Genomics of Kidney Transplantation

NCT01714440 | Completed DMC

• 1 other identifier: DAIT GEN-03
• Study Type: observational
• Target: 1,552
• Locations: 2 countries
• Sites: 5

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.

Conditions

KidneyTransplant Recipients; Simultaneous Kidney/Pancreas Recipients; Kidney Transplant Donor

Keywords

genomics of kidney transplantation; genetic variation; recipient genotypes; donor genotypes

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (5)

• 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

  Day 0 to Year 5

Study Arms (3)

Transplant Recipients Cohort

Main Study Cohort: Kidney (or kidney-pancreas) transplant recipients. Enrollment for this cohort is closed.

Transplant Donors Cohort

Main Study Cohort: The kidney donor for transplant recipients in this study. Enrollment for this cohort is closed.

Activity&mRNA Expression Substudy Cohort

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.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Targeted: 3000 Kidney or Kidney-pancreas transplant recipients and 1300 of the donors

You may qualify if:

• 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.
• 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.

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Genomics of Transplantation Cooperative Research Program: collaborator

Study Sites (5)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Related Publications (3)

• Cao R, Schladt DP, Dorr C, Matas AJ, Oetting WS, Jacobson PA, Israni A, Chen J, Guan W. Polygenic risk score for acute rejection based on donor-recipient non-HLA genotype mismatch. PLoS One. 2024 May 31;19(5):e0303446. doi: 10.1371/journal.pone.0303446. eCollection 2024.

  PMID: 38820342 DERIVED

• 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.

  PMID: 32662547 DERIVED

• 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.

  PMID: 30801535 DERIVED

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

Study Officials

• A Matas, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• A Israni, MD, MS

  University of Minnesota

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2012
• First Posted: October 26, 2012
• Study Start: August 1, 2012
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: June 5, 2017

Record last verified: 2017-06

Locations

CA (1); US (4)