{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:35:29Z","timestamp":1785224129345,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although metabolic, renal, and cardiovascular disorders frequently coexist, little is known about how illness combinations affect prognosis. Cardiovascular disease (CVD), which can manifest as coronary artery disease (CAD), stroke, heart failure (HF), arrhythmias, and sudden cardiac death, is more likely to develop in patients with chronic kidney disease (CKD). This link is closer with regard of heart failure (HF) and renal dysfunction, in which a reciprocal relationship has been demonstrated, with the initial illness of one organ causing the progressive dysfunction of the other system. Common risk factors for both illnesses include obesity, diabetes, metabolic disorders, hypertension, and dyslipemia. Theoretically, each of these factors accelerates the atherosclerotic process or directly damages the endothelium through inflammatory, oxidative, and pro-thrombotic pathways, which in turn causes the beginning of heart dysfunction and renal function deterioration. Although the mechanisms and causes have been identified, there are still a number of unanswered questions regarding classification, development, monitoring, and preventive aspects. Furthermore, the absence of reliable data on cardiac and renal outcomes across different stages contributes to creating confusion in CKM classification and management. This paper discusses the current challenges and perspectives in CKM definition and assessment proposing a specific diagnostic and laboratory fingerprint.<\/jats:p>","DOI":"10.3390\/ijms27041657","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:15:54Z","timestamp":1770624954000},"page":"1657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Current Appraisal and Gaps in Knowledge in Cardio\u2013Kidney Metabolic Syndrome Definition"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-984X","authenticated-orcid":false,"given":"Alberto","family":"Palazzuoli","sequence":"first","affiliation":[{"name":"Cardiovascular Diseases Unit, Cardio Thoracic and Vascular Department, Le Scotte Hospital University of Siena, 53100 Siena, Italy"},{"name":"Istituto Nazionale per le Ricerche Cardiovascolari, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1487-9530","authenticated-orcid":false,"given":"Anna Vittoria","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per le Ricerche Cardiovascolari, 40126 Bologna, Italy"},{"name":"Department of Quality of Life Sciences, University of Bologna-Alma Mater Studiorum, 47921 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fedele","sequence":"additional","affiliation":[{"name":"Istituto Nazionale per le Ricerche Cardiovascolari, 40126 Bologna, Italy"},{"name":"Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1161\/CIRCHEARTFAILURE.111.966242","article-title":"Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) Investigators. Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction: Impact of the new Chronic Kidney Disease-Epidemiology Collaboration Group formula","volume":"5","author":"McAlister","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/eurheartj\/eht386","article-title":"Renal impairment, worsening renal function, and outcome in patients with heart failure: An updated meta-analysis","volume":"35","author":"Damman","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/ejhf.3569","article-title":"Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by diuretic use: A FIDELITY analysis","volume":"27","author":"Mentz","year":"2025","journal-title":"Eur. J. Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e024139","DOI":"10.1161\/JAHA.121.024139","article-title":"Cardiorenal Nexus: A Review with Focus on Combined Chronic Heart and Kidney Failure, and Insights from Recent Clinical Trials","volume":"11","author":"McCullough","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/eurheartj\/ehp507","article-title":"Cardio-renal syndromes: Report from the consensus conference of the acute dialysis quality initiative","volume":"31","author":"Ronco","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0735-1097(02)02663-3","article-title":"Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community","volume":"41","author":"Manjunath","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1007\/s00125-022-05694-6","article-title":"Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: A post hoc analysis of the DAPA-CKD trial","volume":"65","author":"Waijer","year":"2022","journal-title":"Diabetologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1161\/CIRCULATIONAHA.117.028814","article-title":"Cardiorenal Syndrome Revisited","volume":"138","author":"Zannad","year":"2018","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1161\/CIR.0000000000001184","article-title":"Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory from the American Heart Association","volume":"148","author":"Ndumele","year":"2023","journal-title":"Circulation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102344","DOI":"10.1016\/j.cpcardiol.2023.102344","article-title":"Cardiovascular-Kidney-Metabolic (CKM) syndrome: A state-of-the-art review","volume":"49","author":"Sebastian","year":"2024","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1161\/01.CIR.0000143547.55093.17","article-title":"The Clinical Challenge of Cardiorenal Syndrome","volume":"110","author":"Shlipak","year":"2004","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"813","DOI":"10.2215\/CJN.0000000000000361","article-title":"From Cardiorenal Syndrome to Chronic Cardiovascular and Kidney Disorder: A Conceptual Transition","volume":"19","author":"Zoccali","year":"2024","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1186\/s12933-023-01937-x","article-title":"The cardio-renal-metabolic connection: A review of the evidence","volume":"22","author":"Marassi","year":"2023","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nrneph.2016.113","article-title":"Heart failure and kidney dysfunction: Epidemiology, mechanisms and management","volume":"12","author":"Schefold","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1161\/CIR.0000000000001191","article-title":"Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement from the American Heart Association","volume":"148","author":"Khan","year":"2023","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1161\/CIRCULATIONAHA.123.067626","article-title":"Chronic Kidney Disease Prognosis Consortium and the American Heart Association Cardiovascular-Kidney-Metabolic Science Advisory Group. Development and Validation of the American Heart Association\u2019s PREVENT Equations","volume":"149","author":"Khan","year":"2024","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1093\/eurjpc\/zwac176","article-title":"Including measures of chronic kidney disease to improve cardiovascular risk prediction by SCORE2 and SCORE2-OP","volume":"30","author":"Matsushita","year":"2023","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s11897-024-00686-6","article-title":"Screening for Heart Failure: Biomarkers to Detect Heightened Risk in the General Population","volume":"21","author":"Kosyakovsky","year":"2024","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Caba\u0142a, S., and Herosimczyk, A. (2025). Diet-Induced Proteomic and Metabolomic Signatures in Chronic Kidney Disease: A Precision Nutrition Approach. Metabolites, 15.","DOI":"10.20944\/preprints202503.0144.v1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1186\/s12933-025-02881-8","article-title":"Metabolomic profiling reveals interindividual metabolic variability and its association with cardiovascular-kidney-metabolic syndrome risk","volume":"24","author":"Zhou","year":"2025","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100036","DOI":"10.1016\/j.jnha.2023.100036","article-title":"Identification of novel serum metabolic signatures to predict chronic kidney disease among Chinese elders using UPLC-Orbitrap-MS","volume":"28","author":"Liu","year":"2024","journal-title":"J. Nutr. Health Aging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jprot.2018.09.020","article-title":"Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease","volume":"193","author":"Anderson","year":"2019","journal-title":"J. Proteom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e70090","DOI":"10.1002\/dmrr.70090","article-title":"Proteomic and Metabolomic Interplay in the Regulation of Energy Metabolism During Obesity and Metabolic Syndrome","volume":"41","author":"Cataldi","year":"2025","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e202300238","DOI":"10.1002\/prca.202300238","article-title":"Prospecting Specific Protein Patterns for High Body Mass Index (BMI), Metabolic Syndrome and Type 2 Diabetes in Saliva and Blood Plasma from a Brazilian Population","volume":"18","author":"Thompson","year":"2024","journal-title":"Proteom. Clin. Appl."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Panov, A., Mayorov, V.I., and Dikalov, S. (2022). Metabolic Syndrome and \u03b2-Oxidation of Long-Chain Fatty Acids in the Brain, Heart, and Kidney Mitochondria. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23074047"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100868","DOI":"10.1016\/j.jacadv.2024.100868","article-title":"Cardiometabolic Disease Staging and Major Adverse Cardiovascular Event Prediction in 2 Prospective Cohorts","volume":"3","author":"Howell","year":"2024","journal-title":"JACC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lu, Y., Ge, J., Zhu, L., Wang, L., Wu, J., Dong, F., and Deng, J. (2025). Cardiometabolic-kidney indices and machine learning model for predicting all-cause mortality in patients with cardiovascular-kidney-metabolic syndrome: A longitudinal cohort study. Am. J. Nephrol., 1\u201315.","DOI":"10.1159\/000549578"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.2215\/CJN.0000000744","article-title":"The Cardiovascular-Kidney-Metabolic Health Framework: Implications for Nephrology","volume":"20","author":"Rangaswami","year":"2025","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1159\/000519758","article-title":"Disparities in Chronic Kidney Disease Progression by Medicare Advantage Enrollees","volume":"52","author":"Diamantidis","year":"2021","journal-title":"Am. J. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102498","DOI":"10.1016\/j.jchf.2025.03.042","article-title":"Obesity and Risk of Kidney Outcomes in Heart Failure With Preserved Ejection Fraction: A Participant-Level Pooled Analysis of 4 Contemporary Trials","volume":"13","author":"Lassen","year":"2025","journal-title":"JACC Heart Fail."},{"key":"ref_31","first-page":"e984","article-title":"Obesity and cardiovascular disease: A scientific statement from the American Heart Association","volume":"143","author":"Poirier","year":"2021","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1161\/CIR.0000000000001221","article-title":"Implementation of Obesity Science into Clinical Practice: A Scientific Statement From the American Heart Association","volume":"150","author":"Laddu","year":"2024","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1159\/000511023","article-title":"Obesity Prevalence in the Long-Term Future in 18 European Countries and in the USA","volume":"13","author":"Janssen","year":"2020","journal-title":"Obes. Facts"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e028086","DOI":"10.1136\/bmjopen-2018-028086","article-title":"Impact of obesity on life expectancy among different European countries: Secondary analysis of population-level data over the 1975\u20132012 period","volume":"9","author":"Vidra","year":"2019","journal-title":"BMJ Open"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"935","DOI":"10.2337\/dc24-2825","article-title":"Weight gain was associated with worsening glycemia and cardiovascular and kidney outcomes in patients with type 2 diabetes independent of diabetes medication in the GRADE randomized controlled trial","volume":"48","author":"Wexler","year":"2025","journal-title":"Diabetes Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1093\/eurheartj\/ehaf167","article-title":"Cardiovascular disease in chronic kidney disease","volume":"46","author":"Cherney","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101788","DOI":"10.1016\/j.jacadv.2025.101788","article-title":"Lifestyle Interventions in Cardiovascular-Kidney-Metabolic Syndrome JACC: Advances Expert Panel","volume":"4","author":"Shahid","year":"2025","journal-title":"JACC Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3685","DOI":"10.1093\/eurheartj\/ehaf314","article-title":"Clinical staging to guide management of metabolic disorders and their sequelae: A European Atherosclerosis Society consensus statement","volume":"46","author":"Romeo","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.pcad.2021.03.007","article-title":"Current gaps in HFpEF trials: Time to reconsider patients\u2019 selection and to target phenotypes","volume":"67","author":"Palazzuoli","year":"2021","journal-title":"Prog. Cardiovasc. 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