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

Background

Muscle wasting is a common complication in individuals with chronic kidney disease (CKD) and contributes to reduced physical function and poor clinical outcomes. While exercise is recommended for CKD patients, the molecular responses to different exercise modalities remain poorly understood. This study aimed to investigate the anabolic, catabolic, and myogenic responses of skeletal muscle to aerobic exercise (AE) and combined exercise (CE; aerobic plus resistance) in people with CKD.

Methods

Muscle biopsies were collected from participants in a 12-week randomized controlled trial of supervised exercise training, the ExTRA CKD trial. Samples were obtained at baseline, 24 hours after an initial bout of exercise (untrained), and 24 hours after the final training session (trained). Western blotting and RT-qPCR were used to assess changes in key markers of protein synthesis, degradation, and regeneration. To complement these data, in vitro experiments using mechanically stretched primary skeletal muscle cells from CKD and healthy control donors were used to explore the time course of anabolic signalling.

Results

In vivo , Akt phosphorylation was blunted following unaccustomed CE but significantly upregulated following training, indicating partial restoration of anabolic signalling. No change was observed in response to AE. Myostatin expression was significantly downregulated following both AE and CE in the untrained state, while Pax7 and myogenic gene expression were upregulated only in response to CE after training. In vitro , mechanical stretch induced significant phosphorylation of Akt and p70S6K in both CKD and control cells, with no group difference in Akt response and a trend toward faster return to baseline of p70S6K phosphorylation in CKD cells.

Conclusion

These findings demonstrate that CE, but not AE, induces beneficial anabolic and myogenic responses in skeletal muscle in CKD, and highlight the value of combining in vivo and in vitro models to explore temporal dynamics and mechanistic insight into muscle adaptation.

What was known

• People with CKD often have impaired skeletal muscle responses to exercise, termed anabolic resistance, which may contribute to muscle wasting and poor outcomes.

• Resistance exercise activates anabolic and myogenic pathways in healthy muscle, but the extent of these responses in CKD is unclear.

• Limited studies have compared molecular responses to different exercise modalities in CKD, particularly combining in vivo and in vitro approaches.

This study adds

• Combined aerobic–resistance exercise, but not aerobic exercise alone, restored aspects of anabolic signalling (Akt phosphorylation) in CKD skeletal muscle after training.

• Myogenic gene expression was upregulated following combined exercise but not aerobic exercise, indicating a modality-specific regenerative response.

• In vitro , primary muscle cells from CKD and healthy donors showed similar early anabolic responses to mechanical stretch, though CKD cells may return to baseline more rapidly.

Potential Impact

• Supports inclusion of resistance-based modalities in exercise prescriptions for people with CKD to enhance muscle anabolic and regenerative responses.

• Suggests that exercise prescriptions for CKD should prioritise combined modalities to maximise muscle anabolic and regenerative potential.

• Provides mechanistic evidence to inform tailored exercise interventions aimed at preserving muscle health in CKD patients.