Platelet Aggregation in the Diagnosis of Acute Graft Rejection

Overview

The study titled "Platelet Aggregation in the Diagnosis of Acute Graft Rejection" is a pilot observational study evaluating whether alterations in platelet function can serve as non-invasive markers of acute rejection in kidney transplant recipients. Platelet aggregation is assessed using optical aggregometry, flow-cytometric P-selectin (CD62-P) expression, and soluble P-selectin levels before kidney transplantation and at the time of protocol biopsies performed at 3 and 12 months after kidney transplantation. Patients with suspected graft dysfunction undergoing indication biopsy are also included. Platelet activation markers are correlated with histopathological findings, donor-specific antibodies, metabolic parameters, and clinical outcomes. The goal is to determine whether platelet activation profiles can identify acute cellular or antibody-mediated rejection and contribute to the development of a non-invasive diagnostic tool.

Platelets play a key role not only in hemostasis but also in inflammation and immune responses. Their activation, characterized by adhesion, integrin-mediated aggregation, thromboxane A₂ production, and surface expression of markers such as P-selectin, contributes to interactions with T lymphocytes and amplification of immune signaling. Emerging evidence suggests that platelet activation may participate in early mechanisms of kidney graft injury. Studies have demonstrated platelet accumulation in glomerular and peritubular capillaries during antibody-mediated rejection, likely mediated by donor-specific antibodies and endothelial activation via von Willebrand factor. Elevated platelet activation markers such as PF4 and P-selectin have also been associated with T-cell-mediated rejection. This pilot study investigates whether changes in platelet aggregation and platelet activation markers can serve as non-invasive indicators of acute kidney allograft rejection. Platelet function is measured using optical aggregometry, flow cytometry of P-selectin (CD62-P), and soluble P-selectin levels. These parameters are correlated with histological findings from protocol biopsies at 3 and 12 months post-transplant, as well as from indication biopsies performed for suspected rejection. The study includes adult kidney transplant recipients monitored longitudinally and a cohort of patients with graft dysfunction requiring indication biopsy. Concurrent assessments include renal function, donor-specific antibodies, levels of immunosupression (tacrolimus), metabolic parameters, and imaging. By comparing platelet activation profiles with biopsy-proven rejection, the study aims to determine whether platelet-based biomarkers can support early, non-invasive detection of cellular or antibody-mediated allograft injury and complement traditional biopsy-based diagnostics.