From Metabolic Syndrome to Cardiovascular–Kidney–Metabolic Syndrome (CKM): A Clinical and Pathophysiological Continuum

Cardiovascular–kidney–metabolic (CKM) syndrome has emerged as a broader clinical and pathophysiological framework than traditional metabolic syndrome, addressing the limitations of a purely factor-clustering approach by integrating dysfunctional adiposity, metabolic dysfunction, chronic kidney disease, and cardiovascular disease within a dynamic multiorgan continuum. This narrative review critically examines the transition from metabolic syndrome to CKM syndrome, emphasizing why the newer framework may better reflect real-world cardiorenometabolic multimorbidity and provide more clinically meaningful risk stratification through the incorporation of renal markers, subclinical cardiovascular disease, and stage-based progression. The review synthesizes the epidemiological burden of the CKM continuum and discusses the main biological mechanisms linking adipose tissue dysfunction, insulin resistance, inflammation, oxidative stress, endothelial injury, MASLD as the hepatic component of the continuum, renal vulnerability, and cardiovascular remodeling. It also considers the role of social determinants of health and the life-course perspective in shaping disease onset, progression, and access to care. Particular attention is given to the clinical implications of CKM syndrome as an interpretive and organizational model that may support earlier recognition of multiorgan risk, more integrated prevention, and less fragmented multidisciplinary management, while remaining distinct from a self-sufficient diagnostic or therapeutic algorithm. Overall, CKM syndrome should be regarded not as a new nosological entity, but as a clinically useful framework for reclassifying and managing the interconnected progression from metabolic dysfunction to renal and cardiovascular disease.