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      Carnitine Therapy Is Associated with Decreased Hospital Utilization among Hemodialysis Patients

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          Background/Aims: Hospitalizations account for 41% of the total cost of end-stage renal disease (ESRD) care. Carnitine deficiency is common among dialysis patients, and some studies have shown improvements in anemia, and cardiac and skeletal muscle function upon administration of L-carnitine. We hypothesized that L-carnitine may be associated with decreased hospital utilization in these patients. Methods: The Fresenius Medical Care North America dialysis database was used for this retrospective analysis. Adult patients who received carnitine for at least 3 months, and had at least 3 months of pre-carnitine follow-up were included in the study. Hospitalization and hospital day rates were compared before and during carnitine therapy, and with a matched population. Results: Carnitine therapy at a mean dose of 1.5 ± 0.7 g per administration for an average of 9.7 ± 5.4 months was associated with a significant reduction in hospital utilization. Patients with cardiovascular disease, defined as hospitalizations for angina, myocardial infarction, arrhythmia, congestive heart failure, cerebral vascular disease or peripheral vascular disease prior to receiving carnitine, and those with anemia and hypoalbuminemia derived the greatest benefit from carnitine therapy. In a multivariate analysis, compared to 3 months prior to the initiation of carnitine, the adjusted relative risk for hospitalization was 11, 11, and 15% lower at 3, 6, and 9 months, respectively. Among patients with cardiovascular disease, the reduction in risk was even more significant (24, 31, and 34% lower at 3, 6, and 9 months, respectively). Similar results were observed with adjusted relative risk for hospital days. Conclusion: Administration of L-carnitine to chronic hemodialysis patients is associated with lower hospital utilization.

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          Most cited references 7

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          Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects.

          Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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            Carnitine metabolism and function in humans.

            It is apparent from the foregoing discussion that carnitine plays an essential role in human intermediary metabolism. The question of a dietary requirement for carnitine, particularly for the human infant, is of significant theoretical and practical interest. Aberrant carnitine metabolism resulting from abnormal genetic or acquired conditions may have serious consequences for the affected individual. At present many of the treatment modalities for carnitine deficiency are empirical. Further clarification of the mechanisms by which carnitine depletion is manifest in these conditions is essential for designing treatment programs. Moreover, therapeutic use of carnitine in several human diseases not involving carnitine deficiency per se has been indicated. Before such treatment becomes generally accepted, we must determine precisely the role of this amino acid in the biochemical and physiological events that participate in the pathogenesis of each disease.
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              Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial.

              This study was performed to evaluate the effects of L-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. The L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or L-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or L-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with L-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and end-systolic volumes from admission to 3-, 6- and 12-month evaluation was significantly reduced in the L-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the L-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. L-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event.

                Author and article information

                Am J Nephrol
                American Journal of Nephrology
                S. Karger AG
                April 2005
                18 May 2005
                : 25
                : 2
                : 106-115
                aDivision of Nephrology, Tufts-New England Medical Center, Boston, Mass.; bQuartiles Statistical Consulting, LLC, Atlanta, Ga.; cOchsner Hemodialysis Research Program, New Orleans, La.; dDepartment of Medicine, Medical College of Wisconsin, Milwaukee, Wisc., and eTulane University School of Public Health and Tropical Medicine, New Orleans, La., USA
                84853 Am J Nephrol 2005;25:106–115
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, Tables: 5, References: 22, Pages: 10
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                Original Report: Patient-Oriented, Translational Research


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