Benefits of carnitine treatment
Researchers have shown that carnitine treatment improves response to synthetic erythropoietin, nutritional status, QOL, glucose sensitivity, and, most recently, hospitalization rates. Hurot et al (J Am Soc Nephrol. 2002;13:708-714) conducted a meta-analysis that clearly confirmed the positive effects of carnitine treatment on synthetic erythropoietin dose and on hemoglobin concentrations prior to the use of erythropoietin.
In a study of 113 patients who received either carnitine treatment at 20 mg/kg of body weight per treatment or placebo for six months, Savica et al (J Ren Nutr. 2005;15:225-230) found that patients on carnitine had significantly improved BMI and serum albumin compared with placebo recipients. Additionally, patients who had high C-reactive protein (CRP) levels at baseline experienced significant reductions in CRP levels after six months of treatment compared with the placebo group, which had no improvement. The reduction in inflammation may have contributed to the improvement in nutritional parameters, but more studies will be needed to clarify these findings.
QOL domains, as measured by either the Kidney Disease Questionnaire or the 36-Item Short-Form Health Survey (SF-36) questionnaires, have been shown to improve after treatment with carnitine. Brass et al (Am J Kidney Dis. 2001;37:1018-1028) showed improvements in the fatigue domain of the KQOL during and Steiber et al (J Parenter Enteral Nutr. 2006;30:10-15) showed significant improvements in the domains of role physical, bodily pain, and a trend toward increased physical composite score with carnitine treatment of 20mg/kg of body weight per dialysis session.
An elegant metabolic study by Biolo et al (Nephrol Dial Transplant. 2008;23:991-997) demonstrated the impact of carnitine treatment on insulin sensitivity and protein catabolism. Patients with poor insulin sensitivity in the carnitine group had improved sensitivity as measured by a euglycemic insulin-clamp procedure. Additionally, this study used the stable isotope leucine to demonstrate reduced proteolysis and net protein catabolism with carnitine treatment. This is the first study to demonstrate these effects in HD patients and may explain in part the nutritional improvements observed by Savica et al.
Finally, two recently published studies using data from the Centers for Medicare and Medicaid Services (CMS) and the Fresenius Medical Care North America database to show carnitine treatment reduces hospitalizations. In 2005, Kazmi et al (Am J Nephrol. 2005;25:106-115) found that a mean per-treatment dose of 1.5 g for an average of 9.7 months was associated with a significant reduction in hospital stays. These results were supported by a follow-up analysis by Weinhandl et al (Am J Kidney Dis. 2007;50:803-812), who found that 1g or more of carnitine per treatment for 10 or more dialysis sessions was significantly associated with a decrease in hospitalization days during the subsequent month.
The FDA has approved IV carnitine treatment in HD patients, and CMS will reimburse IV carnitine therapy for the following indications: a plasma free carnitine concentration of less than 40 μmol/L and either erythropoietin-resistant anemia or persistent hypotension on HD that requires intervention and which is unresponsive to all usual management measures and interferes with dialysis. Careful documentation of outcomes from initiation to each evaluation point is key in demonstrating efficacy.
In conclusion, carnitine treatment is safe and has been shown to be effective in improving certain parameters of interest to dialysis providers, such as erythropoietin resistance, insulin sensitivity, QOL, and hospitalization rate.
Dr. Steiber is Coordinator of the Dietetic Internship/Master’s Degree Program at Case Western Reserve University in Cleveland.