Dd-cfDNA and Treg in Prediction of Kidney Transplant Acute Rejection

NCT05084768 | Recruiting DMC

• 1 other identifier: 5210340
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Acute rejection after kidney transplantation should ideally be diagnosed prior to immunologic injury in a non-invasive fashion in order to improve long-term graft function. Donor-derived cell-free DNA (ddcfDNA) is a promising method to do so as it is elevated prior to acute rejection and has good predictive performance especially for antibody-mediated and high severity T-cell mediated rejection. Its ability to predict low severity T-cell mediated rejection and future graft function remains equivocal. Regulatory T cells (Tregs) are essential in transplant tolerance by suppressing effector immune responses. Circulating post-transplant highly suppressive HLA-DR+ Tregs were reduced in recipients who developed acute rejection. Preliminary results in a cohort including predominantly low severity T-cell mediated rejection also showed that pre-transplant circulating highly suppressive TNFR2+ Tregs were reduced in and could predict acute rejection. Integrating dd-cfDNA with HLA-DR+TNFR2+ Treg could improve the predictive performance for acute rejection especially of low severity and potentially predict graft function. Plasma dd-cfDNA and HLA-DR+TNFR2+ Tregs will be measured in 150 kidney transplant recipients at scheduled intervals during the first 6 months post-transplant. Predictive accuracy of a model integrating ddcfDNA and HLA-DR+TNFR2+ Treg for acute rejection will be tested using ROC curve analysis and multivariate logistic regression. Predictive accuracy for 1-year graft function will be tested using multivariate linear regression. High predictive performance for acute rejection and graft function using a model integrating dd-cfDNA and HLA-DR+TNFR2+ Treg would help identify kidney transplant recipients at immunologic risk early on and allow personalization of immunosuppression accordingly.

Conditions

Acute Rejection of Renal Transplant; Graft Failure

Outcome Measures

Primary Outcomes (1)

• Number of participants with biopsy-proven acute rejection graded with the Banff score

  TCMR 1A, TCMR 1B, TCMR 2A, TCMR 2B, TCMR 3B, ABMR

  1 year

Secondary Outcomes (1)

• Number of participants with graft failure based on return to chronic dialysis or death

  1 year

Study Arms (2)

Rejection of kidney transplant

Diagnostic test: measurement of regulatory T cell and donor-derived cell-free DNA

Diagnostic Test: Donor-derived cell-free DNA

No rejection of kidney transplant

Diagnostic test: measurement of regulatory T cell and donor-derived cell-free DNA

Diagnostic Test: Donor-derived cell-free DNA

Interventions

Donor-derived cell-free DNA DIAGNOSTIC_TEST

As mentioned previously

Also known as: Regulatory T cell

No rejection of kidney transplant; Rejection of kidney transplant

Eligibility Criteria

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

Study Population

Adult kidney transplant candidates/recipients

You may qualify if:

• Adult kidney transplant candidates/recipients

You may not qualify if:

• Age less than 18
• Multi-organ transplants
• Kidney transplant candidates/recipients with HIV
• Kidney transplant candidates/recipients with HCV

Sponsors & Collaborators

• Loma Linda University: lead

Study Sites (1)

Loma Linda University Health

Loma Linda, California, 92354, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Peripheral blood mononuclear cells

Study Officials

• Minh-Tri Nguyen, MD PhD

  Loma Linda University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan Evans, CCRP

CONTACT

9095583870; rlevans@llu.edu

Study Design

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

Study Record Dates

• First Submitted: September 18, 2021
• First Posted: October 20, 2021
• Study Start: December 7, 2020
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)