Metabolic Dysfunction-Associated Steatotic Liver Disease, Cardiovascular, and Kidney Disease: Triple Challenges.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a central component of cardiovascular-kidney-metabolic syndrome, reflecting shared pathways of insulin resistance, inflammation, and fibrotic injury that drive multiorgan disease. Affecting more than one third of adults worldwide, MASLD frequently coexists with CKD and cardiovascular disease and is associated with higher risks of kidney function decline, cardiovascular (CV) events, and mortality. Hepatic steatosis and fibrosis may amplify systemic metabolic stress and endothelial dysfunction, contributing to progressive kidney injury and adverse cardiometabolic outcomes. Despite this biologic and epidemiologic overlap, MASLD remains underrecognized in nephrology and cardiology practice. This gap represents a missed opportunity to identify patients at a high risk of multiorgan complications early. Noninvasive liver fibrosis assessment, integrated with kidney and CV risk stratification, offers a practical approach to identifying patients who may benefit from intensified preventive strategies. Lifestyle modification remains foundational, while emerging pharmacotherapies, including glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, mineralocorticoid receptor antagonists, and liver-directed agents, demonstrate potential cross-organ benefits. Coordinated management targeting metabolic dysfunction may slow the progression of kidney disease while improving hepatic and CV outcomes. This review highlights the clinical intersection of MASLD, CKD, and cardiovascular disease and proposes a multidisciplinary framework for screening and management. Recognizing MASLD as part of systemic cardiovascular-kidney-metabolic disease can inform risk stratification, guide therapy selection, and support earlier intervention to mitigate the triple burden of liver, kidney, and CV complications.