Abstract: SA-PO755
Identification of Kidney Transcripts Associated with Prognosis in ANCA-Associated Glomerulonephritis
Session Information
- ANCA-Associated Vasculitis, Anti-GBM Disease, and Other RPGN
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Brilland, Benoit, CHU Angers, Angers, France
- Riou, Jérémie, CHU Angers, Angers, France
- Boizard-Moracchini, Andrea, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux, Aquitaine, France
- Merillon, Nathalie, CHU Angers, Angers, France
- Despre, Maïa, CHU Angers, Angers, France
- Piccoli, Giorgina B., Centre Hospitalier du Mans, Le Mans, Pays de la Loire, France
- Djema, Assia Ilham, Centre Hospitalier de Cholet, Cholet, France
- Henry, Nicolas, CH Laval, Laval, France
- Copin, Marie-Christine, CHU Angers, Angers, France
- Langlais, David, McGill University, Montreal, Quebec, Canada
- Blanco, Patrick, CHU Angers, Angers, France
- Augusto, Jean Francois, CHU Angers, Angers, France
Group or Team Name
- Maine-Anjou Registry Research Group.
Background
Kidney involvement in ANCA-associated vasculitis (AAV-GN) predicts poor patient and kidney survival. To get insights into pathogenic mechanisms or identify biomarkers for refining prognosis, we aimed to investigate the potential prognostic value of kidney transcripts associated with kidney survival.
Methods
Immune gene transcript analysis was performed on RNA extracted from 97 adult AAV-GN kidney biopsies from the French Maine-Anjou Registry using NanoString technology. Transcripts of interest were selected, and their prognostic performance was compared to current histological-based classifications. Following the identification of a possible role for clusterin (CLU), the relationship between serum CLU and prognosis was assessed.
Results
Among the 750 evaluated transcripts, we identified a 4-gene signature (XRCC6, PRKCD, TEK, and CLU) strongly associated with kidney survival (Figure 1A). This signature predicted kidney survival better than histological-based classifications (global C-Index 0.87 vs. 0.65 for Berden classification or 0.81 for Renal Risk Score, with better time-dependent AUC and Brier scores) (Figure 1B). Among these 4 transcripts, the expression level of the CLU transcript had the highest correlation with glomerular involvement, kidney function at diagnosis, and kidney survival. Serum CLU levels were associated with kidney survival, especially when assessed at 6 months from diagnosis (Figure 1C, p = 0.023).
Conclusion
Transcriptomic analysis of kidney biopsies of AAV-GN identified potential transcripts that may improve prediction of kidney survival. This transcriptomic signature may help us gain a deeper understanding of the AAV-GN pathogenesis and provide insights for developing new therapeutic options.