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, 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; < 0.001) and 12 months, 16.2 (95% CI, 10.721.7; P < 0.001). The exercise group 12-month muscle fiber diameter increased by 18.6 mu m (95% CI, 8.4-28.5; P = 0.003). Expression immunohistology markers of muscle atrophy decreased significantly. The mean difference 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; < 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 experimental participants. Conclusions: One year of muscle rehabilitation therapy resulted in significant improvements physical performance metrics accompanied by significant improvements in muscle morphology.