Anabolic and catabolic responses to different modes of exercise in patients with chronic kidney disease

Background: Muscle wasting is a common in chronic kidney disease (CKD), contributing to impaired function and poor outcomes. Exercise is recommended, but the molecular responses of skeletal muscle to different exercise modalities remain unclear. This study examined anabolic, catabolic, and myogenic responses to aerobic exercise (AE) versus combined exercise (CE; aerobic plus resistance) in CKD. Methods: Muscle biopsies were collected from participants in a 12-week randomized controlled trial (the ExTra CKD trial) at baseline, 24 hours after initial exercise bout (untrained), and 24 hours after the final session (trained). Western blotting and RT-qPCR assessed markers of protein synthesis, degradation, and regeneration. Complementary in vitro experiments used mechanically stretched primary skeletal muscle cells from CKD patients and healthy controls to investigate the temporal dynamics of anabolic signalling. Results AE did not alter Akt phosphorylation. CE showed no acute effect before training but significantly increased Akt phosphorylation after training, indicating partial restoration of anabolic signalling. CE also upregulated myogenic markers (Pax7, MyoD) and reduced acute catabolic responses, whereas AE effects were minimal. Myostatin was downregulated by AE at both time points, while CE shifted from suppression before training to elevation afterwards. Conclusion: CE, but not AE alone, elicits beneficial anabolic and myogenic adaptations in skeletal in CKD. Combining in vivo and in vitro approaches offers deeper mechanistic insight into exercise-induced molecular adaptations and highlights the importance of including resistance training to overcome anabolic resistance in this population.