Biomarkers for the diagnosis and management of cardiovascular-kidney-metabolic syndrome: recent advances and prospects for clinical application

Abstract

Cardiovascular-kidney-metabolic (CKM) syndrome describes a multidirectional network linking dysfunctional adiposity, metabolic risk factors, kidney disease and cardiovascular injury. Its early stages are often clinically silent, while obesity, impaired kidney function, multimorbidity and recent exercise can alter the concentrations and interpretation of commonly used biomarkers. This narrative review, informed by a structured literature search, evaluates biomarkers across screening, risk stratification, treatment monitoring and precision phenotyping, while distinguishing CKM-specific evidence from evidence extrapolated from chronic kidney disease, diabetes, obesity and heart-failure populations. Established clinical biomarkers, including estimated glomerular filtration rate, urine albumin-to-creatinine ratio, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin, remain the foundation of clinical assessment. Emerging evidence spans directly measured markers of inflammation, oxidative stress and organ injury; indices derived from routine clinical variables; and metabolomic, lipidomic and other multi-omics platforms. Most of these measures provide biological or prognostic information but remain investigational because prospective external validation, analytical standardisation, actionable thresholds, incremental net benefit and biomarker-guided intervention evidence are limited. Lifestyle and exercise act both as upstream modifiers of CKM biology and as interpretive factors for several biomarkers. A clinically useful CKM biomarker framework should therefore integrate evidence maturity, population relevance, cross-organ specificity, serial trajectories, cost and equity. Emerging biomarkers should complement rather than replace established assessment until prospective studies demonstrate that their use changes treatment decisions and improves patient outcomes.