Levocarnitine Improves Cardiac Function in Hemodialysis Patients With Left Ventricular Hypertrophy: A Randomized Controlled Trial

Higuchi, Terumi; Abe, Masanori; Yamazaki, Toshio; Okawa, Erina; Ando, Hisami; Hotta, Sunao; Oikawa, Osamu; Kikuchi, Fumito; Okada, Kazuyoshi; Soma, Masayoshi

doi:10.1053/j.ajkd.2015.09.010

Cited by 61 publications

(52 citation statements)

References 24 publications

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“…In a recent randomized open label trial conducted on HD subjects with mild carnitine deficiency (mean level of 41 µmol/L), it was found that L-carnitine slightly improved cardiac parameters and ESA resistance index [2]. However, a randomized placebo controlled trial recently conducted and completed by our group, did not find a benefit of carnitine supply on ESA resistance index after 1 year of follow-up in incident HD patients [3].…”

Section: Doi: 101159/000494338mentioning

confidence: 58%

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

et al. 2018

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Background: The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. Methods: CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. Results: Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. Conclusion: L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).

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Section: Doi: 101159/000494338mentioning

confidence: 58%

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

et al. 2018

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“…The mean dose of saccharated ferric oxide at baseline and at the end of the study was defined as follows: the mean dose of saccharated ferric oxide per 4 weeks during the 12 weeks before the study period was defined as baseline level and mean dose of saccharated ferric oxide per 4 weeks during the study period was defined as the end of the study. Erythropoietin responsiveness index (ERI) was defined as the average weekly ESA dose divided by clinical dry weight and average blood hemoglobin (weekly ESA dose [units]/dry weight [kg]/hemoglobin [g/dL]) as described previously [14, 15] to normalize the amount of required ESA to the severity of anemia. These variables were evaluated at baseline and at 24 weeks (at the end of the study).…”

Section: Methodsmentioning

confidence: 99%

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

et al. 2018

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Background: Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. Methods: This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. Results: FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline –6,160 vs. –1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). Conclusion: In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level.

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“…Wanic-Kossowska et al [25] reported that a group that received a combination of carnitine and ESA showed improvement in anemia, reduction in ESA requirement, and improvement in red blood cell function as compared to groups that received only carnitine or only ESA. In addition, we have conducted a relatively large-scale study of hemodialysis patients in which 113 patients took oral levocarnitine [14]. We found that the required ESA dose had a tendency to decrease after the study began and decreased significantly in the treatment group compared with the control group at 12 months after the start of the therapy.…”

Section: Discussionmentioning

confidence: 99%

“…ERI (ESA dose·kg -1 ·g -1 ·dL -1 ·week -1 ) was defined as the average weekly units of ESA divided by clinical dry weight (in kg) and average blood hemoglobin (in g/dL) to normalize the amount of required ESA to the severity of anemia [14]. At the beginning of each week, a blood sample was obtained from each patient before dialysis began.…”

Section: Methodsmentioning

confidence: 99%

Levocarnitine Injections Decrease the Need for Erythropoiesis-Stimulating Agents in Hemodialysis Patients with Renal Anemia

et al. 2017

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Aims: The aim of this study was to evaluate the efficacy of levocarnitine injection for renal anemia in hemodialysis patients. Methods: In this randomized controlled clinical trial, we randomly assigned patients on maintenance hemodialysis at our hospital to receive levocarnitine injections (n = 30) or no injection (n = 30) and monitored the patients during 12 months of treatment. In the treatment group, patients received an injection of levocarnitine 1,000 mg 3 times weekly after hemodialysis sessions. All patients received recombinant human erythropoietin as an erythropoiesis-stimulating agent (ESA). Response to ESA therapy was determined by calculating the erythropoietin responsiveness index (ERI; ESA dose·kg^-1·g^-1· dL^-1·week^-1). Results: (1) The target levels of hemoglobin and hematocrit were maintained during the study period in both the levocarnitine group and the control group. (2) The dose of ESAs required to maintain these levels decreased gradually in the levocarnitine group and was significantly lower at 6 and 12 months than at study initiation. Furthermore, the dose of ESAs was significantly lower than that in the control group at 12 months. (3) The ERI showed a significant decrease at 6 and 12 months in the levocarnitine group, with a significant difference between the 2 groups at 12 months. Conclusion: Our results suggest that levocarnitine administration can reduce the dose of ESAs required in patients with renal anemia on hemodialysis and improve the response to ESA therapy.

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Levocarnitine Improves Cardiac Function in Hemodialysis Patients With Left Ventricular Hypertrophy: A Randomized Controlled Trial

Cited by 61 publications

References 24 publications

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

Levocarnitine Injections Decrease the Need for Erythropoiesis-Stimulating Agents in Hemodialysis Patients with Renal Anemia

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