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

Completed

• Conditions: Kidney Transplantation

• Registration Number: NCT06436586
• Lead Sponsor: Paris Translational Research Center for Organ Transplantation

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-01
• Primary Completion: 2023-01-01
• Study Completion: 2023-01-01
• Status Verified: 2024-05
• Study First Submitted: 2024-05-24
• Study First Submitted QC: 2024-05-24
• Last Update Submitted: 2024-05-24
• Study First Posted: 2024-05-31
• Last Update Posted: 2024-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5159

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Antibody-mediated rejection	from 02/01/2004 to 25/01/2021

Secondary Outcome Measures

Name	Time	Method
De novo anti-HLA donor-specific antibody	from 02/01/2004 to 25/01/2021

Trial Locations

Locations (1)

Paris Translational Research Center for Organ Transplantation; 🇫🇷 Paris, France