Molecular Markers of Acute Kidney Injury in Elderly Deceased Donors

Completed

• Conditions: Acute Kidney Injury; Kidney Transplantation

• 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.

Study Timeline

• Study Start: 2021-06-11
• Primary Completion: 2022-12-01
• Study Completion: 2023-10-31
• Study First Submitted: 2023-11-28
• Status Verified: 2023-12
• Study First Submitted QC: 2023-12-12
• Last Update Submitted: 2023-12-12
• Study First Posted: 2023-12-14
• Last Update Posted: 2023-12-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

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