ADIPOSE TISSUE, TYPE 2 DIABETES, AND THE LIVER IN THE CARDIOVASCULAR-KIDNEY-METABOLIC FRAMEWORK: FROM CKM TO CRHM, CARDIAL-MS, AND MALCKS

Abstract

Cardiovascular-Kidney-Metabolic syndrome (CKM), introduced by the American Heart Association in 2023, provides an integrated staging framework for metabolic dysfunction, chronic kidney disease, and cardiovascular disease. In 2025-2026, three proposed extensions emerged: Cardiovascular-Renal-Hepatic-Metabolic syndrome (CRHM), Cardio-Renal-Diabetes-Liver-Metabolic Syndrome (CARDIAL-MS), and Metabolic associated Liver-Cardiovascular-Kidney syndrome (MALCKS). This narrative critical review uses CKM as the comparator and examines how these proposals reposition adipose tissue dysfunction, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease within a shared multiorgan network. Their main differences are conceptual: CRHM names the hepatic component explicitly, CARDIAL-MS foregrounds adiposopathy, ectopic fat, diabetes, and liver disease within a proposed staging system, and MALCKS starts from the MASLD-metabolic axis. None has yet demonstrated standardized operational definitions, incremental prognostic value, or an ability to improve treatment decisions beyond CKM. The 2026 CKM guideline now incorporates MASLD and liver fibrosis assessment, updating-but not closing-the benchmark against which these proposals should be evaluated. Their future value will depend on whether they identify measurable phenotypes that improve prediction, treatment selection, or coordinated care rather than merely expanding nomenclature.