# Role of Mitochondrial Dysfunction in the Response to Exercise in Patients with Advanced Kidney Disease

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $658,388

## Abstract

Project Summary
 End-stage renal disease (ESRD), the final stage of chronic kidney disease (CKD), requires renal
replacement therapy such as hemodialysis. Every year more than 100,000 individuals start hemodialysis.
Patients undergoing hemodialysis are at increased risk of frailty and sarcopenia. Frailty is a multisystem
impairment associated with vulnerability to stressors, and it is characterized by the presence of unintentional
weight loss, self-reported exhaustion or fatigue, measured muscle weakness, slow walking speed, and low
physical activity. Sarcopenia, defined as a reduction of muscle mass and/or muscle strength, is one of the
components of the frailty phenotype. In the general population, physical exercise prevents the loss of muscle
mass and improves frailty status. In patients with ESRD, however, exercise is not as effective as in the general
population. Mitochondria are essential for proper muscle function, and recent studies suggest that
mitochondrial dysfunction contributes to the reduction in muscle mass. We and others have found that
mitochondrial abnormalities and decreased mitochondrial content are present in patients with ESRD. The
number of mitochondria depends on the balance between biogenesis (generation of new mitochondria) and
mitophagy (degradation of mitochondria). Physical exercise improves mitochondrial function and increases the
mitochondrial number in skeletal muscle in the general population. But the benefits of exercise on
mitochondrial function in patients with ESRD have not been studied.
 In this study, we will evaluate the overarching hypothesis that mitochondrial dysfunction hinders the
beneficial effects of exercise in patients with ESRD. Thus, in Specific Aim 1, we will test the hypothesis
that Coenzyme Q10, a mitochondrial-targeted therapy, improves muscle adaptation to exercise training in
patients with ESRD. For this aim, patients with ESRD will be enrolled in a 12-week exercise program or in an
observational group. Patients will also receive either Coenzyme Q10 supplementation or placebo. As a result,
patients will be assigned to four different groups, exercise plus placebo, exercise plus Coenzyme Q10,
observational plus placebo, observational plus Coenzyme Q10. This study design will allow us to evaluate the
individual effect of the interventions and the additive effect of the interventions. We anticipate that the
combination of exercise and Coenzyme Q10 will have an additive effect in improving and mitochondrial function
and physical performance in patients with ESRD. In Specific Aim 2 we will test the hypothesis that the
combination of exercise training and Coenzyme Q10 improves mitochondrial function in patients with ESRD by
increasing mitochondrial respiration and content, and improving mitochondrial dynamics (i.e., remodeling
through fission and fusion). Therefore, we will measure mitochondrial respiration and markers of mitochondrial
biogenesis and dynamics in muscle biopsies within a sub-group ...

## Key facts

- **NIH application ID:** 10491308
- **Project number:** 5R01DK125794-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jorge Luis Gamboa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $658,388
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491308

## Citation

> US National Institutes of Health, RePORTER application 10491308, Role of Mitochondrial Dysfunction in the Response to Exercise in Patients with Advanced Kidney Disease (5R01DK125794-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10491308. Licensed CC0.

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