Kidney TransplantationNCT06436586
Impact of HLA Evolutionary Divergence and HLA Donor-recipient Molecular Mismatches on Kidney Allograft Rejection
An observational study of Kidney Transplantation, run by Paris Translational Research Center for Organ Transplantation at 1 site in France.
Trial summary
The Human Leucocyte Antigen (HLA) system is pivotal in kidney transplant rejection. In-silico methods such as HLA eplet mismatches and PIRCHE-II scores have emerged to refine HLA immunogenicity assessment and stratify patients for immunological risk. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Kidney Transplantation
- How many people
- 5,159 participants
- Where
- 1 siteFrance
- Study dates
- 1 Feb 2022to 1 Jan 2023
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Kidney transplant recipients from four French referral centers
Who may be able to join
- Living or deceased donor kidney recipient transplanted after 2004
- Kidney recipient older than 18 years of age
- Written informed consent at the time of transplantation for the center database
Who cannot join
- Combined transplantation
Trial locations and contacts
1 site in 1 country.
France1 site
Paris Translational Research Center for Organ Transplantation
Paris, 75015
About this study
Official title: Impact of HLA Evolutionary Divergence and HLA Donor-recipient Molecular Mismatches on Kidney Allograft Rejection: a Population-based Study
The Human Leucocyte Antigen (HLA) system is pivotal in kidney transplant rejection. In-silico methods such as HLA eplet mismatches and PIRCHE-II scores have emerged to refine HLA immunogenicity assessment and stratify patients for immunological risk. However, large-scale studies in unselected large kidney transplant cohorts are lacking to support their broader clinical applicability. Additionally, recent studies on HLA evolutionary divergence (HED), quantifying HLA polymorphism, highlight its potential impact on rejection. Yet, the association of HED with kidney allograft rejection or de novo DSA occurrence remains unexplored in kidney transplantation.
The complexity introduced by diverse in-silico methods for assessing HLA immunogenicity necessitates further research to comprehensively understand their role in relation to kidney allograft rejection.
This project thus aims to investigate the association between various aspects of HLA immunogenicity, including HLA molecular mismatches and HLA evolutionary divergence, along with standard immunological and clinical parameters assessed at the time of transplantation, with the occurrence of antibody-mediated rejection and de novo DSA formation post-transplant in a large, comprehensively annotated kidney transplant cohort.
- Conditions
- Kidney Transplantation
- Being tested
- No intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
No intervention
What is being measured
The primary outcome is the main question the study is designed to answer.
Antibody-mediated rejection
Measured: from 02/01/2004 to 25/01/2021
Secondary outcomes (1)
De novo anti-HLA donor-specific antibody
Measured: from 02/01/2004 to 25/01/2021
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2024
- Study start1 Feb 2022
- Primary completion1 Jan 2023
- Study completion1 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies 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
- Prospective
- Enrolment
- 5,159 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paris Translational Research Center for Organ Transplantation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06436586
- Sponsor's protocol ID
- HLA_kidney_001
- Status last verified
- May 2024
- First submitted
- 24 May 2024
- Last updated
- 31 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bestard O, Thaunat O, Bellini MI, Bohmig GA, Budde K, Claas F, Couzi L, Furian L, Heemann U, Mamode N, Oberbauer R, Pengel L, Schneeberger S, Naesens M. Alloimmune Risk Stratification for Kidney Transplant Rejection. Transpl Int. 2022 May 20;35:10138. doi: 10.3389/ti.2022.10138. eCollection 2022.
PubMed 35669972Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012 Feb;12(2):388-99. doi: 10.1111/j.1600-6143.2011.03840.x. Epub 2011 Nov 14.
PubMed 22081892Wiebe C, Rush DN, Nevins TE, Birk PE, Blydt-Hansen T, Gibson IW, Goldberg A, Ho J, Karpinski M, Pochinco D, Sharma A, Storsley L, Matas AJ, Nickerson PW. Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development. J Am Soc Nephrol. 2017 Nov;28(11):3353-3362. doi: 10.1681/ASN.2017030287. Epub 2017 Jul 20.
PubMed 28729289Lachmann N, Niemann M, Reinke P, Budde K, Schmidt D, Halleck F, Pruss A, Schonemann C, Spierings E, Staeck O. Donor-Recipient Matching Based on Predicted Indirectly Recognizable HLA Epitopes Independently Predicts the Incidence of De Novo Donor-Specific HLA Antibodies Following Renal Transplantation. Am J Transplant. 2017 Dec;17(12):3076-3086. doi: 10.1111/ajt.14393. Epub 2017 Jul 28.
PubMed 28613392Feray C, Taupin JL, Sebagh M, Allain V, Demir Z, Allard MA, Desterke C, Coilly A, Saliba F, Vibert E, Azoulay D, Guettier C, Chatton A, Debray D, Caillat-Zucman S, Samuel D. Donor HLA Class 1 Evolutionary Divergence Is a Major Predictor of Liver Allograft Rejection : A Retrospective Cohort Study. Ann Intern Med. 2021 Oct;174(10):1385-1394. doi: 10.7326/M20-7957. Epub 2021 Aug 24.
PubMed 34424731Demir Z, Raynaud M, Divard G, Louis K, Truchot A, Niemann M, Ponsirenas R, Aubert O, Del Bello A, Hertig A, Anglicheau D, Dale B, Kamar N, Mangiola M, Zeevi A, Lefaucheur C, Loupy A. Impact of HLA evolutionary divergence and donor-recipient molecular mismatches on antibody-mediated rejection of kidney allografts. Nat Commun. 2025 Jul 1;16(1):5692. doi: 10.1038/s41467-025-60485-y.
PubMed 40592858
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of HLA Evolutionary Divergence and HLA Donor-recipient Molecular Mismatches on Kidney Allograft Rejection: a Population-based Study
- ClinicalTrials.gov ID
- NCT06436586
- Acronym / sponsor ID
- HLA_kidney_001
- Conditions
- Kidney Transplantation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 5,159 participants (actual)
- Lead sponsor
- Paris Translational Research Center for Organ TransplantationUniversity, hospital or other
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 Jan 2023 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 31 May 2024 (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 Human Leucocyte Antigen (HLA) system is pivotal in kidney transplant rejection. In-silico methods such as HLA eplet mismatches and PIRCHE-II scores have emerged to refine HLA immunogenicity assessment and stratify patients for immunological risk. However, large-scale studies in unselected large kidney transplant cohorts are lacking to support their broader clinical applicability. Additionally, recent studies on HLA evolutionary divergence (HED), quantifying HLA polymorphism, highlight its potential impact on rejection. Yet, the association of HED with kidney allograft rejection or de novo DSA occurrence remains unexplored in kidney transplantation.
The complexity introduced by diverse in-silico methods for assessing HLA immunogenicity necessitates further research to comprehensively understand their role in relation to kidney allograft rejection.
This project thus aims to investigate the association between various aspects of HLA immunogenicity, including HLA molecular mismatches and HLA evolutionary divergence, along with standard immunological and clinical parameters assessed at the time of transplantation, with the occurrence of antibody-mediated rejection and de novo DSA formation post-transplant in a large, comprehensively annotated kidney transplant cohort.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Kidney transplant recipients from four French referral centers
Key inclusion criteria (3 listed)
- Living or deceased donor kidney recipient transplanted after 2004
- Kidney recipient older than 18 years of age
- Written informed consent at the time of transplantation for the center database
Key exclusion criteria (1 listed)
- 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 |
|---|---|---|
| No interventionNo intervention | Other | – |
Primary outcome
Antibody-mediated rejection
Time frame: from 02/01/2004 to 25/01/2021
1 secondary outcome
De novo anti-HLA donor-specific antibody
Time frame: from 02/01/2004 to 25/01/2021
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 31 May 2024.
- Background: PubMed 35669972Bestard O, Thaunat O, Bellini MI, Bohmig GA, Budde K, Claas F, Couzi L, Furian L, Heemann U, Mamode N, Oberbauer R, Pengel L, Schneeberger S, Naesens M. Alloimmune Risk Stratification for Kidney Transplant Rejection. Transpl Int. 2022 May 20;35:10138. doi: 10.3389/ti.2022.10138. eCollection 2022.
- Background: PubMed 22081892Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, Hidalgo LG, Famulski K, Matas A, Halloran PF. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012 Feb;12(2):388-99. doi: 10.1111/j.1600-6143.2011.03840.x. Epub 2011 Nov 14.
- Background: PubMed 28729289Wiebe C, Rush DN, Nevins TE, Birk PE, Blydt-Hansen T, Gibson IW, Goldberg A, Ho J, Karpinski M, Pochinco D, Sharma A, Storsley L, Matas AJ, Nickerson PW. Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development. J Am Soc Nephrol. 2017 Nov;28(11):3353-3362. doi: 10.1681/ASN.2017030287. Epub 2017 Jul 20.
- Background: PubMed 28613392Lachmann N, Niemann M, Reinke P, Budde K, Schmidt D, Halleck F, Pruss A, Schonemann C, Spierings E, Staeck O. Donor-Recipient Matching Based on Predicted Indirectly Recognizable HLA Epitopes Independently Predicts the Incidence of De Novo Donor-Specific HLA Antibodies Following Renal Transplantation. Am J Transplant. 2017 Dec;17(12):3076-3086. doi: 10.1111/ajt.14393. Epub 2017 Jul 28.
- Background: PubMed 34424731Feray C, Taupin JL, Sebagh M, Allain V, Demir Z, Allard MA, Desterke C, Coilly A, Saliba F, Vibert E, Azoulay D, Guettier C, Chatton A, Debray D, Caillat-Zucman S, Samuel D. Donor HLA Class 1 Evolutionary Divergence Is a Major Predictor of Liver Allograft Rejection : A Retrospective Cohort Study. Ann Intern Med. 2021 Oct;174(10):1385-1394. doi: 10.7326/M20-7957. Epub 2021 Aug 24.
- Derived from this study: PubMed 40592858Demir Z, Raynaud M, Divard G, Louis K, Truchot A, Niemann M, Ponsirenas R, Aubert O, Del Bello A, Hertig A, Anglicheau D, Dale B, Kamar N, Mangiola M, Zeevi A, Lefaucheur C, Loupy A. Impact of HLA evolutionary divergence and donor-recipient molecular mismatches on antibody-mediated rejection of kidney allografts. Nat Commun. 2025 Jul 1;16(1):5692. doi: 10.1038/s41467-025-60485-y.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplantation, run by Paris Translational Research Center for Organ Transplantation at 1 site 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 1 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 31 May 2024. 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 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?
Antibody-mediated rejection (time frame: from 02/01/2004 to 25/01/2021). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06436586, which also lists 6 linked publications.
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 31 May 2024.