Abstract
Acute kidney injury (AKI) causes glucose and protein metabolism abnormalities that result in muscle wasting, thereby affecting the long-term prognosis of critical illness survivors. Here, we examined whether early intervention with treadmill exercise and branched-chain amino acids (BCAA) can prevent AKI-related muscle wasting and reduced physical performance in mice. Unilateral 15 min ischemia-reperfusion injury was induced in contralateral nephrectomized mice, and muscle histological and physiological changes were assessed and compared with those of pair-fed control mice, since AKI causes severe anorexia. Mice exercised for 30 min each day and received oral BCAA for 7 days after AKI insult. By day 7, ischemic AKI significantly decreased wet weight, myofiber cross-sectional area, and central mitochondrial volume density of the anterior tibialis muscle, and significantly reduced maximal exercise time. Regular exercise and BCAA prevented AKI-related muscle wasting and low physical performance by suppressing myostatin and atrogin-1 mRNA upregulation, and restoring reduced phosphorylated Akt and PGC-1α mRNA expression in the muscle. Ischemic AKI induces muscle wasting by accelerating muscle protein degradation and reducing protein synthesis; however, we found that regular exercise and BCAA prevented AKI-related muscle wasting without worsening kidney damage, suggesting that early rehabilitation with nutritional support could prevent AKI-related muscle wasting.