Molecular Markers of Acute Kidney Injury in Elderly Deceased Donors (MoliDon)

Institute for Clinical and Experimental Medicine

Status: Completed

Conditions: Kidney Transplantation; Acute Kidney Injury

Treatments: Diagnostic Test: Gene expression profiling of donor kidneys by microarray; Diagnostic Test: Urine Biomarkers; Diagnostic Test: Gene expression profiling of recipient kidneys by microarray

Study type: Observational

Funder types: Other

Identifiers

NCT06171438

G339-2021

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 patients

Sex: All

Volunteers: No Healthy Volunteers

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.

Trial design

200 participants in 6 patient groups

Acute kidney injury (AKI)

Description:

Donors with AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest.

Treatment:

Diagnostic Test: Gene expression profiling of recipient kidneys by microarray

Diagnostic Test: Gene expression profiling of donor kidneys by microarray

Diagnostic Test: Urine Biomarkers

no-AKI

Description:

Donors without AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest.

Treatment:

Diagnostic Test: Gene expression profiling of recipient kidneys by microarray

Diagnostic Test: Gene expression profiling of donor kidneys by microarray

Diagnostic Test: Urine Biomarkers

delayed graft function (DGF)

Description:

Donors and the paired recipients in whom the organ was transplanted in IKEM (Institute for Clinical and Experimental Medicine) who developed delayed graft function (DGF) defined as dialysis in the 1st week after transplantation.

Treatment:

Diagnostic Test: Gene expression profiling of recipient kidneys by microarray

Diagnostic Test: Gene expression profiling of donor kidneys by microarray

Diagnostic Test: Urine Biomarkers

no-DGF

Description:

Donors and the paired recipients in whom the organ was transplanted in IKEM (Institute for Clinical and Experimental Medicine) with immediate graft function (no-DGF).

Treatment:

Diagnostic Test: Gene expression profiling of recipient kidneys by microarray

Diagnostic Test: Gene expression profiling of donor kidneys by microarray

Diagnostic Test: Urine Biomarkers

Recipient IFTA

Description:

Donors and the paired recipients in whom the organ was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA≥2.

Treatment:

Diagnostic Test: Gene expression profiling of recipient kidneys by microarray

Diagnostic Test: Gene expression profiling of donor kidneys by microarray

Recipient no-IFTA

Description:

Donors and the paired recipients in whom the was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA\<2.

Treatment:

Diagnostic Test: Gene expression profiling of recipient kidneys by microarray

Diagnostic Test: Gene expression profiling of donor kidneys by microarray