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IntroductionRenal transplantation is the treatment of choice for patients with end stage renal disease meaning better survival and quality of life. The success of transplantation depends largely on immunosupressive therapy. The major immunosupressive agents that are currently being used in various combination regimens are corticosteroids, azathioprine, mycophenolate mofetil (MMF), cyclosporine, tacrolimus, everolimus, and sirolimus. Immunosuppressive therapy is associated with an increase risk of thromboembolic complications and overall increased riks of morbidity and mortality from cardiovascular disease. Main goal of the study was to investigate the effect of different immunosupressive agents on platelet aggregation in renal transplant patients with stable graft function. Materials and methods The study included renal transplant patients which were controlled in the Department of Nephrology, Hyperthension, Dialysis and Renal Transplantation in Clinical Hospital Center Zagreb, during 3 months period, after providing the informed consent. During the regular visit, together with blood sampling for standard laboratory parameters, an aditional 2 ml of blood was taken for testing platelet aggregation, from all patients who met the inclusion criteria. Platelet function testing was performed on platelet function analyzer (PFA-200) that „in vitro“ simulates the process of aggregation and platelet activation. The test simulates primary hemostasis through interaction of platelets with the aperture of a membrane at the end of the capillary which is coated with collagen and either adenosine diphosphate (COL-ADP) or epinephrine (COL-EPI). Results are reported as the closure time (CT) in seconds for COL-EPI and COL-ADP cartridges. The ranges for control subjects were 85–165 s for the COL - EPI closure time, and 71–118 s for the COL -ADP closure time. Data for analysis for renal transplant patients were taken from the medical records. Control group included healty individuals. Results The study included 85 renal transplant patients (50 male and 35 female, median age 54 (29-76). Patients were divided into four groups based on the type of different immunosuppressive agent (cyclosporine, tacrolimus, everolimus, and sirolimus). All values of „in vitro“ closure times (s) with COL-EPI test were within the reference range, but patients in tacrolimus group had significantly lower values compared to controls (98,5 (IQR:89,0-122,8) : (129(IQR: 107,0-147,3); p=0,006), and compared to cyclosporine group (98,5(IQR:89,0-122,8) : (123,5 (IQR:98,3-166,0); p=0,031). With COL/ADP test, patients in sirolimus group had significantly lower values compared to controls (77 (67,25-87,5) : (96,5 (85,8 – 105,3); p=0,010). Discussion and conclusion Although, all the values of „in vitro“ closure times with both tests (COL-EPI and COL-ADP) were within reference range, tacrolimus group of patients showed significantly lower values compared to cyclosporine and to controls, while sirolimus group of patients showed significantly lower values compared only to controls. Platelet aggregation values in everolimus patient group did not show any significant differences. These findings could have a certain clinical value. The sensitivity and clinical relevance of this test findings should be further investigated. |
