Effects of immunosuppressive drugs on platelet aggregation and soluble P-selectin levels in renal transplant patients

Abstract

Background/aim: Post-transplant cardiovascular events are associated with increased morbidity and mortality after renal transplantation. Though renal transplantation eliminates cardiovascular disease risk factors by restoring renal function, it introduces new cardiovascular risks derived partly from immunosuppressive medications. In this study, to assess the effects of various immunosuppressive drugs on platelet function of renal transplant patients, we measured soluble P selectin levels (sP-selectin) and performed platelet aggregation studies in patients who have undergone renal transplantation.

Methods: sP-selectin levels and platelet aggregation induced by 5 microM adenosine diphosphate (ADP), 5 microM epinephrine, 1.25 mg/mL ristocetin, and 2 microg/mL collagen were studied by whole blood platelet lumi-aggregometer in 40 renal transplant patients. Patients in group 1 (n = 24) were treated with cyclosporine/mycophenolate mofetil/methylprednisolone, and group 2 (n = 16) were treated with tacrolimus/mycophenolate mofetil/methylprednisolone. Effects were compared with those in control groups of hypertensive subjects and healthy subjects.

Results: Platelet aggregation values induced by ADP, epinephrine, ristocetin, and collagen were lower in cyclosporine-treated patients than tacrolimus-treated patients, hypertensive subjects, and healthy subjects, though the difference was not statistically significant (p > 0.05). sP-selectin levels were appreciably higher in cyclosporine-treated patients, and statistically significant differences were observed compared with those of tacrolimus-treated patients (p < 0.05), hypertensive subjects (p < 0.01), and healthy subjects (p < 0.05).

Conclusion: We conclude that cyclosporine-treated renal transplant patients show enhanced platelet activation in which anti-platelet therapy should be considered, in addition to management of other conventional cardiovascular risk factors, to decrease the cardiovascular morbidity and mortality in this high risk population.