Exercise Training in Chronic Kidney Disease: An Exploration of the Effects on Skeletal Muscle Mass, Function, and the Molecular Responses

Chronic kidney disease (CKD) is a catabolic condition associated with skeletal muscle wasting and dysfunction, both of which have important clinical implications. Exercise interventions are capable of improving physical function and exercise capacity in CKD patients; with those incorporating strength training significantly improve muscle size and strength. This thesis investigated the effects of aerobic only (AE) and combined aerobic and resistance exercise (CE) on skeletal muscle hypertrophy and function, and the molecular responses following acute unaccustomed and accustomed bouts of exercise. The primary hypothesis tested was that CE would result in greater muscle hypertrophy and increases in muscle function in comparison to aerobic AE (Chapter 5), and that this would occur with altered expression of genes and proteins associated with the regulation of muscle mass in CKD (Chapters 6, and 7). Both AE and CE resulted in increased quadriceps muscle volume and strength, however these were substantially greater in those performing CE. Muscle biopsies from participants completing both exercise interventions demonstrated a failure to upregulate p-Akt and mRNA expression of the myogenic regulators following the initial bout of exercise indicating that CKD patients may exhibit an impaired response to the exercise stimulus in the untrained state. This response appears to be restored following 12-weeks of CE but following AE. Moreover, both groups demonstrated a substantial increase in the gene expression of inflammatory cytokines following unaccustomed exercise, however this was not observed following accustomed exercise. This thesis demonstrates that CE produces superior increases in muscle size and strength compared to AE alone. This appears to occur through the modulation of intramuscular pathways following regular exercise and therefore highlights the importance of incorporating regular resistance exercise into exercise interventions aiming to improve muscle dysfunction in CKD.