Validation and Evaluation of SPP1 as a Candidate Biomarker for Disease Monitoring in Focal Segmental Glomerulosclerosis

Background: Secreted phosphoprotein 1 (SPP1), a glycoprotein encoded by the SPP1 gene, can be detected in body fluids and tumor tissues of various diseases, representing a promising candidate biomarker. However, its application in focal segmental glomerulosclerosis (FSGS) remains at the exploratory stage. Patients and Methods: In a small-scale cohort, Bulk-RNA sequencing was employed to screen for core differentially expressed genes in urinary cells of FSGS patients, with SPP1 identified as a key candidate. RT-qPCR and ELISA were subsequently used to detect SPP1 expression in clinical urine samples. An adriamycin (ADR)-induced FSGS mouse model was established, and renal histopathological changes were evaluated using hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and Masson staining. Immunohistochemistry and immunofluorescence were performed to examine the expression of SPP1, fibronectin, and F4/80 in renal tissues, with assessment of the effects of prednisone intervention. Results: Urinary SPP1 expression was significantly elevated in FSGS patients, particularly in those with CKD stage III. In the ADR mouse model, as glomerulosclerosis progressed, albuminuria levels increased, accompanied by enhanced expression of SPP1 and F4/80-positive macrophages. Prednisone treatment attenuated these parameters. Conclusion: SPP1 is involved in the progression of FSGS and is closely associated with renal immune inflammation and fibrosis. Prednisone exerts renoprotective effects by downregulating SPP1 expression and inhibiting macrophage infiltration, suggesting that SPP1 represents a promising molecular marker for disease monitoring and targeted intervention in FSGS. Keywords: focal segmental glomerulosclerosis, Bulk-RNA sequencing, SPP1, prednisone