Abstract: TH-PO0728
Arteriolar C4d: A Predictor of Progression to Kidney Failure in Primary IgAN
Session Information
- Glomerular Innovations: Artificial Intelligence, Multiomics, and Biomarkers
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Zagorec, Nikola, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Horvatic, Ivica, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Osmani, Besa, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Kasumovic, Dino, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Batkovic, Patricia, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Toric, Luka, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Abramovic, Ivana, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Senjug, Petar, Department of Pathology and Cytology, Dubrava University Hospital, Zagreb, Croatia
- Galesic, Kresimir, Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, Croatia
- Ljubanovic, Danica Galesic, Department of Pathology and Cytology, Dubrava University Hospital, Zagreb, Croatia
Background
Mesangial C4d deposits are present in up to 50% of patients with primary IgA nephropathy (pIgAN) indicating lectin pathway of complement activation with more severe clinical presentation and worse outcome. Prevalence and significance of arteriolar C4d in pIgAN is still not well known.
Methods
Clinical and histological data of patients with biopsy proven (light, immunofluorescent and electron microscopy) pIgAN (one-center cohort) were analyzed. Additional immunohistochemistry for C4d was performed. Based on the presence of the mesangial and arteriolar C4d deposits (at least in one non-globally sclerosed glomerulus (nGSG) or arteriole), samples were classified as being C4d + or C4d- and C4dA+ and C4dA-, respectively. Kidney failure (KF), defined as permanent decline in eGFR < 15 ml/min/1.73m2 or commencement of renal replacement therapy, was analyzed as a primary outcome.
Results
A total of 95 patients with pIgAN were included (71.6% males, median age at diagnosis 44.6 (IQR 32-52.2) years). Median follow-up was 102 (72-138) mo. Fourty-three (45%) and 18 (19%) were C4d+ and C4dA+, respectively. Only three C4dA+ patients did not have mesangial C4d deposits. Compared to C4d- patients, C4d+ patients had lower baseline eGFR and higher 24-h proteinuria (P<0.001), higher percentage of GSG and IFTA (P<0.001) and worse renal survival ( 143±12.8 vs 198±4.6m, P<0.001). In multimodal Cox regression model, C4d+ status remained an independent predictor of KF (HR=5.87 (1.06-32.42), P=0.031) together with baseline eGFR, 24-h proteinuria and serum urate level. C4dA+ patients had lower baseline eGFR (P=0.039), higher percentage of GSG (P=0.034) and IFTA (P=0.015) and worse renal survival (130.9±18.1 vs 181.4±7.7m, P<0.001). In multimodal Cox regression model, C4dA+ status remained an independent predictor of KF (HR=6.12 (1.68-22.27), P=0.006) together with baseline eGFR (P=0.036) and proteinuria (P<0.001).
Conclusion
Arteriolar C4d (present in 19% of patients with pIgAN) seems to be an independent predictor of disease progression to KF. C4dA+ patients had lower eGFR, more advanced chronic histologic changes and worse renal survival. It is unclear why only a subset of patients with pIgA have arteriolar C4d deposits and what would be therapeutical implication of such finding.