The FGF23–Undercarboxylated Osteocalcin Axis in Predialysis Chronic Kidney Disease: Linking Mineral Homeostasis and Bone Turnover

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Abstract
Fibroblast growth factor 23 (FGF23) and osteocalcin are involved in mineral and bone metabolism, but their relationship in chronic kidney disease (CKD) remains insufficiently characterized. This cross-sectional study investigated the association between FGF23 and undercarboxylated osteocalcin (Glu-OC) and whether this association persisted after accounting for kidney function. The study included 80 adults: 12 healthy controls and 68 patients with non-dialysis CKD stages G1–G4. Associations were assessed using Spearman correlation, partial correlation adjusted for estimated glomerular filtration rate (eGFR), and complementary multivariable linear regression models. Among patients with CKD, FGF23 was inversely correlated with eGFR (ρ = −0.346, p = 0.004) and Glu-OC (ρ = −0.344, p = 0.004), and positively correlated with serum creatinine (ρ = 0.299, p = 0.013). The inverse association between FGF23 and Glu-OC persisted after adjustment for eGFR (partial ρ = −0.475, p < 0.001). In the multivariable regression models, Glu-OC was inversely associated with FGF23 (standardized β = −0.258, p = 0.024), whereas alkaline phosphatase was positively associated with FGF23 (β = 0.369, p = 0.001). In the model with Glu-OC as the dependent variable, FGF23 (β = −0.266, p = 0.020) and serum calcium (β = −0.366, p = 0.002) were inversely associated with Glu-OC. Significant inverse correlations between FGF23 and Glu-OC were observed in CKD stages G1–G3, but not in stage G4 or the control group. These findings support an association between FGF23 and Glu-OC in non-dialysis CKD and provide a rationale for further investigation of a potential FGF23–Glu-OC axis in CKD-associated mineral and bone disorder (CKD-MBD). Longitudinal and mechanistic studies are needed to clarify the nature and clinical relevance of this association.
Funding Information
  • Medical University–Pleven, Bulgaria

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