Genomics of Chronic Renal Allograft Rejection (The GoCAR Study)

Study Overview
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Brief Summary
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Doctors have had success preventing certain types of kidney transplant rejection by suppressing the immune system. However, an individual's genetic make-up and the strength of an immune response to a transplant may also determine whether a transplanted organ is rejected. The purpose of this study is to look at the genetic profile and immune response of people who have had kidney transplants and to correlate the findings with kidney transplant rejection episodes. Donor genetic profiles will also be studied and correlated with the recipient's information.

Detailed Description
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New immunosuppressive drugs have improved short-term transplant survival but have not affected long-term transplant survival. Rejection is caused by both immunological and non-immunological factors from both the donor and the recipient. Although the exact cause of chronic rejection is not known, it is associated with the presence of C4d, a degradation product of the antibody response cascade, and the presence of circulating donor-specific antibodies (DSAs). The purpose of this study is to determine the role of cell- and antibody-mediated responses in chronic rejection of transplants, to determine the gene expression profile associated with the development of chronic rejection, and to determine whether variants of specific genes cause susceptibility to rejection. This is an observational study of people who will be receiving kidney transplants and participants will be followed for 2 years. Study visits for kidney transplant recipients will occur at study entry and at months 3, 6, 12, 18, and 24 after transplant. At these visits, adverse event assessment, rejection assessment, medication history questionnaire, and blood collection will occur. At some visits, a physical exam and a kidney biopsy will occur. Blood will also be collected from living kidney donors at the time of donation if both donor and recipient agree to be in the study. This study will be take place at 4 clinical sites: Mount Sinai School of Medicine, University of Wisconsin-Madison, Westmead Hospital, and Northwestern Memorial Hospital. Brigham and Women's Hospital and Massachusetts General Hospital will also participate in the study as central laboratories.

Official Title
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Genomics of Chronic Renal Allograft Rejection

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Procedure: Kidney biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplant candidates from living or deceased donors Male or female, ages 18-75 years Subject must be able to understand and provide written informed consent Living Donors - Recipient also consents to participate in the study Exclusion Criteria: Presence of Donor Specific Antibodies in living donor recipients prior to transplantation OR positive cross match according to site-specific technique in cadaveric donor recipients Recipients of multiple organ transplants, with the exception of kidney/pancreas transplants. Inability or unwillingness to comply with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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

| Intervention/Treatment |
| --- |
|Procedure: Kidney biopsy|Kidney biopsy (recipients only) will be obtained for RT-PCR, microarray analyses and histology.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of chronic rejection with patterns and intensity of recipient alloreactivity |  | Throughout study | 
| Correlation of chronic rejection with recipient gene expression profiles |  | Throughout study | 
| Correlation of chronic rejection with polymorphic variants of specific susceptibility genes in donor and recipient |  | Throughout study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with patterns and intensity of recipient alloreactivity |  | Throughout study | 
| Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with recipient gene expression profiles |  | Throughout study | 
| Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy with polymorphic variants of specific susceptibility genes in donor and recipient |  | Throughout study | 
| Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy with chronic rejection |  | Throughout study | 
| Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy allograft dysfunction as defined by the protocol |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ELISPOT, RT-PCR, Luminex, Genomics