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



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.



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.



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.
Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.|Faculté de Médecine, Université de Strasbourg, Strasbourg, France.|UMR 1109 Laboratoire d'Immunologie Rhumatologie, Université de Strasbourg, Strasbourg, France.
Clotilde
C
Muller
Pôle d'Activité Médico-Chirurgicale Cardiovasculaire, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Université de Strasbourg, BP 426-67091, Strasbourg, France.
Nathan
N
Messas
Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.|UMR 1109 Laboratoire d'Immunologie Rhumatologie, Université de Strasbourg, Strasbourg, France.
Peggy
P
Perrin
Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.
Jerome
J
Olagne
Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.|Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
Gabriela
G
Gautier-Vargas
Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.|Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
Noelle
N
Cognard
Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.|Faculté de Médecine, Université de Strasbourg, Strasbourg, France.|UMR 1109 Laboratoire d'Immunologie Rhumatologie, Université de Strasbourg, Strasbourg, France.
Sophie
S
Caillard
Néphrologie-Transplantation, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France.|Faculté de Médecine, Université de Strasbourg, Strasbourg, France.|UMR 1109 Laboratoire d'Immunologie Rhumatologie, Université de Strasbourg, Strasbourg, France.
Bruno
B
Moulin
Pôle d'Activité Médico-Chirurgicale Cardiovasculaire, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Université de Strasbourg, BP 426-67091, Strasbourg, France. olivier.morel@chru-strasbourg.fr.|Faculté de Médecine, Université de Strasbourg, Strasbourg, France. olivier.morel@chru-strasbourg.fr.|UMR CNRS 7213 Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France. olivier.morel@chru-strasbourg.fr.
Olivier
O
Morel
D000368:Aged; D000077144:Clopidogrel; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000639:trends; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D012042:Registries; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D012189:Retrospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D013988:Ticlopidine
Cardiovascular disease; Kidney transplantation; Platelet aggregation