Kidney Week

Abstract: TH-PO0332

Urinary Complement Profiling as a Tool for Disease Activity in Glomerular Disorders

Session Information

• Glomerular Diseases: Omics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Tzali, Eleni, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Eleni Tzali, MD, MSc

• Kaforou, Sofia, Proteomics Unit, Institute of Molecular Biology and Biotechnology (IMBB- FORTH), Heraklion, Greece

Sofia Kaforou, MSc

• Kountourakis, Nikos, Proteomics Unit, Institute of Molecular Biology and Biotechnology (IMBB- FORTH), Heraklion, Greece

Nikos Kountourakis, MSc

• Antonakis, Andreas, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Andreas Antonakis, MD, MSc

• Lygerou, Dimitra, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Dimitra Lygerou, MD, PhD

• Drosataki, Eleni, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Eleni Drosataki, MD

• Dermitzaki, Eleftheria-Kleio, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Eleftheria-Kleio Dermitzaki, MD

• Pleros, Christos, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Christos Pleros, MD, PhD

• Androvitsanea, Ariadni, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Ariadni Androvitsanea, MSc

• Gakiopoulou, Harikleia, 1st Department of Pathology, Medical School, National and Kapodistrian Unversity of Athens, Athens, Greece

Harikleia Gakiopoulou, MD, PhD

• Gouridis, Giorgos, Proteomics Unit, Institute of Molecular Biology and Biotechnology (IMBB- FORTH), Heraklion, Greece

Giorgos Gouridis, MSc, PhD

• Stylianou, Konstantinos, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Konstantinos Stylianou, MD, PhD

• Petrakis, Ioannis, Nephrology Clinic, University Hospital of Heraklion, Heraklion, Greece

Ioannis Petrakis, MD, PhD

Background

Complement overactivation is increasingly recognized in glomerular disease, but urinary proteomic studies focused on complement remain limited. This study evaluates urinary complement proteomics as a biomarker of kidney disease activity.

Methods

From May to August 2025, a longitudinal cohort of 27 patients with chronic kidney disease was recruited, yielding 1,416 patient-visits. Twenty patients had active disease (1,029visits), seven had inactive disease (387visits), and five healthy individuals served as controls. Diagnoses included IgA nephropathy, ANCA-associated vasculitis, thrombotic microangiopathy, interstitial nephritis, cryoglobulinemic membranoproliferative glomerulonephritis, and primary membranous nephropathy. Disease activity was assessed by treating nephrologists at sampling. Morning urine samples were analyzed using label-free nLC–MS/MS with a targeted focus on complement proteins. Pathway-level scores and protein-level intensity matrices were evaluated using logistic regression models trained on (i) proteomics, (ii) eGFR and (iii) combined proteomics and eGFR. Performance was assessed using cross-validated ROC AUC and sensitivity at fixed specificity thresholds, with robustness evaluated via bootstrap sampling, Bayesian analyses, non-inferiority testing, and pathway ablation.

Results

Models incorporating urinary complement proteomics consistently outperformed those based on eGFR alone in distinguishing Active from Inactive disease or healthy controls. Adding proteomics to eGFR increased ROC AUC from 0.741 to 0.809. Sensitivity improved from 0.37 to 0.57 (~80% specificity) and from 0.23 to 0.47 (90% specificity), supported by robustness tests. Pathway ablation identified the alternative pathway as the dominant contributor to that gain. Protein-level analyses highlighted CFI, CFB, and C3 fragments as strong standalone markers, while multivariate ablation demonstrated that regulatory components, particularly CFH and CFHR, were central drivers of discrimination, rendering several activation markers redundant.

Conclusion

Urinary complement proteomics provides independent and clinically meaningful information for kidney disease activity detection beyond eGFR.
The signal is driven mainly by dysregulation of the alternative pathway and its regulatory components, supporting urinary proteomics as a minimally invasive tool for activity monitoring. Further validation is necessary in larger cohorts.