Cardio-renal metabolic syndrome (CRMS), also termed cardiovascular-kidney-metabolic (CKM) syndrome, represents the convergence of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD), underpinned by insulin resistance (IR), neurohormonal activation, oxidative stress, and chronic inflammation. This narrative review synthesizes current evidence on the epidemiology, pathophysiology, diagnostic approaches, prevention, and management of CRMS. Globally, CRMS prevalence continues to rise, driven by aging populations, urbanization, obesity, and diabetes, with disproportionate effects in low- and middle-income countries. The syndrome is associated with substantially increased morbidity and premature mortality, reflecting the synergistic effects of overlapping conditions. Advances in diagnostic evaluation, including novel biomarkers and imaging modalities, have improved early detection, but significant gaps remain. Preventive strategies emphasize lifestyle modification, dietary change, weight reduction, and smoking cessation, complemented by pharmacological therapies such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, mineralocorticoid receptor antagonists (MRAs), and renin-angiotensin-aldosterone system (RAAS) blockade, all of which demonstrate cardio-renal protection. Non-pharmacological approaches, including bariatric surgery and renal replacement therapies (RRTs), add to the therapeutic armamentarium. Looking ahead, precision medicine, artificial intelligence (AI)-driven prognostic tools, and emerging biomarkers offer opportunities to refine risk stratification and treatment. An integrated, multidisciplinary framework is essential to reduce the escalating global burden and improve patient-centered outcomes in CRMS.
