Genomics of Kidney Transplantation

Study Overview
=================
Brief Summary
-----------------
The major aim of this research study is to investigate the relationship between genetic variation in DNA (inherited code material in the cells of the body) and factors affecting transplant outcomes, like the drugs people receive or the way their immune systems work, for example. To do this, investigators will collect blood samples from participants. Genetic material will be separated from each blood sample and analyzed, looking for genetic variation.

Detailed Description
-----------------
In the past, the major problems in kidney transplantation were surgical complications, acute rejection, and infections. Right now, researchers are focusing on improving immune suppression therapy and achieving better long-term survival of kidney transplants. One of the ways to try to understand what causes loss of function after many years is to find out if there is a genetic factor involved. There are a number of differences in specific genes that have been identified and are thought to affect transplant outcomes. Studying these gene variations (differences between people or differences between populations) is important in determining whether these variations are related to transplant outcomes and how this information can help patients achieve better long-term transplant survival.

Official Title
-----------------
Genomics of Kidney Transplantation

Conditions
-----------------
KidneyTransplant Recipients, Simultaneous Kidney/Pancreas Recipients, Kidney Transplant Donor

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Kidney (or kidney-pancreas) transplant recipient no more than 10 days post-transplant or kidney donor no more than 30 days post-transplant or previously enrolled in Phase I of the Genomics of Kidney Transplantation Study; No organs other than kidney or pancreas transplanted simultaneously with the qualifying kidney transplant; and Participant or parent/guardian must be able to understand and provide written informed consent. Inclusion for the Activity and mRNA Expression Cohort: Recipient enrolled in the Main Cohort Study; Informed consent for participation in the Activity and mRNA Expression Cohort; Age 18 years or greater as of day of transplantation;and Will receive tacrolimus, cyclosporine or mycophenolate as part of maintenance immunosuppression therapy. Exclusion Criteria: - Inability or unwillingness of the participant or parent/guardian to give a written informed consent or comply with the study protocol. For the Activity and mRNA Expression Cohort: - Inability or unwillingness of the participant or parent/guardian to give a written informed consent for participation in the Activity and mRNA Expression Cohort or comply with the study protocol.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Transplant Recipients Cohort<br>Main Study Cohort: Kidney (or kidney-pancreas) transplant recipients. Enrollment for this cohort is closed. | |
| Transplant Donors Cohort<br>Main Study Cohort: The kidney donor for transplant recipients in this study. Enrollment for this cohort is closed. | |
| Activity&mRNA Expression Substudy Cohort<br>A subset of subjects enrolled in the main study who will receive tacrolimus, cyclosporine or mycophenolate as part of maintenance immunosuppression therapy. This group has a prospective observational cohort design. Enrollment into the Activity and messenger ribonucleic acid (mRNA) Expression Cohort, occurring concurrently with enrollment of the rest of the study, will continue until either the required sample size of 600 is achieved or the protocol team terminates enrollment. Participants in the Activity and mRNA Expression Cohort have additional blood draws up to 2 weeks prior to transplant, at week 1, Month 3 and Month 6 post-transplant. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant recipient genotypes: time to chronic graft disfunction |  | Day 0 to Year 5 | 
| Transplant recipient genotypes: time to a persistent 25% decrease in Estimated Glomerular Filtration Rate (eGFR) | eGFR: Estimated GFR test results are a measure of kidney function. | Day 0 to Year 5 | 
| Transplant recipient genotypes: time to acute rejection |  | Day 0 to Year 5 | 
| Transplant recipient genotypes: time to allograft failure | allograft failure is defined as graft loss or participant death. | Day 0 to Year 5 | 
| Donor Genotypes: time to chronic graft dysfunction | The time to dysfunction of the donated organ. | Day 0 to Year 5 | 
| Donor Genotypes: time to a persistent 25% decrease in eGFR | The time to a persistent 25% decrease in eGFR in the donated organ's recipient. | Day 0 to year 5 | 
| Donor Genotypes: time to allograft failure | The time to the failure of the donated organ (defined as graft loss or participant death). | Day 0 to Year 5 | 
| Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia) |  | Day 0 to Year 5 | 
| Recipient genotypes: time to select Calcineurin Inhibitor (CNI)-related toxicities | Toxicities may include: new onset diabetes or nephrotoxicity. CNI: calcineurin inhibitor | Day 0 to Year 5 | 
| Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels |  | Day 0 to Year 5 | 
| Recipient candidate genotypes: Calcineurin (CN) and IMPDH protein activity and expression | CN: Calcineurin. IMPDH: Inosine-5'-monophosphate dehydrogenase | Day 0 to Year 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine |  | Day 0 to Year 5 | 
| Time to renal biopsy with presence of the following semi-quantitative pathology endpoints: patterns of Banff biopsy score, presence of circulating anti-donor anti-Human Leukocyte Antigen (HLA) antibodies, C4d positivity |  | Day 0 to Year 5 | 
| Slope of eGFR |  | Day 0 to Year 5 | 
| Delayed graft function |  | Day 0 to Year 5 | 
| Time to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection | EBV: Epstein-Barr virus. CMV: cytomegalovirus. | Day 0 to Year 5 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
genomics of kidney transplantation, genetic variation, recipient genotypes, donor genotypes