{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:47:05Z","timestamp":1773852425726,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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. \u03b1-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 \u03b1-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\u2013hypopnea index: 1\u2014simple snoring (n = 44); 2\u2014non-severe OSA (n = 44); and 3\u2014severe OSA (n = 45). Comparisons between two groups were performed using Student\u2019s t-test for normally distributed variables. Comparisons among three or more groups were conducted using one-way ANOVA and the Kruskal\u2013Wallis test. ANCOVA was applied to compare \u03b1-Klotho and FGF-23 levels between groups after adjustment for age, BMI, diabetes, hypertension, asthma, COPD, and thyroid disease. The predictive performance of \u03b1-Klotho and FGF-23 for severe obstructive sleep apnea was evaluated using ROC curve analysis. Results: Serum \u03b1-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, \u03b1-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 \u03b1-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 \u03b1-Klotho levels significantly decrease while FGF-23 levels increase in correlation with OSA severity. \u03b1-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 \u03b1-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.<\/jats:p>","DOI":"10.3390\/jcm15062316","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:11:12Z","timestamp":1773828672000},"page":"2316","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Diagnostic Performance of Serum \u03b1-Klotho and FGF-23 in Predicting Obstructive Sleep Apnea Severity: A Novel Biomarker Approach"],"prefix":"10.3390","volume":"15","author":[{"given":"Nilgun","family":"Erten","sequence":"first","affiliation":[{"name":"Department of Neurology, Istanbul Physical Medicine and Rehabilitation Training and Research Hospital, University of Health Sciences, 34186 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1828-1811","authenticated-orcid":false,"given":"Demet","family":"Aygun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-6102","authenticated-orcid":false,"given":"Aysen Kutan","family":"Fenercioglu","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4735-4091","authenticated-orcid":false,"given":"Naile Fevziye","family":"Misirlioglu","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8893-2926","authenticated-orcid":false,"given":"Seyma","family":"Dumur","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-9865","authenticated-orcid":false,"given":"Ulku Dubus","family":"Hos","sequence":"additional","affiliation":[{"name":"Department of Neurology, \u0130stanbul Ba\u015fak\u015fehir \u00c7am and Sakura City Hospital, University of Health Sciences, 34480 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonul","family":"Simsek","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-8498","authenticated-orcid":false,"given":"Hafize","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34408 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Meliante, P.G., Zoccali, F., Cascone, F., Di Stefano, V., Greco, A., De Vincentiis, M., Petrella, C., Fiore, M., Minni, A., and Barbato, C. 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