title: Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients.
abstract: 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.
authors.affiliation: Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA 90509, USA. ebrass@ucla.edu
authors.forename: E P
authors.initials: EP
authors.lastname: Brass
authors.forename: S
authors.initials: S
authors.lastname: Adler
authors.forename: K E
authors.initials: KE
authors.lastname: Sietsema
authors.forename: W R
authors.initials: WR
authors.lastname: Hiatt
authors.forename: A M
authors.initials: AM
authors.lastname: Orlando
authors.forename: A
authors.initials: A
authors.lastname: Amato
mesh_terms: D000328:Adult; D000368:Aged; D002245:Carbon Dioxide / Q000097:blood; D002331:Carnitine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood*; D004311:Double-Blind Method; D005080:Exercise Test; D017079:Exercise Tolerance / Q000502:physiology*; D005221:Fatigue / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010101:Oxygen Consumption; D011788:Quality of Life; D006435:Renal Dialysis
chemical_list: C116917:acylcarnitine; D002245:Carbon Dioxide; D002331:Carnitine