The evolving concept from Cardiovascular-kidney-metabolic syndrome to metabolic associated liver-cardiovascular-kidney syndrome: insights from endocrinology

Metabolic diseases, cardiovascular diseases (CVD), and chronic kidney disease (CKD) often coexist. To understand the complex relationships between these conditions, the American Heart Association first proposed the concept of cardiovascular-kidney-metabolic (CKM) syndrome in 2023. This syndrome is recognized by pathophysiological interplays among metabolic risk factors, CKD, and CVD, which results in multi-organ disorders and increased adverse cardiovascular outcomes. The core effect of the liver in metabolism has been revealed gradually. Sharing extensive overlapping pathological mechanisms with metabolic syndrome (MS), metabolic dysfunction-associated steatotic liver disease (MASLD) is the hepatic component of MS. The risk of developing CVD and CKD is considerably elevated in patients with MASLD. Therefore, from the perspective of endocrinologists, the concept of metabolic associated liver-cardiovascular-kidney syndrome (MALCKS) more accurately describes the impairment to vital organs caused by metabolic abnormalities. By examining the implications of CKM syndrome and its relationship with MASLD, this article elucidates the mechanisms linking MASLD to metabolic syndrome and cardiorenal diseases, and demonstrates that MASLD is associated with cardiovascular, renal, and endocrine metabolic disorders, thereby expanding the concept of CKM syndrome to MALCKS. Furthermore, multidisciplinary managements under the MALCKS framework are advocated to improve patient prognosis. Nevertheless, its formal adoption as a clinical syndrome will require clear operational definitions, validation through robust cohort studies, demonstration of unique clinical utility, and multidisciplinary consensus.