Impact of HLA Evolutionary Divergence and HLA Donor-recipient Molecular Mismatches on Kidney Allograft Rejection

Kidney Transplantation Clinical Trial

Official title:

Impact of HLA Evolutionary Divergence and HLA Donor-recipient Molecular Mismatches on Kidney Allograft Rejection: a Population-based Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06436586
• Other study ID #: HLA_kidney_001
• Status: Completed
• Start date: February 1, 2022
• Est. completion date: January 1, 2023

Study information

• Verified date: May 2024
• Source: Paris Translational Research Center for Organ Transplantation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5159
• Est. completion date: January 1, 2023
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Combined transplantation

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Other:
• No intervention
No intervention

Locations

Country	Name	City	State
France	Paris Translational Research Center for Organ Transplantation	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Paris Translational Research Center for Organ Transplantation

Country where clinical trial is conducted

France, 

References & Publications (5)

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. — View Citation

Feray 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. — View Citation

Lachmann 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. — View Citation

Sellares 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. — View Citation

Wiebe 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antibody-mediated rejection		from 02/01/2004 to 25/01/2021
Secondary	De novo anti-HLA donor-specific antibody		from 02/01/2004 to 25/01/2021