Donor-derived Cell-free DNA in Kidney Transplant Recipients

Completed

• Conditions: Kidney Transplantation; Acute Rejection of Renal Transplant
• Interventions: Procedure: Biopsy; Diagnostic Test: Blood Biomarkers - cfDNA; Drug: Antirejection therapy

• Registration Number: NCT06476717
• Lead Sponsor: Institute for Clinical and Experimental Medicine

Brief Summary

Donor-derived cell-free DNA (dd-cfDNA) is a promising non-invasive biomarker of kidney allograft rejection. In this prospective, single center, observational monitoring study, we aim to evaluate a role of dd-cfDNA in predicting kidney allograft injuries, i.e. rejection and non-rejection injuries within 12 months, and to monitor the effect of anti rejection treatment.

Detailed Description

Kidney transplantation represents the best therapeutic option in patients with end-stage kidney disease. Among main causes of graft loss belongs kidney allograft rejection which is diagnosed based on histology/molecular assessment of biopsy sample. This is invasive procedure, but provides more precise result regarding type of rejection. Contrary, donor-derived cell-free DNA (dd-cfDNA) is a novel non-invasive biomarker of allograft rejection with excellent negative predictive power. Moreover it may be useful for predicting allograft injuries and resolution of injuries after treatment.

In the prospective cohort, 100 renal allograft patients will be enrolled and dd-cfDNA levels determined from blood collected at predefined time points (preTX, POD14, M1, 2, 3, 4, 6, 9, 12).

In the second cohort, 40 patients will be enrolled at the time of biopsy with histological and/or molecular diagnosis of rejection and dd-cfDNA levels measured just before initiation of treatment and then at week 1, 2 and 3 after biopsy.

Peripheral blood will be collected in 2x 10 ml cfDNA (Streck) collection tubes for each study visit and dd-cfDNA will be quantified by the Prospera™ test (Natera Inc., Austin, Texas).

All patients will receive standard of care treatment according to centre protocol and no patients or providers will receive the results of dd-cfDNA testing during the study. Study protocol and patient informed consent were approved by Ethical committee.

Study Timeline

• Study Start: 2021-10-21
• Primary Completion: 2024-05-12
• Study Completion: 2024-05-20
• Status Verified: 2024-06
• Study First Submitted: 2024-06-21
• Study First Submitted QC: 2024-06-21
• Study First Posted: 2024-06-26
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 143

Inclusion Criteria

• Recipient age ≥ 18 years and <85 years
• Written Informed Consent cohort 1
• deceased donor kidney transplant recipient cohort 2
• patients with kidney allograft biopsy at center showing any type of rejection which is going to be treated
• patient wishing to repeatedly travel to center

Exclusion Criteria

cohort 1

• living donor
• multiple transplant
• dual transplant
• haematopoetic stem cell transplant in a history

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Prospective monitoring within 1 year follow-up	Biopsy	Patients after kidney transplantation from deceased donors (n=100) were prospectively enrolled and dd-cf DNA levels were measured at defined timepoints (0, D14, 1,2,3,4,6,9 and 12 months) within 12 months.
The effect of treatment cohort	Biopsy	Patients were enrolled at the time of biopsy with histologic and /or molecular signs of rejection. Donor-derived cell-free DNA (dd-cf DNA) were measured at the time of biopsy before centre standard of care treatment and then at weeks 1, 2 and 3 after biopsy.
The effect of treatment cohort	Blood Biomarkers - cfDNA	Patients were enrolled at the time of biopsy with histologic and /or molecular signs of rejection. Donor-derived cell-free DNA (dd-cf DNA) were measured at the time of biopsy before centre standard of care treatment and then at weeks 1, 2 and 3 after biopsy.
Prospective monitoring within 1 year follow-up	Blood Biomarkers - cfDNA	Patients after kidney transplantation from deceased donors (n=100) were prospectively enrolled and dd-cf DNA levels were measured at defined timepoints (0, D14, 1,2,3,4,6,9 and 12 months) within 12 months.
The effect of treatment cohort	Antirejection therapy	Patients were enrolled at the time of biopsy with histologic and /or molecular signs of rejection. Donor-derived cell-free DNA (dd-cf DNA) were measured at the time of biopsy before centre standard of care treatment and then at weeks 1, 2 and 3 after biopsy.

Primary Outcome Measures

Name	Time	Method
dd-cfDNA	4 weeks	Monitoring of effects of antirejection treatment

Trial Locations

Locations (1)

Institute for Clinical and Experimental Medicine; 🇨🇿 Prague, Czechia