Friday, August 15, 2025 8/15/2025

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

Award Number: R01DK125794
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2026

Group Awards By:

View Award Description

Role of Mitochondrial Dysfunction in the Response to Exercise in Patients with Advanced Kidney Disease - 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 of patients from Specific Aim 1. Results from these studies could affect millions of people with ESRD by improving physical function and their quality of life.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $646,866 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	8/6/2025	NON-COMPETING CONTINUATION	$646,866
2025	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	6/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $646,866

Issue Date FY: 2024 ( Subtotal = $623,768 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	7/17/2024	NON-COMPETING CONTINUATION	$623,768
														Subtotal = $623,768

Issue Date FY: 2023 ( Subtotal = $641,529 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/23/2023	NON-COMPETING CONTINUATION	$641,529
														Subtotal = $641,529

Issue Date FY: 2022 ( Subtotal = $658,388 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/17/2022	NON-COMPETING CONTINUATION	$658,388
														Subtotal = $658,388

Issue Date FY: 2021 ( Subtotal = $692,926 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	9/20/2021	NEW	$692,926
														Subtotal = $692,926

Grand Total All Awards = $3,263,477

Top

All Categories

About

Search

Reports

Data Submission

Award Information

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

Award Number: R01DK125794

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer