A major goal of the Clinical Trials in Organ Transplantation (CTOT) studies is the identification of biomarkers that predict or diagnose acute graft rejection in transplant patients. Potential gene markers of graft injury have been identified in graft biopsy tissue by means of microarrays and in urine sediment RNA by quantitative PCR. Using Nanostring technology, we compared gene expression changes during acute rejection in tissue and urine sediment RNA from kidney transplant patients on a single platform. Study subjects were enrolled in the CTOT-10, -15 and -16 trials and were treated with either belatacept-based regimens or with conventional immunosuppression. We measured expression of 795 immune function genes in urine sediment RNA collected from 12 subjects undergoing acute rejection and 10 control subjects with stable graft function and observed a set of 27 genes upregulated by five-fold or greater at the time of clinically diagnosed rejection. We then assessed the same 795 genes in graft tissue RNA from a second set of subjects that included 12 with acute rejection and 3 controls with no evidence of rejection. In graft tissue RNA, 159 genes were upregulated by five-fold or greater at the time of rejection. Of the genes upregulated 5-fold or more at the time of rejection, 15 were common to both graft tissue and urine sediment RNA, 144 were unique to graft tissue and 12 were unique to urine. The transcripts overexpressed in rejecting renal allograft tissue were predominantly chemokines and their receptors, immune signaling molecules, and T cell and NK cell-associated markers. A subset of these genes was also upregulated in the urine of transplant recipients undergoing acute rejection. Genes upregulated in the urine sediment but not the tissue of recipients undergoing rejection included complement components and adhesion molecules. Our observation of common genes in the RNA of graft tissue and urine sediment supports the utility of urine as an ideal non-invasive sample site for interrogating graft status.

CITATION INFORMATION: Keslar K, Zmijewska A, Chen J, Newell K, Heeger P, Mannon R, Fairchild R. Detection of Shared and Distinct Gene Expression Signatures in Tissue and Urine During Acute Rejection of Kidney Grafts. Am J Transplant. 2017;17 (suppl 3).

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