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

Sep 25, 2026

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Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized as a central component of the cardiovascular–kidney–metabolic (CKM) syndrome, driven by shared mechanisms of insulin resistance, inflammation, and fibrotic injury. Affecting over one-third of adults globally, MASLD often coexists with chronic kidney disease (CKD) and cardiovascular disease (CVD), raising risks of kidney function decline, cardiovascular events, and mortality. Liver steatosis and fibrosis may worsen systemic metabolic stress and endothelial dysfunction, accelerating kidney injury and adverse cardiometabolic outcomes. Despite this overlap, MASLD is often underrecognized in nephrology and cardiology. Noninvasive fibrosis assessment combined with kidney and cardiovascular risk stratification supports earlier, intensified prevention, alongside lifestyle changes and emerging therapies such as GLP-1 receptor agonists, SGLT2 inhibitors, mineralocorticoid receptor antagonists, and liver-directed agents. A multidisciplinary screening and management framework is proposed to address the triple burden across organs.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages47

Reading Time1 h 58 min

AccessFree to download

Abstract

MASLD within CKM syndrome

Epidemiology and clinical co-morbidity

Pathophysiology linking liver, kidney, and cardiovascular outcomes

Recognition gap and screening strategy

Prevention and emerging cross-organ therapies

Clinical Journal of the American Society of Nephrology Metabolic Dysfunction-Associated Steatotic Liver Disease, Cardiovascular, and Kidney Disease: Triple Challenges --Manuscript Draft-- | Manuscript Number: | CJASN-2026-000380R2 | | --- | --- | | Full Title: | Metabolic Dysfunction-Associated Steatotic Liver Disease, Cardiovascular, and Kidney Disease: Triple Challenges | | Short Title: | MASLD, CVD and CKD | | Article Type: | Bridging Cardiovascular and Kidney Health-Invited | | Corresponding Author: | Lisa B VanWagner, MD MSc
The University of Texas Southwestern Medical Center Dallas, Texas UNITED STATES | | Corresponding Author E-Mail: | [Lisa.Vanwagner@UTSouthwestern.edu](Lisa.Vanwagner@UTSouthwestern.edu) | | Other Authors: | Stephanie Y. Tsai | | | Giselle B. Uwera | | | Bethany Roehm | | | Ambarish Pandey | | Order of Authors (with Contributor Roles): | Stephanie Y. Tsai (Writing – original draft) | | | Giselle B. Uwera (Writing – original draft) | | | Bethany Roehm (Writing – review & editing) | | | Ambarish Pandey (Writing – review & editing) | | | Lisa B. VanWagner, MD MSc (Conceptualization; Project administration; Supervision; Writing – review & editing) | | Manuscript Classifications: | Cardiovascular Disease; Cardiovascular Events; Cardiovascular-kidney-metabolic (CKM) syndrome; Chronic Kidney Disease; Statins | | Abstract: | Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized as a central component of cardiovascular–kidney–metabolic (CKM) syndrome, reflecting shared pathways of insulin resistance, inflammation, and fibrotic injury that drive multi-organ disease. Affecting more than one-third of adults worldwide, MASLD frequently coexists with chronic kidney disease (CKD) and cardiovascular disease (CVD) and is associated with higher risks of kidney function decline, cardiovascular 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 high risk of multi-organ complications early. Noninvasive liver fibrosis assessment, integrated with kidney and cardiovascular 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 cardiovascular outcomes. This review highlights the clinical intersection of MASLD, CKD, and CVD and proposes a multidisciplinary framework for screening and management. Recognizing MASLD as part of systemic CKM disease can inform risk stratification, guide therapy selection, and support earlier intervention to mitigate the triple burden of liver, kidney, and cardiovascular complications. | | Funding Information: | | Copyright © 2026 by the American Society of Nephrology | Additional Information: | | | --- | --- | | Question | Response | | Study Group:
Does your paper include study group(s)? If yes, please provide a list of study group(s) and members that have contributed to or participated in the submitted work in some way. This list may contain either a collaboration of individuals (e.g. , investigators) and/or the name of an organization (e.g. , a laboratory, educational institution, corporation, or department) and its members. | No | Copyright © 2026 by the American Society of Nephrology Clinical Journal of the American Society

FAQs

How is MASLD connected to cardiovascular–kidney–metabolic (CKM) syndrome?

MASLD is described as a central component of CKM syndrome because it shares pathways such as insulin resistance, inflammation, and fibrotic injury that drive multi-organ disease.

What comorbidities and outcomes are MASLD associated with in adults?

MASLD frequently coexists with CKD and CVD and is linked to higher risks of kidney function decline, cardiovascular events, and mortality.

Why is MASLD underrecognized, and what approach is proposed to address this?

MASLD remains underrecognized in nephrology and cardiology practice; the document proposes noninvasive liver fibrosis assessment integrated with kidney and cardiovascular risk stratification to identify high-risk patients earlier.

Sep 25, 2026

Uploaded by Aria