Date: Saturday, June 11, 2016
Session Name: Poster Session A: Kidney: Acute Cellular Rejection
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Halls C&D
Background: A common rejection module (CRM) consisting of 11 genes are expressed in solid organ transplant rejection in kidney, heart, liver and lung transplantation (Khatri, J Exp Med, 2014). We evaluated the PCR measurement of this gene set in urine to evaluate its ability to non-invasively predict biopsy confirmed kidney allograft rejection, in lieu of a graft biopsy.
Methods.232 urine specimens matching with a kidney allograft biopsy from 3 independent cohorts (one training and 2 validation) of kidney transplant patients, with (61) and without (171) AR (Banff classification) were evaluated for the expression of BASP1, CD6, CXCL10, CXCL9, INPP5D, ISG20, LCK, NKG7, PSMB9, RUNX3, and TAP1 by RT-PCR and composite risk score was developed across the set, with a threshold cutoff for a diagnosis of rejection using the training set.
Results. Unlike expression of these genes in the graft, expression of these genes in urine was more variable and only 5/11 genes were highly significant at the time of kidney rejection in the training set of 40 samples; uCRM score for AR had an AUC=0.961; 95% CI 0.911-1), In a validation set of 87 protocol bioopsies with subclinical rejectioon only, the uCRM assay could still diagnose rejection (AUC=0.925; 95% CI 0.851-1) with high specificity and PPV for predicting AR was obtained. In the second valiation cohort of 105 samples the AUC was 75% for AR, as the uCRM score was also found to be elevated in other forms of renal transplant injury such as ATN and BK nephritis. uCRM scores assessed in urine samples obtained prior to AR episodes, showed similarly high scores as those evaluated at the time of AR, whereas those analyzed on urine specimens obtained after AR treatment showed lower scores than at AR (p=0.04). Matched urine protein/creatinine values on the sample samples showed an AUC of 68% for graft injury and 55% for AR diagnosis
Conclusions: A PCR based multigene assay can be rapidly assessed on a urine sample with minimal processing, and provides a non-invasive, quantitative risk score for graft inflammation and rejection, that is superior to current clinical monitoring standards such as the urine protein/creatinine ratio or serum creatinine.
CITATION INFORMATION: Sigdel T, Tran T, Bestard O, Vincenti F, Sarwal M. The Urine Common Rejection Module (uCRM) Is a Sentinal Assay for Graft Rejection. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Sigdel T, Tran T, Bestard O, Vincenti F, Sarwal M. The Urine Common Rejection Module (uCRM) Is a Sentinal Assay for Graft Rejection. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/the-urine-common-rejection-module-ucrm-is-a-sentinal-assay-for-graft-rejection/. Accessed December 2, 2020.
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