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Abstract
Among the homeostatic processes controlling the endogenous L-carnitine pool in humans,
the kidney has a vital role through extensive and adaptive tubular reabsorption. Kidney
disease can lead to disturbances in L-carnitine homeostasis, and long-term hemodialysis
therapy can lead to a significant reduction in plasma and tissue L-carnitine levels
and an increase in the ratio of acyl-L-carnitine to free L-carnitine. These alterations
may interfere with the oxidation of fatty acids and removal from tissues of unwanted
short-chain acyl groups. A dialysis-related carnitine disorder (DCD) arises when these
biochemical abnormalities exist in association with such clinical symptoms as muscle
weakness, cardiomyopathy, intradialytic hypotension, or anemia that is resistant to
erythropoietin therapy. Exogenous L-carnitine, administered intravenously, is approved
for the treatment of secondary carnitine deficiency caused by long-term hemodialysis.
Although intravenous administration of 20-mg/kg doses at the end of each hemodialysis
session leads to supraphysiological levels of the compound in plasma, these levels
do not appear to be associated with adverse effects. Because more than 99% of the
body's carnitine pool is located outside of plasma, supraphysiological plasma levels
appear to be required to ensure that depleted muscle stores can be replenished. Although
oral L-carnitine has been used for the treatment of DCD, the bioavailability of oral
L-carnitine is low (<15%) in healthy subjects and unknown in patients with end-stage
renal disease. Moreover, gastrointestinal degradation of L-carnitine to trimethylamine
and other compounds might limit the usefulness of long-term oral L-carnitine administration
in this patient group.