{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:45:54Z","timestamp":1782452754437,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008107","name":"Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan","doi-asserted-by":"publisher","award":["TCMF-CP 115-01"],"award-info":[{"award-number":["TCMF-CP 115-01"]}],"id":[{"id":"10.13039\/501100008107","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Patients with chronic kidney disease (CKD) often present with peripheral arterial stiffness (PAS), which is associated with an increased cardiovascular risk. This study assessed the association between circulating osteoprotegerin (OPG), a known mediator of vascular calcification, and PAS, measured as brachial\u2013ankle pulse wave velocity (baPWV), in patients with CKD. Methods: This cross-sectional investigation engaged 200 individuals with non-dialysis CKD. Serum OPG concentrations were measured using a commercial enzyme-linked immunosorbent assay. Participants were classified as having PAS when either left or right baPWV was greater than 18.0 m\/s; those with baPWV values of 18.0 m\/s or lower were assigned to the control group. Results: Eighty-six patients (43.0%) had PAS. In comparison to controls, PAS patients were older (p &lt; 0.001) and had higher proportions of diabetes mellitus (p = 0.023) and hypertension (p = 0.010); systolic blood pressure was higher (p &lt; 0.001), urine protein-to-creatinine ratio was elevated (p = 0.004), and serum OPG was markedly greater (p &lt; 0.001), whereas estimated glomerular filtration rate was lower (p = 0.003). After full adjustment, OPG levels, in addition to older age and diabetes mellitus, demonstrated an independent association with PAS (odds ratio: 1.008; 95% confidence interval: 1.002\u20131.015; p = 0.010). The OPG level was positively associated with bilateral baPWV by Spearman\u2019s correlation analysis (p &lt; 0.001). Conclusions: Circulating OPG level showed an independent association with PAS and baPWV in CKD patients not yet on dialysis. Hence, OPG can be a potential marker of vascular risk in this patient population.<\/jats:p>","DOI":"10.3390\/diagnostics16121906","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:04:04Z","timestamp":1781874244000},"page":"1906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Osteoprotegerin Is Associated Independently with Peripheral Arterial Stiffness in Chronic Kidney Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3479-0142","authenticated-orcid":false,"given":"Yahn-Bor","family":"Chern","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Yuan\u2019s General Hospital, Kaohsiung 802635, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9295-8520","authenticated-orcid":false,"given":"Po-Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-1058","authenticated-orcid":false,"given":"Yu-Hsien","family":"Lai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"},{"name":"Department of Pharmacology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-9232","authenticated-orcid":false,"given":"Chih-Hsien","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9405-8649","authenticated-orcid":false,"given":"Jen-Pi","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-4558","authenticated-orcid":false,"given":"Bang-Gee","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan"},{"name":"School of Medicine, Tzu Chi University, Hualien 97004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1016\/S0140-6736(25)01853-7","article-title":"Global, regional, and national burden of chronic kidney disease in adults, 1990\u20132023, and its attributable risk factors: A systematic analysis for the global burden of disease study 2023","volume":"406","author":"Mark","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.semnephrol.2016.12.002","article-title":"Evolution of cardiovascular disease during the transition to end-stage renal disease","volume":"37","author":"Bansal","year":"2017","journal-title":"Semin. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(2024). Kidney disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int., 105, S117\u2013S314.","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1024\/0301-1526\/a001142","article-title":"Arterial stiffness is associated with new-onset chronic kidney disease","volume":"53","author":"Li","year":"2024","journal-title":"Vasa"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1159\/000541076","article-title":"Association of arterial stiffness with chronic kidney disease: A Systematic review","volume":"49","author":"Beros","year":"2024","journal-title":"Kidney Blood Press. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/HJH.0000000000003897","article-title":"The incremental predictive value of arterial stiffness over SCORE2 in the setting of primary cardiovascular prevention: A 6-year follow-up study","volume":"43","author":"Ikonomidis","year":"2025","journal-title":"J. Hypertens."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1159\/000430771","article-title":"Brachial-ankle pulse wave velocity: Myths, misconceptions, and realities","volume":"3","author":"Sugawara","year":"2015","journal-title":"Pulse"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1111\/jch.13966","article-title":"Automated pulse wave velocity assessment using a professional oscillometric office blood pressure monitor","volume":"22","author":"Kollias","year":"2020","journal-title":"J. Clin. Hypertens."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.5551\/jat.RV17041","article-title":"State of the art review: Brachial-ankle PWV","volume":"27","author":"Tomiyama","year":"2020","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1038\/s41440-025-02281-1","article-title":"Comparison between vascular age based on brachial-ankle pulse wave velocity or carotid-femoral pulse wave velocity","volume":"48","author":"Dong","year":"2025","journal-title":"Hypertens. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"121148","DOI":"10.1016\/j.lfs.2022.121148","article-title":"Mechanistic Insights into CKD-MBD-Related Vascular Calcification and Its Clinical Implications","volume":"311","author":"Kaur","year":"2022","journal-title":"Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s40620-014-0092-x","article-title":"Osteoprotegerin and kidney disease","volume":"27","author":"Ucero","year":"2014","journal-title":"J. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1159\/000508978","article-title":"Elevated osteoprotegerin concentration predicts increased risk of cardiovascular mortality in patients with chronic kidney disease: A systematic review and meta-analysis","volume":"45","author":"Huang","year":"2020","journal-title":"Kidney Blood Press. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1038\/s41598-021-82072-z","article-title":"Osteoprotegerin is a marker of cardiovascular mortality in patients with chronic kidney disease stages 3\u20135","volume":"11","author":"Marques","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3758\/BRM.41.4.1149","article-title":"Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses","volume":"41","author":"Faul","year":"2009","journal-title":"Behav. Res. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chern, Y.B., Tsai, J.P., Liu, C.H., Lin, Y.L., Wang, C.H., and Hsu, B.G. (2025). Serum indoxyl sulfate as a potential biomarker of peripheral arterial stiffness in patients with non-dialysis chronic kidney disease stages 3 to 5. Toxins, 17.","DOI":"10.3390\/toxins17060283"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chen, Y.L., Huang, P.Y., Tsai, J.P., Wang, J.H., and Hsu, B.G. (2023). Serum osteoprotegerin levels and the vascular reactivity index in patients with hypertension. Medicina, 59.","DOI":"10.3390\/medicina59101794"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1161\/HYPERTENSIONAHA.118.11554","article-title":"Physiological diagnostic criteria for vascular failure","volume":"72","author":"Tanaka","year":"2018","journal-title":"Hypertension"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1097\/HJH.0b013e32834fa8b0","article-title":"Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity","volume":"30","author":"Laurent","year":"2012","journal-title":"J. Hypertens."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.2215\/CJN.03910411","article-title":"Correlates of osteoprotegerin and association with aortic pulse wave velocity in patients with chronic kidney disease","volume":"6","author":"Scialla","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hou, J.S., Lin, Y.L., Wang, C.H., Lai, Y.H., Kuo, C.H., Subeq, Y.M., and Hsu, B.G. (2019). Serum osteoprotegerin is an independent marker of central arterial stiffness as assessed using carotid-femoral pulse wave velocity in hemodialysis patients: A cross sectional study. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1374-2"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/jch.12288","article-title":"Association of serum osteoprotegerin levels with carotid-femoral pulse wave velocity in hypertensive patients","volume":"16","author":"Wang","year":"2014","journal-title":"J. Clin. Hypertens."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2217\/bmm-2022-0621","article-title":"Prognostic role of osteoprotegerin and risk of coronary artery calcification: A systematic review and meta-analysis","volume":"17","author":"Samadi","year":"2023","journal-title":"Biomark. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/sj.jhh.1001838","article-title":"Brachial-ankle pulse wave velocity: An index of central arterial stiffness?","volume":"19","author":"Sugawara","year":"2005","journal-title":"J. Hum. Hypertens."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3243135","DOI":"10.1155\/2021\/3243135","article-title":"The temporal pattern of arterial stiffness during aging: A large-scale cross-sectional study","volume":"2021","author":"Tang","year":"2021","journal-title":"J. Diabetes Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1016\/j.hlc.2021.08.011","article-title":"Association of arterial stiffness with chronic kidney disease progression and mortality","volume":"30","author":"Voicehovska","year":"2021","journal-title":"Heart Lung Circ."},{"key":"ref_27","first-page":"e76498","article-title":"The pathophysiology and vascular complications of diabetes in chronic kidney disease: A comprehensive review","volume":"16","author":"Hauwanga","year":"2024","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1007\/s12325-025-03185-9","article-title":"Diabetes mellitus and associated vascular disease: Pathogenesis, complications, and evolving treatments","volume":"42","author":"Islam","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1161\/01.HYP.0000157819.31611.87","article-title":"Arterial stiffness and hypertension: A two-way street?","volume":"45","author":"Franklin","year":"2005","journal-title":"Hypertension"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40885-023-00258-1","article-title":"Arterial stiffness and hypertension","volume":"29","author":"Kim","year":"2023","journal-title":"Clin. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1681\/ASN.2019020117","article-title":"Arterial stiffness in the heart disease of CKD","volume":"30","author":"Zanoli","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/jch.14185","article-title":"Noninvasive markers of arterial stiffness and renal outcomes in patients with chronic kidney disease","volume":"23","author":"Guo","year":"2021","journal-title":"J. Clin. Hypertens."},{"key":"ref_33","first-page":"29","article-title":"Inflammation and arterial stiffness as drivers of cardiovascular risk in kidney disease","volume":"15","author":"Lentini","year":"2025","journal-title":"Cardiorenal Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1365-2796.2004.01338.x","article-title":"Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients","volume":"256","author":"Cottone","year":"2004","journal-title":"J. Intern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1042\/CS20200279","article-title":"Microvascular disease in chronic kidney disease: The base of the iceberg in cardiovascular comorbidity","volume":"134","author":"Querfeld","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1161\/CIRCULATIONAHA.124.071079","article-title":"Albuminuria in cardiovascular, kidney, and metabolic disorders: A state-of-the-art review","volume":"151","author":"Claudel","year":"2025","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00223-020-00803-2","article-title":"Role of the RANK\/RANKL\/OPG and Wnt\/\u03b2-catenin systems in CKD bone and cardiovascular disorders","volume":"108","author":"Dusso","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s11914-023-00858-8","article-title":"The bone-vascular axis in chronic kidney disease: From pathophysiology to treatment","volume":"22","author":"Vachey","year":"2024","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1101\/gad.12.9.1260","article-title":"Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification","volume":"12","author":"Bucay","year":"1998","journal-title":"Genes Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1161\/CIRCULATIONAHA.107.707380","article-title":"Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldlr(\u2212\/\u2212) mice","volume":"117","author":"Morony","year":"2008","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhou, S., Fang, X., Xin, H., Li, W., Qiu, H., and Guan, S. (2013). Osteoprotegerin inhibits calcification of vascular smooth muscle cell via down regulation of the Notch1-RBP-Jkappa\/Msx2 signaling pathway. PLoS ONE, 8.","DOI":"10.1371\/annotation\/a4dbf2d2-f1f0-4a71-b856-7a54f7914666"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.cardiores.2007.07.017","article-title":"Osteoprotegerin upregulates endothelial cell adhesion molecule response to tumor necrosis factor-\u03b1 associated with induction of angiopoietin-2","volume":"76","author":"Mangan","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1681\/ASN.2013101062","article-title":"The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: A systematic review","volume":"25","author":"Vanholder","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00223-016-0136-4","article-title":"Osteoprotegerin in chronic kidney disease: Associations with vascular damage and cardiovascular events","volume":"99","author":"Yilmaz","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1053\/j.ajkd.2017.09.026","article-title":"Update on anemia in ESRD and earlier stages of CKD: Core curriculum 2018","volume":"71","author":"Fishbane","year":"2018","journal-title":"Am. J. Kidney Dis."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/12\/1906\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:49:36Z","timestamp":1782449376000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/12\/1906"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":45,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["diagnostics16121906"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16121906","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,19]]}}}