{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:58:00Z","timestamp":1791313080934,"version":"4.3.1"},"reference-count":77,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Proyectos Integrados de Excelencia en los IIS","doi-asserted-by":"publisher","award":["PIE15\/00027"],"award-info":[{"award-number":["PIE15\/00027"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Proyectos Integrados de Excelencia en los IIS","doi-asserted-by":"publisher","award":["AES15"],"award-info":[{"award-number":["AES15"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Proyectos Integrados de Excelencia en los IIS","doi-asserted-by":"publisher","award":["RD12\/0021\/0028"],"award-info":[{"award-number":["RD12\/0021\/0028"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Proyectos Integrados de Excelencia en los IIS","doi-asserted-by":"publisher","award":["RD16\/0009\/0023"],"award-info":[{"award-number":["RD16\/0009\/0023"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Proyectos Integrados de Excelencia en los IIS","doi-asserted-by":"publisher","award":["RICORS 2040"],"award-info":[{"award-number":["RICORS 2040"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Redes Tematicas de Investigacion Cooperativa en Salud, REDINREN","award":["PIE15\/00027"],"award-info":[{"award-number":["PIE15\/00027"]}]},{"name":"Redes Tematicas de Investigacion Cooperativa en Salud, REDINREN","award":["AES15"],"award-info":[{"award-number":["AES15"]}]},{"name":"Redes Tematicas de Investigacion Cooperativa en Salud, REDINREN","award":["RD12\/0021\/0028"],"award-info":[{"award-number":["RD12\/0021\/0028"]}]},{"name":"Redes Tematicas de Investigacion Cooperativa en Salud, REDINREN","award":["RD16\/0009\/0023"],"award-info":[{"award-number":["RD16\/0009\/0023"]}]},{"name":"Redes Tematicas de Investigacion Cooperativa en Salud, REDINREN","award":["RICORS 2040"],"award-info":[{"award-number":["RICORS 2040"]}]},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud","award":["PIE15\/00027"],"award-info":[{"award-number":["PIE15\/00027"]}]},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud","award":["AES15"],"award-info":[{"award-number":["AES15"]}]},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud","award":["RD12\/0021\/0028"],"award-info":[{"award-number":["RD12\/0021\/0028"]}]},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud","award":["RD16\/0009\/0023"],"award-info":[{"award-number":["RD16\/0009\/0023"]}]},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud","award":["RICORS 2040"],"award-info":[{"award-number":["RICORS 2040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Cardiovascular disease (CVD) remains the most common cause of mortality in chronic kidney disease (CKD) patients. Several studies suggest that the Mediterranean diet reduces the risk of CVD due to its influence on endothelial function, inflammation, lipid profile, and blood pressure. Integrating metabolomic and proteomic analyses of CKD could provide insights into the pathways involved in uremia-induced CVD and those pathways modifiable by the Mediterranean diet. Methods: We performed metabolomic and proteomic analyses on serum samples from 19 patients with advanced CKD (aCKD) and 27 healthy volunteers. The metabolites were quantified using four different approaches, based on their properties. Proteomic analysis was performed after depletion of seven abundant serum proteins (Albumin, IgG, antitrypsin, IgA, transferrin, haptoglobin, and fibrinogen). Integrative analysis was performed using MetaboAnalyst 4.0 and STRING 11.0 software to identify the dysregulated pathways and biomarkers. Results: A total of 135 metabolites and 75 proteins were differentially expressed in aCKD patients, compared to the controls. Pathway enrichment analysis showed significant alterations in the innate immune system pathways, including complement, coagulation, and neutrophil degranulation, along with disrupted linoleic acid and cholesterol metabolism. Additionally, certain key metabolites and proteins were altered in aCKD patients, such as glutathione peroxidase 3, carnitine, homocitrulline, 3-methylhistidine, and several amino acids and derivatives. Conclusions: Our findings reveal significant dysregulation of the serum metabolome and proteome in aCKD, particularly in those pathways associated with endothelial dysfunction and CVD. These results suggest that CVD prevention in CKD may benefit from a multifaceted approach, including dietary interventions such as the Mediterranean diet.<\/jats:p>","DOI":"10.3390\/nu16213739","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T09:57:36Z","timestamp":1730368656000},"page":"3739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mediterranean Diet Pattern: Potential Impact on the Different Altered Pathways Related to Cardiovascular Risk in Advanced Chronic Kidney Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8737-5005","authenticated-orcid":false,"given":"Jordi","family":"Rovira","sequence":"first","affiliation":[{"name":"Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d\u2019Investigacions Biom\u00e8tiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0119-1331","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"Ramirez-Bajo","sequence":"additional","affiliation":[{"name":"Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d\u2019Investigacions Biom\u00e8tiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisenda","family":"Ba\u00f1on-Maneus","sequence":"additional","affiliation":[{"name":"Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d\u2019Investigacions Biom\u00e8tiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3381-7503","authenticated-orcid":false,"given":"Pedro","family":"Ventura-Aguiar","sequence":"additional","affiliation":[{"name":"Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d\u2019Investigacions Biom\u00e8tiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain"},{"name":"Department of Nephrology and Kidney Transplantation, Cl\u00ednic\u2019s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-2589","authenticated-orcid":false,"given":"Marta","family":"Arias-Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d\u2019Investigacions Biom\u00e8tiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain"},{"name":"Department of Nephrology and Kidney Transplantation, Cl\u00ednic\u2019s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0746-142X","authenticated-orcid":false,"given":"Barbara","family":"Romano-Andrioni","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Kidney Transplantation, Cl\u00ednic\u2019s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0983-9459","authenticated-orcid":false,"given":"Raquel","family":"Ojeda","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Kidney Transplantation, Cl\u00ednic\u2019s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, 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(BET), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7422-5240","authenticated-orcid":false,"given":"F\u00e0tima","family":"Crispi","sequence":"additional","affiliation":[{"name":"BCNatal|Fetal Medicine Research Center, Hospital Cl\u00ednic and Hospital Sant Joan de D\u00e9u, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08007 Barcelona, Spain"},{"name":"Centre for Biomedical Research on Rare Diseases (CIBER-ER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9032-4954","authenticated-orcid":false,"given":"Juan Carlos","family":"Garc\u00eda-Pag\u00e1n","sequence":"additional","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Cl\u00ednic_Cl\u00ednic Barcelona, Institut de Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-RareLiver), Department of Medicine and Health Sciences, University of Barcelona, CSUR_EVH, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Hep\u00e1ticas y Digestivas (CIBEREHD), 28200 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep M.","family":"Campistol","sequence":"additional","affiliation":[{"name":"Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d\u2019Investigacions Biom\u00e8tiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain"},{"name":"Department of Nephrology and Kidney Transplantation, Cl\u00ednic\u2019s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-3016","authenticated-orcid":false,"given":"Fritz","family":"Diekmann","sequence":"additional","affiliation":[{"name":"Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d\u2019Investigacions Biom\u00e8tiques August Pi i Sunyer (IDIBAPS), 08027 Barcelona, Spain"},{"name":"Red de Investigaci\u00f3n Cooperativa Orientada a Resultados en Salud (RICORS 2040), 28029 Madrid, Spain"},{"name":"Department of Nephrology and Kidney Transplantation, Cl\u00ednic\u2019s Institute of Nephrology and Urology (ICNU), Hospital Clinic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1053\/ajkd.1998.v32.pm9820470","article-title":"Clinical epidemiology of cardiovascular disease in chronic renal disease","volume":"32","author":"Foley","year":"1998","journal-title":"Am. J. Kidney Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/tri.13627","article-title":"Nomenclature for Kidney Function and Disease: Executive Summary and Glossary from a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference","volume":"33","author":"Levey","year":"2020","journal-title":"Transpl. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/00000441-200304000-00002","article-title":"Cardiovascular mortality in end-stage renal disease","volume":"325","author":"Collins","year":"2003","journal-title":"Am. J. Med. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1053\/j.ajkd.2007.03.003","article-title":"A randomized trial of the effect of statin and fibrate therapy on arterial function in CKD","volume":"49","author":"Dogra","year":"2007","journal-title":"Am. J. Kidney Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1056\/NEJMoa0907845","article-title":"A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease","volume":"361","author":"Pfeffer","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2215\/CJN.12011214","article-title":"A Randomized, Controlled Trial of Oral Intestinal Sorbent AST-120 on Renal Function Deterioration in Patients with Advanced Renal Dysfunction","volume":"11","author":"Cha","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/nep.13778","article-title":"Mediterranean diet and the risk of chronic kidney disease: A systematic review and meta-analysis","volume":"25","author":"Hansrivijit","year":"2020","journal-title":"Nephrology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.clnu.2021.12.041","article-title":"Long-term consumption of a mediterranean diet or a low-fat diet on kidney function in coronary heart disease patients: The CORDIOPREV randomized controlled trial","volume":"41","author":"Cardelo","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1053\/j.akdh.2023.07.007","article-title":"Mediterranean Diet for Cardiovascular Risk Reduction in Chronic Kidney Disease","volume":"30","author":"Bakis","year":"2023","journal-title":"Adv. Kidney Dis. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1053\/j.jrn.2009.08.006","article-title":"Adherence to the Mediterranean diet is associated with renal function among healthy adults: The ATTICA study","volume":"20","author":"Chrysohoou","year":"2010","journal-title":"J. Ren. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1053\/j.ajkd.2016.05.019","article-title":"DASH (Dietary Approaches to Stop Hypertension) Diet and Risk of Subsequent Kidney Disease","volume":"68","author":"Rebholz","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Couch, C.A., Ament, Z., Patki, A., Kijpaisalratana, N., Bhave, V., Jones, A.C., Armstrong, N.D., Cheung, K.L., Kimberly, W.T., and Tiwari, H.K. (2024). The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) Diet and Metabolites in Chronic Kidney Disease. Nutrients, 16.","DOI":"10.3390\/nu16152458"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1053\/j.ajkd.2020.05.006","article-title":"KDOQI Clinical Practice Guideline for Nutrition in CKD: 2020 Update","volume":"76","author":"Ikizler","year":"2020","journal-title":"Am. J. Kidney Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1463502","DOI":"10.3389\/fnut.2024.1463502","article-title":"Safety and impact of the Mediterranean diet in patients with chronic kidney disease: A pilot randomized crossover trial","volume":"11","author":"Kwon","year":"2024","journal-title":"Front Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1093\/gerona\/glx227","article-title":"Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms","volume":"73","author":"Tosti","year":"2018","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3945\/ajcn.113.078758","article-title":"Metabolomics in nutritional epidemiology: Identifying metabolites associated with diet and quantifying their potential to uncover diet-disease relations in populations","volume":"100","author":"Guertin","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3945\/ajcn.116.144428","article-title":"Metabolomic profiles as reliable biomarkers of dietary composition","volume":"105","author":"Esko","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1021\/pr500425r","article-title":"Novel multimetabolite prediction of walnut consumption by a urinary biomarker model in a free-living population: The PREDIMED study","volume":"13","author":"Llorach","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1093\/eurheartj\/ehaa209","article-title":"The Mediterranean diet, plasma metabolome, and cardiovascular disease risk","volume":"41","author":"Li","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1001\/archinte.168.22.2449","article-title":"Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: One-year results of the PREDIMED randomized trial","volume":"168","author":"Ros","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cases, A., Cigarran-Guldris, S., Mas, S., and Gonzalez-Parra, E. (2019). Vegetable-Based Diets for Chronic Kidney Disease? It Is Time to Reconsider. Nutrients, 11.","DOI":"10.3390\/nu11061263"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Adair, K.E., and Bowden, R.G. (2020). Ameliorating Chronic Kidney Disease Using a Whole Food Plant-Based Diet. Nutrients, 12.","DOI":"10.3390\/nu12041007"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Molina, P., Gavela, E., Vizcaino, B., Huarte, E., and Carrero, J.J. (2021). Optimizing Diet to Slow CKD Progression. Front. Med., 8.","DOI":"10.3389\/fmed.2021.654250"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/S0140-6736(22)00122-2","article-title":"Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): A randomised controlled trial","volume":"399","author":"Fuentes","year":"2022","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0140-6736(12)60367-5","article-title":"The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials","volume":"380","author":"Mihaylova","year":"2012","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/CIR.0000000000000510","article-title":"Dietary Fats and Cardiovascular Disease: A Presidential Advisory from the American Heart Association","volume":"136","author":"Sacks","year":"2017","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.kint.2017.05.020","article-title":"Kidney function is associated with an altered protein composition of high-density lipoprotein","volume":"92","author":"Rubinow","year":"2017","journal-title":"Kidney Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrneph.2015.180","article-title":"HDL abnormalities in nephrotic syndrome and chronic kidney disease","volume":"12","author":"Vaziri","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1053\/j.ajkd.2018.11.010","article-title":"Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons with CKD","volume":"73","author":"Bajaj","year":"2019","journal-title":"Am. J. Kidney Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/qjmed\/hcx040","article-title":"Meta-analysis of statins in chronic kidney disease: Who benefits?","volume":"110","author":"Messow","year":"2017","journal-title":"QJM"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"368","author":"Tang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"941","DOI":"10.2165\/00003088-200342110-00002","article-title":"Pharmacokinetics of L-carnitine","volume":"42","author":"Evans","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1038\/s41467-019-09329-0","article-title":"Identification of serum metabolites associating with chronic kidney disease progression and anti-fibrotic effect of 5-methoxytryptophan","volume":"10","author":"Chen","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jchromb.2019.04.003","article-title":"Multiplatform metabolomics provides insight into the molecular basis of chronic kidney disease","volume":"1117","author":"Kordalewska","year":"2019","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0014-2999(03)01594-2","article-title":"Relative potencies of statins in reducing cholesterol synthesis and enhancing linoleic acid metabolism","volume":"467","author":"Rise","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12944-020-01258-y","article-title":"The C18:3n6\/C22:4n6 ratio is a good lipid marker of chronic kidney disease (CKD) progression","volume":"19","author":"Szczuko","year":"2020","journal-title":"Lipids Health Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1046\/j.1523-1755.2003.00215.x","article-title":"Dietary conjugated linoleic acid reduces PGE2 release and interstitial injury in rat polycystic kidney disease","volume":"64","author":"Ogborn","year":"2003","journal-title":"Kidney Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jnutbio.2011.04.016","article-title":"A dietary conjugated linoleic acid treatment that slows renal disease progression alters renal cyclooxygenase-2-derived prostanoids in the Han: SPRD-cy rat","volume":"23","author":"Wakefield","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1093\/ndt\/gfs132","article-title":"Essential polyunsaturated fatty acids, inflammation and mortality in dialysis patients","volume":"27","author":"Huang","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Dos Santos, A.L.T., Duarte, C.K., Santos, M., Zoldan, M., Almeida, J.C., Gross, J.L., Azevedo, M.J., Lichtenstein, A.H., and Zelmanovitz, T. (2018). Low linolenic and linoleic acid consumption are associated with chronic kidney disease in patients with type 2 diabetes. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195249"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Espi, M., Koppe, L., Fouque, D., and Thaunat, O. (2020). Chronic Kidney Disease-Associated Immune Dysfunctions: Impact of Protein-Bound Uremic Retention Solutes on Immune Cells. Toxins, 12.","DOI":"10.3390\/toxins12050300"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.yexcr.2018.02.022","article-title":"Chronic kidney disease induces inflammation by increasing Toll-like receptor-4, cytokine and cathelicidin expression in neutrophils and monocytes","volume":"365","author":"Grabulosa","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1053\/j.ajkd.2016.09.018","article-title":"CKD and Risk for Hospitalization with Infection: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"69","author":"Ishigami","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e007818","DOI":"10.1161\/JAHA.117.007818","article-title":"Endothelial Microparticles and Systemic Complement Activation in Patients with Chronic Kidney Disease","volume":"7","author":"Jalal","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Merra, G., Noce, A., Marrone, G., Cintoni, M., Tarsitano, M.G., Capacci, A., and De Lorenzo, A. (2020). Influence of Mediterranean Diet on Human Gut Microbiota. Nutrients, 13.","DOI":"10.3390\/nu13010007"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1093\/ajcn\/nqac175","article-title":"Short-chain fatty acids are key mediators of the favorable effects of the Mediterranean diet on intestinal barrier integrity: Data from the randomized controlled LIBRE trial","volume":"116","author":"Seethaler","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Velasquez, M.T., Centron, P., Barrows, I., Dwivedi, R., and Raj, D.S. (2018). Gut Microbiota and Cardiovascular Uremic Toxicities. Toxins, 10.","DOI":"10.3390\/toxins10070287"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Fryc, J., and Naumnik, B. (2021). Thrombolome and Its Emerging Role in Chronic Kidney Diseases. Toxins, 13.","DOI":"10.3390\/toxins13030223"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1093\/ndt\/gfv254","article-title":"New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis","volume":"30","author":"Glorieux","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_52","first-page":"9","article-title":"Gut microbiota in chronic kidney disease","volume":"37","year":"2017","journal-title":"Nefrologia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e13588","DOI":"10.1111\/eci.13588","article-title":"Interplay between gut microbiota, bone health and vascular calcification in chronic kidney disease","volume":"51","author":"Rodrigues","year":"2021","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1046\/j.1523-1755.2002.00600.x","article-title":"The elephant in uremia: Oxidant stress as a unifying concept of cardiovascular disease in uremia","volume":"62","author":"Himmelfarb","year":"2002","journal-title":"Kidney Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.nephro.2006.04.004","article-title":"New insights on inflammation in chronic kidney disease-genetic and non-genetic factors","volume":"2","author":"Stenvinkel","year":"2006","journal-title":"Nephrol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9036450","DOI":"10.1155\/2017\/9036450","article-title":"Chronic Kidney Disease and Disproportionally Increased Cardiovascular Damage: Does Oxidative Stress Explain the Burden?","volume":"2017","author":"Duni","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Luczak, M., Suszynska-Zajczyk, J., Marczak, L., Formanowicz, D., Pawliczak, E., Wanic-Kossowska, M., and Stobiecki, M. (2016). Label-Free Quantitative Proteomics Reveals Differences in Molecular Mechanism of Atherosclerosis Related and Non-Related to Chronic Kidney Disease. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17050631"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1159\/000495540","article-title":"Antioxidant and Anti-Inflammatory Strategies Based on the Potentiation of Glutathione Peroxidase Activity Prevent Endothelial Dysfunction in Chronic Kidney Disease","volume":"51","author":"Vera","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.bbmt.2009.01.013","article-title":"The release of soluble factors contributing to endothelial activation and damage after hematopoietic stem cell transplantation is not limited to the allogeneic setting and involves several pathogenic mechanisms","volume":"15","author":"Palomo","year":"2009","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1055\/s-0037-1616539","article-title":"Uremic medium disturbs the hemostatic balance of cultured human endothelial cells","volume":"86","author":"Serradell","year":"2001","journal-title":"Thromb. Haemost."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Barbouti, A., and Goulas, V. (2021). Dietary Antioxidants in the Mediterranean Diet. Antioxidants, 10.","DOI":"10.3390\/antiox10081213"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1681\/ASN.2012030254","article-title":"Protein carbamylation predicts mortality in ESRD","volume":"24","author":"Koeth","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nrneph.2017.103","article-title":"Mechanisms and consequences of carbamoylation","volume":"13","author":"Delanghe","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1523-1755.2005.00391.x","article-title":"Carbamylated low-density lipoprotein induces death of endothelial cells: A link to atherosclerosis in patients with kidney disease","volume":"68","author":"Ok","year":"2005","journal-title":"Kidney Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1093\/ndt\/gfx203","article-title":"Nutritional therapy reduces protein carbamylation through urea lowering in chronic kidney disease","volume":"33","author":"Marzocco","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1178646917694600","article-title":"Tryptophan Metabolism in Patients with Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers","volume":"10","author":"Debnath","year":"2017","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.atherosclerosis.2008.10.002","article-title":"Kynurenine, quinolinic acid--the new factors linked to carotid atherosclerosis in patients with end-stage renal disease","volume":"204","author":"Pawlak","year":"2009","journal-title":"Atherosclerosis"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Dahabiyeh, L.A., Nimer, R.M., Sumaily, K.M., Alabdaljabar, M.S., Jacob, M., Sabi, E.M., Hussein, M.H., and Abdel Rahman, A. (2023). Metabolomics profiling distinctively identified end-stage renal disease patients from chronic kidney disease patients. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-33377-8"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/ki.2014.237","article-title":"Altered tryptophan metabolism and CKD-associated fatigue","volume":"86","author":"Mutsaers","year":"2014","journal-title":"Kidney Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"C701","DOI":"10.1152\/ajpcell.00098.2019","article-title":"Uremic metabolites impair skeletal muscle mitochondrial energetics through disruption of the electron transport system and matrix dehydrogenase activity","volume":"317","author":"Thome","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1093\/ajcn\/nqab238","article-title":"Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: Potential modification effect of Mediterranean diet","volume":"114","author":"Razquin","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.redox.2017.03.017","article-title":"Gene and protein expressions and metabolomics exhibit activated redox signaling and wnt\/beta-catenin pathway are associated with metabolite dysfunction in patients with chronic kidney disease","volume":"12","author":"Chen","year":"2017","journal-title":"Redox Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1053\/ajkd.2002.29904","article-title":"Vitamin B6 metabolism and homocysteine in end-stage renal disease and chronic renal insufficiency","volume":"39","author":"Lindner","year":"2002","journal-title":"Am. J. Kidney Dis."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Cappuccilli, M., Bergamini, C., Giacomelli, F.A., Cianciolo, G., Donati, G., Conte, D., Natali, T., La Manna, G., and Capelli, I. (2020). Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery. Nutrients, 12.","DOI":"10.3390\/nu12051234"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbagen.2008.11.010","article-title":"Epigenetics in hyperhomocysteinemic states. A special focus on uremia","volume":"1790","author":"Ingrosso","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kochlik, B., Stuetz, W., Peres, K., Feart, C., Tegner, J., Rodriguez-Manas, L., Grune, T., and Weber, D. (2019). Associations of Plasma 3-Methylhistidine with Frailty Status in French Cohorts of the FRAILOMIC Initiative. J. Clin. Med., 8.","DOI":"10.3390\/jcm8071010"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/21\/3739\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:25:39Z","timestamp":1760113539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/21\/3739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,31]]},"references-count":77,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["nu16213739"],"URL":"https:\/\/doi.org\/10.3390\/nu16213739","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,31]]}}}