Frontiers in Physiology · Nov 9, 2026
Cardiovascular-Kidney-Metabolic Syndrome: Contemporary Management and Emerging Therapies
By Matteo Marchetti, Farhang Aminfar, Aurelia Zimmerli et al.
Cardiovascular-kidney-metabolic (CKM) syndrome captures the interconnected pathophysiology linking excess or dysfunctional adiposity, metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). The recently introduced CKM concept unifies these interrelated conditions within a single framework, staging their progression from excess or dysfunctional adiposity to clinical CVD. Importantly, CKM staging was designed not only to classify patients but also to identify increasing absolute cardiovascular and kidney risk and windows for earlier intervention. This approach coincides with the emergence of therapies whose benefits extend beyond traditional organ-specific indications. Sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists, and the nonsteroidal mineralocorticoid receptor antagonist finerenone have demonstrated cardiovascular, kidney, and/or metabolic benefits across overlapping patient populations. This mini review summarizes contemporary management across the CKM continuum, with particular emphasis on therapies with multisystem effects. We also outline emerging therapies, including next-generation incretin-based agents, aldosterone synthase inhibitors, and anti-inflammatory strategies, for which evidence remains largely limited to surrogate endpoints, and discuss the limitations of a stage-based therapeutic approach, uncertainties regarding treatment combinations and sequencing, barriers to implementation and access, and persistent evidence gaps in advanced CKD.