Aging-related skeletal muscle loss on the incidence of chronic kidney disease in patients with metabolic dysfunction-associated steatotic liver disease

Background and aim Metabolic dysfunction–associated steatotic liver disease (MASLD) is an increasingly prevalent metabolic condition closely linked to aging and is associated with an elevated risk of chronic kidney disease (CKD). Sarcopenia, a hallmark of aging, has emerged as a major global health concern; however, its role in the development of CKD among patients with MASLD remains unclear. This study aimed to investigate whether sarcopenia and progressive muscle loss increase CKD risk in patients with MASLD. Methods This cohort included 19,867 MASLD adults without baseline CKD. Sarcopenia was defined using the skeletal muscle mass index (SMI), and muscle change was calculated from baseline to follow-up. MASLD severity was assessed using the fibrosis-4 score. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m². Results Over 124,236 person-years (median 5.6 years), 993 participants developed CKD. In patients with MASLD, the adjusted hazard ratio (aHR) for incident CKD in participants with sarcopenia compared to those without was 1.41 (95% CI: 1.12–1.77). Furthermore, gradual muscle loss was associated with a higher CKD risk, demonstrating a dose-dependent relationship. Participants with progressive muscle loss had an aHR of 1.13 (95% CI: 1.00–1.29) for CKD development compared to those with preserved or increased muscle mass. The risk of CKD also increased with MASLD severity. Conclusion Sarcopenia and progressive muscle loss were independently associated with CKD development in patients with MASLD, with a greater risk observed among those with advanced fibrosis. Assessment of muscle mass and prevention of muscle decline may help identify aging individuals with MASLD who are at increased risk of CKD and potentially delay its onset.