Rejection Diagnosis in Kidney Transplants Patients (KTD-innov)

Prospective KTD-innov Cohort of Kidney Transplants Patients

Main objective: To constitute a prospective multicentre French cohort of kidney transplant recipients including clinical, biological and immunological evaluation combined with non-invasive biomarkers in peripheral blood and urine, and gene expression assessment in allograft biopsy in order to increase the performance of rejection diagnosis in kidney transplant patients.

the investigators hypothesise that the addition of non-invasive biomarkers and intragraft assessment of gene expression profiles will improve the diagnosis capacity of histology in kidney transplant recipients as it reveals pathophysiological pathways that are not captured by light microscopy.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation; Transplant Rejection; Graft Survival
• Intervention / Treatment: Procedure: Kidney transplantation

Detailed Description

Rejection currently represents the major cause of allograft failure worldwide, with immediate consequences for the patients in terms of mortality, morbidity and costs for the society. The field of transplantation lacks robust assessments for immune monitoring and diagnoses. Currently, light microscopy still represents the gold standard, which has clearly been identified as imperfect. Given those facts, success of clinical trials is impaired with space for improvement of current diagnosis standards that should eventually lead to improved outcomes for kidney transplant recipients.

This study will provide the investigators with prospective data of kidney transplant patient that will allow the improvement of rejection diagnosis and individual immune monitoring for precision medicine: improvement of rejection diagnosis, stage and assessment of response to therapy. In order to estimate for each patient a probability of rejection, The investigators will generate algorithms using traditional clinical, biological and histological data that will be enriched by tissue as well as blood and urine non-invasive immune biomarkers.

These algorithms will be encapsulated in a "user-friendly" web-based application with best in-class visualisation : the TransplanScreen will display individual information with comparative and predictive context for clinicians and patients and better interfacing and communication. It will include a comprehensive TransplanScreen report based on the algorithms and included in Electronic Medical Record databases (object-oriented). It aims to provide visual and contextual information to promote personalised decision making, addressing the demand of public health authorities for improving efficiency and quality of care.

The expected benefit for participants and society will be to reduce the financial burden of graft rejection for society.

The cohort will include n=750 kidney transplant recipients in 8 French centres : 3 Parisian ones: Necker hospital, Saint-Louis Hospital and Bichat hospital and 4 regional ones: CHU Nantes, Toulouse and Bordeaux, Montpellier and Lyon Hospitals. Bichat hospital will not be recruiting but will contribute to the research.

Vulnerable participants excluded.

Schedule for the study:

• inclusion period: 12 months
• participation period (treatment - follow-up): 12 months
• total duration of the study: 24 months

Exclusion period for participation in other studies, and justification: the participation to other minimal risks and constraints studies and observational non-interventional studies is allowed during this study. There is no exclusion period at the end of study. The participation to other interventional and observational non-interventional studies is allowed after the end of the study.

Number of enrolments expected per site and per month :

• Necker Hospital: 14 patients / month
• Saint-Louis Hospital: 8 patients / month
• CHU Nantes: 10 patients / month
• Lyon Hospitals: 9 patients / month
• CHU Toulouse: 13 patients / month
• CHU Bordeaux: 9 patients / month.
• CHU Montpelier: 8/month

• Study Type: Observational
• Enrollment (Actual): 824

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hôpital Saint-Louis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

New kidney transplants patients

Description

Inclusion Criteria:

Men or female patients, Age ≥ 18 years old at the time of transplantation. Patients receiving a kidney transplant from a living or deceased donor. Patients who signed the informed consent form and willing to comply with study procedures.

Female patients of child-bearing potential must have a negative pregnancy test (serum beta-hCG) and must be practicing an effective, reliable and medically approved contraceptive regimen

Patients with a minimum weight of 40 kg

Exclusion Criteria:

History of multi-organ transplant (interference with rejection natural history).

Unable/unwilling to comply with study procedures (including foreign language speakers who are not assisted by a native French speaker).

Vulnerable participants (minors, protected adults, pregnant women, legally detained

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Prospective cohort; Kidney transplantation

Procedure: Kidney transplantation; For the patients with the kidney transplantation, these parameters will be analysis: Transcriptomics analysis Characteristics of anti HLA DSA analysis Non-HLA antibodies analysis Omics blood analysis Urine chemokines analysis; Other Names: Transcriptomics analysis; Non-HLA antibodies analysis; Omics blood analysis; Urine chemokines analysis,; Characteristics of anti HLA DSA analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance of invasive/non-invasive biomarkers with allograft rejection	Concordance of invasive/non-invasive biomarkers with allograft rejection diagnosed by the gold standard (histology) in kidney transplant recipients.	month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of non-invasive biomarkers with different subtypes of rejection	Association of non-invasive biomarkers with different subtypes of rejection	month 12
Association of gene sets with different subtypes of rejection in the biopsy.	Association of gene sets with different subtypes of rejection in the biopsy.	month 12
Reclassification capacity of gene sets and non-invasive biomarkers to define allograft rejection.	Reclassification capacity of gene sets and non-invasive biomarkers to define allograft rejection	month 12
Variation of the non-invasive biomarker signature of allograft rejection	ariation of the non-invasive biomarker signature of allograft rejection as a response to the standard of care in kidney transplant recipients.	month 12
Variation of the gene set signature	Variation of the gene set signature of allograft rejection from the biopsy as a response to the standard of care in kidney transplant recipients.	month 12
Cumulative incidence of antibody-mediated rejection (ABMR)	Cumulative incidence of antibody-mediated rejection (ABMR) that occurs between D0 and M12 (ABMR that meets Banff 2015 criteria)	month 12
Cumulative incidence of T-cell-mediated rejection (TCMR)	Cumulative incidence of T-cell-mediated rejection (TCMR) that occurs between D0 and M12 (TCMR that meets Banff 2015 criteria)	month 12
Treatment failure rate	Treatment failure rate defined as the occurrence of 1) biopsy proven ABMR and/or TCMR, 2) graft loss, 3) patient death	month 12
Graft and patient survival	Graft and patient survival at M6 and M12 post-transplantation	month 12
Histological evidence of ABMR and/or TCMR on protocol biopsies	Histological evidence of ABMR and/or TCMR on protocol biopsies without other clinical findings at M3 and M12 post-transplantation	month 12
Overall pathological changes, including chronic ABMR	Overall pathological changes, including chronic ABMR, on protocol biopsies M3 and M12 post-transplantation	month 12
Incidence of delayed graft function	Incidence of delayed graft function (DGF) post-transplantation	month 12
Cumulative incidence and duration of dialysis.	Cumulative incidence and duration of dialysis between 7 days and M12 post- transplantation	month 12

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 25, 2018
• Primary Completion (ACTUAL): March 18, 2021
• Study Completion (ACTUAL): March 18, 2021

Study Registration Dates

• First Submitted: June 25, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (ACTUAL): July 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Rejection; Cohort study; Biomarkers; Kidney; Integrative medicine; Allogeneic transplantation
• Other Study ID Numbers: K170909J; 2018-A00090-55 (REGISTRY: IDRCB number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No