L-carnitine use in dialysis patients: is national coverage for supplementation justified? What were CMS regulators thinking--or were they?
Careful review of all available clinical trials of L-carnitine leads to the conclusion that there is insufficient evidence to support the routine use of L-carnitine for any indication in dialysis patients. The literature suffers from a lack of adequately designed studies, and many of the studies which supposedly justify payment for L-carnitine supplementation are more than 10 years old. While some studies support a subjective improvement in symptoms after a few months of L-carnitine treatment, there is little confirming objective data. Biochemical parameters show minimal, if any, improvements. A major criticism is that many of the reported symptoms could be attributable to anemia, which at the time the L-carnitine studies were taking place, was generally being corrected with EPO. On the other hand, there is little data to support the hypothesis that L-carnitine enhances the response to EPO or overcomes EPO resistance. The decrease in the use of L-carnitine in the past several years may be related in part to difficulty with reimbursement. The decrease also suggests that practitioners have abandoned the hypothesis that L-carnitine supplementation provides substantial clinical benefits, and therefore no longer prescribe it for dialysis patients. For those physicians who plan to prescribe L-carnitine based on the recent CMS reimbursement decision, it must be remembered that the laboratory measurement of free carnitine may be difficult and inaccurate. For those patients with private insurance, payment for the lab test is out of pocket. If the free carnitine level is measured once dialysis starts, a value in the CMS "deficient" range can occur since carnitine drops early in the dialysis procedure and slowly rebounds after the treatment. Therefore, it is critical that the measurement be done pre-dialysis after a three-day interdialytic interval to obtain the most accurate value. If strict guidelines for use of L-carnitine are adhered to (i.e., the patient has true EPO-resistant anemia unexplained by any identifiable factor and true unexplained hypotension), then the use of L-carnitine in ESRD patients should be very uncommon. In conclusion, the clinical value of L-carnitine supplementation in hemodialysis patients remains to be documented by credible evidence from rigorous scientific studies. While "proof beyond a reasonable doubt" need not always be the requirement for reimbursement from payers, at a minimum "a preponderance of the evidence" should be documented in the literature. L-carnitine may prove to be a beneficial supplement. However, before justifying a national coverage policy, a new randomized, prospective controlled trial should be conducted to determine the utility of i.v. L-carnitine supplementation for anemia management and refractory dialysis-associated hypotension. Cost-benefit analysis is a critical aspect of such a study because it is important to determine the total cost (no matter who pays) of L-carnitine supplementation as compared to money saved by a reduction in EPO and iron administration. When reimbursement policies are developed, they need to be rational and based on the best evidence that is available. An NKF Carnitine Consensus Conference concluded that current literature and clinical experience leave unanswered questions regarding the use of L-carnitine in dialysis patients. Until there is scientific evidence to support use of L-carnitine supplementation, and it proves to be cost-effective, reimbursement is not justified. Therefore, the current CMS reimbursement decision for L-carnitine appears to be flawed.