Mechanism-based therapeutic strategies in cardiovascular-kidney-metabolic syndrome: integrating biological pathways with evidence from clinical trials
Year: 2026
Type: article
Abstract: Cardiovascular-kidney-metabolic (CKM) syndrome describes the close relationship between metabolic dysfunction, chronic kidney disease, and cardiovascular disease, which share several biological pathways and frequently progress together. This review examines the mechanisms and clinical trial evidence supporting established and emerging therapies relevant to CKM syndrome. Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, and lipid-lowering therapies have shown cardiovascular, kidney, and metabolic benefits across several high-risk populations. However, most evidence comes from trials enrolling patients with individual conditions, such as type 2 diabetes, chronic kidney disease, heart failure, obesity, or atherosclerotic cardiovascular disease, rather than populations defined by CKM stage or phenotype. Evidence for the added clinical benefit of specific treatment combinations also remains limited. Newer therapies targeting aldosterone synthesis, endothelin signaling, inflammation, incretin pathways, and lipid-related pathways may broaden treatment options. In clinical practice, CKM stage and the predominant clinical phenotype may help identify treatment priorities while accounting for coexisting conditions, safety, treatment burden, cost, and access. This approach may provide a practical basis for selecting therapies across the CKM spectrum, although prospective studies are needed to determine whether phenotype-directed treatment improves clinical outcomes.
Source: Frontiers in Endocrinology
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223180767