Clinical trial NCT01714440: Genomics of Kidney Transplantation
Official title: Genomics of Kidney Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: KidneyTransplant Recipients
Simultaneous Kidney/Pancreas Recipients
Kidney Transplant Donor
Keywords: genomics of kidney transplantation
genetic variation
recipient genotypes
donor genotypes
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Genomics of Transplantation Cooperative Research Program
First posted: 2012-10-26
Enrollment: 1552
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Targeted: 3000 Kidney or Kidney-pancreas transplant recipients and 1300 of the donors

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.

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.

Primary outcomes:
measure: Transplant recipient genotypes: time to chronic graft disfunction
timeFrame: Day 0 to Year 5
measure: Transplant recipient genotypes: time to a persistent 25% decrease in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Day 0 to Year 5
measure: Transplant recipient genotypes: time to acute rejection
timeFrame: Day 0 to Year 5
measure: Transplant recipient genotypes: time to allograft failure
timeFrame: Day 0 to Year 5
measure: Donor Genotypes: time to chronic graft dysfunction
timeFrame: Day 0 to Year 5
measure: Donor Genotypes: time to a persistent 25% decrease in eGFR
timeFrame: Day 0 to year 5
measure: Donor Genotypes: time to allograft failure
timeFrame: Day 0 to Year 5
measure: Recipient genotypes: time to select mycophenolate-related toxicities (leukopenia, anemia)
timeFrame: Day 0 to Year 5
measure: Recipient genotypes: time to select Calcineurin Inhibitor (CNI)-related toxicities
timeFrame: Day 0 to Year 5
measure: Recipient genotypes: repeated measures of clinically obtained tacrolimus trough blood levels
timeFrame: Day 0 to Year 5
measure: Recipient candidate genotypes: Calcineurin (CN) and IMPDH protein activity and expression
timeFrame: Day 0 to Year 5
Secondary outcomes:
measure: Time to composite endpoint of graft loss or death or persistent 25% increase in serum creatinine
timeFrame: Day 0 to Year 5
measure: 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
timeFrame: Day 0 to Year 5
measure: Slope of eGFR
timeFrame: Day 0 to Year 5
measure: Delayed graft function
timeFrame: Day 0 to Year 5
measure: Time to Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection
timeFrame: Day 0 to Year 5
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Minnesota
name: A Matas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: A Israni, MD, MS
role: STUDY_CHAIR
References:
citation: Nguyen TT, Pearson RA, Mohamed ME, Schladt DP, Berglund D, Rivers Z, Skaar DJ, Wu B, Guan W, van Setten J, Keating BJ, Dorr C, Remmel RP, Matas AJ, Mannon RB, Israni AK, Oetting WS, Jacobson PA. Pharmacogenomics in kidney transplant recipients and potential for integration into practice. J Clin Pharm Ther. 2020 Dec;45(6):1457-1465. doi: 10.1111/jcpt.13223. Epub 2020 Jul 14.
citation: Oetting WS, Schladt DP, Dorr CR, Wu B, Guan W, Remmel RP, Ikle D, Mannon RB, Matas AJ, Israni AK, Jacobson PA; DeKAF Genomics and GEN03 Investigators. Analysis of 75 Candidate SNPs Associated With Acute Rejection in Kidney Transplant Recipients: Validation of rs2910164 in MicroRNA MIR146A. Transplantation. 2019 Aug;103(8):1591-1602. doi: 10.1097/TP.0000000000002659.