{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:50:23Z","timestamp":1790891423616,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"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>Cardiovascular\u2013kidney\u2013metabolic syndrome (CKMS) represents the intricate interconnection of cardiovascular, kidney, and metabolic disorders, with systemic inflammation now recognized as a key driver of both pathogenesis and prognosis. This systematic review aimed to synthesize current evidence on the prognostic value of inflammatory biomarkers in individuals with CKMS. A systematic search of PubMed, Embase, CINAHL, Web of Science, and Scopus were conducted to identify studies published between 1 January 2024 and 30 June 2025, following the recognition of CKMS as a distinct syndrome in December 2023. Eligible studies included adults (aged \u2265 18 years) with CKMS, that assesses one or more inflammatory markers and reported prognostic outcomes such as mortality or disease progression. Data extracted included study characteristics, biomarker types, outcome measures, and key findings. In addition to longitudinal cohorts, we included a small number of cross-sectional studies and treated them as association (non-prognostic) evidence analyzed in a separate stream from prognostic cohorts. Risk of bias was evaluated using the Quality in Prognostic Studies (QUIPS) tool. Due to considerable variability in prognostic outcomes, follow-up durations, and inflammatory indices, a meta-analysis was not feasible. Instead, a narrative synthesis was undertaken to summarize the evidence, identify consistent associations, and emphasize the need for standardized approaches and biomarker validation in future CKMS research. Analysis was conducted in line with the SWiM guidelines. Thirteen studies (n = 13) comprising 282,016 participants (100,590 males; 97,295 females) were included from 1404 initial records. Five of the studies were cross-sectional, providing information on associations rather than prognostic outcomes. Most were large-scale cohort studies conducted in the USA and China. Frequently assessed biomarkers included systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (hs-CRP\/HDL-C), dietary inflammatory index (DII), and triglyceride\u2013glucose (TyG) index. Elevated levels of these biomarkers were consistently associated with higher risk of all-cause and cardiovascular mortality, CKMS progression, and adverse metabolic outcomes. This review highlights systemic inflammation as a critical and associated marker of CKMS prognosis. Inflammatory biomarkers may assist in hypothesis generation, but clinical utility remains to be established pending standardized adjustment and external validation. Because CKMS has only recently been operationalized, we limited inclusion to studies published from 1 January 2024 onward, enhancing definitional comparability but narrowing the evidence base and potentially emphasizing early-adopter regions (predominantly the U.S. and China). Accordingly, these findings should be interpreted as early signals that require replication in diverse settings and confirmation through longitudinal and interventional studies to inform integrative CKMS management strategies. Across observational studies, the certainty of evidence is low to moderate due to indirectness and imprecision; findings should be treated as associational signals pending external validation.<\/jats:p>","DOI":"10.3390\/ijms27010134","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T16:19:26Z","timestamp":1766420366000},"page":"134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inflammation as a Prognostic Marker in Cardiovascular Kidney Metabolic Syndrome: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8388-132X","authenticated-orcid":false,"given":"Sihle E.","family":"Mabhida","sequence":"first","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9054-7242","authenticated-orcid":false,"given":"Haskly","family":"Mokoena","sequence":"additional","affiliation":[{"name":"Department of Physiology and Environmental Health, University of Limpopo, Sovenga, Polokwane 0727, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1041-7941","authenticated-orcid":false,"given":"Mamakase G.","family":"Sello","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, University of the Western Cape, Bellville, Cape Town 7535, South Africa"},{"name":"Department of Nutrition, Faculty of Health Sciences, National University of Lesotho, Maseru 100, Lesotho"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-0529","authenticated-orcid":false,"given":"Cindy","family":"George","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musawenkosi","family":"Ndlovu","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9735-9057","authenticated-orcid":false,"given":"Thabsile","family":"Mabi","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4697-4476","authenticated-orcid":false,"given":"Sisa","family":"Martins","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Innocent S.","family":"Ndlovu","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-7184","authenticated-orcid":false,"given":"Onyemaechi","family":"Azu","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, University of the Western Cape, Bellville, Cape Town 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5183-131X","authenticated-orcid":false,"given":"Andr\u00e9 P.","family":"Kengne","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"},{"name":"Department of Medicine, University of Cape Town, Cape Town 7700, South Africa"},{"name":"African Population and Health Research Center, Nairobi P.O. Box 10787-00100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2515-9184","authenticated-orcid":false,"given":"Zandile J.","family":"Mchiza","sequence":"additional","affiliation":[{"name":"Non-Communicable Diseases Research Unit, South African Medical Research Council, Tygerberg, Cape Town 7505, South Africa"},{"name":"Department of Medical Biosciences, University of the Western Cape, Bellville, Cape Town 7535, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1161\/CIR.0000000000001186","article-title":"A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: A scientific statement from the American Heart Association","volume":"148","author":"Ndumele","year":"2023","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"118585","DOI":"10.1016\/j.atherosclerosis.2024.118585","article-title":"Association between different stages of cardiovascular-kidney-metabolic syndrome and the risk of all-cause mortality","volume":"397","author":"Li","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1001\/jama.2024.6892","article-title":"Prevalence of cardiovascular-kidney-metabolic syndrome stages in US adults, 2011\u20132020","volume":"331","author":"Aggarwal","year":"2024","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"111926","DOI":"10.1016\/j.diabres.2024.111926","article-title":"Increased prevalence of cardiovascular-kidney-metabolic syndrome during COVID-19: A propensity score-matched study","volume":"218","author":"Trimarco","year":"2024","journal-title":"Diabetes Res. 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