Comparative Analysis of Proteinuria and Longitudinal Outcomes in Immune Complex Membranoproliferative Glomerulonephritis and C3 Glomerulopathy
Fernando Caravaca‐Fontán, Remedios Toledo-Rojas, Ana Huerta, José Luis Pérez Canga, Patricia Martínez‐Miguel, Rosa Miquel, Iara Da Silva, Úrsula Verdalles, M. C. Bastardo de Albornoz, Carmen Lopez, Carmen Mon, Gema Fernández‐Juárez, Manuel Praga, Teresa Cavero, Luis F. Quintana, Helena Marco, Xoana Barros, Natalia Ramos, Nuria Rodríguez Mendiola, Sonia Cruz, Adela Rodríguez, 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, 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, Santiago Rodríguez de Córdoba, Elena Goicoechea de Jorge
Abstract
Introduction C3 glomerulopathy (C3G) and primary immune complex–mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases that share a similar pathogenesis; however, the prognostic significance of proteinuria reduction remains poorly characterized. This study compared the outcomes in C3G and IC-MPGN and assessed the impact of changes in proteinuria on kidney prognosis. Methods This retrospective, longitudinal, multicenter study used joint linear mixed-effects models to assess proteinuria trajectories, and Cox regression to evaluate their association with kidney failure. In addition, time-averaged proteinuria (TA-P) was calculated to determine its impact on kidney prognosis. Results The study included 149 patients: 98 with C3G (66%) and 51 with IC-MPGN (34%) with a median age of 35 (interquartile range [IQR]: 22–53) years. During a median follow-up of 65 (IQR: 32–114) months, 44 patients (30%) progressed to kidney failure without differences across C3G or IC-MPGN. A strong association was observed between longitudinal increase in proteinuria and the risk of kidney failure. In addition, a ≥ 50% proteinuria reduction over time was associated with a lower risk of kidney failure (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.46–0.75, P < 0.001). Results were consistent in both C3G and IC-MPGN, and in those with baseline estimated glomerular filtration rate (eGFR) ≥ 30 ml/min per 1.73 m 2 and proteinuria ≥ 1 g/d. A ≥30% proteinuria reduction at 6 months or a ≥50% proteinuria reduction at 12 months were associated with a slower eGFR decline. Patients were categorized into 4 subgroups based on TA-P levels, with TA-P values < 1 g/d indicating better kidney outcomes. Conclusion Proteinuria reduction was associated with improved kidney outcomes and slower eGFR decline in both C3G and IC-MPGN.