Cardiovascular-Kidney-Metabolic (CKM) syndrome: A state-of-the-art review

The correlation between obesity, type 2 diabetes mellitus (DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) is an escalating and widely acknowledged epidemic in industrialized nations. Recently, this complex web of interrelated health conditions has been collectively defined as the Cardiovascular-Kidney-Metabolic (CKM) syndrome by the American Heart Association (AHA). The molecular mechanisms underlying CKM disease contain a spectrum of interconnected factors, including hyperglycemia, insulin resistance, heightened activity of the renin-angiotensin-aldosterone system (RAAS), the generation of advanced glycation end-products, oxidative stress, lipotoxicity, endoplasmic reticulum stress, abnormalities in calcium handling, malfunctioning of mitochondria and impaired energy production, as well as persistent chronic inflammation. Addressing their prevention, management, and treatment is of paramount importance to promote better patient health outcomes. The objective of this review is to provide a comprehensive and critical examination of the current state-of-the-art regarding the recently defined CKM syndrome. This includes an exploration of epidemiological evidence establishing connections between cardio-renal-metabolic diseases, an examination of the underlying pathophysiological mechanisms, and a comprehensive overview of existing treatment modalities.