Kidney Week

Abstract: TH-PO0316

Proteomic Profiling Reveals Complement Activation and Extracellular Matrix Remodeling in Renal Amyloidosis

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

• Feitosa, Valkercyo Araújo, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil

Valkercyo Araújo Feitosa

• Neves, Precil D., Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil

Precil D. Neves, MD, PhD

• Siqueira, Talita Souza, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil

Talita Souza Siqueira, PhD

• Murata, Gilson Masahiro, Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil

Gilson Masahiro Murata, DrPH

• Watanabe, Elieser H., Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil

Elieser H. Watanabe, MD, PhD

• Carvalho, Valdemir Melechco, Fleury Group, Sao Paulo, Brazil

Valdemir Melechco Carvalho, PhD

• Araujo, Stanley A., Instituto de Nefropatologia, Belo Horizonte, Minas Gerais, Brazil

Stanley A. Araujo, MD, MBBS

• Wanderley, David Campos, Instituto de Nefropatologia, Belo Horizonte, Minas Gerais, Brazil

David Campos Wanderley

• Noronha, Irene L., Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil

Irene L. Noronha, MD, PhD

• Onuchic, Luiz F., Universidade de Sao Paulo Faculdade de Medicina, São Paulo, SP, Brazil

Luiz F. Onuchic, MD, PhD

Background

Renal amyloidosis (RA) is characterized by extracellular deposition of insoluble amyloid fibrils within glomeruli, vessels, and interstitium. The glomerular extracellular matrix (ECM) is a key interface for amyloid accumulation. While its remodeling may contribute to proteinuria and kidney dysfunction, the mechanisms underlying RA remain largely unclear.

Methods

Proteomic analyses of glomerular ECM were performed in light chain RA (AL; n=6), secondary RA (AA; n=5), and fibrinogen RA (AFib; n=6). Normal kidney (NK) tissue from non-neoplastic nephrectomy areas (n=4) served as controls. RA biopsy samples underwent glomerular laser microdissection, ECM enrichment, and mass spectrometry–based proteomic analysis to characterize subtype-specific ECM profiles in glomeruli with minimal amyloid deposition.

Results

We identified 340 ECM proteins in RA and NK glomeruli, including 249 previously described and 91 novel glomerular ECM candidates. Protein–protein interaction analysis of 116 differentially abundant ECM proteins identified 6 functional clusters involving ECM structural proteins, fibrillar and glomerular basement membrane (GBM) collagens, terminal complement pathway components, amyloid-associated lipoproteins, coagulation-related proteins, and laminin subunits. Network enrichment analysis highlighted complement activation and ECM remodeling pathways. Coordinated enrichment of ECM glycoproteins and structural proteins, including FN1, HSPG2, DCN, BGN, COL1A1, COL4A1, COL4A5, and laminin chains, supported activation of collagen biosynthesis, fibrillogenesis, and GBM remodeling pathways. Complement pathway components, including CFHR5, C1QA, C1QB, C1QC, C5, C6, C7, C8A, and C8G, were among the 20 most differentially abundant proteins. IHC and IF assessment validated such findings, revealing C4d and C5b-9 staining across all amyloid subtypes and absent signal in NK. Mesangial deposition of APOE (94.5% of cases), C4d (88.9%), and C5b-9 (66.7%), associated with minimal C3 deposition despite absent C1q, supports activation of the classical and terminal complement pathways.

Conclusion

Proteomic analysis of RA revealed activation of the classical complement pathway and subtype-specific ECM remodeling, including enrichment of structural ECM proteins, collagens, and laminin networks, implicating complement-mediated injury and active matrix reorganization as potential drivers of glomerular damage.

Funding

• Private Foundation Support