Resistance-Based Muscle Therapy, Frailty, and Muscle Biopsy Findings in Kidney Transplant Candidates: A Clinical Trial

Rationale & Objective

Frailty is associated with increased morbidity and mortality in kidney transplant recipients. We hypothesized that frailty may be attributable to diminished muscle function associated with muscle morphologic changes. This trial in kidney transplant candidates tested the reversibility of frailty by specifically targeting the affected major muscle groups.

Study Design

Randomized clinical trial.

Setting & Participants

Kidney transplant candidates.

Exposure

Supervised, resistance-based muscle therapy program delivered for 1 hour, 2 times per week for 1 year.

Outcomes

Baseline, 6-month, and 12-month Short Physical Performance Battery, gait speed, grip strength, sit-to-stand in 30 s, 36-item Short Form Survey, Patient-Reported Outcomes Measurement Information System-29, and muscle biopsy light and electron microscopy and immunohistochemistry.

Analytic Approach

Paired 2-tailed t test, 1-way repeated measures analysis of variance.

Results

Twenty-nine participants (mean age, 55 years; female, 55%; African American, 65%) were analyzed: 23 intervention and 6 control. Exercise intervention participants had significant improvements in Short Physical Performance Battery, baseline 5.2 (95% CI, 3.6-6.7) versus 6 months, 6.9 (95% CI, 5.2-8.5; P < 0.001) and 12 months, 7.2 (95% CI, 5.6-8.8; P < 0.001); baseline hand grip, 14.3 kg (95% CI, 10.3-18.4) versus 6 months, 16.9 kg (95% CI, 13.1-20.8; P < 0.05) and 12 months, 17.4 kg (95% CI, 13.9-21.0; P < 0.05); and baseline sit-to-stand in 30 s, 8.0 (95% CI, 3.8-12.2) versus 6 months, 12.7 (95% CI, 8.2-17.1; P < 0.001) and 12 months, 16.2 (95% CI, 10.7-21.7; P < 0.001). The exercise group 12-month muscle fiber diameter increased by 18.6 μm (95% CI, 8.4-28.5; P = 0.003). Expression of immunohistology markers of muscle atrophy decreased significantly. The mean difference in immunohistology score of mitochondrial oxidative function improved for cytochrome c oxidase complex IV, 1.00 (95% CI, 0.71-1.29; P < 0.001) and ATP5I increased by 0.74 (95% CI, 0.49-0.99; P < 0.001). Increased mitochondrial count did not achieve statistical significance (P = 0.096). Controls showed no improvement in either physical performance or histology.

Limitations

Significant under-enrollment in the control group required a paired t test analysis of experimental participants.

Conclusions

One year of muscle rehabilitation therapy resulted in significant improvements in physical performance metrics accompanied by significant improvements in muscle morphology.

Plain Language Summary

Dialysis patients often develop muscle weakness and frailty that adversely impacts candidacy for and the results of kidney transplantation. Muscle rehabilitative therapy was tested in a randomized, controlled clinical trial in potential kidney transplant recipients. After 1 year of therapy, patients who exercised had marked improvements in muscle strength, walking speed, and self-assessed improvements in several domains of health and wellness; those outcomes did not improve in control patients. Muscle biopsies performed in exercise patients showed enlarged muscle fibers and evidence of improved muscle metabolism along with markedly decreased biological markers of muscle atrophy. Muscle rehabilitative therapy dramatically improved perceptions of health, objective measurements of strength, and the microscopic appearance of muscle tissue in kidney transplant candidates.