Debate Forum: Levocarnitine Therapy Is Rational and Justified in Selected Dialysis Patients

Abstract

Carnitine is a metabolic cofactor which is essential for normal fatty acid metabolism. Patients with chronic kidney disease on dialysis have been shown both to suffer from disordered fatty acid metabolism and to have a significant deficiency in plasma and tissue carnitine. Aberrant fatty acid metabolism has been associated with a number of cellular abnormalities such as increased mitochondrial permeability (a promoter of apoptosis), insulin resistance, and enhanced generation of free radicals. These cellular abnormalities have, in turn, been correlated with pathological clinical conditions common in dialysis patients including cardiomyopathy with attendant hypotension and resistance to the therapeutic effect of recombinant human erythropoietin (EPO). In 1999, the Food and Drug Administration approved levocarnitine injection for the prevention and treatment of carnitine deficiency in patients on dialysis based on documentation of free plasma carnitine levels in dialysis patients similar to other serious carnitine deficiency states for which treatment was required. Data analysis performed by expert panels convened by both the American Association of Kidney Patients and, subsequently, the National Kidney Foundation recommended a trial of levocarnitine therapy for specific subsets of dialysis patients including those with EPO resistance, dialysis-related hypotension, cardiomyopathy and muscle weakness. In 2003, the Centers for Medicare and Medicaid services convened a Medical Advisory Committee which established reimbursement on a national level for carnitine-deficient dialysis patients who had either dialysis-related hypotension or EPO resistance. Recently, a correlation between reductions in hospitalization rates of dialysis patients receiving levocarnitine therapy has been demonstrated in a large retrospective study. Despite data-based recommendations and national reimbursement, only a small minority of dialysis patients have been prescribed a therapeutic trial of levocarnitine. Whereas the reasons for the reluctance of nephrologists to prescribe this therapeutic trial are unclear, possible explanations include a lack of appreciation of the pivotal role played by carnitine in cellular metabolism and the strength of evidence for a substantial deficiency of carnitine in dialysis patients, an underestimation of the prognostic import of EPO resistance and dialysis-related hypotension, inadequate dissemination of the clinical trial data supporting the use of levocarnitine in dialysis patients, and the heterogeneous clinical response of dialysis patients to levocarnitine therapy. Difficulties in documenting both initial eligibility and evidence of improvement as a result of therapy may also be a contributing factor. This paper discusses the biological role of carnitine and its particular relevance to dialysis patients. Clinical trial data concerning an effect of therapy on EPO resistance and dialysis-related hypotension are summarized along with a discussion of the logic behind the use of levocarnitine in dialysis. Fin...

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis

“…To date, most clinical practice guidelines do not recommend routine carnitine supplementation in uremic patients [3,6,7]. However, carnitine supplementation is often recommended in symptomatic dialysis patients who do not respond to standard therapy [3,8].…”

Clinical significance of different carnitine levels for improving the prognosis of patients undergoing hemodialysis

“…Repeated dialysis treatment over an extended period results in a deficiency of tissue carnitine. 9 Carnitine insufficiency in patients on long-term HD affects dialysis-related symptoms such as skeletal myopathy, cardiomyopathy, poor exercise performance, anemia, and dialytic complications, such as hypotension, cramps, weakness, and fatigue, 10,11 which decrease dialysis tolerance and reduce the long-term survival rate. Consequently, carnitine therapy has been used and extensively studied in patients with ESRD.…”

Long-Term Effects of Oral <smlcap>L</smlcap>-Carnitine Supplementation on Anemia in Chronic Hemodialysis

“…However, several studies could not demonstrate the beneficial effect of LC on renal anemia [11,12,13]. Thus, the therapeutic role of LC in the anemia of chronic hemodialysis patients is still debated [4,6,7,8,9,10]. …”

“…Although the possibility of the improvement of renal anemia has been emphasized by means of LC supplementation, the results of clinical trials were conflicting [4,6,7,8,9,10]. This is an open observational study to evaluate the long-term effects of LC on renal anemia.…”