Z94.0
Conditions
Interventions
Group 1: Surveillance-Setting:
Adult kidney transplant recipients (=18 years) are prospectively followed during the first year after transplantation. Blood and urine samples are collected at predefine
Sponsors
Innere Medizin X: Klinik für Nephrologie, Universitätsklinikum Heidelberg
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: -Age = 18 years -Kidney transplant recipients (living or deceased donor) with a transplantation date after January 2026 -Kidney transplant recipients with a clinical indication for biopsy -Written informed consent obtained after appropriate explanation of the study -Willingness and ability to participate in all scheduled visits and examinations during the 36-month follow-up period (as part of routine care) -Assignment to an immunological risk category (high, intermediate-high, intermediate-low, low) according to center practice
Exclusion criteria
Exclusion criteria: -Minors (<18 years) -Refusal or inability to provide informed consent (e.g., cognitive impairment, language barrier without translation support) -Participation in an interventional clinical study that influences immunological monitoring or therapy and could therefore bias the evaluation of study endpoints -Other serious medical, psychological, or social reasons which, in the judgment of the investigators, make study participation unreasonable or infeasible
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| (1) Predictive performance of the combined biomarker signature Objective: To determine the AUC/ROC of the combined biomarkers (donor-derived cell-free DNA [dd-cfDNA], urinary chemokines, immune cell phenotyping in blood and urine, Torque Teno Virus [TTV], and—if available—molecular biopsy signatures) for the prediction of biopsy-proven acute rejection (T-cell mediated rejection [TCMR] or antibody-mediated rejection [ABMR], including Banff borderline lesions) or clinically relevant allograft injury: a) in the surveillance setting, within 30 days after a scheduled study visit (day 7 or 14 [depending on timing of routine testing], 30, 90, 180, and 360 post-transplant), and b) in the for-cause setting, at the time of indication biopsy performed due to clinical abnormalities (e.g., increase in serum creatinine, proteinuria) at any time after transplantation. The aim is to analyze the predictive performance of the biomarker signature separately in both settings and to evaluate differences in sensitivity, specificity, and predictive value in the context of different pre-test probabilities for rejection. Comparator: ?AUC compared with a reference model based on standard parameters (serum creatinine, immunosuppressive drug levels, DSA status, baseline variables). (2) Time-dependent association between biomarker increase and rejection events Objective: To determine the hazard ratio of a pre-specified biomarker increase (e.g., dd-cfDNA >0.5% or =67% individual increase compared to the reference change value) as a time-dependent covariate for the time to the first biopsy-proven acute rejection within the first year after transplantation in the surveillance setting. | — |
Secondary
| Measure | Time frame |
|---|---|
| (1) Performance of individual biomarkers (AUC, sensitivity, specificity, PPV, NPV) at each measurement time point for near-term (=30 days) and short-term (=90 days) rejection, stratified by immunological risk class (high-, intermediate-high-, intermediate-low-, and low-risk) (2) Incremental value of biomarkers compared with standard monitoring (?AUC) with regard to: -biopsy-proven acute rejection, -development of de novo donor-specific antibodies (dnDSA), -deterioration of graft function (=30% decline in eGFR compared with 1-month baseline, confirmed for =4 weeks), -composite endpoint: biopsy-proven rejection or persistent graft function decline (=30% eGFR decrease confirmed for =4 weeks) or de novo DSA or graft failure/death. | — |
Countries
Germany
Contacts
Public ContactLouise Benning
Innere Medizin X: Klinik für Nephrologie, Universitätsklinikum Heidelberg
Outcome results
None listed