{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:23:09Z","timestamp":1792012989958,"version":"4.4.0"},"reference-count":103,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Plovdiv","award":["HO-05\/2025"],"award-info":[{"award-number":["HO-05\/2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This review aims to synthesize current evidence on the role of chronic stress and hypothalamic\u2013pituitary\u2013adrenal (HPA) axis dysregulation in the pathogenesis of chronic kidney disease (CKD). The focus is on the interplay between cortisol, oxidative stress, inflammation, and metabolic risk factors within the psycho-neuro-endocrine-immune (PNEI) system. CKD is a multifactorial disease characterized by oxidative stress, chronic low-grade inflammation, and neuroendocrine imbalance. These processes interact to accelerate renal injury and systemic complications. Pro-inflammatory mediators such as tumor necrosis factor-alpha (TNF-\u03b1), interleukin-1 beta (IL-1\u03b2), and interleukin-6 (IL-6), together with oxidative stress markers including malondialdehyde (MDA), advanced oxidation protein products (AOPPs), and 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG), are strongly associated with disease progression. Altered cortisol dynamics\u2014assessed in serum, saliva, and hair\u2014further reflect chronic HPA activation and contribute to immune dysfunction, metabolic disturbances, and cardiovascular risk. By integrating experimental and clinical findings, this review highlights how stress-induced dysregulation of the PNEI system amplifies CKD progression. Understanding these interconnected mechanisms underscores the potential of combining oxidative, inflammatory, and neuroendocrine biomarkers for improved risk stratification and targeted therapeutic interventions.<\/jats:p>","DOI":"10.3390\/antiox14101259","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:44:10Z","timestamp":1760957050000},"page":"1259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Stress Pathways in Chronic Kidney Disease: Linking Cortisol, Oxidative Stress, and Inflammation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8513-2242","authenticated-orcid":false,"given":"Maria","family":"Motrenikova","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4260-3868","authenticated-orcid":false,"given":"Krasimir","family":"Boyanov","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neli","family":"Bojinova","sequence":"additional","affiliation":[{"name":"Dietary Nutrition Instructor, Medical College, Medical University of Plovdiv, Bratya Bukston Str. 120, 4004 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2157-3858","authenticated-orcid":false,"given":"Anelia","family":"Bivolarska","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of Chronic Kidney Disease: An Update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. 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