Acute cellular rejection and BK virus nephropathy both cause deteriorating graft function that can lead to graft loss. Distinguishing the two conditions rapidly and accurately is vital for immunosuppression management. Currently, repeated biopsies are required for differential diagnosis and disease monitoring. Using the Nanostring platform to measure gene expression in urine sediment RNA as a noninvasive means to assess the status of renal allografts, we investigated the hypothesis that gene expression patterns in urine sediment will distinguish acute rejection from BK virus nephropathy without the need for a biopsy.

Using the Nanostring PanCancer Immunology panel, we measured expression of 795 immune function genes in RNA isolated from urine sediment of 61 renal transplant patients: 29 control subjects with stable graft function and no clinical signs of rejection, 17 subjects with biopsy-proven acute T-cell mediated rejection, and 15 subjects with biopsy-proven BK virus nephropathy.

When compared with control samples, the most significantly upregulated genes at the time of acute rejection were the same as those most upregulated during BK virus nephropathy (CXCL9, CXCL10, CXCL11, CX3CL1 and IDO1). Using the elastic net, a penalized regression method that applies both the lasso and ridge penalties, we developed a set of 24 genes that can distinguish transplant recipients experiencing acute rejection from transplant recipients with BK virus nephropathy (area under the curve 0.92; 95% confidence interval 0.78-0.99 by receiver operating characteristic curve analysis).

These data indicate that Nanostring analysis of gene expression in urine sediments of kidney transplant patients can provide a noninvasive means to detect the presence vs. absence of ongoing graft injury and to distinguish graft injury caused by acute rejection from that caused by BK virus nephropathy. These data support the need to perform prospective studies to assess whether Nanostring-guided therapy improves kidney transplant outcomes.

CITATION INFORMATION: Keslar K., Gotwald P., Xu W., Zmijewska A., Chen J., Newell K., Heeger P., Bromberg J., Mannon R., Fairchild R., The CTOT Consortium Unique Gene Expression Signatures in Urine Distinguish BK Virus Nephropathy from Acute Rejection in Kidney Transplant Patients with Graft Dysfunction Am J Transplant. 2017;17 (suppl 3).

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