Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection

Charite University, Berlin, Germany40 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Kidney Transplant Rejection Antibody-mediated Rejection Kidney Transplant Failure

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: 12 months after inclusion

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 12 Months

Clinical Outcome - estimated glomerular filtration rate (eGFR) 12 Months

Difference between eGFR decline after 12 months between control group and intervention group.

Time frame: 12 Months

Clinical Outcome - eGFR 24 Months

Difference between eGFR decline after 24 months between control group and intervention group.

Time frame: 24 Months

Clinical Outcome - albuminuria 12 Months

Difference between albuminuria after 12 months between control group and intervention group.

Time frame: 12 Months

Clinical Outcome - albuminuria 24 Months

Difference between albuminuria after 24 months between control group and intervention group.

Time frame: 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.

Time frame: 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.

Time frame: 24 Months

Clinical Outcome - Mortality 12 Months

Difference in Mortality after 12 months between control group and intervention group.

Time frame: 12 Months

Clinical Outcome - Mortality 24 Months

Difference in Mortality after 24 months between control group and intervention group.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 12 Months

Rate of ABMR

Number of biopsy proven active or chronic active ABMR in the cohort.

Time frame: 12 Months

DSA Levels 0 Months

Mean fluorescence intensity of immunodominant DSA

Time frame: at inclusion

DSA Levels 12 Months

Mean fluorescence intensity of immunodominant DSA at 12 months

Time frame: 12 months

DSA Levels 24 Months

Mean fluorescence intensity of immunodominant DSA at 24 months

Time frame: 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.

Time frame: 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

Time frame: 12 months after inclusion

Donor-derived Cell-free DNA for Early Diagnosis of Antibody-mediated Rejection

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes