Lower serum C3 levels are associated with glomerulosclerosis in membranous nephropathy and ANCA-glomerulonephritis
Year: 2026
Type: article
Study design: Observational Study
Abstract: ABSTRACT Background Despite the key pathogenetic role of the complement cascade in various immune-mediated kidney diseases, the clinical significance of serum C3/C4 levels in conditions where most patients exhibit complement levels within normal limits, such as membranous nephropathy (MN) and ANCA (antineutrophil cytoplasmic antibody)-glomerulonephritis (ANCA-GN), remains underexplored. This study focused on the clinico-pathological correlates of serum complement C3/C4 levels in two cohorts of patients with biopsy-proven MN and ANCA-GN. Methods Based on median C3 and C4 levels at time of diagnostic biopsy, the cohorts were stratified into four groups, referred to as “complement component-high” and “-low.” Clinico-pathological features were compared between these groups and correlated with C3/C4 levels. Results In the MN cohort (n = 44), patients in the C3-low group showed a higher degree of global (8.3% vs 0%, p = .015) and combined global and segmental glomerulosclerosis (9.5% vs 0%, p = .032) compared to the C3-high group. In the ANCA-GN cohort (n = 198), serum C3 levels were lower in cases with the sclerotic class according to Berden classification (107 [98–123] mg/dl) compared to those classified as focal (138 [112–151] mg/dl, p < .001), crescentic (127 [107–151] mg/dl, p = .003), or mixed (123 [101–140] mg/dl, p = .018). Furthermore, ANCA-GN patients in the C3-low group showed lower estimated glomerular filtration rate at presentation and serum C3 was inversely associated with the risk of kidney failure, independently of several confounders (Hazard ratio [HR] for 10 mg/dl increase in C3: 0.91, 95% Confidence Interval [CI] 0.83–1.00, p = .049). Conclusions Serum C3 levels in the low-normal range were associated with glomerulosclerosis in both ANCA-GN and MN, and with poorer kidney outcome in ANCA-GN, supporting a potentially cross-disease role of the complement cascade in mediating glomerular injury.
Source: Clinical Kidney Journal
DOI: 10.1093/ckj/sfag350
Authors: Martina Tedesco, Elisa Delbarba, Martina Uzzo, Gianmarco Lugli, Chiara Bedognè, Marta Salti, Francesco Ravelli, Corrado Damilano, Eva Sestagalli, Marta Arrighini, Simona Fisogni, Vincenzo L’Imperio, Fabio Pagni, The REASSESS Study Group, Jennifer Scott, Jennifer O’Brien, Kresimir Galesic, Simonetta Genovesi, Giorgio Trivioli, Marco Allinovi, Iva Gunnarsson, Anna Juto, Robert Hall, Silke R. Brix, Federica Maritati, Anisa Idrizi, Anna Ricchiuto, Annette Bruchfeld, Gaetano La Manna, Mario Cozzolino, Renato A Sinico, Augusto Vaglio, Giacomo Emmi, Ingeborg Bajema, Andreas Kronbichler, Matija Crnogorac, Stephen McAdoo, Mark A Little, David R W Jayne, Federica Mescia, Federico Alberici
Institutions: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Humanitas University, IRCCS Humanitas Research Hospital, Azienda Ospedaliera San Gerardo, University of Milano-Bicocca, Karolinska Institutet, Linköping University Hospital, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of Bologna, University of Milan, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Meyer Children's Hospital, University of Florence, University of Trieste, Monash Medical Centre, Centre Hospitalier Universitaire Vaudois, Monash University, University of Lausanne, University Medical Center Groningen, University of Groningen, Innsbruck Medical University, Universität Innsbruck, University Hospital Dubrava, Imperial College Healthcare NHS Trust, Hammersmith Hospital, Imperial College London, Trinity College Dublin, University of Cambridge
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,335
OpenAlex ID: W7220705819