Molecular Markers of Acute Kidney Injury in Elderly Deceased Donors

Acute Kidney Injury Clinical Trial

— MoliDon  

Official title:

Molecular Markers of Acute Kidney Injury in Elderly Deceased Donors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06171438
• Other study ID #: G339-2021
• Status: Completed
• Start date: June 11, 2021
• Est. completion date: October 31, 2023

Study information

• Verified date: December 2023
• Source: Institute for Clinical and Experimental Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 31, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Kidney Transplantation
• Wounds and Injuries

Intervention

Diagnostic Test:
• Urine 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.
• Gene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
• Gene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).

Locations

Country	Name	City	State
Czechia	Institute for Clinical and Experimental Medicine	Prague

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Clinical and Experimental Medicine

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kidney graft function at month 3	Kidney graft function is measured as estimated glomerular filtration in ml/s/1.73m2.	3 months
Secondary	Kidney graft survival	Measured as numbers of patients with graft loss censored to death.	1 year
Secondary	Delayed graft function	The need of dialysis in the 1st week after transplantation. Measured as numbers of patients.	1 week
Secondary	Fibrosis grade at month 3	Histologic result of interstitial fibrosis and atrophy at protocol biopsy. Min 0, Max 3, higher means worse	3 months
Secondary	Gene expression in Donor kidney	Whole transcriptome microarray profiling of wedge biopsy taken immediately after organ procurement.	3 months
Secondary	Gene expression in 3-month protocol biopsy of recipient	Whole transcriptome microarray profiling of 3-months protocol biopsies of recipients .	3 months
Secondary	Urinary biomarkers of AKI in donors before organ taking	NGAL, Neutrophil gelatinase-associated lipocalin, ng/ml.	3 months
Secondary	Urinary biomarkers of AKI in donors before organ taking (NAG)	NAG, N-acetyl-beta-D-glucosamine, in IU/l	3 months
Secondary	Urinary biomarkers of AKI in donors before organ taking (beta 2 microglobulin)	beta 2 microglobulin, in mg/l	3 months
Secondary	Urinary biomarkers of AKI in donors before organ taking (alfa1 microglobulin)	alfa1 microglobulin, in mg/l	3 months
Secondary	Urinary biomarkers of AKI in donors before organ taking (alfa2 macroglobulin)	alfa2 macroglobulin, in mg/l	3 months
Secondary	Urinary biomarkers of AKI in donors before organ taking (transferrin)	transferrin, in mg/l	3 months