Dual Biomarker System of RBP4sRAGE in CKD Mechanistic Validation and Clinical Translation via TGF-β1Smad3 Pathway

Abstract Objective : Early diagnosis and progression monitoring of chronic kidney disease (CKD) remain challenging. Serum retinol-binding protein 4 (RBP4) and soluble receptor for advanced glycation end products (sRAGE) show promise as potential biomarkers. This study investigates their expression profiles in CKD patients, correlation with renal dysfunction, and combined diagnostic utility. Methods : A single-center cross-sectional study was conducted involving 53 CKD patients (CKD stages 1–5) and 53 age-matched healthy controls (May 2024-May 2025). Serum RBP4 and sRAGE levels were quantified via ELISA. Correlation analyses assessed relationships with estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) curves evaluated diagnostic performance for CKD detection. Results :Biomarker dysregulation: CKD patients exhibited significantly elevated RBP4 (5.2 ± 1.3 vs. 2.1 ± 0.7 mg/L, P < 0.001) and reduced sRAGE (812 ± 204 vs. 1,203 ± 315 pg/mL, P < 0.001) versus controls.Renal function correlations:RBP4 inversely correlated with eGFR (r=-0.661, P < 0.001).sRAGE positively correlated with eGFR (r = 0.524, P = 0.019).Diagnostic efficacy:Individual biomarkers:RBP4 (AUC = 0.788, 95%CI:0.702–0.874; sensitivity 68.8%, specificity 82.1%).sRAGE (AUC = 0.773, 95%CI:0.681–0.865; sensitivity 28.6%, specificity 56.7%).Combined model (RBP4 + sRAGE):AUC = 0.898 (95%CI:0.842–0.954; sensitivity 87.5%, specificity 88.6%). Conclusion : Serum RBP4 and sRAGE levels strongly correlate with CKD severity. Their combined measurement provides an effective screening tool for early detection, potentially enabling targeted interventions in high-risk populations.