Molecular Markers of Acute Kidney Injury in Elderly Deceased Donors
- Conditions
- Acute Kidney InjuryKidney Transplantation
- Interventions
- Diagnostic Test: Gene expression profiling of donor kidneys by microarrayDiagnostic Test: Urine BiomarkersDiagnostic Test: Gene expression profiling of recipient kidneys by microarray
- Registration Number
- NCT06171438
- Lead Sponsor
- Institute for Clinical and Experimental Medicine
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 200
- 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.
- Donors with circulatory death
- Donors with machine perfusion
- Donors with multiorgan transplantation.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Acute kidney injury (AKI) Gene expression profiling of recipient kidneys by microarray Donors with AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest. Recipient IFTA Gene expression profiling of recipient kidneys by microarray Donors and the paired recipients in whom the organ was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA≥2. Recipient no-IFTA Gene expression profiling of donor kidneys by microarray Donors and the paired recipients in whom the was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA\<2. Recipient no-IFTA Gene expression profiling of recipient kidneys by microarray Donors and the paired recipients in whom the was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA\<2. no-AKI Gene expression profiling of donor kidneys by microarray Donors without AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest. delayed graft function (DGF) Gene expression profiling of recipient kidneys by microarray 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. no-DGF Urine Biomarkers 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). no-DGF Gene expression profiling of donor kidneys by microarray 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). no-DGF Gene expression profiling of recipient kidneys by microarray 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). Recipient IFTA Gene expression profiling of donor kidneys by microarray Donors and the paired recipients in whom the organ was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA≥2. Acute kidney injury (AKI) Urine Biomarkers Donors with AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest. no-AKI Urine Biomarkers Donors without AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest. delayed graft function (DGF) Urine Biomarkers 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. Acute kidney injury (AKI) Gene expression profiling of donor kidneys by microarray Donors with AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest. no-AKI Gene expression profiling of recipient kidneys by microarray Donors without AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest. delayed graft function (DGF) Gene expression profiling of donor kidneys by microarray 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.
- Primary Outcome Measures
Name Time Method Kidney graft function at month 3 3 months Kidney graft function is measured as estimated glomerular filtration in ml/s/1.73m2.
- Secondary Outcome Measures
Name Time Method Delayed graft function 1 week The need of dialysis in the 1st week after transplantation. Measured as numbers of patients.
Gene expression in 3-month protocol biopsy of recipient 3 months Whole transcriptome microarray profiling of 3-months protocol biopsies of recipients .
Urinary biomarkers of AKI in donors before organ taking (NAG) 3 months NAG, N-acetyl-beta-D-glucosamine, in IU/l
Urinary biomarkers of AKI in donors before organ taking (alfa1 microglobulin) 3 months alfa1 microglobulin, in mg/l
Urinary biomarkers of AKI in donors before organ taking (transferrin) 3 months transferrin, in mg/l
Kidney graft survival 1 year Measured as numbers of patients with graft loss censored to death.
Fibrosis grade at month 3 3 months Histologic result of interstitial fibrosis and atrophy at protocol biopsy. Min 0, Max 3, higher means worse
Gene expression in Donor kidney 3 months Whole transcriptome microarray profiling of wedge biopsy taken immediately after organ procurement.
Urinary biomarkers of AKI in donors before organ taking (beta 2 microglobulin) 3 months beta 2 microglobulin, in mg/l
Urinary biomarkers of AKI in donors before organ taking 3 months NGAL, Neutrophil gelatinase-associated lipocalin, ng/ml.
Urinary biomarkers of AKI in donors before organ taking (alfa2 macroglobulin) 3 months alfa2 macroglobulin, in mg/l
Trial Locations
- Locations (1)
Institute for Clinical and Experimental Medicine
🇨🇿Prague, Czechia