Cardio–kidney–metabolic syndrome: Underutilized screening and management in primary care settings

Cardio–kidney–metabolic (CKM) syndrome represents a significant and growing global health challenge characterized by a complex interplay between cardiovascular disease, chronic kidney disease, and metabolic disorders. Despite its high prevalence and substantial impact on morbidity, mortality, and healthcare costs, CKM syndrome remains under-recognized and suboptimally managed in primary care settings. A comprehensive literature review was conducted using PubMed, Scopus, and Web of Science databases to identify recent landmark studies, clinical guidelines, and health economic analyses related to CKM syndrome, focusing on articles published between 2020 and 2025. The American Heart Association’s staging framework provides a valuable foundation for risk stratification, though its translation into routine clinical practice remains challenging. Key pathophysiological drivers include chronic inflammation, neurohormonal activation, endothelial dysfunction, and frontier mechanisms encompassing the gut–kidney–heart axis, cellular senescence, epigenetic modifications, and multi-organ crosstalk. Established biomarkers — including estimated glomerular filtration rate, urine albumin-to-creatinine ratio, and N-terminal pro-B-type natriuretic peptide — are underutilized in primary care due to structural barriers, knowledge gaps, and resource constraints. Evidence supports the cost-effectiveness of early screening and intervention with sodium–glucose cotransporter 2 inhibitors and other guideline-directed medical therapies. Integrated care models bridging primary and specialty care show promise for improving CKM outcomes. Overcoming barriers to effective screening and management in primary care is critical to mitigating CKM syndrome progression and reducing its associated burden. This review highlights the need for simplified screening protocols, clinical decision support tools, and implementation of integrated care models to improve outcomes for millions of patients affected by this complex syndrome.