Beyond the Muscle–Kidney Paradigm: Liver–Muscle–Kidney Interactions in Rhabdomyolysis

Rhabdomyolysis is classically understood as skeletal muscle injury complicated by myoglobin-mediated acute kidney injury, but this framework does not fully explain the diagnostic and clinical complexity created by liver disease, aminotransferase abnormalities, and multiorgan dysfunction. This narrative review summarizes clinical and experimental evidence on liver, muscle, and kidney interactions in rhabdomyolysis. Relevant studies addressing aminotransferase elevation, liver-related susceptibility to muscle injury, rhabdomyolysis-associated kidney injury, interorgan communication, and shared systemic insults were reviewed. The evidence indicates that aminotransferase elevation in rhabdomyolysis often reflects muscle injury rather than primary hepatic damage, requiring interpretation with serial enzyme trends, liver-specific markers, and clinical context. Liver disease may increase vulnerability to muscle injury and kidney injury through sarcopenia, metabolic disturbance, altered drug handling, and impaired perfusion. Severe rhabdomyolysis may also contribute to hepatic stress through inflammation, heme-related pathways, and AKI-mediated effects, although direct causal evidence remains limited. A liver–muscle–kidney framework may improve integrated assessment, but prospective studies are needed to clarify temporal relationships and validate clinically useful biomarkers.