Platelet Aggregation in the Diagnosis of Acute Graft Rejection

NCT ID: NCT07275541

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-11-26
• Study Completion Date: 2027-11-26

Brief Summary

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.

Detailed Description

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.

Conditions

Platelet Aggregation; Kidney Transplant Rejection

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

kidney transplant recipients - Protocol Biopsy Cohort

Adult kidney transplant recipients undergoing routine protocol biopsies at 3 and 12 months post-transplant, regardless of clinical graft function. Platelet aggregation, flow-cytometric P-selectin expression, soluble P-selectin levels, and biochemical and immunological parameters are collected at each time point.

Findings from platelet function testing are subsequently correlated with the histopathological results of the protocol biopsy, including the presence or absence of subclinical rejection.

No interventions assigned to this group

kidney transplant recipients - Indication Biopsy Cohort

Kidney transplant recipients presenting with clinical signs of graft dysfunction-such as rising serum creatinine, increasing proteinuria, or abnormal ultrasound findings or with newly positive donor-specific antibodies (DSA) detected by Luminex testing, prompting the need for an indication biopsy due to suspected acute rejection. At the time of biopsy, platelet aggregation testing, P-selectin markers, comprehensive biochemical parameters, and DSA levels are collected. This cohort represents patients with clinically or immunologically apparent graft injury, allowing comparison with protocol-biopsied patients, including those with subclinical or biopsy-confirmed rejection.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• adult patients (≥18 years)
• primary kidney transplantation
• living / deceased donor kidney transplantation
• ability and consent to participate

Exclusion Criteria

• non-adult patients
• secondary / tertiary kidney transplantation
• antiplatelet therapy
• patients unable to provide informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Martin

OTHER

Sponsor Role: lead

Responsible Party

Matej Vnucak

ass. prof., Deputy Head of Transplant-Nephrology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Matej Vnucak, ass prof, MD, PhD.

Role: STUDY_CHAIR

University Hospital Martin and Jessenius Faculty of Medicine, Comenius University

Locations

Transplant-Nephrology Department, University Hospital Martin

Martin, , Slovakia

Site Status: RECRUITING

Countries

Slovakia

Central Contacts

Timea Blichova, MD

Role: CONTACT

tc@unm.sk

+421434203184

Patricia Kleinova, MD

Role: CONTACT

tc@unm.sk

+421434203184

Facility Contacts

Timea Blichova, MD

Role: primary

tc@unm.sk

+421434203184

Matej Vnucak, ass prof., MD, PhD.

Role: backup

tc@unm.sk

+421434203184

Other Identifiers

UK/3248/2024

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

TNO_AGRE

Identifier Type: -

Identifier Source: org_study_id