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.
Adult patients transplanted within 6-12 months (retrospective recruitment)
Patients admitted for renal transplant or within the first 6 months following transplant (prospective recruitment)
Patients must have capacity to provide informed consent
Patients must have received a high-risk transplant defined as level 4 mismatch, cRF >20, second or subsequent transplant, ABO or HLA incompatible
Transplanted for longer than 12 months;
Low risk transplants;
Patients lacking capacity;
Patients lacking capacity
1. cf-DNA arm: Patients who have undergone a "high risk" renal transplant in our unit within the last 6-12 months will be retrospectively recruited to the study. 2. Older Age Immunological Events: Post-transplant patients prospectively recruited, irrespective of age, undergoing transplant to determine the overall frequency of immunological events and de novo HLA specific antibody formation. We will collect data on clinical outcomes and would look to compare the \<60s with those 60 or older looking for a difference in immunological events beteween the 2 groups. 3. Predictive models: 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.
Cohort
Other
cf-DNA
Diagnostic testIn 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 testDetermine 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 interventionA 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.
dd-cf DNA
Occurrence of a positive cell free DNA test in high-risk post-transplant patients at 6-12 months
Immunological events in older age
Frequency of the development of immunological events in the over 60s versus \<60 cohorts
Longitudinal DSA monitoring
Frequency of development of de novo HLA specific antibody in the 1st year following transplantation in patients previously unsensitised.
Occurrence of UTIs, viral reactivation and structural transplant abnormalities in high-risk post-transplant patients at 6-12 months
as above
Association of cell free DNA result and any identified pathology (DSA, UTI, viral infection)
as above
Comparison of graft and patient survival to 12 months in the over 60s and <60
as above
Comparison of renal function, viral reactivation, readmission and reoperation rates between the 2 age groups (over 60s and <60)
as above
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Liverpool University Hospitals NHS Foundation Trust
Lead sponsor
Kidney Research United Kingdom
Collaborator
