Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection
- Conditions
- Antibody-mediated RejectionKidney Transplant RejectionKidney Transplant Failure
- Interventions
- Procedure: Kidney allograft biopsy depending on donor-derived cell-free DNA levels
- Registration Number
- NCT04897438
- Lead Sponsor
- Charite University, Berlin, Germany
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention Kidney allograft biopsy depending on donor-derived cell-free DNA levels 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.
- Primary Outcome Measures
Name Time Method Time from study inclusion to diagnosis of antibody-mediated rejection 12 months after inclusion Time from study inclusion date to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection
- Secondary Outcome Measures
Name Time Method Sensitivity of intraindividual dd-cfDNA changes for detection of ABMR 12 Months Sensitivity of dd-cfDNA increase of \> 25% to predict the occurence of active or chronic active ABMR in patients with DSA.
Clinical Outcome - Death-censored Graft Failure 24 Months 24 Months Difference in Death-censored Graft Failure after 24 months between control group and intervention group.
Clinical Outcome - estimated glomerular filtration rate (eGFR) 12 Months 12 Months Difference between eGFR decline after 12 months between control group and intervention group.
Clinical Outcome - eGFR 24 Months 24 Months Difference between eGFR decline after 24 months between control group and intervention group.
Rate of ABMR 12 Months Number of biopsy proven active or chronic active ABMR in the cohort.
Clinical Outcome - albuminuria 12 Months 12 Months Difference between albuminuria after 12 months between control group and intervention group.
Clinical Outcome - Mortality 24 Months 24 Months Difference in Mortality after 24 months between control group and intervention group.
Specificity of absolute dd-cfDNA for detection of ABMR 12 Months Specificity of dd-cfDNA \> 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.
DSA Levels 0 Months at inclusion Mean fluorescence intensity of immunodominant DSA
Sensitivity of absolute dd-cfDNA for detection of ABMR 12 Months Sensitivity of dd-cfDNA \> 50 copies/ml to predict the occurence of active or chronic active ABMR in patients with DSA.
Receiver operating characteristics (ROC) analysis of absolute dd-cfDNA for detection of ABMR 12 Months ROC analysis for dd-cfDNA to predict the occurence of active or chronic active ABMR in patients with DSA.
Sensitivity of combined dd-cfDNA criterion for detection of ABMR 12 Months 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.
Clinical Outcome - Death-censored Graft Failure 12 Months 12 Months Difference in Death-censored Graft Failure after 12 months between control group and intervention group.
DSA Levels 12 Months 12 months Mean fluorescence intensity of immunodominant DSA at 12 months
Immunosuppressive Regimen 24 months 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.
Time from first DSA occurrence to diagnosis of antibody-mediated rejection 12 months after inclusion Time from first DSA occurrence to biopsy-proven diagnosis of active or chronic active antibody-mediated rejection
Clinical Outcome - albuminuria 24 Months 24 Months Difference between albuminuria after 24 months between control group and intervention group.
Clinical Outcome - Mortality 12 Months 12 Months Difference in Mortality after 12 months between control group and intervention group.
Clinical Outcome - Severe Infection 12 Months 12 Months Difference in occurence of severe infections (hospitalization, organ failure, death) during 12 months between control group and intervention group.
Clinical Outcome - Severe Infection 24 Months 24 Months Difference in occurence of severe infections (hospitalization, organ failure, death) during 24 months between control group and intervention group.
Adverse Events of Kidney Transplant Biopsy 12 Months Occurence of Complications from Kidney Transplant Biopsies, including Duration and potential therapy to treat the adverse event.
DSA Levels 24 Months 24 months Mean fluorescence intensity of immunodominant DSA at 24 months
Trial Locations
- Locations (1)
Charité-Universitätsmedizin
🇩🇪Berlin, Germany