Saudi Heart Association Scientific Statement on Cardiovascular-Kidney-Liver-Metabolic (CKLM) Syndrome

Cardiovascular, kidney, metabolic, and liver diseases are closely interconnected and frequently coexist. While the cardiovascular-kidney-metabolic (CKM) framework provides a unified model, increasing evidence supports a central role for hepatic disease, particularly metabolic dysfunction-associated steatotic liver disease (MASLD), in this continuum. The Saudi Heart Association (SHA) therefore aimed to introduce the cardiovascular-kidney-liver-metabolic (CKLM) syndrome as an expanded framework and provide expert guidance on its pathophysiology, staging, screening, and management, with relevance to the Saudi population.

A multidisciplinary expert panel convened under the auspices of the SHA conducted a comprehensive, non-systematic literature review and developed consensus-based recommendations through iterative discussion and critical appraisal of the evidence.

CKLM syndrome is a progressive multisystem disorder driven by shared mechanisms, including insulin resistance, inflammation, and fibrosis, with bidirectional interactions across cardiovascular, kidney, metabolic, and hepatic domains. A stage-based framework is proposed to support risk stratification and guide management. Therapeutic strategies include agents with established cardiovascular, kidney and metabolic benefits, with emerging evidence supporting combination approaches. The high prevalence and coexistence of CKLM-related conditions in Saudi Arabia highlight the need for integrated care. The CKLM framework extends existing models by incorporating hepatic disease into the cardiometabolic-kidney continuum, enabling a more comprehensive approach to risk assessment and management. Multidisciplinary, stage-based strategies are recommended as they are expected to improve outcomes, although further validation is required.