Comparative Diagnostic Performance of Serum α-Klotho and FGF-23 in Predicting Obstructive Sleep Apnea Severity: A...

Background/Objectives: Obstructive sleep apnea (OSA) syndrome is characterized by recurrent upper airway obstruction during sleep and is closely associated with systemic inflammation and cardiometabolic risk. α-Klotho and fibroblast growth factor-23 (FGF-23) are emerging biomarkers with potential roles in vascular homeostasis, inflammation, and metabolic regulation. However, their relevance in OSA remains insufficiently elucidated. The aim of this study was to evaluate serum α-Klotho and FGF-23 levels in patients with OSA and to investigate their associations with disease severity. This represents a novel approach that may provide new insights into the pathophysiological mechanisms linking OSA with cardiometabolic risk. Methods: A total of 133 participants were included in this study and categorized into three groups according to apnea-hypopnea index: 1-simple snoring (n = 44); 2-non-severe OSA (n = 44); and 3-severe OSA (n = 45). Comparisons between two groups were performed using Student's t-test for normally distributed variables. Comparisons among three or more groups were conducted using one-way ANOVA and the Kruskal-Wallis test. ANCOVA was applied to compare α-Klotho and FGF-23 levels between groups after adjustment for age, BMI, diabetes, hypertension, asthma, COPD, and thyroid disease. The predictive performance of α-Klotho and FGF-23 for severe obstructive sleep apnea was evaluated using ROC curve analysis. Results: Serum α-Klotho levels decreased significantly with increasing OSA severity (p = 0.001). Serum FGF-23 levels increased significantly across AHI groups (p = 0.001). After adjustment for age, BMI, diabetes, hypertension, asthma, thyroid disease, COPD and vitamin D levels, α-Klotho levels were lower in the severe and non-severe OSA group (p = 0.001, both) compared to the simple snoring group, whereas FGF-23 levels were higher in the severe and non-severe OSA group (p = 0.001; both) compared to the simple snoring group. In predicting the risk of severe OSA compared with non-severe OSA, an α-Klotho cut-off value of 280.3 yielded a sensitivity of 84.44% and specificity of 75%, whereas an FGF-23 cut-off value of 75.5 yielded a sensitivity of 62.2% and specificity of 72.7%. Conclusions: Serum α-Klotho levels significantly decrease while FGF-23 levels increase in correlation with OSA severity. α-Klotho exhibited superior predictive performance over FGF-23 in identifying severe OSA, suggesting its potential as a more sensitive biomarker for systemic involvement. These results indicate that the α-Klotho/FGF-23 axis is independently associated with OSA and may play a pivotal role in the pathophysiological mechanisms linking intermittent hypoxia to increased cardiometabolic risk.