Abstract: FR-PO0633
Nephrin Autoantibodies in Idiopathic Nephrotic Syndrome Represent a Disease Endotype Associated with Good Long-Term Prognosis
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - ANCA/FSGS
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Chan, Chang-Yien, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
- Quek, Li Ling, Khoo Teck Puat - National University Children's Medical Institute, Singapore, Singapore
- Teo, Sharon, Khoo Teck Puat - National University Children's Medical Institute, Singapore, Singapore
- Than, Mya, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
- Lau, Yew Weng Perry, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
- Ng, Kar Hui, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
- Yap, Hui Kim, National University of Singapore Yong Loo Lin School of Medicine, Singapore, Singapore
- Lu, Liangjian, Khoo Teck Puat - National University Children's Medical Institute, Singapore, Singapore
Background
The long-term implications of nephrin autoantibody positivity in idiopathic nephrotic syndrome (INS) remain unknown. Its relationship with histological diagnosis is also uncertain in children, unlike in adults in which it has been mainly associated with minimal change disease (MCD) rather than focal segmental glomerulosclerosis (FSGS). Here, we aimed to correlate nephrin autoantibody titres with histological diagnosis and long-term clinical outcomes.
Methods
Patients with childhood-onset INS who had historical plasma samples obtained during periods of nephrotic relapse, and who had previously undergone renal biopsy for clinical indications were included. Historical samples were used to determine nephrin autoantibody titres via an immunoprecipitation-ELISA method.
Results
Nephrin autoantibody titres were determined in 68 INS patients (69% steroid-dependent frequently relapsing, 22% steroid-resistant) and 26 controls. Autoantibody titres were elevated in INS patients compared to controls [90.8 (IQR: 46.9-165.4) vs 28.3 (IQR: 20.8-48.0) RU/ml, p<0.001], and in relapse compared to remission (p<0.001). Titres were elevated in patients with MCD [116.1 (IQR: 64.6-210.4) RU/ml] compared to patients with FSGS on initial biopsy [43.8 (IQR: 21.1-118.4) RU/ml, p=0.025] or patients who had MCD but developed FSGS on subsequent biopsies [52.6 (IQR: 12.9- 95.8) RU/ml, p=0.042]. Long-term outcome was assessed in 59 patients with ≥5 years of follow-up. Immunosuppression-free remission, defined as ≥2 years without relapses whilst off immunosuppression, was more likely to occur with higher nephrin autoantibody titres [Hazard ratio 8.9 (95% CI: 2.01-39.00) per log RU/ml, p=0.004], even after adjusting for histological diagnosis [Hazard ratio 6.9 (95% CI: 1.45-33.01) log RU/ml, p=0.015]. Nephrin autoantibody titres were also higher in patients who responded to steroids (p=0.024), and who did not require Rituximab in their disease course (p=0.047).
Conclusion
Elevated nephrin autoantibody titres are associated with MCD and eventual immunological remission, as well as greater drug-responsiveness. Nephrin autoantibody-mediated disease may constitute a disease endotype that represents the archetypical childhood-onset nephrotic syndrome.
Funding
- Government Support – Non-U.S.