What is the role of carnitine (L-carnitine) supplementation in patients with Chronic Kidney Disease (CKD)?

L-Carnitine Supplementation in Chronic Kidney Disease

There is currently insufficient evidence to support the routine use of L-carnitine supplementation for patients with chronic kidney disease (CKD), including those on maintenance dialysis. 1

Pathophysiology and Deficiency in CKD

• L-carnitine is an essential cofactor in fatty acid metabolism and energy production
• CKD patients, particularly those on hemodialysis, are at risk for carnitine deficiency due to:
  • Loss of carnitine during dialysis procedures
  • Reduced dietary intake
  • Impaired endogenous synthesis
• Carnitine deficiency is confirmed by:
  • Acyl-to-free carnitine ratio >0.4 (normal ratio ≤0.25)
  • Total serum carnitine <40 μmol/L 1, 2

Potential Benefits in Select CKD Patients

While routine use is not recommended, L-carnitine may provide benefits in specific clinical scenarios:

• Most promising application: Treatment of erythropoietin-resistant anemia 1, 3
• May improve certain dialysis-related symptoms:
  • Intradialytic muscle cramps and hypotension
  • Malaise and muscle weakness
  • Asthenia (profound fatigue)
  • Cardiomyopathy with reduced ejection fraction 1, 4

Evidence Quality and Limitations

• Current evidence quality is low to moderate 3
• A 2022 Cochrane review found:
  • L-carnitine may slightly improve anemia markers (hemoglobin and hematocrit)
  • Little to no effect on quality of life physical component scores
  • Possible improvement in mental component scores
  • No significant difference in adverse events, muscle cramps, or intradialytic hypotension 3

Clinical Approach to L-Carnitine Use in CKD

1. Do not routinely prescribe L-carnitine for all CKD or dialysis patients
2. Consider a therapeutic trial only when:
   • Patient has specific symptoms mentioned above
   • Standard therapies have failed
   • Laboratory evidence confirms carnitine deficiency
3. If initiating therapy:
   • Intravenous route: 20 mg/kg after each hemodialysis session (typically 3 times weekly)
   • Oral route: 2-4 g daily in divided doses (bioavailability 15-16%) 5, 6
   • Monitor response after 8-12 weeks (trough levels typically reach 190-240 μmol/L) 5

Monitoring and Considerations

• Potential side effects of high-dose therapy (≥3g/day):
  • Gastrointestinal symptoms (nausea, vomiting, abdominal cramps, diarrhea)
  • "Uremic breath" due to accumulation of trimethylamine metabolites 1, 2
• Monitor:
  • Clinical symptoms
  • Hemoglobin/hematocrit if treating anemia
  • Plasma carnitine levels (free and total)

Conclusion

The current guidelines from the National Kidney Foundation and KDOQI do not support routine L-carnitine supplementation in CKD patients. A therapeutic trial may be considered in select patients with specific symptoms who have failed standard therapies, with erythropoietin-resistant anemia being the most promising indication.