{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:18:00Z","timestamp":1793085480711,"version":"4.5.0"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Chronic kidney disease (CKD) is associated with a markedly increased risk of cardiovascular (CV) morbidity and mortality that cannot be fully explained by traditional risk factors. Emerging evidence highlights the central role of the gut\u2013kidney\u2013heart axis, whereby gut microbiota dysbiosis promotes the generation and systemic accumulation of uremic toxins, including indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO). These metabolites contribute to endothelial dysfunction, oxidative stress, inflammation, and vascular remodeling, thereby accelerating CV disease progression in CKD. Dietary patterns represent a key modifiable factor influencing gut microbiota composition and metabolic activity. The Mediterranean diet, characterized by high intake of plant-based foods, dietary fiber, and polyphenols, and low consumption of red and processed meats, has emerged as a promising microbiota-targeted strategy. It promotes saccharolytic fermentation, enhances short-chain fatty acid production, and reduces proteolytic pathways responsible for uremic toxin generation. Accumulating evidence from observational studies, meta-analyses, and dietary intervention trials suggests that adherence to Mediterranean and plant-based dietary patterns is associated with reduced uremic toxin burden, improved renal outcomes, and lower CV risk in CKD populations. However, direct interventional evidence linking Mediterranean diet adherence to changes in specific uremic toxin levels remains limited. This narrative review summarizes current evidence on diet\u2013microbiota interactions in CKD and highlights the Mediterranean diet as a biologically plausible strategy for targeting the gut\u2013kidney\u2013heart axis. Future well-designed randomized controlled trials (RCTs) are needed to confirm causal relationships and support clinical implementation.<\/jats:p>","DOI":"10.3390\/nu18091451","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:50:01Z","timestamp":1777618201000},"page":"1451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting the Gut\u2013Kidney\u2013Heart Axis in Chronic Kidney Disease: The Mediterranean Diet as a Strategy to Reduce Uremic Toxins and Cardiovascular Risk"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2645-7597","authenticated-orcid":false,"given":"Josipa","family":"Radi\u0107","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Dialysis and Arterial Hypertension, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Be\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijana","family":"Vu\u010dkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, Dialysis and Arterial Hypertension, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4669-666X","authenticated-orcid":false,"given":"Ivana","family":"Juki\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"},{"name":"Faculty of Health Sciences, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7878-7988","authenticated-orcid":false,"given":"Jonatan","family":"Vukovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, Croatia"},{"name":"Department of Internal Medicine, Division of Gastroenterology, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4199-3905","authenticated-orcid":false,"given":"Damir","family":"Fabijani\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Diseases, University Hospital of Split, 21000 Split, Croatia"},{"name":"Department of Clinical Propedeutics, School of Medicine, University of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0350-6800","authenticated-orcid":false,"given":"Mislav","family":"Radi\u0107","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, University of Split, 21000 Split, Croatia"},{"name":"Department of Internal Medicine, Division of Rheumatology, Allergology and Clinical Immunology, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"El Chamieh, C., Liabeuf, S., and Massy, Z. 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