Effects of N-acetylcysteine on Muscle Fatigue in Hemodialysis (NAC)

• change in quadriceps muscle endurance during intermittent submaximal contractions [ Time Frame: 6 days ] [ Designated as safety issue: No ]
• change in exercise-induced markers of oxidative stress [ Time Frame: 8 days ] [ Designated as safety issue: No ]

• change in quadriceps muscle endurance during intermittent submaximal contractions
• change in exercise-induced markers of oxidative stress

The purposes of the study are to determine whether oxidative stress causes the muscle of dialysis patients to tire more quickly than muscle of people without kidney disease and to determine whether treatment with N-acetylcysteine, an antioxidant, can improve muscle endurance.

Muscle dysfunction is a major problem for patients with end-stage renal disease (ESRD). Specifically, these patients experience approximately three-fold greater muscle fatigue of the lower extremities during intermittent submaximal contractions than healthy control subjects. Thus, a treatment that could ameliorate muscle fatigue in this population has the potential to increase endurance during activities of daily living and improve quality of life. Dialysis patients have been shown to have high levels of various markers of oxidative stress, and oxidative stress has been associated with excessive muscle fatigue in other patient populations, but this link has not been established in the ESRD population.

Comparisons: The amount of muscle fatigue during intermittent submaximal quadriceps exercise between dialysis patients and controls will be compared. In addition, the degree of exercise-induced increase in markers of oxidative stress in muscle and in plasma will be compared between dialysis patients and controls and between dialysis patients who have received N-acetylcysteine for 6 days and those who have received placebo capsules.

• End-Stage Renal Disease
• Dialysis
• Hemodialysis

• Dietary Supplement: N-acetylcysteine
  600 mg po bid
• Dietary Supplement: placebo
  bid oral dosing

• Experimental: N-acetylcysteine
  Active
  Intervention: Dietary Supplement: N-acetylcysteine
• Placebo Comparator: placebo
  placebo
  Intervention: Dietary Supplement: placebo

Inclusion Criteria:

• age greater than 18 years
• undergoing hemodialysis for 3 months or more or healthy control without kidney disease

Exclusion Criteria:

• inability to give informed consent
• diagnosis of diabetes mellitus
• musculoskeletal contraindication to exercise
• infection requiring intravenous antibiotics within 2 months
• hospitalization within 2 months
• ingestion of antioxidant supplements within one month
• requirement for systemic anticoagulation
• estimated GFR <60 ml/min/1.73 m2 for healthy controls