Abstract: TH-PO0694
Composite Scoring System for Identifying Patients with Recurrent FSGS
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Mukherjee, Kamalika, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Cicalese, Luca, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Rastellini, Cristiana, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Iyer, Sudhanvan, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Reiser, Jochen, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
- Alachkar, Nada, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Sever, Sanja, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
Background
Focal segmental glomerulosclerosis (FSGS) recurs in an estimated 30-60% of patients, compromising graft survival. To aid recurrence risk prediction, we developed a scoring system relying on three immune activation markers: serum soluble urokinase plasminogen activator receptor (suPAR) concentration, circulating D2D3 protein, and serum-induced activated β3 integrin in cultured podocytes. We are also investigating anti-nephrin autoantibodies, considering their recent association with FSGS.
Methods
We analyzed sera from post-transplant patients with primary FSGS. Recurrent FSGS (rFSGS) was confirmed by the onset of proteinuria, and electron microscopy verified podocyte foot process effacement. Serum analyses were blinded to clinical diagnosis, estimated glomerular filtration rate (eGFR), and urinary protein creatinine ratio (UPCR). suPAR was measured by ELISA. D2D3 was detected by immunoprecipitation and Western blot. Activated β3 integrin was assessed by immunofluorescence. Cutoffs for each marker were established to assign binary values: a score of 1 for values above the cutoff and 0 for those below. A cumulative score integrating all three markers was generated for each serum and assessed for its ability to identify rFSGS.
Results
(i) D2D3 was identified in a subset of sera from patients with primary FSGS. (ii) D2D3’s presence was significantly associated with high UPCR and low eGFR. (iii) D2D3 and activated β3 integrin were significantly higher in rFSGS (iv) Lower composite score associated with nrFSGS compared to rFSGS. A cumulative score of 2 and 3 was observed in ~14% of nrFSGS, while ~78% of rFSGS scored the same. (v) The receiver operating characteristics (ROC) curve for our binary composite score efficiently separated rFSGS from nrFSGS, with an area under the curve of 0.8888 (95% CI: 0.7770-0.9990).
Conclusion
Our study identifies D2D3’s association with primary FSGS and proposes its candidacy as an indicator of declining renal function. Our composite score’s ability to distinguish between rFSGS and nrFSGS suggests its potential to complement current gold standards for earlier risk stratification of patients.
Funding
- NIDDK Support