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Resistance-Based Muscle Therapy, Frailty, and Muscle Biopsy Findings in Kidney Transplant Candidates: A Clinical
Stephen T Bartlett1, Ilaria Santi1, Greg Hachaj1
1Department of Surgery, College of Medicine.
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.
Insights
Frailty in kidney transplant candidates can be reversed with a year of resistance-based muscle therapy. This intervention significantly improved physical function and muscle morphology, offering a potential strategy to combat frailty in this population.
Area of Science:
- Nephrology
- Gerontology
- Exercise Physiology
Background:
- Frailty is a significant predictor of poor outcomes, including morbidity and mortality, in kidney transplant recipients.
- Muscle dysfunction and morphological changes are hypothesized contributors to frailty in this patient group.
- Targeting muscle health may offer a reversible pathway to mitigate frailty.
Purpose of the Study:
- To investigate the reversibility of frailty in kidney transplant candidates.
- To assess the impact of a targeted resistance-based muscle therapy program on physical performance and muscle morphology.
- To determine if frailty in this population can be improved through specific muscle interventions.
Main Methods:
- A randomized clinical trial involving kidney transplant candidates.
- Participants underwent a supervised, resistance-based muscle therapy program for 1 hour, twice weekly, for 1 year.
- Outcomes were measured using the Short Physical Performance Battery, gait speed, grip strength, sit-to-stand tests, surveys, and muscle biopsies.
Main Results:
- The exercise intervention group showed significant improvements in the Short Physical Performance Battery, grip strength, and sit-to-stand tests.
- Muscle biopsies revealed increased muscle fiber diameter and improved markers of mitochondrial oxidative function.
- Control participants demonstrated no significant improvements in physical performance or muscle histology.
Conclusions:
- A one-year muscle rehabilitation therapy program significantly enhanced physical performance metrics in kidney transplant candidates.
- The therapy also led to significant improvements in muscle morphology, including increased fiber diameter and enhanced mitochondrial function.
- Resistance-based exercise is a viable strategy to reverse frailty and improve muscle health in kidney transplant candidates.
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