Exercise in CKM syndrome progression: a stage-specific approach to cardiovascular, metabolic, and renal health

Cardiovascular-Kidney-Metabolic (CKM) syndrome progresses through distinct stages, from early metabolic risk factors to advanced cardiovascular disease and kidney dysfunction. Across these stages, exercise remains a central yet underutilized intervention, offering physiological adaptations that address metabolic dysregulation, vascular dysfunction, and inflammation. This review evaluates the stage-specific effects of moderate-intensity continuous exercise (MICE), high-intensity interval exercise (HIIE), and resistance training (RT) on CKM syndrome. In Stage 0, exercise augments insulin sensitivity, endothelial function, and mitochondrial biogenesis, preserving optimal health in individuals without metabolic risk factors. Stage 1, marked by excess adiposity, sees structured exercise regimens effectively reducing visceral fat, improving lipid profiles, and enhancing glucose regulation. During Stage 2, encompassing metabolic risk factors and early chronic kidney disease (CKD), aerobic and resistance exercise improve endothelial responsiveness, glycemic control, and renal outcomes. In Stage 3, subclinical cardiovascular disease, targeted exercise interventions strengthen vascular integrity, boost cardiac efficiency, and enhance metabolic resilience. Finally, Stage 4 entails clinical CVD, where exercise-based rehabilitation programs (e.g., moderate-intensity continuous training [MICT], high-intensity interval training [HIIT]) raise functional capacity, improve quality of life, and support favorable prognosis. Sex differences in exercise adaptations underscore the importance of individualized prescriptions. Emphasizing a multidisciplinary strategy that integrates lifestyle modifications and clinical measures can mitigate CKM-associated morbidity and mortality. Future research should investigate long-term exercise adherence, sex-specific responses, and the role of digital health tools to optimize CKM management and patient outcomes.