## Protocol Section
### Identification Module
**NCT ID:** NCT06436586

**Brief Title:** Impact of HLA Evolutionary Divergence and HLA Donor-recipient Molecular Mismatches on Kidney Allograft Rejection

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

#### Organization Study ID Info
**ID:** HLA_kidney_001
#### Organization
**Class:** OTHER
**Full Name:** Paris Translational Research Center for Organ Transplantation
### Status Module
#### Completion Date
**Date:** 2023-01-01

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-24

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-01-01

**Type:** ACTUAL

#### Start Date
**Date:** 2022-02-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-31
**Type:** ESTIMATED
**Study First Submit Date:** 2024-05-24
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Paris Translational Research Center for Organ Transplantation

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Kidney Transplantation

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 5159

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

### Interventions

#### Intervention 1

**Description:** No intervention

**Name:** No intervention

**Type:** OTHER

### Outcomes Module

#### Primary Outcomes

**Measure:** Antibody-mediated rejection

**Time Frame:** from 02/01/2004 to 25/01/2021

#### Secondary Outcomes

**Measure:** De novo anti-HLA donor-specific antibody

**Time Frame:** from 02/01/2004 to 25/01/2021

### Eligibility Module

**Eligibility Criteria:** 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

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Kidney transplant recipients from four French referral centers

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Paris

**Country:** France

**Facility:** Paris Translational Research Center for Organ Transplantation

**Zip:** 75015

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** 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.

**PMID:** 35669972

**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.

**PMID:** 22081892

**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.

**PMID:** 28729289

**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.

**PMID:** 28613392

**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.

**PMID:** 34424731

## Derived Section

### Misc Info Module

- Version Holder: 2024-05-31
