What is the role of Levocarnitine (L-carnitine) in patients with anuric (end-stage) kidney disease?

From the Guidelines

Levocarnitine supplementation may be considered in patients with anuric kidney disease, particularly those on dialysis, to address symptoms associated with carnitine deficiency, but its routine use is not recommended due to insufficient evidence.

Key Considerations

• Patients with end-stage kidney disease, especially those on dialysis, are at risk of carnitine deficiency due to loss of carnitine during dialysis and possible reductions in dietary intake and endogenous synthesis 1.
• Carnitine deficiency can lead to symptoms such as anemia, cardiomyopathy, muscle weakness, and intradialytic hypotension, which are common in the dialysis population 1.
• While there is limited evidence to support the therapeutic use of supplemental L-carnitine in dialysis patients, a trial of L-carnitine may be indicated in selected individuals with suggestive clinical symptoms and laboratory evidence compatible with a diagnosis of carnitine deficiency, after excluding other causes and standard therapies have been unsuccessful 1.

Dosing and Administration

• For patients on dialysis, a typical starting dose could be considered as 10-20 mg/kg after each dialysis session, which can be titrated based on clinical response and carnitine levels.
• For non-dialysis anuric patients, lower doses may be recommended with careful monitoring.
• Intravenous administration may be preferred for dialysis patients, while oral formulations can be used for maintenance therapy, though they have lower bioavailability.

Monitoring and Safety

• Regular monitoring of carnitine levels is crucial to avoid potential side effects, which may include gastrointestinal disturbances, seizures in susceptible individuals, and a fishy body odor at higher doses.
• The decision to use L-carnitine should be made on a case-by-case basis, considering the individual patient's symptoms, response to standard therapies, and potential risks and benefits of supplementation 1.

From the FDA Drug Label

The safety and efficacy of oral levocarnitine has not been evaluated in patients with renal insufficiency Chronic administration of high doses of oral levocarnitine in patients with severely compromised renal function or in ESRD patients on dialysis may result in accumulation of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), since these metabolites are normally excreted in the urine

The role of Levocarnitine (L-carnitine) in patients with anuric (end-stage) kidney disease is to potentially accumulate toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide (TMAO), due to the kidneys' inability to excrete them, which may be harmful. The safety and efficacy of levocarnitine in patients with renal insufficiency, including those with anuric kidney disease, has not been evaluated 2 3.

From the Research

Role of Levocarnitine in Anuric Kidney Disease

• Levocarnitine is a molecule required in mammalian energy metabolism, helping to maintain normal metabolic functions and facilitating the transport of long-chain fatty acids across the mitochondrial membrane for beta oxidation and subsequent energy production in skeletal muscle and myocardium 4.
• In patients with end-stage renal disease, levocarnitine metabolism is abnormal, with significant dialytic loss of levocarnitine and decreased dietary intake, leading to carnitine deficiency 4, 5.
• Carnitine deficiency in dialysis patients may contribute to several clinical disorders, including erythropoiesis-stimulating agent-resistant anemia, myopathy, muscle weakness, and intradialytic muscle cramps and hypotension 5, 6.
• Levocarnitine administration may replenish free carnitine and help increase carnitine levels in muscle, improving exercise performance, intradialytic muscle cramps and hypotension episodes, and overall well-being in hemodialysis patients 4, 6.
• Studies have shown that L-carnitine supplementation in HD patients improves several complications, including cardiac complications, limitation of exercise capacity, increased intradialytic hypotension, and muscle symptoms, with the most promising results noted in the treatment of erythropoietin-resistant anemia 6.
• A randomized controlled trial found that levocarnitine therapy improved cardiac function in hemodialysis patients with left ventricular hypertrophy, increasing ejection fraction and reducing left ventricular mass index 7.

Potential Benefits of Levocarnitine Supplementation

• Improved exercise performance and overall well-being in hemodialysis patients 4, 6
• Reduced intradialytic muscle cramps and hypotension episodes 4, 6
• Improved cardiac function, including increased ejection fraction and reduced left ventricular mass index 7
• Potential treatment for erythropoietin-resistant anemia 6

Limitations and Controversies

• Despite potential benefits, the use of levocarnitine supplementation in dialysis patients is not universally recommended, with some studies suggesting a lack of scientific justification for its use 8.
• The Centers for Medicare and Medicaid Services (CMS) has established criteria for the use of levocarnitine in end-stage renal disease patients, but these criteria have been criticized for being overly broad and lacking scientific rigor 8.