Diagnostic and Therapeutic Applications in Microarrays in Organ Transplantation

Study Overview
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Brief Summary
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The current standard for biopsy-based diagnoses of dysfunction of kidney transplants is the Banff Classification which represents arbitrary international consensus. Recent data-driven approaches using molecular and conventional technologies indicate that mere consensus produces frequently incorrect diagnoses with potential harm to patients due to inappropriate treatment. To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC) has developed a new diagnostic system that combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The present study will validate and refine this system in 500 prospectively unselected biopsies for clinical indications from American, Canadian and European centres in addition to 300 biopsies already collected. Due to a considerable interest and support from participating Centers, the study is further extended to 1500 prospective biopsies. Thus this is the extension of the INTERCOM study (INTERCOMEX). In addition to demonstrating the feasibility and value of this System in routine patient care and clinical trials, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback on how this system can best improve patient care.

Detailed Description
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The study has enrolled so far 3012 biopsies from 2313 participants and the results are analyzed for these biopsies. Follow-up data is, and will be collected.

Official Title
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Multi-centric Observational Study to Analyse the Diagnostic Molecular Features in the Clinical Setting of Kidney Allograft Biopsies

Conditions
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Validation Study of Molecular Diagnostic System, Development of Reporting System for Molecular Diagnosis, Incorporate Molecular Diagnosis Into Diagnostic Standards

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All kidney transplant recipients ≥18yrs of age undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enrol in the study. Exclusion Criteria: Patients will be excluded from the study if they decline participation or are unable to give informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Kidney Transplant Biopsies for Cause<br>The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care to determine the cause of their graft dysfunction (deterioration in graft function, delayed graft function, proteinuria). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Validate the Integrated Diagnostic System in the International Collaborative Microarray (INTERCOM) Study | The rejection classifier predicts Banff diagnosis of any rejection: ABMR, TCMR, or mixed ABMR and TCMR; The TCMR classifier predicts the presence of Banff TCMR lesions/diagnoses; The ABMR classifier predicts the presence of ABMR lesions; In late (>1yr) biopsies for clinical indications, the failure classifier predicts failure within three years. | 2013-2016 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate the feasibility of molecular phenotyping of 300 + 500 kidney transplant biopsies for clinical indications. | To test the hypothesis that the molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample. | 2014-2016 | 
| Demonstrate the feasibility of molecular phenotyping of 500 biopsies in real time i.e. returning the molecular phenotyping report in two working days upon sample arrival. | Refine the reports based on feedback from the participants. | 2015-2016 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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global gene expression, molecular diagnostic classifiers