Cyclosporine Metabolites’ Metabolic Ratios May Be Markers of Cardiovascular Disease in Kidney Transplant Recipients Treated with Cyclosporine A-Based Immunosuppression Regimens.
PBN-AR
Instytucja
Instytut Biochemii i Biofizyki Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
EN
Czasopismo
Cardiovascular Toxicology
ISSN
1530-7905
EISSN
1559-0259
Wydawca
HUMANA PRESS INC
DOI
URL
Rok publikacji
2019
Numer zeszytu
3
Strony od-do
255-263
Numer tomu
19
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
EN
Arrhythmia;
Cardiovascular disease;
Cyclosporine;
Cyclosporine metabolites;
Hypertriglyceridemia;
Kidney transplantation;
Obesity;
Overweight
Streszczenia
Język
EN
Treść
Cardiovascular disease (CVD) remains one of the primary causes of death after kidney transplantation (KTX). Cyclosporine (CsA) metabolites may play a role in CVD. Metabolic ratio (MR) may be considered a measure of intra-individual differences of CsA metabolism. The study was aimed at analysis of associations of CVD with indices of CsA metabolism: MRs and dose-adjusted CsA concentrations (C/D and C/D/kg). The study was performed in the Department of Immunology, Transplant Medicine, and Internal Diseases of the Medical University of Warsaw and involved 102 KTX recipients. Whole blood concentrations of cyclosporine A, AM1, AM9, AM4N, demethylcarboxylated (dMC-CsA), dihydroxylated (DiH-CsA), trihydroxylated (TriH-CsA) cyclosporine metabolites were determined by liquid chromatography coupled with tandem mass spectrometry. Lower AM9/CsA were observed in diabetics. Patients with coronary disease and/or myocardial infarction had lower dMC-CsA/CsA and higher AM4N/CsA. Supraventricular arrhythmia (SVA) was associated with higher AM1/CsA and AM4N/CsA. Hypertriglyceridemia (hTG) was associated with lower AM9/CsA, higher C/D and C/D/kg. Decrease of AM9/CsA and AM4N and higher D/C were associated with overweight/obesity. Systolic blood pressure (BP) positively correlated with dMC-CsA/CsA and negatively with C/D/kg. Diastolic BP correlated positively with AM1/CsA, dMC-CsA/CsA, DiH-CsA/CsA and TriH-CsA/CsA. We have demonstrated the association of coronary disease/myocardial infarction, SVA, hTG, overweight/obesity and elevated arterial BP with higher MRs of AM1, AM4N, dMC-CsA, DiH-CsA and TriH-CsA, and lower MRs of AM9, which may indicate deleterious and favourable effects of individual CsA metabolites on cardiovascular system and suggest engagement of specific enzymatic pathways.
Inne
System-identifier
PX-5ce7cfacd5de0de4fd56e9ad
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