Brain metabolic alterations in patients with long-term calcineurin inhibitor therapy after liver transplantation.
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
29
11
2018
revised:
24
12
2018
accepted:
20
03
2019
pubmed:
23
4
2019
medline:
15
4
2020
entrez:
23
4
2019
Statut:
ppublish
Résumé
Calcineurin inhibitor (CNI) neurotoxicity after liver transplantation might be due to impairment of the cerebral metabolism. To investigate CNI-related alterations of brain metabolite distributions and associations between cognitive function and brain metabolism in patients with long-term CNI treatment after liver transplantation. Eighty-two patients (19 CNI free, 34 CNI low-dose and 29 standard-dose CNI immunosuppression) 10 years after liver transplantation and 32 adjusted healthy controls underwent nonlocalised brain phosphorus magnetic resonance spectroscopy (MRS) and single voxel proton MRS in the parietal white matter to estimate brain metabolite contents. The MRS results were correlated with psychometric data assessing cognitive function. Phosphorus metabolite concentrations with the exception of phosphocreatine (PCr) were reduced in patients compared to controls. Particularly, patients with low-dose CNI therapy showed a significant decrease in adenosine triphosphate (0.209 ± 0.012 vs 0.222 ± 0.010; P < 0.001) and a significant increase in PCr (0.344 ± 0.026 vs 0.321 ± 0.017; P < 0.001) compared to controls. Myo-Inositol in the CNI free group (2.719 ± 0.549 institutional unit [iu]) was significantly lower compared to controls (3.181 ± 0.425 iu; P = 0.02), patients on low-dose (3.130 ± 0.513 iu; P < 0.05) and standard-dose CNI therapy (3.207 ± 0.632 iu; P < 0.02). Glutamate and glutamine levels correlated negatively with cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status Total Scale: R = -0.362, P = 0.029). Long-term CNI therapy after liver transplantation might be associated with alterations of brain metabolites.
Sections du résumé
BACKGROUND
Calcineurin inhibitor (CNI) neurotoxicity after liver transplantation might be due to impairment of the cerebral metabolism.
AIMS
To investigate CNI-related alterations of brain metabolite distributions and associations between cognitive function and brain metabolism in patients with long-term CNI treatment after liver transplantation.
METHODS
Eighty-two patients (19 CNI free, 34 CNI low-dose and 29 standard-dose CNI immunosuppression) 10 years after liver transplantation and 32 adjusted healthy controls underwent nonlocalised brain phosphorus magnetic resonance spectroscopy (MRS) and single voxel proton MRS in the parietal white matter to estimate brain metabolite contents. The MRS results were correlated with psychometric data assessing cognitive function.
RESULTS
Phosphorus metabolite concentrations with the exception of phosphocreatine (PCr) were reduced in patients compared to controls. Particularly, patients with low-dose CNI therapy showed a significant decrease in adenosine triphosphate (0.209 ± 0.012 vs 0.222 ± 0.010; P < 0.001) and a significant increase in PCr (0.344 ± 0.026 vs 0.321 ± 0.017; P < 0.001) compared to controls. Myo-Inositol in the CNI free group (2.719 ± 0.549 institutional unit [iu]) was significantly lower compared to controls (3.181 ± 0.425 iu; P = 0.02), patients on low-dose (3.130 ± 0.513 iu; P < 0.05) and standard-dose CNI therapy (3.207 ± 0.632 iu; P < 0.02). Glutamate and glutamine levels correlated negatively with cognitive function (Repeatable Battery for the Assessment of Neuropsychological Status Total Scale: R = -0.362, P = 0.029).
CONCLUSION
Long-term CNI therapy after liver transplantation might be associated with alterations of brain metabolites.
Substances chimiques
Calcineurin Inhibitors
0
Glutamine
0RH81L854J
Glutamic Acid
3KX376GY7L
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1431-1441Subventions
Organisme : German Federal Ministry of Education and Research
ID : 01EO1302
Pays : International
Organisme : German Research Foundation
Pays : International
Informations de copyright
© 2019 John Wiley & Sons Ltd.