Chronic kidney disease is associated with the loss of skeletal muscle mass and function. This process detrimentally impacts mobility, functional independence, and quality of life. Mounting evidence suggests that chronic kidney disease impairs skeletal muscle functioning by injuring mitochondria, the central energy producing units of cells.

Potential treatment options to restore mitochondrial function include aerobic and weight bearing exercise and medications that directly improve mitochondrial energetics. Unfortunately, exercise programs may be difficult to implement in people who have chronic diseases, such as kidney disease.. Coenzyme Q10 (coQ10) and nicotinamide riboside (NR) are naturally occurring supplements that can directly improve mitochondrial efficiency. Both compounds help mitochondria produce more energy while generating less waste.

The primary purpose of this study is to test whether coQ10 and NR can improve muscle function among people with chronic kidney disease. What we learn in this study may help us better understand the mechanisms of skeletal muscle impairment among people with kidney disease and ultimately improve their ability to be active and independent.

Sarcopenia (decreased muscle mass or function) is common in patients with chronic kidney disease (CKD) patients with direct impacts on their metabolic and clinical outcomes. Existing evidence and the investigator's preliminary data suggest that mitochondrial dysfunction is a key underlying mechanism of sarcopenia in CKD. However, the ability of treatments to modify mitochondrial functioning in CKD patients is unknown. Coenzyme Q10 (coQ10) and nicotinamide riboside (NR) are naturally occurring supplements that reduce oxidative stress and restore substrate delivery to mitochondria, respectively.

Both processes have the potential to increase mitochondrial energy production with direct consequences for many metabolic and physical processes, including:

• aerobic capacity
• work efficiency
• mitochondrial energetics
• fatigue
• physical function
• inflammation
• oxidative stress
• heart failure symptoms
• metabolomics

These outcomes will assessed in all study participants who enroll in the trial. Addressing these knowledge gaps is necessary to shed new light on the pathophysiology of sarcopenia in CKD and suggest future interventions that reduce morbidity and mortality.

This is a randomized, placebo-controlled, double-blind crossover trial of coQ10 and NR treatments. Participants will receive coQ10 (1000 mg daily), NR (1200 mg daily), or placebo each for six-weeks in random order with a 7-day washout between treatment periods. The primary outcomes are aerobic capacity and muscle work efficiency, measured during cycle ergometry.

Inclusion Criteria:

• Chronic kidney disease, defined in this study as an estimated glomerular filtration rate (eGFR) of <50ml/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration equation

Exclusion Criteria:

• 6-minute walking distance >500meters
• Pregnancy
• Receiving renal replacement therapy (dialysis or kidney transplantation)
• Expectation to start dialysis within 6 months
• Insulin dependent diabetes mellitus
• Severe anemia: hemoglobin <8 g/dL
• Hyperkalemia: K >5.7 mEq/L
• Weight >300 lbs
• HIV
• End stage liver disease with cirrhosis
• Oxygen-dependent Chronic Obstructive Pulmonary Disease (COPD)
• Unable to walk unassisted from room to room in own house
• Institutionalization, or inability to consent
• Use of immunosuppressive medications (i.e. steroids, calcineurin inhibitors)
• Malignancy requiring active treatment or currently under surveillance (at the discretion of the investigator)
• Cardiac pacemaker
• Current participation in another interventional trial
• Non-English speaking
• Hospitalization for heart attack, stroke, or unstable cardiac chest pain within the previous 3 months (e.g. myocardial infarction, unstable angina, cerebrovascular accident)
• Any medical condition that the investigator feels would prevent the participant from safely completing the exercise-based outcome measurements.
• Baseline systolic blood pressure >170 or diastolic blood pressure >100
• Persistent or permanent uncontrolled arrhythmia (at the discretion of the investigator)

For each treatment arm, adverse events are reported from the start of the treatment until the next visit (approximately 6 weeks total for each treatment).

Definitions used were consistent with clinicaltrials.gov. At each visit potential adverse events were assessed by participant interview.