Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection (cfDNA-DSA)

Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection in Kidney Transplant Recipient with Donor-specific Antibodies

Patients after kidney transplantation who develop donor-specific antibodies (DSA) are at high risk for antibody-mediated rejection (ABMR). Donor-derived cell-free DNA (dd-cfDNA) levels have been shown to be increased in patients with active or chronic active ABMR. This study aims to evaluate if repeated analysis of dd-cfDNA in patients with DSA and kidney allograft biopsy which is triggered by increased levels of dd-cfDNA can lead to early diagnosis of active or chronic active ABMR among these patients.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Rejection; Antibody-mediated Rejection; Kidney Transplant Failure
• Intervention / Treatment: Procedure: Kidney allograft biopsy depending on donor-derived cell-free DNA levels

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité-Universitätsmedizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients 18 years or older
• patients provided written informed consent
• patients after kidney transplantation
• functioning kidney allograft, at least after 180 days after last transplantation
• estimated glomerular filtration rate above 20 ml/min/1.73m^2
• detection of DSA

Exclusion Criteria:

• patients younger than 18 years
• patients unable or did not provide written informed consent
• pregnant or breastfeeding persons
• patients with increased bleeding risk
• patients with multi-organ transplantation
• patients who underwent kidney allograft biopsy after first detection of DSA
• biopsy-proven antibody-mediated rejection
• participation in another interventional clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Additionally to standard of care, measurements for donor-derived cell-free DNA (dd-cfDNA) are performed at months 0, 1, 3, 6, 9, and 12. If absolute levels of dd-cfDNA are > 50 copies/ml, the patients receive a kidney allograft biopsy. Additionally, kidney allograft biopsies are performed according to standard of care as determined by the treating physicians.	Procedure: Kidney allograft biopsy depending on donor-derived cell-free DNA levels; Kidney allograft biopsy is performed, when absolute levels of donor-derived cell-free DNA are above 50 copies/ml
No Intervention: Control; Additionally to standard of care, measurements for donor-derived cell-free DNA (dd-cfDNA) are performed at months 0, 1, 3, 6, 9, and 12. These measurements are not used to guide kidney allograft biopsies. Those are performed according to standard of care as determined by the treating physicians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from study inclusion to diagnosis of antibody-mediated rejection	Time from study inclusion date to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection	12 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of absolute dd-cfDNA for detection of ABMR	Sensitivity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Specificity of absolute dd-cfDNA for detection of ABMR	Specificity of dd-cfDNA > 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Receiver operating characteristics (ROC) analysis of absolute dd-cfDNA for detection of ABMR	ROC analysis for dd-cfDNA to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Sensitivity of intraindividual dd-cfDNA changes for detection of ABMR	Sensitivity of dd-cfDNA increase of > 25% to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Sensitivity of combined dd-cfDNA criterion for detection of ABMR	Sensitivity of the combination of "dd-cfDNA increase of > 25%" OR "absolute dd-cfDNA > 50 copies/ml" to predict the occurence of active or chronic active ABMR in patients with DSA.	12 Months
Clinical Outcome - estimated glomerular filtration rate (eGFR) 12 Months	Difference between eGFR decline after 12 months between control group and intervention group.	12 Months
Clinical Outcome - eGFR 24 Months	Difference between eGFR decline after 24 months between control group and intervention group.	24 Months
Clinical Outcome - albuminuria 12 Months	Difference between albuminuria after 12 months between control group and intervention group.	12 Months
Clinical Outcome - albuminuria 24 Months	Difference between albuminuria after 24 months between control group and intervention group.	24 Months
Clinical Outcome - Death-censored Graft Failure 12 Months	Difference in Death-censored Graft Failure after 12 months between control group and intervention group.	12 Months
Clinical Outcome - Death-censored Graft Failure 24 Months	Difference in Death-censored Graft Failure after 24 months between control group and intervention group.	24 Months
Clinical Outcome - Mortality 12 Months	Difference in Mortality after 12 months between control group and intervention group.	12 Months
Clinical Outcome - Mortality 24 Months	Difference in Mortality after 24 months between control group and intervention group.	24 Months
Clinical Outcome - Severe Infection 12 Months	Difference in occurence of severe infections (hospitalization, organ failure, death) during 12 months between control group and intervention group.	12 Months
Clinical Outcome - Severe Infection 24 Months	Difference in occurence of severe infections (hospitalization, organ failure, death) during 24 months between control group and intervention group.	24 Months
Adverse Events of Kidney Transplant Biopsy	Occurence of Complications from Kidney Transplant Biopsies, including Duration and potential therapy to treat the adverse event.	12 Months
Rate of ABMR	Number of biopsy proven active or chronic active ABMR in the cohort.	12 Months
DSA Levels 0 Months	Mean fluorescence intensity of immunodominant DSA	at inclusion
DSA Levels 12 Months	Mean fluorescence intensity of immunodominant DSA at 12 months	12 months
DSA Levels 24 Months	Mean fluorescence intensity of immunodominant DSA at 24 months	24 months
Immunosuppressive Regimen	Report of immunosuppressive medication at the following time points: 0,1,3,6,9,12,24 months, changes of medication, additional therapies such as plasmapheresis, or experimental therapies.	24 months
Time from first DSA occurrence to diagnosis of antibody-mediated rejection	Time from first DSA occurrence to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection	12 months after inclusion

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Klemens Budde, MD, Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): July 18, 2023
• Study Completion (Actual): September 9, 2024

Study Registration Dates

• First Submitted: May 18, 2021
• First Submitted That Met QC Criteria: May 18, 2021
• First Posted (Actual): May 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: CHA-NTX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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