Effects of L-carnitine administration on metabolism of short-chain fatty acid (acetic acid) and long-chain fatty acid during hemodialysis

憲志, 前田; 高弘, 新里; 文直, 吉田; 裕之, 小早川

doi:10.4009/jsdt1985.20.457

Cited by 4 publications

(6 citation statements)

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“…Bartel et al [26] demonstrated an increase in circulating plasma fatty acids during a 4-hour hemodialysis. Similar increases in plasma fatty acid levels were demonstrated by Maeda et al [27] and Suzuki et al [7] . Dialysis is not only associated with quantitative changes in fatty acid levels but also with alterations in the distribution of fatty acid moieties.…”

Section: Fatty Acid Abnormalities In Chronic Kidney Diseasesupporting

confidence: 72%

“…Maeda et al [27] documented a signifi cant reduction in intradialytic free fatty acid concentrations in the plasma of hemodialysis patients following 12 weeks of administration of oral levocarnitine. A similar decrease in intradialytic and postdialysis plasma fatty acid levels was recorded by Suzuki et al [7] when levocarnitine was administered to hemodialysis patients with carnitine defi ciency.…”

Section: Fatty Acid Abnormalities In Chronic Kidney Diseasementioning

confidence: 99%

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

Schreiber¹

2005

Blood Purif

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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...

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Section: Fatty Acid Abnormalities In Chronic Kidney Diseasesupporting

confidence: 72%

Section: Fatty Acid Abnormalities In Chronic Kidney Diseasementioning

confidence: 99%

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

Schreiber¹

2005

Blood Purif

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“…Maeda et al. [ 7 ] evaluated the carnitine concentrations after repeated oral doses before the patient underwent dialysis and found that dialysis reduced the plasma carnitine concentration, although high levels of carnitine were maintained after the dialysis. We obtained similar results in our study and hence confirmed that the oral mode of administration was effective.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of carnitine concentration after switching from oral administration to intravenous injection in hemodialysis patients

et al. 2018

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Carnitine has high dialyzability and is often deficient in dialysis patients. This deficiency is treated by either intravenous (IV) or oral supplementation of carnitine. In this study, the mode of carnitine administration was changed from oral to IV in 17 hemodialysis (HD) patients, and the treatment was discontinued after 1 year. We found that the levels of total carnitine (TC), free-carnitine (FC), and acyl-carnitine (AC) significantly increased after 3 months of switching to IV administration (p < .05). After discontinuation of carnitine administration, the TC, FC, and AC levels decreased before dialysis. The average FC value was maintained at the normal levels until 9 months, but fell below the normal values when measured at the 12th month of discontinuation. In conclusion, carnitine was maintained at significantly high levels despite the smaller dose by IV infusion as compared with that by oral administration. We therefore suggest that our results be considered while determining both the carnitine administration route and the administration period in dialysis patients under clinical settings.

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“…It is well known that propionate and other short-and mediumchain fatty acids can impair mitochondrial function, in particular mitochondrial b-oxidation [1,22]. This inhibition may at least partially explain increased plasma concentrations of free fatty acids in patients on longterm haemodialysis [1,23] and suggests that removal of short-and medium-chain acyl-groups may be potentially beneficial for this group of patients. Since the administration of exogenous carnitine is associated not only with an increase in free carnitine, but also in the respective acylcarnitine fractions, and since acylcarnitines are removed efficiently by haemodialysis, carnitine supplementation is indeed associated with an increased removal of acyl groups by haemodialysis (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Effect of L-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis

Vernez¹,

Dickenmann²,

Steiger³

et al. 2006

Nephrology Dialysis Transplantation

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Background. The current study was performed to investigate the kinetics of carnitine, individual acylcarnitines and butyrobetaine in patients on haemodialysis. Methods. Eight stable long-term haemodialysis patients were studied under basal conditions (no carnitine supplementation) and 3 weeks after intravenous supplementation with L-carnitine (10 or 20 mg/kg body weight) after each haemodialysis session. The kinetic studies included serial determinations of carnitine and metabolites just before, during or between haemodialysis sessions. Analysis was performed by liquid chromatography-tandem mass spectrometry. Results. Before haemodialysis, the plasma concentrations were (mmol/l) 15.1±0.6 (mean±SEM) for carnitine, 5.9±0.7 for acetylcarnitine, 0.66±0.04 for propionylcarnitine and 0.98±0.08 for butyrobetaine (basal conditions) or 142±23 for carnitine, 69±12 for acetylcarnitine, 6.0±1.1 for propionylcarnitine and 2.6±0.3 for butyrobetaine (carnitine 20 mg/kg). During haemodialysis, the plasma concentrations dropped by $80% for all compounds determined, with extraction coefficients ranging from 0.65 to 0.86. In patients supplemented with 20 mg/kg carnitine, the amount of carnitine removed by haemodialysis equalled 42% of the dose administered, consisting of 2.08 mmol carnitine, 1.03 mmol acetylcarnitine and 0.051 mmol propionylcarnitine. Between the haemodialysis sessions, carnitine, acylcarnitines and butyrobetaine reached apparent steady-state concentrations within 1 day both under basal conditions and after supplementation. Conclusions. Patients on haemodialysis have reduced carnitine, acylcarnitine and butyrobetaine plasma levels, which can be increased by supplementing carnitine. Propionylcarnitine, an important constituent of the acylcarnitine pool, can be removed by haemodialysis. Removal of potentially toxic acyl-groups may represent a mechanism for a beneficial effect of carnitine in these patients.

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Effects of L-carnitine administration on metabolism of short-chain fatty acid (acetic acid) and long-chain fatty acid during hemodialysis

Cited by 4 publications

References 14 publications

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

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

Kinetics of carnitine concentration after switching from oral administration to intravenous injection in hemodialysis patients

Effect of L-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis

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