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Kidney Week

Abstract: SA-PO572

Roles of Irisin, a Myokine on Uremic Sarcopenia

Session Information

Category: Dialysis

  • 801 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Okuma, Teruyuki, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Ueda, Seiji, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Nagasawa, Hajime, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Otsuka, Tomoyuki, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Suzuki, Yusuke, Juntendo Daigaku, Bunkyo-ku, Tokyo, Japan
Background

The prevalence of sarcopenia is high in patients with CKD. Further, sarcopenia is reported to be closely associated not only with reduced physical activity but also with mortality. Recently, it has been noticed that skeletal muscles immediately after exercise secrete bioactive substances called myokines, which are associated with metabolic improvement and muscle mass increase. Irisin, one of the myokines, has been found to play an important role in the maintenance of endothelial function, thus contributing to the development of atherosclerotic vascular diseases. Furthermore, Irisin is known to be decreased in CKD condition and its levels are associated with the severity of atherosclerosis, possibly contributing to the increase in cardiovascular complications in CKD. In this study, we investigated the role of Irisin in uremic sarcopenia.

Methods

In the clinical study, we examined the relationship between serum Irisin and sarcopenia, exercise intensity, and atherosclerosis in 65 hemodialysis patients in our hospital. In vivo study, we performed 5/6 nephrectomy on C57BL/6J mice as a CKD model, and the exercise group received an exercise intervention for 10 weeks. We measured serum Irisin, the expression levels of FNDC5 (a precursor of Irisin) in skeletal muscle, serum creatinine, muscle mass, and grip strength, and evaluated renal lesions, especially endothelial damage by PAS staining and glycocalyx staining.

Results

In dialysis patients, Irisin levels tended to be lower in the patients with low physical performance/activity. The same tendency was also found between Irisin levels and the markers of atherosclerosis such as ABI or Agatston score. In vivo study, the expression levels of FNDC5 were significantly decreased in the skeletal muscle of CKD model mice compared to sham mice. Along with decreased Irisin levels, glomerular endothelial injury assessed by glycocalyx staining and glomerular sclerosis was observed in the CKD model. Exercise intervention significantly not only ameliorated FNDC5 expression and increased serum Irisin levels but also halted progressive renal dysfunction by inhibiting endothelial damage in CKD model mice.

Conclusion

These observations suggest that impaired Irisin release could be a culprit for CVD in CKD, which could be restored by exercise training.