Unique Gene Expression Signatures in Urine Distinguish T Cell Mediated Acute Rejection from BK Virus Nephropathy in Kidney Transplant Patients
1Cleveland Clinic, Cleveland, OH, 2Nanostring Technologies, Seattle, WA, 3Univ. Alabama Birmingham, Birmingham, AL, 4Emory Univ., Atlanta, GA, 5Northwestern Univ., Chicago, IL, 6Icahn School of Med., New York, NY, 7Univ. Maryland, Baltimore, MD
Meeting: 2019 American Transplant Congress
Abstract number: 429
Keywords: Monitoring, Multicenter studies, Non-invasive diagnosis
Session Information
Session Name: Concurrent Session: Kidney: Acute Cellular Rejection
Session Type: Concurrent Session
Date: Tuesday, June 4, 2019
Session Time: 2:30pm-4:00pm
Presentation Time: 3:30pm-3:42pm
Location: Ballroom C
*Purpose: There is a need to develop non-invasive approaches to detect ongoing kidney graft injury and distinguish immune from non-immune inflammation to guide therapy. Ideally the approach should be accurate to the cause of the injury, sensitive, and rapid. Currently, biopsies are required for differential diagnosis and monitoring of suspected kidney graft injury. We used the Nanostring platform to test whether gene expression patterns in urine sediment will distinguish T cell mediated acute rejection from BK virus nephropathy.
*Methods: We measured expression of 795 immune function genes in RNA isolated from urine sediment of 61 renal transplant patients enrolled in the CTOT-10, 15, and 16 studies: 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.
*Results: 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). The elastic net, a penalized regression method that applies both the lasso and ridge penalties, indicated a set of 24 genes that distinguish transplant recipients experiencing acute rejection from transplant recipients with BK virus nephropathy (AUC 0.92; 95% CI 0.78-0.99 by ROC curve analysis). In a separate analysis we developed a unique 9 gene signature that detects ongoing acute T cell mediated rejection. We applied this signature to 15 control urine RNA samples and 7 with biopsy-proven T cell mediated rejection of Banff grades I-III from the CTOT-08 study. The signature distinguished samples with ongoing rejection vs. no rejection with an AUC of 0.981 (95% CI 0.93-1.0).
*Conclusions: These data indicate that Nanostring analysis of gene expression in urine sediments from kidney transplant patients can provide a sensitive and rapid noninvasive means to detect the presence vs. absence of ongoing graft injury and to distinguish graft injury caused by T cell mediated acute rejection from that caused by BK virus nephropathy.
To cite this abstract in AMA style:
Keslar KS, Xu W, Zmijewska AA, Newell KA, Friedewald JJ, Abecassis MI, Heeger PS, Bromberg JS, Mannon RB, Fairchild RL. Unique Gene Expression Signatures in Urine Distinguish T Cell Mediated Acute Rejection from BK Virus Nephropathy in Kidney Transplant Patients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/unique-gene-expression-signatures-in-urine-distinguish-t-cell-mediated-acute-rejection-from-bk-virus-nephropathy-in-kidney-transplant-patients/. Accessed May 11, 2025.« Back to 2019 American Transplant Congress