Serum Soluble Klotho, Intact FGF-23, and Oxidative Stress in Rheumatoid Arthritis: Associations with DAS28-CRP in a Case-Control Study
TL;DR
RA was associated with lower circulating s-Klotho and FRAP-derived reducing capacity together with higher FGF-23 and TBARS-derived lipid peroxidation, and an endocrine-redox association with disease activity supports an endocrine-redox association with disease activity.
Abstract
Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease in which chronic inflammation and oxidative stress interact with metabolic and endocrine pathways. Disturbance of the soluble Klotho (s-Klotho)/FGF-23 axis may provide a link between inflammatory burden, redox imbalance, and disease activity. Objective: To compare serum s-Klotho, intact fibroblast growth factor-23 (FGF-23), MDA measured by the thiobarbituric acid reactive substances (TBARS) assay, and FRAP-derived total reducing capacity between patients with RA and matched healthy controls, and to evaluate their relationships with DAS28-CRP. Methods: Ninety patients with RA and 90 age- and sex-matched healthy controls were studied. s-Klotho and intact FGF-23 were measured by ELISA. Lipid peroxidation was estimated using the TBARS assay and total reducing capacity using the FRAP assay. Between-group comparisons, effect sizes, Pearson correlations, Holm-Bonferroni correction for 15 pairwise correlations, and a simultaneous multivariable biomarker model were used. Multicollinearity was assessed by variance inflation factors (VIFs). Results: RA patients had lower s-Klotho (385.4 ± 88.2 vs. 742.1 ± 135.6 pg/mL) and TAC (FRAP assay) (0.81 ± 0.16 vs. 1.48 ± 0.21 mmol/L), but higher intact FGF-23 (88.6 ± 21.4 vs. 41.8 ± 10.5 pg/mL) and MDA by TBARS (5.24 ± 1.12 vs. 1.92 ± 0.41 nmol/mL); all p < 0.001. s-Klotho correlated inversely with MDA (r = -0.642) and DAS28-CRP (r = -0.615), whereas MDA correlated positively with DAS28-CRP (r = 0.638). All 15 pairwise correlations remained significant after Holm-Bonferroni correction. In the biomarker model, MDA and s-Klotho showed the strongest independent statistical associations with DAS28-CRP; all predictor VIFs were <2.1. Conclusion: RA was associated with lower circulating s-Klotho and FRAP-derived reducing capacity together with higher FGF-23 and TBARS-derived lipid peroxidation. The results support an endocrine-redox association with disease activity, but the case-control design and incomplete adjustment for renal, mineral-metabolism, and treatment variables require cautious interpretation.