Kidney Transplant RejectionNCT04702022
Added Value of 18 FDG Pet-scanner in Diagnosis and Management of Subclinical Rejection in Kidney Transplant Patients
A study testing 18FDG PET / CT in people with Kidney Transplant Rejection and Kidney Transplant; Complications, run by University of Liege at 1 site in Belgium.
Trial summary
The renal biopsy (RB) represents the gold-standard for the diagnosis of acute renal transplant rejection (AR), and allows early verification of a so-called "subclinical" rejection, ie without any clinical or biological abnormality detectable in a stable kidney transplant patient. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant Rejection, Kidney Transplant; Complications
- What is being tested?
- 18FDG PET / CT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteBelgium
- Study dates
- 4 Jan 2021to 1 Jan 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Kidney recipients aged over 18 and of all sexes
Who cannot join
- Pregnant patients
- Polyomavirus nephropathy
- Highly sensitised patients (historical or at 3 months Donor specific antibodies)
- No corticosteroids withdrawal allowed (second kidney transplantation or primary disease)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site, 1 recruiting
- Recruiting
Antoine Bouquegneau
Liège, Liège, 4000
Antoine Bouquegneau, MD, +32473353321, antoine.bouquegneau@gmail.com
Francois Jouret, PhD, francois.jouret@chuliege.be
About this study
Official title: Non-invasive Diagnosis and Management of Subclinical Rejection in Kidney Transplant Patients Using 18F-fluorodeoxy Glucose Positron Emission Tomography (18FDG-PET/CT)
The renal biopsy (RB) represents the gold-standard for the diagnosis of acute renal transplant rejection (AR), and allows early verification of a so-called "subclinical" rejection, ie without any clinical or biological abnormality detectable in a stable kidney transplant patient. The RB also makes it possible to certify a strictly normal renal histology and thus to motivate the withdrawal of corticosteroid therapy. It is this 3-month post-transplant protocol RB protocol that has been effective since 2007 at the CHU Liège.
However, RB is an invasive procedure, contraindicated in patients taking anticoagulants, and carrying a significant risk of complications. The potential complications associated with RB motivate the identification and validation of other diagnostic means. In the present project, the investigators propose to study the relevance of positron emission tomography (PET), coupled with conventional tomography (CT), after intravenous injection of 18-fluoro-deoxy-glucose (18FDG) in the overall protocol of the renal transplant patient at 3 months post-transplant to:
Read more
(i) allow protocol renal biopsy only in patients with suspicion of an acute rejection (ii) be a decision maker for withdrawal from corticosteroids in the absence of rejection
In practice, the investigators suggest performing 18FDG PET / CT imaging on the day of the surveillance biopsy, which is systematically performed in all kidney transplant patients at University Hospital of Liège 3 months after transplant. The investigators are considering 3 scenarios:
- Scenario 1. The renal biopsy shows signs of humoral rejection: the patient is excluded from the study and is treated "as usual" on the basis of the histological results.
- Scenario 2. The renal biopsy does not show signs of humoral rejection but the 18FDG PET / CT shows a high metabolic activity of the graft (> 2.4): the patient is treated "as usual" on the basis of histological findings.
- Scenario 3. The renal biopsy does not show signs of humoral rejection and the 18FDG PET / CT shows a weak metabolic activity of the graft (<2.4): the immunosuppressive treatment is gradually weaned off corticosteroids.
This clinical research project is interested in a major health problem in the follow-up of renal transplant patients, and could make it possible to improve the management of a subclinical rejection of the renal transplant and to increase the withdrawal of corticosteroids including side effects are well known.
Read the detailed description
Subclinical rejection (SCR) has been defined as "the documentation by light histology of unexpected evidence of acute rejection (AR) in a stable patient". The diagnosis of SCR is important given that the treatment of subclinical T-cell-mediated AR results in similar long-term graft survival to that in patients without rejection. Surveillance transplant biopsies are, by definition, required for the diagnosis of SCR. Still, only 17% of transplant centers in the United States perform surveillance biopsies in all patients, whereas 62% do not perform surveillance biopsies at all because the incidence of SCR is low3. Non-invasive biomarkers may thus be developed as "rule out" tests, with the highest negative predictive value, in order to reduce the indiscriminate use of allograft biopsies in stable kidney transplant recipients (KTR). Beside urine-derived and blood-based biomarkers of SCR, the investigators have recently reported in a monocentric prospective pilot study that 18F-Fluorodeoxyglucose Positron Emission Tomography coupled with Computed Tomography (18F-FDG PET/CT) non-invasively rules out SCR at ~3 months post kidney transplantation (KTx).
In previous 92-patient cohort published by the investigators, the ratio between the mean standardized 18F-FDG uptake values (SUVs) of the renal allograft and the psoas muscle (used as reference tissue) was significantly higher in the group with biopsy-proven SCR versus the group with strictly normal histology. The area under the ROC curve (AUC) reached 0.79, with a negative predictive value of 98% using an mSUVR threshold of 2.4.
All adult KTR who undergo surveillance transplant biopsy at ~3 months post KTx are eligible for the present study, except pregnant women and patients PCR-proven BK nephropathy. Written informed consent will be obtained. KTx will be performed in accordance with the Declaration of Istanbul. Surveillance biopsies will be locally (in each participating centers) and centrally (at ULiège CHU) assessed by pathologists blinded to the results of 18F-FDG PET/CT. Banff 2017 classification will be conventionally used. Total inflammation (ti) will take into account interstitial inflammation in both non-sclerotic and sclerotic areas. C4d staining will be performed in all cases. PET/CT will be performed with late acquisitions (~180 minutes) after 18F-FDG intravenous injection (~3 Mbq/kg) within a 48-hour period around the biopsy, before any modification of immunosuppressive regimens. The mean standardized uptake value (mSUV) of kidney cortex will be measured and averaged from 4 volumes of interest (VOI) distributed in the upper (n=2) and lower (n=2) poles, both locally (in each participating centers) and centrally (at ULiège CHU)10. The mSUV of kidney will be normalized to the mSUV of psoas muscle (VOI of 20 ml) or the liver (VOI of 20 ml), considered as reference tissues in order to obtain the corresponding mean SUV Ratios (mSUVR).
The patients will be afterwards in one of these three categories :
- The renal biopsy shows signs of humoral rejection: the patient is excluded from the study and is treated "as usual" on the basis of the histological results.
- The renal biopsy does not show signs of humoral rejection but the 18FDG PET / CT shows a high metabolic activity of the graft (> 2.4): the patient is treated "as usual" on the basis of histological findings.
- The renal biopsy does not show signs of humoral rejection and the 18FDG PET / CT shows a weak metabolic activity of the graft (<2.4): the immunosuppressive treatment is gradually weaned off corticosteroids.
The goals are :
(i) to use the measurement of renal accumulation of the 18FDG marker at the level of the renal graft as a non-invasive indicator of the absence of a subclinical cellular rejection and to use the information from the renal biopsy only if the metabolic activity of the graft is increased.
(ii) to use the measurement of renal accumulation of the 18FDG marker in the renal graft as a non-invasive indicator of the absence of cell rejection and to initiate the withdrawal of corticosteroids if the metabolic activity of the graft is normal.
- Being tested
- 18FDG PET / CT
- Keywords
- PET/CT imaging, Corticoids withdrawal, SubClinical Rejection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
18FDG PET / CTDiagnostic test
The PET/CT procedure was performed using cross-calibrated Philips Gemini TF Big Bore or TF 16 PET/CT systems (Philips Medical Systems, Cleveland, OH) at 201 18 minutes following intravenous injection of a mean dose of 3.2 0.2 MBq/kg of body weight of 18 F-FDG. A low-dose helical CT (5-mm slice thickness, 120-kV tube voltage, and 40-mAs tube current-time product) centered to the renal transplant was performed, followed by PET scanning with two bed positions, each lasting 240 seconds. Images were reconstructed using iterative list mode time-of-flight algorithms. Corrections for attenuation, dead time and random and scatter events will be applied.
| Study group | Role | What they receive |
|---|---|---|
| Humoral Arm | Other | The renal biopsy shows signs of humoral rejection: the patient is excluded from the study and is treated "as usual" on the basis of the histological results. Receives: Diagnostic Test: 18FDG PET / CT |
| "Highly Metabolic patients" | Other | The renal biopsy does not show signs of humoral rejection but the 18FDG PET / CT shows a high metabolic activity of the graft (> 2.4): the patient is treated "as usual" on the basis of histological findings. Receives: Diagnostic Test: 18FDG PET / CT |
| " Low metabolic patients" | Other | The renal biopsy does not show signs of humoral rejection and the 18FDG PET / CT shows a weak metabolic activity of the graft (<2.4): the immunosuppressive treatment is gradually weaned off corticosteroids. Receives: Diagnostic Test: 18FDG PET / CT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prediction of rejection with 18 FDG data
use the measurement of renal accumulation of the 18FDG marker at the level of the renal graft as a non-invasive indicator of the absence of a subclinical cellular rejection and to use the information from the renal biopsy only if the metabolic activity of the graft is increased.
Measured: at 3 months
Withdrawal of corticosteroids with 18FDG data
use the measurement of renal accumulation of the 18FDG marker in the renal graft as a non-invasive indicator of the absence of cell rejection and to initiate the withdrawal of corticosteroids if the metabolic activity of the graft is normal
Measured: At 6 months
Secondary outcomes (1)
Allograft rejection
Incidence of rejection in patient with corticosteroids withdrawal
Measured: at 6 months and 1year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2021
- Study start4 Jan 2021
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Transplant RejectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Liege
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Antoine Bouquegneau, University of Liege
- Investigators
- Francois Jouret, Principal investigator, University of Liege
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04702022
- Sponsor's protocol ID
- Liege AVOID
- Status last verified
- May 2024
- First submitted
- 6 Jan 2021
- Last updated
- 9 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Diagnosis and Management of Subclinical Rejection in Kidney Transplant Patients Using 18F-fluorodeoxy Glucose Positron Emission Tomography (18FDG-PET/CT)
- ClinicalTrials.gov ID
- NCT04702022
- Acronym / sponsor ID
- Liege AVOID
- Keywords
- PET/CT imaging, Corticoids withdrawal, SubClinical Rejection
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of LiegeUniversity, hospital or other
- Study start
- 4 Jan 2021 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 8 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The renal biopsy (RB) represents the gold-standard for the diagnosis of acute renal transplant rejection (AR), and allows early verification of a so-called "subclinical" rejection, ie without any clinical or biological abnormality detectable in a stable kidney transplant patient. The RB also makes it possible to certify a strictly normal renal histology and thus to motivate the withdrawal of corticosteroid therapy. It is this 3-month post-transplant protocol RB protocol that has been effective since 2007 at the CHU Liège.
However, RB is an invasive procedure, contraindicated in patients taking anticoagulants, and carrying a significant risk of complications. The potential complications associated with RB motivate the identification and validation of other diagnostic means. In the present project, the investigators propose to study the relevance of positron emission tomography (PET), coupled with conventional tomography (CT), after intravenous injection of 18-fluoro-deoxy-glucose (18FDG) in the overall protocol of the renal transplant patient at 3 months post-transplant to:
(i) allow protocol renal biopsy only in patients with suspicion of an acute rejection (ii) be a decision maker for withdrawal from corticosteroids in the absence of rejection
In practice, the investigators suggest performing 18FDG PET / CT imaging on the day of the surveillance biopsy, which is systematically performed in all kidney transplant patients at University Hospital of Liège 3 months after transplant. The investigators are considering 3 scenarios:
- Scenario 1. The renal biopsy shows signs of humoral rejection: the patient is excluded from the study and is treated "as usual" on the basis of the histological results.
- Scenario 2. The renal biopsy does not show signs of humoral rejection but the 18FDG PET / CT shows a high metabolic activity of the graft (> 2.4): the patient is treated "as usual" on the basis of histological findings.
- Scenario 3. The renal biopsy does not show signs of humoral rejection and the 18FDG PET / CT shows a weak metabolic activity of the graft (<2.4): the immunosuppressive treatment is gradually weaned off corticosteroids.
This clinical research project is interested in a major health problem in the follow-up of renal transplant patients, and could make it possible to improve the management of a subclinical rejection of the renal transplant and to increase the withdrawal of corticosteroids including side effects are well known.
Detailed description
Subclinical rejection (SCR) has been defined as "the documentation by light histology of unexpected evidence of acute rejection (AR) in a stable patient". The diagnosis of SCR is important given that the treatment of subclinical T-cell-mediated AR results in similar long-term graft survival to that in patients without rejection. Surveillance transplant biopsies are, by definition, required for the diagnosis of SCR. Still, only 17% of transplant centers in the United States perform surveillance biopsies in all patients, whereas 62% do not perform surveillance biopsies at all because the incidence of SCR is low3. Non-invasive biomarkers may thus be developed as "rule out" tests, with the highest negative predictive value, in order to reduce the indiscriminate use of allograft biopsies in stable kidney transplant recipients (KTR). Beside urine-derived and blood-based biomarkers of SCR, the investigators have recently reported in a monocentric prospective pilot study that 18F-Fluorodeoxyglucose Positron Emission Tomography coupled with Computed Tomography (18F-FDG PET/CT) non-invasively rules out SCR at ~3 months post kidney transplantation (KTx).
In previous 92-patient cohort published by the investigators, the ratio between the mean standardized 18F-FDG uptake values (SUVs) of the renal allograft and the psoas muscle (used as reference tissue) was significantly higher in the group with biopsy-proven SCR versus the group with strictly normal histology. The area under the ROC curve (AUC) reached 0.79, with a negative predictive value of 98% using an mSUVR threshold of 2.4.
All adult KTR who undergo surveillance transplant biopsy at ~3 months post KTx are eligible for the present study, except pregnant women and patients PCR-proven BK nephropathy. Written informed consent will be obtained. KTx will be performed in accordance with the Declaration of Istanbul. Surveillance biopsies will be locally (in each participating centers) and centrally (at ULiège CHU) assessed by pathologists blinded to the results of 18F-FDG PET/CT. Banff 2017 classification will be conventionally used. Total inflammation (ti) will take into account interstitial inflammation in both non-sclerotic and sclerotic areas. C4d staining will be performed in all cases. PET/CT will be performed with late acquisitions (~180 minutes) after 18F-FDG intravenous injection (~3 Mbq/kg) within a 48-hour period around the biopsy, before any modification of immunosuppressive regimens. The mean standardized uptake value (mSUV) of kidney cortex will be measured and averaged from 4 volumes of interest (VOI) distributed in the upper (n=2) and lower (n=2) poles, both locally (in each participating centers) and centrally (at ULiège CHU)10. The mSUV of kidney will be normalized to the mSUV of psoas muscle (VOI of 20 ml) or the liver (VOI of 20 ml), considered as reference tissues in order to obtain the corresponding mean SUV Ratios (mSUVR).
The patients will be afterwards in one of these three categories :
- The renal biopsy shows signs of humoral rejection: the patient is excluded from the study and is treated "as usual" on the basis of the histological results.
- The renal biopsy does not show signs of humoral rejection but the 18FDG PET / CT shows a high metabolic activity of the graft (> 2.4): the patient is treated "as usual" on the basis of histological findings.
- The renal biopsy does not show signs of humoral rejection and the 18FDG PET / CT shows a weak metabolic activity of the graft (<2.4): the immunosuppressive treatment is gradually weaned off corticosteroids.
The goals are :
(i) to use the measurement of renal accumulation of the 18FDG marker at the level of the renal graft as a non-invasive indicator of the absence of a subclinical cellular rejection and to use the information from the renal biopsy only if the metabolic activity of the graft is increased.
(ii) to use the measurement of renal accumulation of the 18FDG marker in the renal graft as a non-invasive indicator of the absence of cell rejection and to initiate the withdrawal of corticosteroids if the metabolic activity of the graft is normal.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Humoral Arm | Other | Diagnostic Test: 18FDG PET / CTThe renal biopsy shows signs of humoral rejection: the patient is excluded from the study and is treated "as usual" on the basis of the histological results. |
| "Highly Metabolic patients" | Other | Diagnostic Test: 18FDG PET / CTThe renal biopsy does not show signs of humoral rejection but the 18FDG PET / CT shows a high metabolic activity of the graft (> 2.4): the patient is treated "as usual" on the basis of histological findings. |
| " Low metabolic patients" | Other | Diagnostic Test: 18FDG PET / CTThe renal biopsy does not show signs of humoral rejection and the 18FDG PET / CT shows a weak metabolic activity of the graft (<2.4): the immunosuppressive treatment is gradually weaned off corticosteroids. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Kidney recipients aged over 18 and of all sexes
Key exclusion criteria (4 listed)
- Pregnant patients
- Polyomavirus nephropathy
- Highly sensitised patients (historical or at 3 months Donor specific antibodies)
- No corticosteroids withdrawal allowed (second kidney transplantation or primary disease)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 18FDG PET / CTThe PET/CT procedure was performed using cross-calibrated Philips Gemini TF Big Bore or TF 16 PET/CT systems (Philips Medical Systems, Cleveland, OH) at 201 18 minutes following intravenous injection of a mean dose of 3.2 0.2 MBq/kg of body weight of 18 F-FDG. A low-dose helical CT (5-mm slice thickness, 120-kV tube voltage, and 40-mAs tube current-time product) centered to the renal transplant was performed, followed by PET scanning with two bed positions, each lasting 240 seconds. Images were reconstructed using iterative list mode time-of-flight algorithms. Corrections for attenuation, dead time and random and scatter events will be applied. | Diagnostic test | " Low metabolic patients", "Highly Metabolic patients", Humoral Arm |
Primary outcome
Prediction of rejection with 18 FDG data
Time frame: at 3 months
use the measurement of renal accumulation of the 18FDG marker at the level of the renal graft as a non-invasive indicator of the absence of a subclinical cellular rejection and to use the information from the renal biopsy only if the metabolic activity of the graft is increased.
Withdrawal of corticosteroids with 18FDG data
Time frame: At 6 months
use the measurement of renal accumulation of the 18FDG marker in the renal graft as a non-invasive indicator of the absence of cell rejection and to initiate the withdrawal of corticosteroids if the metabolic activity of the graft is normal
1 secondary outcome
Allograft rejection
Time frame: at 6 months and 1year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Francois Jouret principal investigator
University of Liege
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 18FDG PET / CT in people with Kidney Transplant Rejection and Kidney Transplant; Complications, run by University of Liege at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Antoine Bouquegneau (+32473353321, antoine.bouquegneau@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prediction of rejection with 18 FDG data (time frame: at 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.