Effectiveness of L-Carnitine for the Treatment of Erythropoietin-Resistant Renal Anemia: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

OBJECTIVE: Despite its use in the treatment of renal anemia, no adequately controlled studies have examined the impact of L-carnitine administration in the patient population for which it is indicated (i.e., those hyporesponsive to erythropoiesis-stimulating agents [ESAs]). This randomized, double-blind, placebo-controlled pilot study evaluated the potential benefit of L-carnitine supplementation for the treatment of renal anemia in chronic hemodialysis patients who were hyporesponsive to ESA treatment. METHODS: Patients shown to be hyporesponsive to ESA treatment were administered intravenous L-carnitine (10-20 mg/kg/dialysis session) or placebo for 3 months, during which erythropoietin resistance index (ERI) was measured as an indicator of treatment effectiveness. Secondary validation was conducted using an independent dataset. RESULTS: L-carnitine supplementation was associated with a 25% reduction in ERI, significantly greater than that seen in placebo-treated patients (3% reduction). This was supported by a 42% reduction after 6 months of treatment in the validation dataset. Overall, 88% of L-carnitine-treated patients had a clinically significant improvement in ERI, compared to 0% of placebo-treated patients. CONCLUSIONS: These findings provide evidence to support the National Kidney Foundation's practice recommendations with respect to the clinical use of L-carnitine for renal anemia. While the exact mechanism is yet to be elucidated, it is proposed that L-carnitine treatment improves carnitine palmitoyltransferase activity via carnitine pool normalization, thereby resulting in stabilization of the erythrocyte membrane. If this is the case, then it is feasible that a dual approach to increase erythrocyte production and lifespan through co-administration of ESA and L-carnitine provides a viable treatment option for ESA-resistant patients.