Nat Rev Nephrol. 2026 May 7. doi: 10.1038/s41581-026-01078-w. Online ahead of print.
ABSTRACT
Cardiovascular-kidney-metabolic (CKM) syndrome, defined by the American Heart Association in 2023, describes the interconnected risks of metabolic dysfunction, chronic kidney disease and cardiovascular disease. By unifying these conditions, CKM highlights shared pathophysiology, overlapping risk factors and common therapeutic approaches. The staging framework, from ideal CKM health (stage 0) to clinical cardiovascular disease (stage 4), underscores the importance of prevention and captures the escalating risk of morbidity and mortality with advancing stage. Epidemiological data demonstrate increasing global prevalence and that most adults already meet criteria for stage ≥1 CKM syndrome, with stage 2 (defined by metabolic risk factors or the presence of kidney disease) being the most common. The burden of CKM syndrome is characterized by demographic, socio-economic and geographic disparities, with men and older adults most affected. Established determinants of CKM health include genetics, diet, smoking and physical inactivity, as well as social and structural factors; emerging environmental risk factors, such as climate-related stressors, are increasingly investigated but have a less established evidence base. Lifestyle interventions remain foundational and modern therapeutic classes - including glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors and non-steroidal mineralocorticoid receptor antagonists - offer multisystem benefits, although cost, access and variable uptake remain important barriers. Here, we examine current CKM epidemiological evidence and highlight priorities for prevention, equity and future research.
PMID:42098477 | DOI:10.1038/s41581-026-01078-w