Abstract: TH-PO1221
Unmasking the Role of Antinephrin Antibodies in FSGS Recurrence After Transplantation: A Multicenter Study from the TANGO Consortium
Session Information
- Late-Breaking Research Posters
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
- Lafargue, Marie-Camille, Massachusetts General Hospital, Boston, Massachusetts, United States
- Hullekes, Frank E., Massachusetts General Hospital, Boston, Massachusetts, United States
- Verhoeff, Rucháma, Massachusetts General Hospital, Boston, Massachusetts, United States
- Leguern, Christian, Massachusetts General Hospital, Boston, Massachusetts, United States
- Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Riella, Leonardo V., Massachusetts General Hospital, Boston, Massachusetts, United States
Group or Team Name
- TANGO Consortium.
Background
Recurrent primary FSGS (pFSGS) remains a devastating complication in kidney transplantation (KTx), often culminating in early allograft loss. Despite decades of research, precise biomarkers for disease activity and recurrence risk remain elusive. Anti-nephrin antibodies, recently implicated in the pathogenesis of a subset of podocytopathies, offer a compelling target, but their clinical utility remains unproven in KTx populations. We sought to assess the prevalence and predictive value of anti-nephrin IgG in the largest known multicenter cohort of pFSGS KTx recipients to date, as part of the TANGO Consortium.
Methods
We conducted a retrospective multicenter cohort study of 161 KTx recipients with ESKD attributed to pFSGS. Circulating anti-nephrin IgG levels were measured by ELISA (Shu et al.) in pre-KTx sera (n=75) and post-KTx sera (n=90). Comparisons were made to healthy controls (n=95) and KTx recipients with other causes of kidney disease (n=160).
Results
Median age at transplantation was 41 years, 62.6% self-identified as White, 54.6% were male, and 42.8% received a deceased donor allograft. Over a median follow-up of 49 months, 76 of 161 patients (47.2%) experienced pFSGS recurrence. Age, sex, and race were similar between recurrence and non-recurrence groups. Using a cut-off of 98 RU/mL, 7 out of 161 patients (4.3%) had positive anti-nephrin IgG. Importantly, none of the healthy controls or other disease cohorts were positive (p < 0.03). Pre-KTx anti-nephrin IgG was more frequently observed in those with rFSGS (5/30) versus non-recurrence (2/45), though not statistically significant (ROC curve: p = 0.93).
Conclusion
This is the largest transplant-based study to date evaluating anti-nephrin antibodies in patients with pFSGS. Anti-nephrin IgG appeared more frequently in patients with recurrence. Two patients with positive pre-KTx anti-nephrin IgG did not develop recurrence, highlighting the limitations of antibody detection as a standalone predictive tool. These findings underscore the importance of prospective studies, including immunofluorescence-based tissue validation and exploration of other slit diaphragm–targeting autoantibodies, to fully delineate the diagnostic and prognostic utility of anti-podocyte antibodies in the context of pFSGS recurrence.
Funding
- Other U.S. Government Support