Antibody-mediated Rejection, Kidney Transplant Failure, Kidney Transplant Rejection
Conditions
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.
Interventions
PROCEDUREKidney 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
Sponsors
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 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. |
| 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 - 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. |
| Clinical Outcome - albuminuria 12 Months | 12 Months | Difference between albuminuria after 12 months between control group and intervention group. |
| Clinical Outcome - albuminuria 24 Months | 24 Months | Difference between albuminuria after 24 months between control group and intervention group. |
| 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. |
| 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. |
| 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. |
| Clinical Outcome - Mortality 24 Months | 24 Months | Difference in Mortality after 24 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. |
| Rate of ABMR | 12 Months | Number of biopsy proven active or chronic active ABMR in the cohort. |
| DSA Levels 0 Months | at inclusion | Mean fluorescence intensity of immunodominant DSA |
| DSA Levels 12 Months | 12 months | Mean fluorescence intensity of immunodominant DSA at 12 months |
| DSA Levels 24 Months | 24 months | Mean fluorescence intensity of immunodominant DSA at 24 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 - Mortality 12 Months | 12 Months | Difference in Mortality after 12 months between control group and intervention group. |
Countries
Germany
Outcome results
None listed