Kidney Disease
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The bottom line of this study is that carnitine is so important for the body, the kidneys are able to recover it back from the urine.

[5-56]

Pharmacokinetics of propionyl-L-carnitine in humans: evidence for saturable tubular reabsorption.

Pace S, Longo A, Toon S, Rolan P, Evans AM.

Sigma Tau Industrie Farmaceutiche Riunite s.p.a., Pomezia, Rome, Italy.

AIMS: Propionyl-L-carnitine (PLC) is an endogenous compound which, along with L-carnitine (LC) and acetyl-L-carnitine (ALC), forms a component of the endogenous carnitine pool in humans and most, if not all, animal species. PLC is currently under investigation for the treatment of peripheral artery disease, and the present study was conducted to assess the pharmacokinetics of intravenous propionyl-L-carnitine hydrochloride. METHODS: This was a placebo-controlled, double-blind, parallel group, dose-escalating study in which 24 healthy males were divided into four groups of six. Four subjects from each group received propionyl-L-carnitine hydrochloride and two received placebo. The doses (1 g, 2 g, 4 g and 8 g) were administered as a constant rate infusion over 2 h and blood and urine were collected for 24 h from the start of the infusion. PLC, ALC and LC in plasma and urine were quantified by h.p. I.e. RESULTS: All 24 subjects successfully completed the study and the infusions were well tolerated. In addition to the expected increase in PLC levels, the plasma concentrations and urinary excretion of LC and ALC also increased above baseline values following intravenous propionyl-L-carnitine hydrochloride administration. At a dose of 1 g, PLC was found to have a mean (+/- s.d.) half-life of 1.09 +/- 0.15 h, a clearance of 11.6 +/- 0.24 I h-1 and a volume of distribution of 18.3 +/-2.4 I. None of these parameters changed with dose. In placebo-treated subjects, endogenous PLC, LC and ALC underwent extensive renal tubular reabsorption, as indicated by renal excretory clearance to GFR ratios of less than 0.1. The renal-excretory clearance of PLC, which was 0.33 +/-0.38 I h-1 under baseline condition, increased (P < 0. 001) from 1.98 +/- 0.59 I h-1 at a dose of 1 g to 5.55 +/- 1.50 I h-1 at a dose of 8 g (95% confidence interval for the difference was 2.18,4.97). As a consequence, the percent of the dose excreted unchanged in urine increased (P < 0.001) from 18.1 +/- 5.5% (1 g) to 50.3 +/- 13.3% (8 g). The renal-excretory clearance of LC and ALC also increased substantially after PLC administration and there was evidence for renal metabolism of PLC to LC and ALC. CONCLUSIONS: Intravenous administration of propionyl-L-carnitine hydrochloride caused significant increases in the renal excretory clearances of PLC, LC and ALC, due to saturation of the renal tubular reabsorption process - as a consequence there was a substantial increase with dose in the fraction excreted unchanged in urine. Despite the marked increase in the renal clearance of PLC, total clearance remained unchanged, suggesting a compensatory reduction in the clearance of the compound by non excretory routes.

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Since carnitine is made in the kidney, those with kidney disease benefit from supplementing it.

[5-11]

Carnitine nutriture of dialysis patients.

Borum PR, Taggart EM.

Hemodialysis patients often experience muscle weakness, cardiac arrhythmias, and hypertriglyceridemia, along with other conditions that may lead to atherosclerosis and coronary heart disease. A contributing factor in the etiology of the symptoms may be carnitine deficiency. Patients undergoing renal dialysis treatment are at risk for developing a carnitine deficiency. The small carnitine molecule can be easily lost into the dialysate. A diseased kidney may lead to a decrease in the endogenous supply of carnitine since the kidney is a major site of carnitine biosynthesis. The diet of dialysis patients may be limiting in preformed carnitine as well as in the precursors and micronutrients required for carnitine biosynthesis. Both oral and intravenous supplementation of L-carnitine have been shown to alleviate muscle weakness, reduce the incidence and severity of arrhythmias, and decrease plasma triglyceride levels, along with alleviating other complications noted in dialysis patients. Health care professionals must be aware of the possible benefits of providing carnitine supplementation for renal dialysis patients.

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Carnitine is approved by the FDA for treatment of those who have kidney disease.

[5-41]

[we need to find the name of this and tidy it up]

Carnitine is an endogenous molecule that serves as a carrier in the transport of long-chain fatty acids across the inner mitochrondrial membrane, facilitating oxidation and energy production. Dialytic losses, combined with reduced renal synthesis and reduced intake of meat and dairy products, can cause carnitine deficiency in end stage renal disease (ESRD) patients. Levocarnitine injection has been approved by the Food and Drug Administration (FDA) for the "prevention and treatment of carnitine deficiency in ESRD patients who are undergoing dialysis. Levocarnitine injection was first approved by the in FDA 1992. The FDA approved the drug's indication for ESRD patients on December 15, 1999. Given inconsistencies among the fiscal intermediaries' local coverage policies for this drug, the Centers for Medicare and Medicaid Services (CMS) believes a national review is appropriate. Among other issues, CMS plans to examine, in this review, the clinical significance of carnitine deficiency and the issue of intravenous administration of carnitine supplementation versus oral administration.