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Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study


Background:
Cardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation.

Methods:
The study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared.

Results:
The mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03–6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status.

Conclusions:
KT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.

Keywords:
Cardiovascular disease, Kidney transplantation, Platelet aggregation


Autoři: Clotilde Muller† 1,3,4;  Nathan Messas† 2;  Peggy Perrin 1,4;  Jerome Olagne 1;  Gabriela Gautier-Vargas 1,3;  Noelle Cognard 1,3;  Sophie Caillard 1,3,4;  Bruno Moulin 1,3,4;  Olivier Morel 2,3,5*
Působiště autorů: Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France. 1;  Pôle d’Activité Médico-Chirurgicale Cardiovasculaire, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Université de Strasbourg, BP 26-67091 Strasbourg, France. 2;  Faculté de Médecine, Université de Strasbourg, Strasbourg, France. 3;  UMR 1109 Laboratoire d’Immunologie Rhumatologie, Université de Strasbourg, Strasbourg, France. 4;  UMR CNRS 7213 Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France. 5
Vyšlo v časopise: BMC Nefrol 2016, 17:58
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12882-016-0270-2

© The Author(s). 2016
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: http://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-016-0270-2

Souhrn

Background:
Cardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation.

Methods:
The study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared.

Results:
The mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03–6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status.

Conclusions:
KT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.

Keywords:
Cardiovascular disease, Kidney transplantation, Platelet aggregation


Zdroje

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