Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients

Exercise capacity in patients with end-stage renal disease (ESRD) remains impaired despite correction of anemia. Carnitine insufficiency may contribute to impaired exercise and functional capacities in patients with ESRD. Two randomized placebo-controlled trials were conducted to test whether intravenous L-carnitine improves exercise capacity (assessed by maximal rate of oxygen consumption [VO2max]) and quality of life (measured by the Kidney Disease Questionnaire [KDQ]) in patients with ESRD. In study A, patients were administered L-carnitine, 20 mg/kg (n = 28), or placebo (n = 28) intravenously at the conclusion of each thrice-weekly dialysis session for 24 weeks. In study B, a dose-ranging study, patients were administered intravenous L-carnitine, 10 mg/kg (n = 32), 20 mg/kg (n = 30), or 40 mg/kg (n = 32), or placebo (n = 33) as in study A. The prospective primary statistical analysis evaluated changes in VO2max in each study and specified that changes in the KDQ were assessed only in the combined populations. L-Carnitine supplementation increased plasma carnitine concentrations, but did not affect VO2max in either study. Because change in VO2max showed significant heterogeneity, a secondary analysis using a mixture of linear models approach on the combined study populations was performed. L-Carnitine therapy (combined all doses) was associated with a statistically significant smaller deterioration in VO2max (-0.88 +/- 0.26 versus -0.05 +/- 0.19 mL/kg/min, placebo versus L-carnitine, respectively; P = 0.009). L-Carnitine significantly improved the fatigue domain of the KDQ after 12 (P = 0.01) and 24 weeks (P = 0.03) of treatment compared with placebo using the primary analysis but did not significantly affect the total score (P = 0.10) or other domains of the instrument (P > 0.11). Carnitine was well tolerated, and no drug-related adverse effects were identified. Intravenous L-carnitine treatment increased plasma carnitine concentrations, improved patient-assessed fatigue, and may prevent the decline in peak exercise capacity in hemodialysis patients. VO2max in the primary analysis and other assessed end points were unaffected by carnitine therapy. (C) 2001 by the National Kidney Foundation, Inc.