Background: Long-term graft survival in renal transplantation relies on continuous immunosuppression with drugs that can cause high morbidity. Tolerance is an emerging clinically recognised event. A set of biomarkers has been previously defined in peripheral blood and is currently being validated within the GAMBIT study.

Aims: To test whether the proposed biomarkers of tolerance in kidney transplant recipients’ blood are expressed in urine samples to allow a completely non-invasive diagnostic test.

Methods: Recruited groups include (HC) healthy controls (n=9); (TOL) recipients with stable kidney function that have stopped taking all immunosuppression (n=12); (STA) recipients with stable kidney function on standard immunosuppression (n=22) and (CR) recipients with immunologically driven chronic allograft nephropathy despite standard immunosuppression (n=5). RNA was extracted from urinary sediment and pre-amplified. Quantitative RT-PCR was performed with the housekeeping gene of reference HPRT and results were analysed using the Mann-Whitney U-test.

Results: Most of the previously reported tolerance-related overexpressed genes in blood were not observed in urine samples. Interestingly FOXP3 is overexpressed in TOL vs. HC (p<0.001) and TOL vs. transplanted patients (p=0.057), in parallel to what is observed in blood. Whereas H3ST1 was underexpressed in TOL vs. transplanted patients (p<0.005) and TOL vs. HC (p<0.004), the latter also in parallel to blood. An expression algorithm is being developed for a diagnostic test in urine. This test will complement the already available algorithm for blood.

Conclusions: Validation of the urine algorithms in addition to blood will provide an additional tool for the detection of biomarkers of tolerance. This will form the basis for a test for safe immunosuppression minimization or withdrawal.

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