Clinical trial NCT06476717: Donor-derived Cell-free DNA in Kidney Transplant Recipients
Official title: Donor-derived Cell-free DNA (Dd-cfDNA) Monitoring to Detect Kidney Allograft Injury and Monitor the Effect Anti-rejection Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Acute Rejection of Renal Transplant
Keywords: Kidney Transplantation
Acute Rejection of Renal Transplant
dd-cfDNA
non-invasive test
Lead sponsor: Institute for Clinical and Experimental Medicine
Sponsor class: OTHER_GOV
Collaborators: name: Natera, Inc.
First posted: 2024-06-26
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Kidney transplant recipients. Patients will receive standard immunosuppression based on tacrolimus, mycophenolate mofetil and steroids along with induction (basiliximab in low risk and rATG in high-risk) according to center protocol. All procedures in transplant recipients will be routine ones, included for cause biopsies and 3M protocol biopsy or antirejection therapy (standard of care in the center). Antirejection therapies are defined by center protocol and clinical team decision.

Brief summary: Donor-derived cell-free DNA (dd-cfDNA) is a promising non-invasive biomarker of kidney allograft rejection. In this prospective, single center, observational monitoring study, we aim to evaluate a role of dd-cfDNA in predicting kidney allograft injuries, i.e. rejection and non-rejection injuries within 12 months, and to monitor the effect of anti rejection treatment.

Detailed description: Kidney transplantation represents the best therapeutic option in patients with end-stage kidney disease. Among main causes of graft loss belongs kidney allograft rejection which is diagnosed based on histology/molecular assessment of biopsy sample. This is invasive procedure, but provides more precise result regarding type of rejection. Contrary, donor-derived cell-free DNA (dd-cfDNA) is a novel non-invasive biomarker of allograft rejection with excellent negative predictive power. Moreover it may be useful for predicting allograft injuries and resolution of injuries after treatment.

In the prospective cohort, 100 renal allograft patients will be enrolled and dd-cfDNA levels determined from blood collected at predefined time points (preTX, POD14, M1, 2, 3, 4, 6, 9, 12).

In the second cohort, 40 patients will be enrolled at the time of biopsy with histological and/or molecular diagnosis of rejection and dd-cfDNA levels measured just before initiation of treatment and then at week 1, 2 and 3 after biopsy.

Peripheral blood will be collected in 2x 10 ml cfDNA (Streck) collection tubes for each study visit and dd-cfDNA will be quantified by the Prospera™ test (Natera Inc., Austin, Texas).

All patients will receive standard of care treatment according to centre protocol and no patients or providers will receive the results of dd-cfDNA testing during the study. Study protocol and patient informed consent were approved by Ethical committee.

Eligibility criteria: Inclusion Criteria:

* Recipient age ≥ 18 years and \<85 years
* Written Informed Consent cohort 1
* deceased donor kidney transplant recipient cohort 2
* patients with kidney allograft biopsy at center showing any type of rejection which is going to be treated
* patient wishing to repeatedly travel to center

Exclusion Criteria:

cohort 1

* living donor
* multiple transplant
* dual transplant
* haematopoetic stem cell transplant in a history

Primary outcomes:
measure: dd-cfDNA
timeFrame: 12 months
measure: dd-cfDNA
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
Study officials:
affiliation: Dept. of Nephrology, IKEM
name: Ondrej Viklicky, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: