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

December 12, 2023 updated by: Prof. Ondřej Viklický, M.D., Ph.D., Institute for Clinical and Experimental Medicine
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Czechia
      • Prague, Czechia, 140 21
        • Institute for Clinical and Experimental Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All DBD donors whose kidneys will be procured by IKEM transplant team either in donor hospital or at IKEM. Corresponding recipients, transplanted at IKEM will be further monitored. Patients will receive standard immunosuppression based on tacrolimus, mycophenolate mofetil and steroids along with induction (basiliximab in low risk and rATG in high-risk) according to center protocol. All procedures in transplant recipients will be routine ones, included for cause biopsies and 3M protocol biopsy (standard of care in the center).

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Acute kidney injury (AKI)
Donors with AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest.
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.
Diagnostic test: Gene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Diagnostic test: Gene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
no-AKI
Donors without AKI (acute kidney injury) defined based on the results of creatinine increase and diuresis decrease before organ harvest.
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.
Diagnostic test: Gene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Diagnostic test: Gene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
delayed graft function (DGF)
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.
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.
Diagnostic test: Gene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Diagnostic test: Gene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
no-DGF
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).
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.
Diagnostic test: Gene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Diagnostic test: Gene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Recipient IFTA
Donors and the paired recipients in whom the organ was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA≥2.
Diagnostic test: Gene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Diagnostic test: Gene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Recipient no-IFTA
Donors and the paired recipients in whom the was transplanted in IKEM with 3-month protocol biopsy histology finding of IFTA<2.
Diagnostic test: Gene expression profiling of donor kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).
Diagnostic test: Gene expression profiling of recipient kidneys by microarray
Gene expression profiling of donor kidney biopsies using Affymetrix microarray platform (PrimeView Human Gene Expression Array).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Kidney graft function at month 3
Time Frame: 3 months
Kidney graft function is measured as estimated glomerular filtration in ml/s/1.73m2.
3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Kidney graft survival
Time Frame: 1 year
Measured as numbers of patients with graft loss censored to death.
1 year
Delayed graft function
Time Frame: 1 week
The need of dialysis in the 1st week after transplantation. Measured as numbers of patients.
1 week
Fibrosis grade at month 3
Time Frame: 3 months
Histologic result of interstitial fibrosis and atrophy at protocol biopsy. Min 0, Max 3, higher means worse
3 months
Gene expression in Donor kidney
Time Frame: 3 months
Whole transcriptome microarray profiling of wedge biopsy taken immediately after organ procurement.
3 months
Gene expression in 3-month protocol biopsy of recipient
Time Frame: 3 months
Whole transcriptome microarray profiling of 3-months protocol biopsies of recipients .
3 months
Urinary biomarkers of AKI in donors before organ taking
Time Frame: 3 months
NGAL, Neutrophil gelatinase-associated lipocalin, ng/ml.
3 months
Urinary biomarkers of AKI in donors before organ taking (NAG)
Time Frame: 3 months
NAG, N-acetyl-beta-D-glucosamine, in IU/l
3 months
Urinary biomarkers of AKI in donors before organ taking (beta 2 microglobulin)
Time Frame: 3 months
beta 2 microglobulin, in mg/l
3 months
Urinary biomarkers of AKI in donors before organ taking (alfa1 microglobulin)
Time Frame: 3 months
alfa1 microglobulin, in mg/l
3 months
Urinary biomarkers of AKI in donors before organ taking (alfa2 macroglobulin)
Time Frame: 3 months
alfa2 macroglobulin, in mg/l
3 months
Urinary biomarkers of AKI in donors before organ taking (transferrin)
Time Frame: 3 months
transferrin, in mg/l
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institute for Clinical and Experimental Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ondrej Viklicky, Prof., Institute for Clinical and Experimental Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 11, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 28, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 14, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • G339-2021

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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