This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Steiber, A. L. Articles by Weatherspoon, L. J. Search for Related Content PubMed PubMed Citation Articles by Steiber, A. L. Articles by Weatherspoon, L. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Dialysis Kidney Failure Social Bookmarking                   What's this?

Carnitine Treatment Improved Quality-of-Life Measure in a Sample of Midwestern Hemodialysis Patients

Alison L. Steiber, PhD, RD, LD^*,, Alan T. Davis, PhD, Leslie Spry, MD, Jennifer Strong, MS, RD, Mary Lou Buss, MSW, Michelle M. Ratkiewicz, BS^|| and Lorraine J. Weatherspoon, PhD, RD

From the ^* Department of Nutrition, Case Western Reserve University, Cleveland, Ohio; Human Nutrition and Food Science, Michigan State University, East Lansing, Michigan; Departments of Surgery, Michigan State University and Spectrum Health, Grand Rapids, Michigan; Dialysis Center of Lincoln, Lincoln, Nebraska; and the ^|| School of Osteopathic Medicine, Michigan State University, East Lansing, Michigan

Correspondence: Alison L. Steiber, PhD, RD, LD, Department of Nutrition, Case Western Reserve University, Dental Bldg, Room 201, 10900 Euclid Ave, Cleveland, OH 44106. Electronic mail may be sent to Alison.steiber{at}case.edu.

Background: Previously, we demonstrated that selected groups of hemodialysis patients might be more likely to have abnormalities of carnitine metabolism. The purpose of the present study was to examine the effects of carnitine therapy in these selected groups of hemodialysis patients on quality-of-life measures and erythropoietin dose. Methods: This was a double-blind, randomized, controlled trial, in which 50 hemodialysis patients were treated with either 2 g IV carnitine or placebo. The treatment period was for 24 weeks. Results: Thirty-four patients (15 in the treatment group) completed the study. The mean age was 69 ± 15 years, 35% were women, and 44% had diabetes. Mean initial plasma total, free, short-chain acyl and long-chain acyl carnitine concentrations (µmol/L; mean ± SEM) were 35.9 ± 1.8, 18.2 ± 1.1, 11.6 ± 0.6, and 6.0 ± 0.3, whereas the plasma acyl-to-free-carnitine ratio was 1.02 ± 0.05. With respect to the Medical Outcomes Short Form-36 (SF-36), improvements from baseline were noted in the treatment group (n = 13) for role-physical (33.9 ± 1.9 to 43.2 ± 3.0, p < .05) and the SF-36 physical component summary score (36.1 ± 2.7 to 39.7 ± 2.3, p = .09) relative to changes in the control group (n = 14). The erythropoietin dose over the 24-week period was reduced from baseline in the treatment group relative to the placebo group (–1.62 ± 0.91 vs 1.33 ± 0.79 units erythropoietin/dry weight/hemoglobin concentration, respectively, p < .05). Conclusions: After 24 weeks of IV carnitine therapy, SF-36 scores were improved and erythropoietin doses were reduced in hemodialysis patients, relative to the control group.

L-carnitine is a compound found in high-protein foods and is produced by the liver, kidney, and brain. The metabolic functions of carnitine are to transport fatty acyl-Coenzyme A (CoA) into the mitochondrial matrix, export products of β-oxidation from peroxisomes, and release mitochondrial CoA from acyl-CoA when free CoA supplies are limited. Research has demonstrated altered free and acylcarnitine concentrations in patients receiving hemodialysis treatment.^1–3

Recently, L-carnitine treatment was approved by the Centers for Medicare & Medicaid Services (CMS) for national reimbursement in hemodialysis patients with either erythropoietin resistance or chronic hypotensive episodes during dialysis treatment. After the establishment of the CMS reimbursement policy, a carnitine consensus group performed a thorough review of the existing literature and determined that there were 4 main types of symptoms that may accompany altered carnitine metabolism in dialysis patients: anemia hyporesponsive to synthetic erythropoietin, intradialytic hypotension, cardiomyopathy, and skeletal muscle weakness.⁴ The current title for this set of symptoms is "dialysis-related carnitine disorder" (DCD).

The mechanism for DCD has yet to be determined and in fact is probably multifactorial. Research has been done to suggest that the alteration of carnitine may occur before dialysis is initiated^5,6 and therefore may be due to dietary intake or uremia itself. High-protein foods containing increased amounts of carnitine are often restricted in the diets of patients with renal insufficiency to preserve kidney function and decrease uremic side effects. Uremia has been shown to alter fatty acid⁷ and amino acid⁸ composition in chronic kidney disease patients. Therefore, uremia may alter the type (free or acylated), the use, or the function of carnitine.

L-carnitine treatment in chronic kidney disease patients has been shown to improve red blood cell membrane functions by increasing the activity of sodium transport⁹ and improving membrane fragility.¹⁰ Improvement in red blood cell functions may increase red blood cell half-life and thereby decrease erythropoietin requirements. Additionally, muscle cells have benefited from L-carnitine treatment,¹¹ which, when combined with the effects on red blood cells, may improve patients' overall sense of well-being, as can be measured by quality-of-life instruments.

Treatment of DCD with L-carnitine has achieved inconsistent results. Data have shown that treatment with L-carnitine increases plasma concentrations of total and free carnitine. However, clinical endpoints have not as clearly increased. Brass et al,² Ahmad et al,¹² and Sloan et al³ have conducted randomized clinical trials with L-carnitine to demonstrate improved cardiopulmonary outcomes and quality of life in dialysis patients with some, but not complete, success.

We suggest that by identifying patients at increased carnitine risk, L-carnitine treatment can achieve clear improvements in quality of life and the erythropoietin doses needed to maintain hemoglobin concentrations. Previous work in this laboratory has shown that a subset of hemodialysis patients may be at greater risk for plasma carnitine alterations.¹ This group of hemodialysis patients has lower plasma free carnitine concentrations but normal total carnitine concentrations. According to our previous results, we reasoned that the administration of L-carnitine as a therapeutic agent in this group of patients increases plasma free carnitine concentrations and by mass action leads to a shift of acylcarnitine moieties into the plasma. We hypothesize that treatment with IV L-carnitine will cause a change in acylcarnitine moieties that will result in improvement in red blood cell half-life and an increase in muscle function, resulting in improved quality of life and decreased erythropoietin requirements. The purpose of this project was to select a sample of hemodialysis patients at increased risk for altered carnitine metabolism and monitor these patients for benefits from L-carnitine treatment, including perceived quality of life, mean erythropoietin dose, and selected clinical outcomes.

	MATERIALS AND METHODS

Top MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS

 
Subjects
This study was conducted at a Midwestern dialysis center. Required approvals for conducting this study were obtained from the medical director and the administrator at the Dialysis Center of Lincoln, the Community Institutional Review Board in Lincoln, NE, and the University Committee on Research Involving Human Subjects at Michigan State University. All procedures followed were in accordance with the ethical standards of Michigan State University's Committee on Research Involving Human Subjects.

The population from which the sample was taken included patients 18 years of age, who had been receiving a minimum of 3 hours of bicarbonate, low-acetate hemodialysis treatments 3 times per week and who had been receiving dialysis for at least 1 year. In addition, those patients admitted into the study met 2 or more risk factors for a compromised serum carnitine as established in our previous study.¹ These risk factors were 65 years of age or older; at least 1 year's duration of treatment; female sex; use of aspirin or mannitol; and the presence of type 2 diabetes mellitus, left atrial dilation, or left ventricular hypertrophy. Exclusion criteria were current or previous treatment (within the last 2 months) with L-carnitine, a severe blood loss, disease affecting skeletal muscle function, severe liver disease, pregnancy, or free carnitine >40 µmol/L.

Patients with severe blood loss were excluded because they are typically given increased doses of Epogen (Amgen, Thousand Oaks, CA) and iron supplements to help increase blood volume. Patients who have diseases affecting skeletal muscle function were excluded because the disease may confound the impact of carnitine on the skeletal muscle fibers. Patients with severe liver disease and pregnancy may have altered carnitine metabolism for reasons other than uremia. Additionally, in order to comply with the US Federal Drug Administration's criteria for supplementation with IV levocarnitine in the hemodialysis population, all patients with a plasma free carnitine concentration >40 µmol/L were excluded. Patients included in this study signed a consent form. Patients were stratified by age, using 50 years old as a cut point, and then each age section was randomized into control and treatment groups by a co-investigator who did not participate in the data collection process. Simple randomization was used, using random numbers generated from an Excel spreadsheet (Microsoft Corp, Redmond, WA). This investigator and the pharmacist were the only persons not blinded.

Procedures
This was a prospective, randomized, double blind, clinical research study performed between September 2001 and March 2002. The variables and their times of collection are outlined in Table I. The patients had their blood drawn for carnitine analysis during the study on the first week of the baseline month and at 12 and 24 weeks, in accordance with routine monthly blood draws. The blood sample was collected in a heparin tube, from which the plasma was obtained and stored at –80°C until analysis. The radioenzymatic method was used to analyze plasma carnitine concentrations. In this method, sodium tetrathionate catalyzed the reaction between plasma carnitine and labeled [1-¹⁴C] acetyl CoA, resulting in labeled acetyl-carnitine that is then separated out by ion exclusion chromatography. Acid-insoluble (long-chain acylcarnitine) carnitine is separated out from the acid-soluble carnitine using perchloric acid.^13,14 This method was first determined by Cederblad and Lindstedt¹⁵ and Bohmer et al¹⁶ and later modified by Brass and Hoppel.¹³

The mean erythropoietin dose was recorded monthly during the course of the study. The erythropoietin administration data were analyzed as the change from baseline to posttreatment. Erythropoietin usage was analyzed using an erythropoietin-resistance index, created by dividing the patients' pre- and posttreatment erythropoietin doses by the patients' dry weight and their hemoglobin concentration.

To determine changes in kcal and protein consumption, dietary recalls were collected using the multiple pass method,¹⁷ a 24-hour recall, and a typical-day recall. These values were averaged in order to account for individual variations. Nutritionist V, produced by N² Computing (First Databank, Inc, San Bruno, CA), was used for nutrient analysis. Normalized protein catabolic rate (nPCR) was calculated using the following formula:

To normalize the PCR:

The 7-point Subjective Global Analysis (SGA) form¹⁸ and midarm muscle circumference (MAMC)¹⁹ were used to assess nutrition status at baseline, 12 weeks, and 24 weeks. SGA is a subjective tool used to assess nutrition status and does not require laboratory values. The tool combines a series of dietary, gastrointestinal, clinical, and functional status questions in combination with a brief physical examination to assess nutrition status. MAMC was used as a surrogate marker of lean body mass.

The Medical Outcomes Short Form-36 (SF-36) surveys were administered and scored by the social worker at the dialysis centers²⁰ at baseline and at 24 weeks. The SF-36 is a perceived quality-of-life assessment that has 8 domains used to comprise either a mental (MCS) or a physical (PCS) composite score. Each domain was scored on a scale of 0–100, with 100 being the highest perception of functioning. The domains are physical functioning, role-physical, bodily pain, general health, mental health, role-emotional, social functioning, and vitality. The MCS and PCS were normalized as described by Ware and Kosinski.²¹ Further data were collected from medical records, and random data audits were conducted to ensure consistency and accuracy of collection.

Treatment
Those patients who signed an informed consent and met basic inclusion criteria were screened for selected "high carnitine risk" criteria, stratified by age, and then randomized into groups. Patients randomized into the treatment group received 20 mg/kg Carnitor (Sigma-Tau Pharmaceuticals, Gaithersburg, MD) actual body weight IV, posthemodialysis treatment, 3 times per week IV. The carnitine was administered to the patients in an infusion of 100 mL of normal saline over 10 minutes by the dialysis center nursing staff. Patients randomized into the control group received an IV placebo of 100 mL of normal saline over 10 minutes. The amount of carnitine needed was calculated using the patients' dry weight from the baseline of the study. By diluting the carnitine in normal saline and giving it in an infusion, the potential odor of the drug was masked and blindness maintained. The treatment period was for 24 weeks.

Analysis of Data
Data were analyzed using SPSS version 11.0 (SPSS Inc, Chicago, IL). Primary end points were perceived quality-of-life domains, the quality-of-life PCS, and erythropoietin dose. Secondary end points were the clinical and nutrition variables. All of the continuous variables were analyzed using a repeated-measures analysis of variance. However, in the case of the SF-36 domain role-physical, where the baseline measurement was trending toward a significant difference between the treatment and the placebo groups, analysis of covariance (ANCOVA), using the baseline measurement as the covariate, was used to determine whether the group still predicted postintervention values. Differences in variables at baseline were determined using either the t-test for continuous variables, or the ² test for nominal variables. Associations were analyzed using Pearson's correlation coefficient. Significance was assessed at p < .05.

Power for the sample size of this study was determined from Caruso et al²² using the following mean ± standard deviations: 3778 ± 3193 units and 5500 ± 3505, with the assumption of equal variations.

	RESULTS

Top MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS

 
Of the 48 patients who consented to participate in the study, 27 completed the final measurement, 13 in the carnitine group and 14 in the placebo group. Twenty-one patients dropped out before completion of the study due to various reasons: 7 voluntarily withdrew, 7 died from causes unrelated to carnitine, and 7 declined to complete the final SF-36 survey. However, data for the other variables were collected on these last 7 patients.

Table I outlines the baseline descriptive data for the study patients. The primary etiologies for the patients receiving hemodialysis were diabetes and hypertension. At baseline, there were significant differences between treatment and placebo groups for the variable nPCR, whereas the remaining baseline descriptive and primary outcome variables were not significantly different between the 2 groups. There were no statistically significant differences at baseline for any of the carnitine variables between the 2 treatment groups (Table II). There were numerous correlations between the carnitine fractions at baseline and some of the descriptive parameters (Table III). When the independent predictors were analyzed using multiple regression to determine predictors for the 3-month MAMC measurements, baseline plasma free carnitine and baseline BMI were significant (r = 0.83).

Primary outcome variables for this study were perceived quality-of-life questionnaire, SF-36 domains. There was a statistically significant improvement in the carnitine group for SF-36 domain role-physical (Table IV), with a trend toward significance noted for the PCS (p = .09), relative to the control group. To rule out baseline value effects on postintervention measurements, baseline measurements were included as covariates in the ANCOVA model. The baseline measurement of the role physical score as the covariate in ANCOVA did not achieve statistical significance, indicating that the significant effect noted for the SF-36 domain role-physical resulted from the intervention and not from baseline discrepancies.

There was a significant difference in change in use of erythropoietin in the carnitine-treated group relative to the controls. Relative to baseline, at 6 months the carnitine group showed a decrease of 1.62 ± 0.91 units erythropoietin/dry weight/[Hb], relative to an increase of 1.33 ± 0.79 units erythropoietin/dry weight/[Hb] in the control group. Of the other variables analyzed for changes between pre- and posttreatment with carnitine (dietary intake, nPCR, SGA, MAMC, BUN, triacylglycerols, hemoglobin, hematocrit), none demonstrated statistically significant changes between the treatment and the control group.

	DISCUSSION

Top MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS

 
The main endpoints for this study were the SF-36 domains and the PCS. Within the treatment group, a significant increase was seen in the SF-36 domain role-physical relative to controls. Furthermore, the PCS was trending strongly toward significance. This was particularly striking, given the small sample size and the high attrition rate experienced in this study.

The SF-36 is a self-reported assessment tool designed to measure the patient's health-related quality of life. It has been well validated in the hemodialysis population by Kutner et al,²³ Kutner,²⁴ and others.^25,26 As a group, the baseline mean composite scores (before normalization) found in our study were similar to the ones documented by Curtin et al²⁶ for the PCS but slightly higher than the reported MCS.

Other interventions, such as exercise, have been reported to increase the SF-36 scores of end-stage renal disease patients.²⁷ However, previous studies with levocarnitine treatment have been unable to demonstrate increases in the physical and MCS of the SF-36. Sloan et al³ reported findings from a randomized clinical trial where the levocarnitine was given orally for 6 months. In the Sloan study, the SF-36 was given every 1.5 months. After the first 1–1/2 month period, an improvement could be seen in the physical functioning and general health domains. However, this effect seemed to disappear by the 6th month. Baseline descriptive data were not reported for the Sloan study; therefore, it is difficult to compare their patient sample to that obtained for the current study. However, it may have been the route of administration of the levocarnitine that led to the discrepancy between the study by Sloan et al³ and the current study. Oral levocarnitine is only partially absorbed, and a bacteria-mediated process degrades the unabsorbed portion.^28,29 The by-products of this degradation process, trimethylamine and -butrobetaine, may be toxic and are excreted by the kidney. Patients with end-stage renal disease are not able to excrete these by-products. Therefore, it is possible that, over time, the by-products increase in concentration to a toxic level.³⁰

The Chief trial² was recently conducted using quality of life as one of its main end points. In this trial, patients were given IV levocarnitine for 6 months, and the Kidney Disease Questionnaire (KDQ) was the assessment tool used to measure perceived quality of life. The KDQ is validated for measuring quality of life in patients with end-stage renal disease, and it was assessed at baseline, midpoint, and at the end of the trial.² The subjects in the Chief trial were younger than in this trial (mean age, 42–48 vs 67 years), the Chief trial treatment groups had fewer patients with diabetes (11%–25% vs 45%), and their mean nPCR was higher (1.02–1.17 vs 0.9). At the end of the Chief trial, the researchers did not find an improvement in the total score of the KDQ. However, they did find a significant improvement in the fatigue portion of the tool.

The results found in this study may have been due in part to the way the patients were selected or the elderly, comorbid status of the patients. Other factors that may have played a role are the patients' familiarity with the SF-36 and the people administering it.

The difference in the change of the erythropoietin doses between the treatment and placebo groups is not unexpected. Other researchers such as Caruso et al²² and Kletzmayr et al³¹ have reported improvements in erythropoietin dosing with levocarnitine treatment. Caruso et al specifically reported this finding in hemodialysis patients >65 years of age,²² whereas Kletzmayr et al found anemia and erythropoietin resistance index responders and nonresponders. In the Kletzmayr et al³¹ study those patients who responded had significantly reduced erythropoietin resistance indexes. About 50% of the treatment group in this study were responders to levocarnitine treatment.

Although nutrition status was not affected by levocarnitine treatment, it did seem to be associated with baseline plasma carnitine status. The independent variables that were correlated with baseline carnitine were for the most part nutrition assessment indicators (nPCR, serum BUN, albumin, dietary protein intake, and SGA). All of the correlations were positive, indicating the better the nutrition status, the higher the baseline plasma carnitine concentrations.

Furthermore, baseline plasma carnitine was associated with 12-week BMI and MAMC values, and, as can be seen by the multiple linear regression model, plasma free carnitine is predictive, along with BMI, for the 12-week MAMC. Plasma free carnitine may be an early indicator of lean body mass atrophy. Plasma free and acyl carnitine are lost in the dialysis process. The body stores (97% of which are in the muscle) may be partly responsible for restoring plasma carnitine concentrations, especially when the diet is low in levocarnitine sources (red meats, poultry, and dairy).

The limitations of this study were low subject numbers and high attrition due to death, voluntary withdrawal, refusal to participate, and the statistically significant levels of normalized protein catabolic rate at baseline. Furthermore, although the nutrition indicators are associated with plasma carnitine concentrations, the change in carnitine cannot be associated with the change in nutrition parameters, which may reduce the importance of these associations. The study was conducted solely by the volunteer time and effort of the patients, nurses, social workers, and dietitians at the dialysis unit. Therefore, missing data did occur, and patients were less likely to complete the quality-of-life questionnaire. Strengths of the study included the knowledge of the social workers with the SF-36, patient randomization with a placebo group, and double blinding the participants throughout the study period.

	CONCLUSIONS

Top MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSIONS

 
In conclusion, this study was unique due to the specific selection criteria of the participants and the dietary data collected. Quality of life was significantly improved in the treatment group of this hemodialysis patient sample in the area of the domain role-physical, with a trend toward improvement in the PCS. Furthermore, mean erythropoietin dose changes between the groups were significantly different, with the treatment group dose decreasing and the placebo group increasing. Significant associations were found between the dependent variables (total, free, short-chain acyl and long-chain acylcarnitine) and many nutrition-related independent variables. Future studies could focus on further narrowing the selection criteria and more detailed investigation of the relationship between quality of life and physical functioning with levocarnitine treatment.

Sigma Tau Pharmaceuticals donation of levocarnitine and ROIP Grant, Michigan State University. Dr Davis was supported by a grant from the Blodgett Butterworth Health Care Foundation. Data collected when primary investigator was a doctoral student at Michigan State University.

Received for publication April 2, 2005. Accepted for publication September 7, 2005.

1. Steiber AL, Weatherspoon LJ, Spry L, Davis AT. Serum carnitine concentrations correlated to clinical outcome parameters in chronic hemodialysis patients. Clin Nutr.2004; 23:27 –34.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
2. Brass EP, Adler S, Sietsema KE, Hiatt WR, Orlando AM, Amato A. Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients. Am J Kidney Dis. 2001;37:1018 –1028.[Web of Science][Medline] [Order article via Infotrieve]
3. Sloan RS, Kastan B, Rice SI, et al. Quality of life during and between hemodialysis treatments: role of L-carnitine supplementation.Am J Kidney Dis. 1998;32:265 –272.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
4. Eknoyan G, Latos DL, Lindberg J. Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder: National Kidney Foundation Carnitine Consensus Conference. Am J Kidney Dis.2003; 41:868 –876.[Web of Science][Medline] [Order article via Infotrieve]
5. Ricanati ES, Tserng KY, Hoppel CL. Abnormal fatty acid utilization during prolonged fasting in chronic uremia. Kidney Int Suppl.1987; 22:S145 –S148.[Medline] [Order article via Infotrieve]
6. Rodriguez-Segade S, Alonso de la Pena C, Paz M, et al. Carnitine concentrations in dialysed and undialysed patients with chronic renal insufficiency. Ann Clin Biochem.1986; 23(pt 6):671 –675.[Web of Science][Medline] [Order article via Infotrieve]
7. Ando M, Sanaka T, Nihei H. Eicosapentanoic acid reduces plasma levels of remnant lipoproteins and prevents in vivo peroxidation of LDL in dialysis patients. J Am Soc Nephrol.1999; 10:2177 –2184.[Abstract/Free Full Text]
8. Nohara Y, Suzuki J, Kinoshita T, Watanabe M. Creatinine inhibits D-amino acid oxidase. Nephron.2002; 91:281 –285.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
9. Labonia WD, Morelli OH Jr, Gimenez MI, Freuler PV, Morelli OH. Effects of L-carnitine on sodium transport in erythrocytes from dialyzed uremic patients. Kidney Int.1987; 32:754 –759.[Web of Science][Medline] [Order article via Infotrieve]
10. Matsumura M, Hatakeyama S, Koni I, Mabuchi H, Muramoto H. Correlation between serum carnitine levels and erythrocyte osmotic fragility in hemodialysis patients. Nephron.1996; 72:574 –578.[Web of Science][Medline] [Order article via Infotrieve]
11. Giovenali P, Fenocchio D, Montanari G, et al. Selective trophic effect of L-carnitine in type I and IIa skeletal muscle fibers. Kidney Int. 1994;46:1616 –1619.[Web of Science][Medline] [Order article via Infotrieve]
12. Ahmad S, Robertson HT, Golper TA, et al. Multicenter trial of L-carnitine in maintenance hemodialysis patients, II: clinical and biochemical effects: dietary intake of whole grains. Kidney Int.1990; 38:912 –918.[Web of Science][Medline] [Order article via Infotrieve]
13. Brass EP, Hoppel CL. Carnitine metabolism in the fasting rat.J Biol Chem. 1978;253:2688 –2693.[Free Full Text]
14. Hoppel C. Determination of Carnitine: Techniques in Diagnostic Human Biochemical Genetics: A Laboratory Manual. Hoboken, NJ: Wiley-Liss, Inc; 1991:309 –326.
15. Cederblad G, Lindstedt S. A method for the determination of carnitine in the picomole range. Clin Chim Acta.1972; 37:235 –243.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
16. Bohmer T, Rydning A, Solberg HE. Carnitine levels in human serum in health and disease. Clin Chim Acta.1974; 57:55 –61.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
17. Moshfegh AJ, Borrud L, Perloff B, et al. Improved method for the 24-hour dietary recall for use in national surveys [abstract]. FASEB J. 1999;13:A603 .
18. McCann L. Using subjective global assessment to identify malnutrition in the ESRD patient. Nephrol News Issues.1999; 13:18 –19.[Medline] [Order article via Infotrieve]
19. Clinical practice guidelines for nutrition in chronic renal failure: K/DOQI, National Kidney Foundation. Am J Kidney Dis.2000; 35:S1 –S140.[Web of Science][Medline] [Order article via Infotrieve]
20. Ware JE, Kosinski M, Gandek B. SF-36 Health Survey. Lincoln, RI: Quality Metric Incorporated; 2002.
21. Ware JE, Kosinski M. SF-36 Physical and Mental Health Summary Scales: A Manual for Users of Version 1. 2nd ed. Lincoln, RI: Quality Metric Incorporated; 2002.
22. Caruso U, Leone L, Cravotto E, Nava D. Effects of L-carnitine on anemia in aged hemodialysis patients treated with recombinant human erythropoietin: a pilot study. Dialysis Transplant.1998; 27:498 –504.[Web of Science]
23. Kutner NG, Brogan D, Fielding B. Physical and psychosocial resource variables related to long-term survival in older dialysis patients.Geriatr Nephrol Urol.1997; 7:23 –28.[CrossRef][Medline] [Order article via Infotrieve]
24. Kutner NG. Assessing end-stage renal disease patients' functioning and well-being: measurement approaches and implications for clinical practice.Am J Kidney Dis. 1994;24:321 –333.[Web of Science][Medline] [Order article via Infotrieve]
25. Rettig RA, Sadler JH, Meyer KB, et al. Assessing health and quality of life outcomes in dialysis: a report on an Institute of Medicine workshop.Am J Kidney Dis. 1997;30:140 –155.[Web of Science][Medline] [Order article via Infotrieve]
26. Curtin RB, Lowrie EG, DeOreo PB. Self-reported functional status: an important predictor of health outcomes among end-stage renal disease patients. Adv Ren Replace Ther.1999; 6:133 –140.[Web of Science][Medline] [Order article via Infotrieve]
27. Painter P, Carlson L, Carey S, Paul SM, Myll J. Physical functioning and health-related quality-of-life changes with exercise training in hemodialysis patients. Am J Kidney Dis.2000; 35:482 –492.[Web of Science][Medline] [Order article via Infotrieve]
28. Rebouche CJ, Chenard CA. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J Nutr.1991; 121:539 –546.[Abstract/Free Full Text]
29. Sahajwalla CG, Helton ED, Purich ED, Hoppel CL, Cabana BE. Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330-mg tablet versus 1-g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci.1995; 84:627 –633.[Web of Science][Medline] [Order article via Infotrieve]
30. Evans A. Dialysis-related carnitine disorder and levocarnitine pharmacology. Am J Kidney Dis.2003; 41(suppl):S13 –S26.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
31. Kletzmayr J, Mayer G, Legenstein E, et al. Anemia and carnitine supplementation in hemodialyzed patients. Kidney Int Suppl.1999; 69:S93 –S106.[Medline] [Order article via Infotrieve]

Journal of Parenteral and Enteral Nutrition, Vol. 30, No. 1, 10-15 (2006)
DOI: 10.1177/014860710603000110


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Steiber, A. L. Articles by Weatherspoon, L. J. Search for Related Content PubMed PubMed Citation Articles by Steiber, A. L. Articles by Weatherspoon, L. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Dialysis Kidney Failure Social Bookmarking                   What's this?