8 Pathophysiology and Outcomes CKM syndrome is a multidimensional pathophysiology leading to increased morbidity and mortality that goes well beyond the sum of its individual components.4-The current scientific understanding of CKM Syndrome Dysfunctional adiposity, particularly visceral adipose tissue, secretes proinflammatory and prooxidative products that damage arterial, heart and kidney tissues. Inflammatory processes reduce sensitivity to insulin, resulting in impaired glucose tolerance affecting multiple organs and tissues. Metabolic dysfunction-associated steatotic liver disease (MASLD), previously called nonalcoholic steatohepatitis, or NASH, amplifies systemic inflammation and insulin resistance. MASLD has become the leading cause of liver failure and need for liver transplantation.4-The current scientific understanding of CKM Syndrome, Fig. 1 Proinflammatory and prooxidative mediators released into circulation exacerbate pathophysiologic processes involved in atherosclerosis and myocardial injury, glomerulosclerosis, kidney tubular inflammation, kidney fibrosis and the development of additional metabolic risk factors.3-The current scientific understanding of CKM Syndrome, Fig. 1 Ectopic fat may also produce local dysfunctional mediators and can cause compressive organ damage. When deposited in the epicardium, ectopic fat can promote arrhythmogenesis myocardial dysfunction and coronary atherosclerosis. When deposited “within” and around the kidney, ectopic fat can contribute to hypertension and abnormal variation in blood pressure.4-The current scientific understanding of CKM Syndrome, Fig. 1 The constellation of risk factors that make up metabolic syndrome (MetS), including abdominal obesity, dysglycemia, atherogenic dyslipidemia and hypertension, has multiple pathophysiologic consequences. MetS contributes to endothelial dysfunction, atherogenesis, thrombosis, myocardial injury, fibrosis and cardiac remodeling. Adipose Tissue ADIPONECTIN Causation CKM syndrome most commonly originates from excess or dysfunctional adipose tissue or both.Adiposity can lead to inflammation, insulin resistance and the emergence of myriad metabolic risk factors and systemic effects, including increased CVD risk. Metabolic abnormalities play key pathophysiologic roles in bi-directional cardiovascular-kidney interactions with kidney dysfunction a key mediator between metabolic risk factors and CVD in the CKM syndrome.
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