Role of Mitochondrial Dysfunction in the Response to Exercise in Patients With Advance Kidney Disease

221073

Frailty and sarcopenia are modifiable risk factors for morbidity and mortality in patients with ESRD. Exercise is the recommended intervention to prevent frailty and sarcopenia, however, many clinical trials have shown limited clinical improvement in muscle mass and physical function. We propose that mitochondrial dysfunction is one of the deterrents to the effectiveness of the exercise. We plan to evaluate the additive effect of HIIT and CoQ10, a mitochondrial-targeted therapy, on mitochondrial function and physical performance. Understanding the interplay among CoQ10, exercise, and mitochondrial function will identify novel mechanisms to improve the efficiency of exercise. This will also serve to prevent frailty, sarcopenia, and muscle dysfunction in patients with ESRD.

2023-06-01

2027-06-20

2027-10-01

Recruiting

Early phase I

156

Inclusion Criteria: * Subjects age 18 to 75 years * On thrice-weekly chronic hemodialysis for at least 6 months (only applicable for patients with ESRD on maintenance hemodialysis). * Clinically stable, adequately dialyzed (single-pool Kt/V \>1.2) thrice weekly, for at least 3 consecutive months prior to the study (only applicable for patients with ESRD on maintenance hemodialysis) Exclusion Criteria: * Body mass index \> 35 mg/kg2 * History of functional transplant less than 6 months prior to study * Use of immunosuppressive drugs within 1 month prior to study * Active connective tissue disease * Acute infectious disease within 1 month prior to study * AIDS (HIV seropositivity is not an exclusion criterion) * Acute myocardial infarction or cerebrovascular event within 3 months * Uncontrolled blood pressure * New or worsening mitral regurgitation murmur * Hypotension, bradycardia, or tachycardia * Prolonged ongoing (greater than 20 minutes) angina at rest * Angina at rest with transient ST changes greater than 0.05 mV on ECG * Sustained ventricular tachycardia on ECG * Elevated cardiac enzymes (e.g., troponin Tor I greater than 0.1mg/ml) * Advanced liver disease, with a modified Child-Turcotte-Pugh score equal or greater than 10. * Gastrointestinal dysfunction requiring parental nutrition * Active malignancy excluding basal cell carcinoma of the skin * Ejection fraction less than 30% * Pre-dialysis potassium repeatedly higher than 5.5 mmol/L (confirmed on a repeated blood draw) * Anticipated live donor kidney transplant * History of poor adherence to hemodialysis or medical regimen * Inability to provide consent * Subjects with cardiac pacemaker, artificial heart valve, any metallic implant, permanent tattoo, or any retained foreign metallic bodies. * Inability to perform exercise * Contraindication for exercise such as electrolyte abnormalities, uncontrolled arrhythmias, or pulmonary congestion.

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2023-08-01