Resistance training increases muscle mitochondrial biogenesis in patients with chronic kidney disease

Abstract

Background and objectives: Muscle wasting, a common complication in chronic kidney disease (CKD), contributes to poor outcomes. Mitochondrial biogenesis is critical for the maintenance of skeletal muscle function and structural integrity. The present study--a secondary analysis from a published randomized controlled trial--examined the effect of resistance exercise training on skeletal muscle mitochondrial (mt)DNA copy number and determined its association with skeletal muscle phenotype (muscle mass and strength).

Design, setting, participants, & measurements: Twenty-three patients with moderate-to-severe CKD were randomized to resistance training (n = 13) or an attention-control (n = 10) group for 12 weeks. After a run-in period of a low-protein diet that continued during the intervention, mtDNA copy number in the vastus lateralis muscle was estimated by quantitative real-time PCR at baseline and 12 weeks.

Results: Participants mean age was 64 +/- 10 (SD) years and median (interquartile range, IQR) GFR 27.5 (37.0) ml/min. There were no differences between groups at baseline. Median (IQR) mtDNA copy number was 13,713 (10,618). There was a significant increase in muscle mtDNA with exercise compared with controls (1306 [13306] versus -3747 [15467], P = 0.01). The change in muscle mtDNA copy number was positively correlated with previously reported changes in types I and II muscle fiber cross-sectional area.

Conclusions: In this pilot study, resistance training was highly effective in enhancing mitochondrial content in patients with moderate-to-severe CKD. This finding suggests that the mitochondrial dysfunction observed with chronic disease could potentially be restored with this exercise modality and should be investigated further.

Figure 1.

Flow of patients through the study.

Figure 2.

Box plot showing the relative difference in the distribution of log-transformed skeletal muscle mtDNA copy number between groups at baseline (open bars) and after the 12-week intervention (gray bars). Time × group comparisons of the distribution of log-transformed mtDNA copy number after the intervention was determined by repeated measures ANOVA.

Figure 3.

Univariate associations between the change (week 12 − baseline) in skeletal muscle mtDNA copy number and the changes in type I (r = 0.56, P = 0.01) and type II (r = 0.46, P = 0.05) muscle fiber cross-sectional area are shown for each subject in the resistance-training (squares) and attention-control (triangles) groups. mtDNA was log-transformed for analysis. 19 participants with complete data were included in this analysis (11 from the resistance-training group and 8 from the attention-control group).