{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:49:28Z","timestamp":1789616968933,"version":"build-2803163510"},"reference-count":201,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HEAL ITALIA\u2014Health Extended Alliance for Innovative Therapies, Advanced Lab-research and Integrated Approaches of Precision Medicine","award":["PE_00000019"],"award-info":[{"award-number":["PE_00000019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Chronic kidney disease is a significant global health burden and a leading cause of cardiovascular morbidity and mortality. Diabetes mellitus is the primary cause of kidney disease, driving the progression of both micro- and macrovascular complications. Sustained hyperglycemia initiates a cascade of deleterious molecular and cellular events, including mitochondrial dysfunction, inflammation, oxidative stress, and dysregulated apoptosis and autophagy, which collectively contribute to the progression of renal injury. Beyond these well-established mechanisms, a compelling body of evidence highlights the pivotal role of epigenetic alterations (such as DNA methylation, histone post-translational modifications, and non-coding RNAs) in mediated long-term kidney damage. The interplay between transcriptional and epigenetic regulation underlies the phenomenon of the \u201cmetabolic memory\u201d, wherein cellular dysfunction persists even after glycemic control is achieved. This review synthesizes the current knowledge on mechanisms sustaining metabolic and epigenetic memory, with a particular focus on the epigenetic machinery that establishes and maintains these signals, a concept increasingly termed \u201cepigenetic memory.\u201d Given their reversible nature, epigenetic determinants are emerging as promising biomarkers and a compelling therapeutic avenue. Targeting these \u201cepifactors\u201d offers a novel strategy to halt progression to end-stage renal disease, thereby paving the way for precision medicine approaches in diabetes-related renal disease.<\/jats:p>","DOI":"10.3390\/genes16121442","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:39:43Z","timestamp":1764679183000},"page":"1442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["From Metabolic to Epigenetic Memory: The Impact of Hyperglycemia-Induced Epigenetic Signature on Kidney Disease Progression and Complications"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6678-3819","authenticated-orcid":false,"given":"Sara","family":"Cannito","sequence":"first","affiliation":[{"name":"Laboratory Medicine, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Giardino","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9170-4668","authenticated-orcid":false,"given":"Maria","family":"D\u2019Apolito","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ranaldi","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Scaltrito","sequence":"additional","affiliation":[{"name":"Residency Course in Pediatrics, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Pettoello-Mantovani","sequence":"additional","affiliation":[{"name":"Italian Academy of Pediatrics, 20126 Milan, Italy"},{"name":"Department of Pediatrics, Institute for Scientific Research \u00abCasa Sollievo\u00bb, University of Foggia, 71122 Foggia, Italy"},{"name":"European Pediatric Association, Union of National European Pediatric Societies and Associations, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2772-3869","authenticated-orcid":false,"given":"Annamaria","family":"Piscazzi","sequence":"additional","affiliation":[{"name":"Laboratory Medicine, Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1053\/j.ajkd.2014.01.416","article-title":"KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD","volume":"63","author":"Inker","year":"2014","journal-title":"Am. 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