Effect of L-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis.
BACKGROUND
The current study was performed to investigate the kinetics of carnitine, individual acylcarnitines and butyrobetaine in patients on haemodialysis.


METHODS
Eight stable long-term haemodialysis patients were studied under basal conditions (no carnitine supplementation) and 3 weeks after intravenous supplementation with l-carnitine (10 or 20 mg/kg body weight) after each haemodialysis session. The kinetic studies included serial determinations of carnitine and metabolites just before, during or between haemodialysis sessions. Analysis was performed by liquid chromatography-tandem mass spectrometry.


RESULTS
Before haemodialysis, the plasma concentrations were (micromol/l) 15.1+/-0.6 (mean+/-SEM) for carnitine, 5.9+/-0.7 for acetylcarnitine, 0.66+/-0.04 for propionylcarnitine and 0.98+/-0.08 for butyrobetaine (basal conditions) or 142+/-23 for carnitine, 69+/-12 for acetylcarnitine, 6.0+/-1.1 for propionylcarnitine and 2.6+/-0.3 for butyrobetaine (carnitine 20 mg/kg). During haemodialysis, the plasma concentrations dropped by approximately 80% for all compounds determined, with extraction coefficients ranging from 0.65 to 0.86. In patients supplemented with 20 mg/kg carnitine, the amount of carnitine removed by haemodialysis equalled 42% of the dose administered, consisting of 2.08 mmol carnitine, 1.03 mmol acetylcarnitine and 0.051 mmol propionylcarnitine. Between the haemodialysis sessions, carnitine, acylcarnitines and butyrobetaine reached apparent steady-state concentrations within 1 day both under basal conditions and after supplementation.


CONCLUSIONS
Patients on haemodialysis have reduced carnitine, acylcarnitine and butyrobetaine plasma levels, which can be increased by supplementing carnitine. Propionylcarnitine, an important constituent of the acylcarnitine pool, can be removed by haemodialysis. Removal of potentially toxic acyl-groups may represent a mechanism for a beneficial effect of carnitine in these patients.
Vernez
Laurence
L
Division of Clinical Pharmacology and Toxicology and Department of Research, University Hospital, Basel, Switzerland.
Dickenmann
Michael
M
Steiger
Jürg
J
Wenk
Markus
M
Krähenbühl
Stephan
S
D000328:Adult; D000368:Aged; D001622:Betaine / Q000031:analogs & derivatives* / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013997:Time Factors
C116917:acylcarnitine; D001622:Betaine; C002889:gamma-butyrobetaine; D002331:Carnitine