observational study. Patients diagnosed with C3G-MIg between 1995 and 2021 were enrolled. All had genetic studies of the alternative complement pathway. The degree of disease activity and chronicity were analysed 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)]. RESULTS: The study group included 23 patients with a median age 63 of years [interquartile range (IQR) 48-70], and 57% were males. Immunoglobulin G kappa was the most frequent MIg (65%). The diagnosis of C3G-MIg was made in transplanted kidneys in seven patients (30%). Five (22%) patients had C3 nephritic factor and five (22%) had anti-factor H antibodies. One patient carried a pathogenic variant in the CFH gene. During a follow-up of 40 months (IQR 14-69), nine patients (39%) reached KF and these patients had a significantly higher total chronicity score on kidney biopsy. Patients who received clone-targeted therapy had a significantly higher survival compared with other management. Those who achieved haematological response had a significantly higher kidney survival. Outcome was remarkably poor in kidney transplant recipients, with five 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. CONCLUSIONS: The 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 a haematological response are associated with better kidney prognosis.
Authors: Fernando Caravaca-Fontán; Marta Rivero; Teresa Cavero; Montserrat Díaz-Encarnación; Virginia Cabello; Gema Ariceta; Luis F Quintana; Helena Marco; Xoana Barros; Natalia Ramos; Nuria Rodríguez-Mendiola; Sonia Cruz; Gema Fernández-Juárez; Adela Rodríguez; Ana Pérez de José; Cristina Rabasco; Raquel Rodado; Loreto Fernández; Vanessa Pérez-Gómez; Ana Ávila; Luis Bravo; Natalia Espinosa; Natalia Allende; Maria Dolores Sanchez de la Nieta; Eva Rodríguez; Teresa Olea; Marta Melgosa; Ana Huerta; Rosa Miquel; Carmen Mon; Gloria Fraga; Alberto de Lorenzo; Juliana Draibe; Fayna González; Amir Shabaka; Maria Esperanza López-Rubio; María Ángeles Fenollosa; Luis Martín-Penagos; Iara Da Silva; Juana Alonso Titos; Santiago Rodríguez de Córdoba; Elena Goicoechea de Jorge; Manuel Praga Journal: Clin Kidney J Date: 2022-04-28