Molecular Expression of FGF23 Signaling Components (FGFR1 and α-Klotho) and Their Biochemical Correlation in Early Kidney Impairment

Abstract

Background: Chronic kidney disease and mineral and bone disorder (CKD-MBD) is associated with dysfunction of the FGF23-FGFR1-a-Klotho signaling pathway involved in phosphate regulation and renal function. Early molecular changes may precede biochemical abnormalities. Objective: This study aimed to determine FGFR1 and α-Klotho gene expression in early renal impairment and evaluate their relation to biochemical renal markers. Methods: Diagnostic performance of the markers was evaluated in a case-control study including 80 patients with early renal impairment and 40 healthy controls. Gene expression was quantified in peripheral blood by qRT-PCR. Results: Patients showed higher levels of urea, creatinine, uric acid, phosphorus, and FGF23, while eGFR was significantly lower (p<0.0001). FGFR1 expression decreased from 1.15±0.22 to 0.38±0.04 (p<0.0001), and α-Klotho from 1.18±0.25 to 0.27±0.03 (p<0.0001). ROC analysis showed excellent predictive power for urea (AUC=1.00) and creatinine (AUC=0.99), fair performance for FGF23 (AUC=0.70), and FGFR1 showed excellent diagnostic performance (AUC=0.9995), while α-klotho showed modest diagnostic value (AUC=0.6021). Conclusion: Dysregulation of FGF23, FGFR1, and α-Klotho is associated with early renal impairment, and FGFR1 quantification alongside biochemical markers may improve early detection and patient stratification.