Kidney Week

Abstract: SA-PO794

Clinical and Histological Predictors of Outcomes in C3 Glomerulopathy

Session Information

• C3G, TMA, MGRS, Amyloidosis, and More
  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

• Ghaddar, Malak Ali, The University of British Columbia, Vancouver, British Columbia, Canada

Malak Ali Ghaddar, MD

• Lomax-Browne, Hannah J., Imperial College London Department of Immunology and Inflammation, London, London, United Kingdom

Hannah J. Lomax-Browne, PhD

• Cook, H. Terence, Imperial College London Department of Immunology and Inflammation, London, London, United Kingdom

H. Terence Cook, MBBS

• Daina, Erica, Istituto di Ricerche Farmacologiche Mario Negri Centro Aldo e Cele Dacco, Ranica, Lombardia, Italy

Erica Daina, MD

• Noris, Marina, Istituto di Ricerche Farmacologiche Mario Negri Centro Aldo e Cele Dacco, Ranica, Lombardia, Italy

Marina Noris, PhD

• Remuzzi, Giuseppe, Istituto di Ricerche Farmacologiche Mario Negri Centro Aldo e Cele Dacco, Ranica, Lombardia, Italy

Giuseppe Remuzzi, MD

• Praga, Manuel, Universidad Complutense de Madrid Facultad de Medicina, Madrid, Comunidad de Madrid, Spain

Manuel Praga, MD

• Caravaca-Fontan, Fernando, Universidad Complutense de Madrid Facultad de Medicina, Madrid, Comunidad de Madrid, Spain

Fernando Caravaca-Fontan, MD, PhD

• Induruwage, Dilshani, BC Provincial Renal Agency, Vancouver, British Columbia, Canada

Dilshani Induruwage, MS

• Pickering, Matthew C., Imperial College London Department of Immunology and Inflammation, London, London, United Kingdom

Matthew C. Pickering, MD, PhD

• Barbour, Sean, The University of British Columbia, Vancouver, British Columbia, Canada

Sean Barbour, MD, MS, MSc

Background

C3 glomerulopathy (C3G) is a rare disease that has significant overlap with idiopathic membranoproliferative glomerulonephritis (MPGN). Risk factors for kidney outcomes remains poorly defined, limited by small cohorts. We aimed to determine risk factors for kidney outcomes and to incorporate them into a prediction model

Methods

Using a cohort of 225 patients with C3G or idiopathic MPGN from three international centers, we evaluated the association between clinical and histologic variables at biopsy and the composite outcome of 30% decline in eGFR or ESKD using Cox proportional hazards models. A prediction model was derived and internally validated through bootstrap resampling

Results

In a multivariable model, lower eGFR, paraprotein presence, and interstitial fibrosis were associated with higher risk of outcome, while native (versus transplant) disease and lower C4 levels were associated with lower risk (Table1). The prediction model including these variables performed well (R²_D: 53.14%, C-statistic: 0.84 (95% CI 0.82-0.86), integrated calibration index: 0.31), maintaining robustness after internal validation. Adding proteinuria over time showed that a 50% reduction from baseline to <1g/day was associated with a lower risk of outcome (HR 0.35, 95% CI 0.12-0.97)

Conclusion

In the largest C3G/MPGN study to date, baseline eGFR, paraprotein, interstitial fibrosis, low C4 and transplant status were independently associated with kidney outcome. These factors can be used in a prediction model to predict individual patient risk. A 50% reduction in proteinuria to <1g/day was associated with lower kidney risk, suggesting it may be an evidence-based definition of proteinuria remission to use in clinical trials

Covariates for the risk of progression to the composite outcome in a multivariable model

Interstitial fibrosis score: 0 (<10%), 1 (10%-25%), 2 (26%-50%) and 3 (>50%)