Cardiovascular-Kidney-Metabolic Syndrome: Integrating Metabolism, Kidney Health, and Cardiovascular Disease into a Unified Clinical Framework

Cardiovascular-Kidney-Metabolic (CKM) syndrome reflects the convergence of metabolic dysfunction, chronic kidney disease, and cardiovascular pathology into a unified disease network. Once viewed as parallel comorbidities, these conditions are now recognized as interdependent processes driven by shared mechanisms including insulin resistance, inflammation, neurohormonal activation, oxidative stress, and microvascular dysfunction. This review synthesizes emerging evidence across disciplines to articulate a cohesive framework for CKM syndrome, emphasizing epidemiology, pathophysiology, diagnostic challenges, and therapeutic innovations. We highlight the shift from organ?specific management to integrated, phenotype?driven care and outline future directions in precision medicine and tri?organ clinical trial design. CKM syndrome is rapidly becoming the dominant phenotype in contemporary cardiovascular practice, demanding a unified approach to prevention and treatment.