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September 3, 2026Current Opinion in Nephrology & HypertensionOpen Access

Integrating the liver into the cardiovascular-kidney-metabolic syndrome: pathophysiology and therapeutic implications

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Authors

WMWilliam MarshallOak Ridge National LaboratorySSSmeeta SinhaManchester Academic Health Science CentreDGDarren GreenManchester Academic Health Science Centre

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Implication

Review demonstrates additive mortality risks from coexistent liver and kidney disease in metabolic patients, highlighting the need for comprehensive multiorgan staging.

Key Points

  • To evaluate the mechanistic, epidemiological, and therapeutic rationale for incorporating metabolic dysfunction-associated steatotic liver disease into the cardiovascular-kidney-metabolic framework.
  • Synthesized large cohort epidemiological data evaluating the interaction and prognosis of coexistent liver and chronic kidney disease.
  • Reviewed recent multi-trial therapeutic data across the cardiovascular-renal-hepatic-metabolic spectrum, including trials of thyroid hormone receptor-β agonists and incretin-based agents.
  • Coexisting metabolic dysfunction-associated steatotic liver disease and chronic kidney disease confer additive, stage-dependent mortality risk, driven primarily by hepatic fibrosis severity rather than steatosis.
  • Resmetirom secured accelerated regulatory approvals as the first dedicated therapy for metabolic dysfunction-associated steatohepatitis.
  • Incretin-based therapies, including semaglutide and tirzepatide, demonstrated cross-spectrum efficacy in kidney disease, obesity-related heart failure with preserved ejection fraction, and steatohepatitis.

Cite This Study

Marshall et al. (2026) studied this question.

synapsesocial.com/papers/6a9934b4636c6408cfa7c6cfhttps://doi.org/10.1097/mnh.0000000000001225
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Also Consider

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  1. 1Contemporary and Emerging Therapeutics in Cardiovascular-Kidney-Metabolic (CKM) Syndrome: In Memory of Professor Akira Endo2025
  2. 2Contemporary and Emerging Therapeutics in Cardiovascular-Kidney-Metabolic (CKM) Syndrome: In Memory of Professor Akira Endo2025 · 2 citations
  3. 3The impact of metabolic dysfunction-associated steatotic liver disease (MASH) on the high risk of cardiovascular disease in CKD: interconnections and management2025 · 19 citations
  4. 4MASLD, MASH, and the CKM Spectrum2026 · 26 citations
  5. 5Metabolic Dysfunction-Associated Steatotic Liver Disease, Cardiovascular, and Kidney Disease2026