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The prevalence of sarcopenia is high in patients with CKD. Furthermore, sarcopenia has been reported to be closely associated with decreased physical activity and mortality. Recently, attention has focused on the secretion of bioactive substances called myokines from skeletal muscle immediately after exercise, which is associated with improved metabolism and increased muscle mass. Irisin, one of the myokines, has been shown to play an important role in maintaining endothelial function. Furthermore, Irisin is known to be decreased in the pathogenesis of CKD, and its level is associated with the severity of atherosclerosis in CKD. In this study, we investigated the role of Irisin in uremic sarcopenia.
In a clinical study, we examined the relationship between serum Irisin and sarcopenia, exercise intensity, and atherosclerosis in 65 hemodialysis patients at our hospital. In vivo study, C57BL/6J mice underwent 5/6 nephrectomy as a CKD model, with or without exercise intervention for 10 weeks. Serum Irisin, FNDC5 (precursor of Irisin) expression in skeletal muscle, serum creatinine, muscle mass, and grip strength were measured, and we evaluated endothelial damage and glomerular sclerosis in renal tissue by PAS staining and glycocalyx staining.
There was a trend toward lower Irisin levels in dialysis patients with lower physical capacity and activity. A similar trend was also observed between Irisin levels and atherosclerosis markers such as ABI and Agatston score. In vivo studies showed significantly decreased FNDC5 expression levels in the skeletal muscle of CKD model mice compared to sham mice. In CKD models, Irisin levels along with the reduction, glomerular endothelial injury, and glomerular stiffness assessed by glycocalyx staining were observed. Exercise intervention not only significantly improved FNDC5 expression and elevated serum Irisin levels in the CKD model mice, but also halted the progression of renal dysfunction by suppressing endothelial damage.
Decreased Irisin levels in CKD may contribute to endothelial damage, resulting in progressive renal failure. Exercise improves Irisin expression and secretion and may have beneficial effects on CKD patients.