Donor-derived Cell-free DNA in Kidney Transplant Recipients (DEFILE)

Donor-derived Cell-free DNA (Dd-cfDNA) Monitoring to Detect Kidney Allograft Injury and Monitor the Effect Anti-rejection Treatment

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation; Acute Rejection of Renal Transplant
• Intervention / Treatment: Procedure: Biopsy; Diagnostic test: Blood Biomarkers - cfDNA; Drug: Antirejection therapy

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 Type: Observational
• Enrollment (Actual): 143

Contacts and Locations

Study Locations

• Czechia
  • Prague, Czechia, 140 21
    • Institute for Clinical and Experimental Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Kidney transplant recipients. Patients will receive standard immunosuppression based on tacrolimus, mycophenolate mofetil and steroids along with induction (basiliximab in low risk and rATG in high-risk) according to center protocol. All procedures in transplant recipients will be routine ones, included for cause biopsies and 3M protocol biopsy or antirejection therapy (standard of care in the center). Antirejection therapies are defined by center protocol and clinical team decision.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Prospective monitoring within 1 year follow-up; 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.	Procedure: Biopsy; Kidney allograft biopsy; Diagnostic test: Blood Biomarkers - cfDNA; dd-cfDNA; Other Names: dd-cfDNA
The effect of treatment cohort; 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.	Procedure: Biopsy; Kidney allograft biopsy; Diagnostic test: Blood Biomarkers - cfDNA; dd-cfDNA; Other Names: dd-cfDNA; Drug: Antirejection therapy; Patients will receive standard antirejection therapy according to center protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dd-cfDNA	dd-cfDNA monitoring active rejection and other allograft injuries	12 months
dd-cfDNA	Monitoring of effects of antirejection treatment	4 weeks

Collaborators and Investigators

• Sponsor: Institute for Clinical and Experimental Medicine
• Collaborators: Natera, Inc.
• Investigators: Principal Investigator: Ondrej Viklicky, M.D., Ph.D., Dept. of Nephrology, IKEM

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2021
• Primary Completion (Actual): May 12, 2024
• Study Completion (Actual): May 20, 2024

Study Registration Dates

• First Submitted: June 21, 2024
• First Submitted That Met QC Criteria: June 21, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 29, 2025
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Kidney Transplantation; dd-cfDNA; Acute Rejection of Renal Transplant; non-invasive test
• Other Study ID Numbers: 15689/21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No