Clinical trial NCT06171438: Molecular Markers of Acute Kidney Injury in Elderly Deceased Donors
Official title: Molecular Markers of Acute Kidney Injury in Elderly Deceased Donors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Acute Kidney Injury
Keywords: kidney transplantation
donor kidney
microarray
Lead sponsor: Institute for Clinical and Experimental Medicine
Sponsor class: OTHER_GOV
First posted: 2023-12-14
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All DBD donors whose kidneys will be procured by IKEM transplant team either in donor hospital or at IKEM. Corresponding recipients, transplanted at IKEM will be further monitored. 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 (standard of care in the center).

Brief summary: Scoring systems that combine donor clinical and morphological parameters to predict outcome of kidney transplantation lack enough specificity to be generally accepted. Compare to classical histology, molecular assessment of renal tissue offers unbiased and technically robust approach. In this prospective 3-months' observational study procurement biopsies in 180 brain death donors will be performed. Using microarray which detect top differently regulated genes, conventional histology, urinary AKI biomarkers, renal function and clinical variables models predicting DGF and early graft scarring (IFTA, poor graft function) in recipients will be constructed. The associations of AKI in donors with distinct fibrosis atrophy and AKI molecular signals will be found. Molecular techniques and final models may help to improve the decision-making process for the acceptance of kidneys from marginal donors but more importantly, it may help clinicians to guide less toxic immunosuppression in identified problematic grafts.

Detailed description: The aim is to create a prediction model of early clinical outcome (delayed graft function) based on donor and recipient clinical variables, donor eGFR, urinary AKI biomarkers, histology (glomerulosclerosis, interstitial fibrosis, vascular changes) and top differently regulated genes found in microarray of wedge procurement donor biopsy. Construct a model capable to predict early renal allograft scarring (IFTA\>2), and impaired graft function (eGFR\<45 mL/min), as early as at 3 months. Describe renal molecular changes associated with established AKI in brain-death deceased donor and with aging.

Eligibility criteria: Inclusion Criteria:

* All DBD (donation after brain death) donors whose kidneys will be procured by transplant team of Institute for Clinical and Experimental Medicine (IKEM) in donor hospital.
* All DBD (donation after brain death) donors whose kidneys will be procured by transplant team of Institute for Clinical and Experimental Medicine (IKEM) at IKEM.

Exclusion Criteria:

* Donors with circulatory death
* Donors with machine perfusion
* Donors with multiorgan transplantation.

Primary outcomes:
measure: Kidney graft function at month 3
timeFrame: 3 months
Secondary outcomes:
measure: Kidney graft survival
timeFrame: 1 year
measure: Delayed graft function
timeFrame: 1 week
measure: Fibrosis grade at month 3
timeFrame: 3 months
measure: Gene expression in Donor kidney
timeFrame: 3 months
measure: Gene expression in 3-month protocol biopsy of recipient
timeFrame: 3 months
measure: Urinary biomarkers of AKI in donors before organ taking
timeFrame: 3 months
measure: Urinary biomarkers of AKI in donors before organ taking (NAG)
timeFrame: 3 months
measure: Urinary biomarkers of AKI in donors before organ taking (beta 2 microglobulin)
timeFrame: 3 months
measure: Urinary biomarkers of AKI in donors before organ taking (alfa1 microglobulin)
timeFrame: 3 months
measure: Urinary biomarkers of AKI in donors before organ taking (alfa2 macroglobulin)
timeFrame: 3 months
measure: Urinary biomarkers of AKI in donors before organ taking (transferrin)
timeFrame: 3 months
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
Study officials:
affiliation: Institute for Clinical and Experimental Medicine
name: Ondrej Viklicky, Prof.
role: PRINCIPAL_INVESTIGATOR
References: