Cardiovascular–kidney–metabolic syndrome: a comprehensive review of pathophysiology, epidemiology, diagnosis, and management

Cardiovascular-kidney-metabolic (CKM) syndrome is a multisystem condition integrating metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease into a unified framework. CKM syndrome encompasses progressive metabolic derangements, renal injury, and cardiovascular remodeling, which interact to amplify morbidity and mortality. Lifestyle interventions (including structured weight loss, dietary modification, physical activity, and sleep optimization) form a cornerstone of prevention and management. Pharmacologic strategies targeting the renin-angiotensin-aldosterone system, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and lipid-lowering therapies provide additional multisystem benefits. In this comprehensive review, we systematically examine the most updated evidence on CKM syndrome, in terms of pathophysiology, epidemiology, clinical manifestations, diagnostic evaluation, and therapeutic strategies. We also highlight future research directions and precision medicine approaches.