Abstract
Background: Muscle wasting is a common complication of Chronic Kidney Disease (CKD) and is clinically important given its strong association with morbidity and mortality in many other chronic conditions. Exercise provides physiological benefits for CKD patients, however the molecular response to exercise remains to be fully determined. We investigated the inflammatory and molecular response to resistance exercise before and after training in these patients.Methods: This is a secondary analysis of a randomized trial that investigated the effect of 8 week progressive resistance training on muscle mass and strength compared to non-exercising controls. A sub-set of the cohort consented to vastus lateralis skeletal muscle biopsies (n = 10 exercise, n = 7 control) in which the inflammatory response (IL-6, IL-15, MCP-1 TNF-α), myogenic (MyoD, myogenin, myostatin), anabolic (P-Akt, P-eEf2) and catabolic events (MuRF-1, MAFbx, 14 kDa, ubiquitin conjugates) and overall levels of oxidative stress have been studied.Results: A large inflammatory response to unaccustomed exercise was seen with IL-6, MCP-1, and TNF-α all significantly elevated from baseline by 53-fold (P < 0.001), 25-fold (P < 0.001), and 4-fold (P < 0.001), respectively. This response was reduced following training with IL-6, MCP-1, and TNF-α elevated non-significantly by 2-fold (P = 0.46), 2.4-fold (P = 0.19), and 2.5-fold (P = 0.06), respectively. In the untrained condition, an acute bout of resistance exercise did not result in increased phosphorylation of Akt (P = 0.84), but this was restored following training (P = 0.01). Neither unaccustomed nor accustomed exercise resulted in a change in myogenin or MyoD mRNA expression (P = 0.88, P = 0.90, respectively). There was no evidence that resistance exercise training created a prolonged oxidative stress response within the muscle, or increased catabolism.Conclusions: Unaccustomed exercise creates a large inflammatory response within the muscle, which is no longer present following a period of training. This indicates that resistance exercise does not provoke a detrimental on-going inflammatory response within the muscle.
Highlights
Patients with Chronic Kidney Disease (CKD) commonly experience muscle wasting which can start early in the disease process impacting upon their quality of life and physical functioning, but there is evidence that it increases their risk of death (Carrero et al, 2008; Isoyama et al, 2014; Harada et al, 2017) as in other chronic diseases (Zhou et al, 2010; Greening et al, 2015)
There is a growing body of evidence demonstrating exercise provides a multitude of benefits for CKD patients including improved physical functioning and exercise tolerance, increased muscle mass, reduced cardiovascular risk and systemic inflammation and improved quality of life, (Castaneda et al, 2001, 2004; Moinuddin and Leehey, 2008; Mustata et al, 2011; Kosmadakis et al, 2012; Baria et al, 2014; Viana et al, 2014; Greenwood et al, 2015) and which is discussed in more depth a recent review (Gould et al, 2014)
Unaccustomed resistance exercise induced a large increase in the expression of a number of inflammatory cytokines within skeletal muscle (Figure 2). 24 h after the first resistance exercise training session IL-6, MCP-1 and TNF-α mRNA expression were all upregulated from baseline by means of 53-fold (P < 0.001), 25-fold (P < 0.001) and 4-fold (P < 0.001), respectively
Summary
Patients with Chronic Kidney Disease (CKD) commonly experience muscle wasting which can start early in the disease process impacting upon their quality of life and physical functioning, but there is evidence that it increases their risk of death (Carrero et al, 2008; Isoyama et al, 2014; Harada et al, 2017) as in other chronic diseases (Zhou et al, 2010; Greening et al, 2015). There is a growing body of evidence demonstrating exercise provides a multitude of benefits for CKD patients including improved physical functioning and exercise tolerance, increased muscle mass, reduced cardiovascular risk and systemic inflammation and improved quality of life, (Castaneda et al, 2001, 2004; Moinuddin and Leehey, 2008; Mustata et al, 2011; Kosmadakis et al, 2012; Baria et al, 2014; Viana et al, 2014; Greenwood et al, 2015) and which is discussed in more depth a recent review (Gould et al, 2014). We investigated the inflammatory and molecular response to resistance exercise before and after training in these patients
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