Carnitine, 3-hydroxy-4-N-trimethylammoniobutanoate, is a small, water soluble molecule found in most cells of the body.
The renal community has given much attention to this important molecule, but as yet there is no consensus on whether carnitine treatment improves outcomes in hemodialysis (HD) patients.
Early work done in the 1980s tested a variety of hypotheses and various studies have examined the effect of carnitine in HD patients. While some studies, such as those conducted by Labonia et al (Am J Kidney Dis.1995;26:757-764) and Kletzmayr et al (Kidney Int. Suppl. 1999;69:S93-106), clearly showed clinical benefits, some studies were not as clear, such as a study conducted by Sloan et al (Am J Kidney Dis. 1998;32:265-272). Recently published work, however, provides provocative data suggesting that HD patients can benefit from carnitine treatment.
Altered carnitine status
Altered carnitine status, sometimes referred to as dialysis-related carnitine disorder or deficiency, is a multi-factorial issue in CKD. Carnitine is a small compound (molecular weight 162D), so it is easily removed by the dialysis process. Initially, researchers believed dialysis itself caused a deficiency in patients, but pharmacological studies by Evans et al (Clin Pharmacol Ther. 2000:68:238-249) showed that the cause of altered carnitine was more complicated than originally thought. In healthy individuals, 99% of free carnitine (carnitine not bound to fatty acids) is reabsorbed by the kidneys and acylcarnitine is excreted at a rate of less than 5 μmol/kg/day or approximately 2,800 μmol/week.
In an HD patient, both free carnitine and acylcarnitine are lost in the dialysate at approximately the same rate. Therefore, the ratio of free carnitine to acylcarnitine is altered. The ratio of plasma-free carnitine to plasma acylcarnitine in HD patients is high, which indicates a reduction in free carnitine concentrations (Clin Nutr. 2004;23:27-34). Interestingly, some research shows that long-term supplementation does not appear to correct the ratio even while it is effective in improving serum values and quality of life (QOL) parameters.
Other ways in which carnitine status may be altered include low dietary intake and decreased synthesis by the body, but neither of these has been proven to be a primary etiology of altered carnitine status in HD patients.
Whatever the cause, it is clear that carnitine concentrations are altered in HD patients. Studies involving HD patients have shown that, compared with healthy patients, mean free carnitine concentrations are lower and acylcarnitine concentrations are higher.