{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:25:38Z","timestamp":1765182338069,"version":"3.46.0"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine,\u201d Victor Babes\u201d University of Medicine and Pharmacy","award":["5439-3\/5.03.2021"],"award-info":[{"award-number":["5439-3\/5.03.2021"]}]},{"name":"\u201cVictor Babes\u201d University of Medicine and Pharmacy","award":["GD 2020"],"award-info":[{"award-number":["GD 2020"]}]},{"name":"Internal Grant of \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara","award":["6 EXP\/2020"],"award-info":[{"award-number":["6 EXP\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic kidney disease (DKD) is a major complication of type 2 diabetes mellitus (T2DM) and a leading cause of morbidity and mortality. Both metabolic and inflammatory pathways have emerged as potential sources of biomarkers that may improve DKD detection and treatment. This study investigated the relationship between gut-derived metabolites, such as acylcarnitines (ACs), uremic toxins (UTs), polyol pathway intermediates (PIs), and amino acid derivatives (AADs), and renal inflammation markers, detected in serum and urine. It included 20 healthy controls and 90 patients with T2DM, divided into normoalbuminuria, microalbuminuria, and macroalbuminuria. Serum and urine metabolites were analyzed using untargeted and targeted metabolomic assessments, whereas inflammatory markers were quantified using the ELISA technique. Statistical analysis consisted of descriptive statistics followed by univariable and multivariable linear regression analyses. Our findings revealed that serum AADs contribute to renal fibrosis progression, whereas urinary AADs indicate impaired tubular reabsorption in inflammatory conditions. Additionally, UTs and PIs are linked to inflammatory processes mediated by TNF-\u03b1 but not by early renal fibrosis, whereas serum ACs appear to modulate immune responses, exerting pro-inflammatory and cytotoxic effects on tubular epithelial cells in early DKD. Thus, the metabolic and inflammatory pathways are tightly interconnected and synergistically contribute to the pathogenesis of early DKD.<\/jats:p>","DOI":"10.3390\/ijms262411776","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T13:17:07Z","timestamp":1764940627000},"page":"11776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut-Derived Metabolomic Biomarkers as Mediators of the Inflammatory Pathway in Early Diabetic Kidney Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2125-5419","authenticated-orcid":false,"given":"Lavinia","family":"Marcu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Division of Nephrology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7352-5057","authenticated-orcid":false,"given":"Carmen","family":"Socaciu","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Research Center for Applied Biotechnology and Molecular Therapy Biodiatech, SC Proplanta, Trifoiului 12G, 400478 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreea Iulia","family":"Socaciu","sequence":"additional","affiliation":[{"name":"Department of Occupational Health, University of Medicine and Pharmacy \u201cIuliu Ha\u0163ieganu\u201d, Victor Babes 8, 400347 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1824-2628","authenticated-orcid":false,"given":"Adrian","family":"Vlad","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"},{"name":"Department of Internal Medicine II, Division of Diabetes and Metabolic Diseases, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7026-7566","authenticated-orcid":false,"given":"Florica","family":"Gadalean","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Nephrology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flaviu","family":"Bob","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Nephrology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oana","family":"Milas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Nephrology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Octavian Marius","family":"Cretu","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Division of Surgical Semiology I, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Emergency Clinical Municipal Hospital Timisoara, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anca","family":"Suteanu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Nephrology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Glavan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Nephrology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. 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No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9215-5154","authenticated-orcid":false,"given":"Sorin","family":"Ursoniu","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"},{"name":"Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Department of Functional Sciences III, Division of Public Health and History of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Centre for Translational Research and Systems Medicine, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie, Murgu Sq. No. 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Dumitrascu","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Department of Biochemistry and Pharmacology IV, Division of Pharmacology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9243-1865","authenticated-orcid":false,"given":"Daliborca","family":"Vlad","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. 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No. 2, 300041 Timisoara, Romania"},{"name":"Department of Microscopic Morphology II, Division of Cell and Molecular Biology II, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3138-3051","authenticated-orcid":false,"given":"Ligia","family":"Petrica","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Nephrology, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Sq. 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