Kidney Transplant Failure and RejectionNCT03466775
Anti-Angiotensin II Type 1 Receptor Antibodies and Kidney Transplant Outcomes
An observational study of Kidney Transplant Failure and Rejection, run by Paris Translational Research Center for Organ Transplantation at 2 sites in France.
Trial summary
Incompatibility between non-genetically identical donors and recipients has been increasingly recognized as the main contributing factor to solid allograft rejection and failure, through the triggering of donor-specific responses mediated by T- and B-lymphocytes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant Failure and Rejection
- What is being tested?
- Anti-angiotensin II type 1 receptor antibody measurement, Measurement of ENDAT expression level allograft and Allograft survival
- How many people
- 1,845 participants
- Where
- 2 sitesFrance
- Study dates
- 1 Jan 2008to 31 Dec 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: The study population includes kidney recipients undergoing transplantation between January 1, 2008 and December 31, 2012 at Necker and Saint-Louis Hospitals (Paris, France).
Who may be able to join
- Kidney recipient transplanted between January 1, 2008 and December 31, 2012
- Kidney recipient over 18 years of age
- Simultaneous histological and serological assessment within the first year after transplantation, including i) kidney allograft biopsy, ii) assessment of donor-specific anti-HLA antibodies, and available stored serum for anti-angiotensin II type 1 receptor antibody assessment
Who cannot join
- No simultaneous histological and serological assessment within the first year after transplantation, including i) absence of serum available for anti-angiotensin II type 1 receptor antibody assessment, and/or ii) absence of donor-specific anti-HLA antibody testing, and/or iii) absence of kidney allograft biopsy
- Inadequate kidney allograft biopsy according to the Banff classification for allograft rejection
- Combined transplantation
Trial locations and contacts
2 sites in 1 country.
France2 sites
Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Paris, 75010
Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
Paris, 75015
About this study
Incompatibility between non-genetically identical donors and recipients has been increasingly recognized as the main contributing factor to solid allograft rejection and failure, through the triggering of donor-specific responses mediated by T- and B-lymphocytes. The Human Leucocyte Antigen (HLA) system has been identified as the main target of donor-specific responses, especially through the production by the recipient of antibodies directed toward non-self donor HLA molecules expressed on the allograft endothelium. As a consequence, in organ transplantation, the current approach to immunological risk stratification, patient monitoring and rejection diagnosis is based on biomarkers derived from the HLA system. However, this approach does not provide a sufficient accuracy for the risk stratification and the diagnosis of immunological complications in solid organ transplantation, which still remain the dominant cause of allograft failure.
A recent body of evidence supports that specific non-HLA antigens expressed on the allograft endothelium may be relevant to allograft rejection, suggesting that a new strategy to transplant diagnostic testing at a non-HLA level would help to overcome the limitations of the current HLA-based approach to immunological assessment of transplant recipients. Among antibodies to non-HLA endothelial antigens, angiotensin II type 1 receptor activating antibodies have been the most widely reported antibodies to associate with the occurrence of allograft rejection, dysfunction and loss, even if their independent role, with respect to the presence of concomitant anti-HLA antibodies, has not been demonstrated.
Read the detailed description
The aims of this study are:
- To assess the incidence of post-transplant anti-angiotensin II type 1 receptor antibodies within the first year after transplantation in an unselected population of kidney transplant recipients.
- To investigate the incidence of biopsy-proven kidney allograft rejection according to the presence of post-transplant anti-angiotensin II type 1 receptor antibodies and of post-transplant concomitant donor-specific anti-HLA antibodies within the first year after transplantation, and to evaluate the incidence of rejection cases associated with anti-angiotensin II type 1-receptor antibodies that are not recognized by the current diagnostic approach based on HLA testing.
- To investigate the allograft injury phenotype associated with post-transplant anti-angiotensin II type 1 receptor, using histopathology, immunochemistry and measurement of endothelial-associated transcript (ENDAT) expression level in allograft.
- To evaluate the impact of post-transplant anti-angiotensin II type 1 receptor antibodies on kidney allograft survival up to 7 years after inclusion, in univariate and multivariable survival models including clinical, histological and immunological risk factors for allograft loss.
This study includes kidney recipients transplanted between January 1, 2008 and December 31, 2012 at Necker and Saint-Louis Hospitals (Paris, France), who undergo screening for post-transplant anti-angiotensin II type 1 receptor antibodies and simultaneous kidney allograft biopsy within the first year after transplantation, either at the time of an episode of rejection in the first year after transplantation or at 1 year after transplantation in the absence of previous rejection episode.
- Conditions
- Kidney Transplant Failure and Rejection
- Being tested
- Anti-angiotensin II type 1 receptor antibody measurement, Measurement of ENDAT expression level allograft, Allograft survival, Allograft rejection appearance
- Keywords
- Kidney transplantation, Allograft rejection, Allograft survival, Anti-angiotensin II type 1 receptor antibody
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-angiotensin II type 1 receptor antibody measurementDiagnostic test
Anti-angiotensin II type 1 receptor antibodies are assessed using quantitative ELISA in stored serum samples obtained within the first year after transplantation
Measurement of ENDAT expression level allograftDiagnostic test
Endothelial-associated transcript expression level is assessed using microarray in stored kidney allograft biopsies obtained within the first year after transplantation
Allograft survivalOther
Allograft rejection appearanceOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of biopsy-proven kidney allograft rejection according to the presence of post-transplant circulating anti-angiotensin II type 1 receptor antibodies within the first year after transplantation
Anti-angiotensin II type 1 receptor antibody positivity is defined by serum concentration >10 U/mL using quantitative ELISA. Stratified analysis is performed according to the presence of post-transplant concomitant circulating donor-specific anti-HLA antibodies detected by single antigen bead assay in serum. Allograft rejection is defined on the basis of the 2015 update of the Banff classification for allograft rejection.
Measured: One year after transplantation
Comparison of allograft injury phenotype according to post-transplant anti-angiotensin II type 1 receptor antibody status and concomitant donor-specific anti-HLA antibody status
Injury phenotype is based on histological allograft elementary lesions defined by the Banff classification (glomerulitis, peritubular capillaritis, interstitial inflammation, tubulitis, endarteritis, chronic allograft glomerulopathy, interstitial fibrosis, tubular atrophy, arteriosclerosis, arteriolar hyalinosis, C4d deposition in peritubular capillaries).
Measured: One year after transplantation
Association between the presence of post-transplant circulating anti-angiotensin II type 1 receptor antibodies and time to kidney allograft
Univariate and multivariable models are performed, including adjustment for recipient age and gender, biopsy indication, glomerular filtration rate, proteinuria, presence of post-transplant circulating donor-specific anti-HLA antibodies and histological elementary lesions defined by the Banff classification, assessed at the time of antibody detection.
Measured: Up to seven years after inclusion
Secondary outcomes (2)
Incidence of anti-angiotensin II Type 1 receptor antibodies in kidney transplant recipients within the first year after transplantation
Anti-angiotensin II type 1 receptor antibody positivity is defined by serum concentration >10 U/mL using quantitative ELISA.
Measured: One year after transplantation
Comparison of endothelial-associated transcript expression (ENDAT) levels according to anti-angiotensin II type 1 receptor antibody status and donor-specific anti-HLA antibody status
ENDAT expression levels are measured in kidney allograft biopsies performed at the time of antibody detection, showing microcirculation inflammation (sum of glomerulitis and peritubular capillaritis Banff scores >1), using microarray technology.
Measured: One year after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2018
- Study start1 Jan 2008
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Transplant Failure and 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,845 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paris Translational Research Center for Organ Transplantation
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Cardiovascular Research Berlin
- Responsible party
- Principal investigator, Carmen Lefaucheur, Paris Translational Research Center for Organ Transplantation
- Investigators
- Carmen Lefaucheur, Principal investigator, Paris Translational Research Center for Organ TransplantationAlexandre Loupy, Principal investigator, Paris Translational Research Center for Organ TransplantationDuska Dragun, Principal investigator, Clinic for Nephrology and Critical Care Medicine, Campus Virchow-Klinikum and Center for Cardiovascular Research, Medical Faculty of the Charité Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03466775
- Sponsor's protocol ID
- AT1R001
- Status last verified
- Mar 2018
- First submitted
- 9 Mar 2018
- Last updated
- 15 Mar 2018
- Results posted
- 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 15 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-Angiotensin II Type 1 Receptor Antibodies and Kidney Transplant Outcomes
- ClinicalTrials.gov ID
- NCT03466775
- Acronym / sponsor ID
- AT1R001
- Conditions
- Kidney Transplant Failure and Rejection
- Keywords
- Kidney transplantation, Allograft rejection, Allograft survival, Anti-angiotensin II type 1 receptor antibody
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,845 participants (actual)
- Lead sponsor
- Paris Translational Research Center for Organ TransplantationUniversity, hospital or other
- Collaborators
- Center for Cardiovascular Research Berlin
- Study start
- 1 Jan 2008 (actual)
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 15 Mar 2018 (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.
Incompatibility between non-genetically identical donors and recipients has been increasingly recognized as the main contributing factor to solid allograft rejection and failure, through the triggering of donor-specific responses mediated by T- and B-lymphocytes. The Human Leucocyte Antigen (HLA) system has been identified as the main target of donor-specific responses, especially through the production by the recipient of antibodies directed toward non-self donor HLA molecules expressed on the allograft endothelium. As a consequence, in organ transplantation, the current approach to immunological risk stratification, patient monitoring and rejection diagnosis is based on biomarkers derived from the HLA system. However, this approach does not provide a sufficient accuracy for the risk stratification and the diagnosis of immunological complications in solid organ transplantation, which still remain the dominant cause of allograft failure.
A recent body of evidence supports that specific non-HLA antigens expressed on the allograft endothelium may be relevant to allograft rejection, suggesting that a new strategy to transplant diagnostic testing at a non-HLA level would help to overcome the limitations of the current HLA-based approach to immunological assessment of transplant recipients. Among antibodies to non-HLA endothelial antigens, angiotensin II type 1 receptor activating antibodies have been the most widely reported antibodies to associate with the occurrence of allograft rejection, dysfunction and loss, even if their independent role, with respect to the presence of concomitant anti-HLA antibodies, has not been demonstrated.
Detailed description
The aims of this study are:
- To assess the incidence of post-transplant anti-angiotensin II type 1 receptor antibodies within the first year after transplantation in an unselected population of kidney transplant recipients.
- To investigate the incidence of biopsy-proven kidney allograft rejection according to the presence of post-transplant anti-angiotensin II type 1 receptor antibodies and of post-transplant concomitant donor-specific anti-HLA antibodies within the first year after transplantation, and to evaluate the incidence of rejection cases associated with anti-angiotensin II type 1-receptor antibodies that are not recognized by the current diagnostic approach based on HLA testing.
- To investigate the allograft injury phenotype associated with post-transplant anti-angiotensin II type 1 receptor, using histopathology, immunochemistry and measurement of endothelial-associated transcript (ENDAT) expression level in allograft.
- To evaluate the impact of post-transplant anti-angiotensin II type 1 receptor antibodies on kidney allograft survival up to 7 years after inclusion, in univariate and multivariable survival models including clinical, histological and immunological risk factors for allograft loss.
This study includes kidney recipients transplanted between January 1, 2008 and December 31, 2012 at Necker and Saint-Louis Hospitals (Paris, France), who undergo screening for post-transplant anti-angiotensin II type 1 receptor antibodies and simultaneous kidney allograft biopsy within the first year after transplantation, either at the time of an episode of rejection in the first year after transplantation or at 1 year after transplantation in the absence of previous rejection episode.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes kidney recipients undergoing transplantation between January 1, 2008 and December 31, 2012 at Necker and Saint-Louis Hospitals (Paris, France).
Key inclusion criteria (3 listed)
- Kidney recipient transplanted between January 1, 2008 and December 31, 2012
- Kidney recipient over 18 years of age
- Simultaneous histological and serological assessment within the first year after transplantation, including i) kidney allograft biopsy, ii) assessment of donor-specific anti-HLA antibodies, and available stored serum for anti-angiotensin II type 1 receptor antibody assessment
Key exclusion criteria (3 listed)
- No simultaneous histological and serological assessment within the first year after transplantation, including i) absence of serum available for anti-angiotensin II type 1 receptor antibody assessment, and/or ii) absence of donor-specific anti-HLA antibody testing, and/or iii) absence of kidney allograft biopsy
- Inadequate kidney allograft biopsy according to the Banff classification for allograft rejection
- Combined transplantation
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 |
|---|---|---|
| Anti-angiotensin II type 1 receptor antibody measurementAnti-angiotensin II type 1 receptor antibodies are assessed using quantitative ELISA in stored serum samples obtained within the first year after transplantation | Diagnostic test | – |
| Measurement of ENDAT expression level allograftEndothelial-associated transcript expression level is assessed using microarray in stored kidney allograft biopsies obtained within the first year after transplantation | Diagnostic test | – |
| Allograft survival | Other | – |
| Allograft rejection appearance | Other | – |
Primary outcome
Incidence of biopsy-proven kidney allograft rejection according to the presence of post-transplant circulating anti-angiotensin II type 1 receptor antibodies within the first year after transplantation
Time frame: One year after transplantation
Anti-angiotensin II type 1 receptor antibody positivity is defined by serum concentration >10 U/mL using quantitative ELISA. Stratified analysis is performed according to the presence of post-transplant concomitant circulating donor-specific anti-HLA antibodies detected by single antigen bead assay in serum. Allograft rejection is defined on the basis of the 2015 update of the Banff classification for allograft rejection.
Comparison of allograft injury phenotype according to post-transplant anti-angiotensin II type 1 receptor antibody status and concomitant donor-specific anti-HLA antibody status
Time frame: One year after transplantation
Injury phenotype is based on histological allograft elementary lesions defined by the Banff classification (glomerulitis, peritubular capillaritis, interstitial inflammation, tubulitis, endarteritis, chronic allograft glomerulopathy, interstitial fibrosis, tubular atrophy, arteriosclerosis, arteriolar hyalinosis, C4d deposition in peritubular capillaries).
Association between the presence of post-transplant circulating anti-angiotensin II type 1 receptor antibodies and time to kidney allograft
Time frame: Up to seven years after inclusion
Univariate and multivariable models are performed, including adjustment for recipient age and gender, biopsy indication, glomerular filtration rate, proteinuria, presence of post-transplant circulating donor-specific anti-HLA antibodies and histological elementary lesions defined by the Banff classification, assessed at the time of antibody detection.
2 secondary outcomes
Incidence of anti-angiotensin II Type 1 receptor antibodies in kidney transplant recipients within the first year after transplantation
Time frame: One year after transplantation
Comparison of endothelial-associated transcript expression (ENDAT) levels according to anti-angiotensin II type 1 receptor antibody status and donor-specific anti-HLA antibody status
Time frame: One year after transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2018.
- 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. This study is not recruiting at the moment.
Carmen Lefaucheur principal investigator
Paris Translational Research Center for Organ Transplantation
Alexandre Loupy principal investigator
Paris Translational Research Center for Organ Transplantation
Duska Dragun principal investigator
Clinic for Nephrology and Critical Care Medicine, Campus Virchow-Klinikum and Center for Cardiovascular Research, Medical Faculty of the Charité Berlin
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplant Failure and Rejection, run by Paris Translational Research Center for Organ Transplantation at 2 sites in France.
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 3 inclusion and 3 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: finished, as of the sponsor's last update on 15 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of biopsy-proven kidney allograft rejection according to the presence of post-transplant circulating anti-angiotensin II type 1 receptor antibodies within the first year after transplantation (time frame: One year after transplantation). The study lists 3 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 15 Mar 2018.