Abstract: FR-PO724
Unravelling the Pathophysiology of C3G/IC-MPGN and How to Predict Disease Progression and Orient Therapies
Session Information
- Clinical/Diagnostic Renal Pathology and Lab Medicine - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Glomerular
- 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine
Authors
- Iatropoulos, Paraskevas, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Daina, Erica, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Curreri, Manuela, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Piras, Rossella, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Valoti, Elisabetta, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Mele, Caterina, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Bresin, Elena, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Gamba, Sara, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Alberti, Marta, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Breno, Matteo, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Sabadini, Ettore, Ospedale Papa Giovanni XXIII, Bergamo, BG, Italy
- Noris, Marina, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
- Remuzzi, Giuseppe, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
Group or Team Name
- Registry of Membranoproliferative Glomerulonephritis/C3 Glomerulopathy
Background
Membranoproliferative glomerulonephritis (MPGN) was recently reclassified into alternative pathway (AP) complement-mediated C3 glomerulopathy (C3G) and immune-complex-mediated MPGN (IC-MPGN). However, genetic and acquired AP abnormalities are also observed in IC-MPGN. Here, in patients with C3G/IC-MPGN, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms.
Methods
We performed unsupervised hierarchical clustering, a data-driven statistical approach not biased by operator hypotheses, on 163 C3G/IC-MPGN patients using histology, genetic, serum complement and clinical features.
Results
This approach divided C3G/IC-MPGN patients into four clusters, characterized by specific histology, clinical and complements features indicating the existence of four different pathogenetic patterns. Specifically, patients with fluid-phase complement activation, showing low serum C3 and a high prevalence of AP gene mutations and/or C3NeF (clusters 1-3), were separated from patients with solid-phase complement activation (cluster 4), showing likely normal serum C3, late onset and poor renal survival. In patients with fluid-phase complement activation, clusters 1 and 2 were characterized by massive AP activation as far as the terminal pathway and the highest prevalence of subendothelial deposits, but cluster 2 was characterized by the additional activation of the classical pathway and the highest prevalence of nephrotic syndrome at onset. Patients in cluster 3 were characterized by prevalent activation of the C3 convertase and highly electron-dense deposits.
Conclusion
These clusters of C3G/IC-MPGN patients may be useful for better clarifying disease etiology, defining the risk of ESRD and paving the way for personalized treatment.