Identification of Potential Focal Segmental Glomerulosclerosis (FSGS) Through Evaluation of Parietal Epithelial Cells Status Changes Using Integrin α3 Immunostaining.

Diagnosing primary focal segmental glomerulosclerosis (FSGS) remains challenging due to the lack of reliable biomarkers. This study investigates integrin α3 as a diagnostic biomarker to differentiate FSGS from minimal change disease (MCD) and to predict progression risk in patients with MCD. Renal biopsies were obtained from 64 patients with idiopathic nephrotic syndrome and analyzed, comprising 36 patients with MCD and 28 patients with FSGS. Integrin α3 expression and distribution were assessed via immunohistochemistry using a novel semiquantitative scoring system (Int score, 0-3). Clinical correlations were analyzed using Pearson's correlation. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic utility of the Int score and established a cutoff to stratify MCD patients at risk for FSGS progression. We found that integrin α3 was markedly upregulated in perilesional areas of FSGS glomeruli, colocalizing with Annexin A3, Claudin-1, and CD44. Focal integrin α3 overexpression was observed in 73.08% of FSGS cases vs 19.44% of MCD. In MCD, 60.62% of glomeruli scored Int 0, whereas 74.36% of FSGS scored ≥1. ROC curve analysis revealed the strong discrimination ability of the Int score (area under the curve = 0.91). The Int score correlated positively with podocyte damage, 24-hour proteinuria, and the proportion of glomeruli with segmental sclerosis and inversely with serum albumin and estimated glomerular filtration rate (eGFR). Based on the Int score, 7 patients with MCD were stratified into the high-FSGS probability group. These patients exhibited broader foot process widths and longer durations of proteinuria compared with other MCD patients. Overall, parietal epithelial cells with integrin α3 overexpression invading the glomerular tuft contribute to the sclerotic lesion. Integrin α3 expression patterns may serve as a histopathological biomarker to distinguish FSGS from MCD and identify patients initially misdiagnosed as MCD, enabling early intervention and tailored monitoring.