Expanding the Scope of Post-transplant HLA-specific Antibody Detection and Monitoring in Renal Transplant Recipients

Sponsor
Liverpool University Hospitals NHS Foundation Trust
Study ID
NCT06025240
Status
Recruiting
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Conditions

  • Diagnosis
  • Frailty
  • Kidney Transplant
  • Kidney Transplant Rejection
  • Kidney Transplant; Complications
  • Renal Transplant
  • Renal Transplant Failure
  • Transplant Dysfunction

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • cf-DNA — DIAGNOSTIC_TEST
    In addition to the standard of care tests, participants will have an additional blood sample (dd-cf DNA). A cohort study patients who have undergone high immunological risk kidney transplant at our centre defined as a re-transplant, where the cRF is \>20% or where there is a level 4 HLA-mismatch. We will take a single plasma sample for dd-cfDNA testing at 6-12 months post-transplant and pair this with an assessment of renal function (creatinine, eGFR), MSU, BK and CMV PCR, single antigen bead (SAB) monitoring of HLA-specific antibodies and allograft USS.
  • Immunological Events following renal transplant in older age — DIAGNOSTIC_TEST
    Determine the overall frequency of immunological events and de novo HLA specific antibody formation in the \<60 and \>60 age population. Standard of care test taken at the different time intervals for routine storage. We will use those samples for HLA testing (either screening alone or screening and single antigen bead testing if screening yields a positive result).
  • Determining Predictive Models for Post-transplant HLA-specific Antibody Formation — OTHER
    A machine learning model will be developed in Python using a range of pre- and post-transplant variables to determine a predictive model for de novo HLA-specific antibody following renal transplant.

Study Details

The purpose of this study is to assess a new test to detect antibodies which may form following kidney transplant. These antibodies can be difficult to detect as they do not cause any symptoms but can lead to kidney damage. A new blood test will be performed alongside existing antibody tests to see how well the test functions in comparison and to see how well it is able to distinguish between inflammation caused by antibodies and other sorts of inflammation such as a urinary tract infection. The investigators also want to determine whether it is predictable whom will develop antibodies after a transplant and use these results to change the current way patients are monitored for antibodies after receiving a transplant. In addition to this, the investigators want to establish if patients over 60 years of age are relatively protected against immunological events such as rejection compared to patients who are under 60 years of age. The results could potentially lead to using a different immunosuppression regime based on which population age group patients belong to and lowering the risks associated with these drugs.

Key Dates

First listed
Sep 6, 2023
Start date
Oct 13, 2023
Status verified
Apr 2024
Primary completion
Oct 13, 2025
Completion
Oct 13, 2026

Study Design

Enrollment
282 participants (estimated)

Arms

  • Arm: cf-DNA arm
    Participants will be recruited on the basis of having received a renal transplant within the last 6-12 months which has been deemed high risk. They will be identified from a database currently held within the renal transplant unit by members of the direct care team. They will be approached at a routine outpatient appointment for inclusion into the study and testing can be performed at their time of routine post-transplant testing where they will undergo blood (dd-cf DNA NGS assay), standard of care tests: blood count, renal profile, donor specific antibodies (DSA) sample, BK virus PCR, CMV PCR, urine testing and an ultrasound of the graft.
  • Arm: Immunological Events following renal transplant in older age
    The renal transplant population will be divided on the basis of age into two cohort: ≥60 and \<60. All renal transplant patients are regularly followed up in the outpatient clinic where blood and urine tests are collected, and clinical evaluations are performed. It is not foreseen that this study will necessitate any additional hospital visits or testing above and beyond the usual standard of care. Serum samples are taken at the time intervals indicated for routine storage and we will simply use those samples for HLA testing (either screening alone or screening and single antigen bead testing if screening yields a positive result).
  • Arm: Determining Predictive Models for Post-transplant HLA-specific Antibody Formation
    A subset of the cohort of recruits to the immunological factors in older age study will be used to determine machine learning algorithms of predictive factors for the development of de novo donor specific antibody. Only patients who were unsensitised prior to the kidney transplant will be included into the study because prior sensitisation makes determining de novo specificities much harder. The follow up period will be set at 1 year to synchronise with the older age study.

Primary Outcome Measure

dd-cf DNA [ Time Frame: 6-12 months post-transplant ]

Central Contacts

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