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 [VO(2max)]) 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 VO(2max) 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 VO(2max) in either study. Because change in VO(2max) 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 VO(2max) (-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. VO(2max) in the primary analysis and other assessed end points were unaffected by
carnitine therapy.