Acute Kidney Injury, Kidney Transplantation
Conditions
Keywords
kidney transplantation, donor kidney, microarray
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.
Interventions
DIAGNOSTIC_TESTUrine Biomarkers
Biomarkers of kidney damage in donors, such as neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), beta2-microglobulin, alpha1-microglobulin, alpha2-macroglobulin and transferrin will be measured by ELISA.
DIAGNOSTIC_TESTGene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
DIAGNOSTIC_TESTGene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Sponsors
Institute for Clinical and Experimental Medicine
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kidney graft function at month 3 | 3 months | Kidney graft function is measured as estimated glomerular filtration in ml/s/1.73m2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delayed graft function | 1 week | The need of dialysis in the 1st week after transplantation. Measured as numbers of patients. |
| 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. |
| 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 | 3 months | NGAL, Neutrophil gelatinase-associated lipocalin, ng/ml. |
| Kidney graft survival | 1 year | Measured as numbers of patients with graft loss censored to death. |
| 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 (alfa1 microglobulin) | 3 months | alfa1 microglobulin, in mg/l |
| Urinary biomarkers of AKI in donors before organ taking (alfa2 macroglobulin) | 3 months | alfa2 macroglobulin, in mg/l |
| Urinary biomarkers of AKI in donors before organ taking (transferrin) | 3 months | transferrin, in mg/l |
| Urinary biomarkers of AKI in donors before organ taking (NAG) | 3 months | NAG, N-acetyl-beta-D-glucosamine, in IU/l |
Countries
Czechia
Outcome results
None listed