A Non-Invasive Urinary Common Rejection Module (uCRM) Gene Expression Score Enables Accurate Discrimination of Acute Rejection in Kidney Transplant Patients
1Department of Transplant Surgery, UCSF, San Francisco, CA
2Kidney Transplant Unit, Bellvitge University Hospital, Barcelona, CAT, Spain.
Meeting: 2015 American Transplant Congress
Abstract number: C236
Keywords: Gene expression, Kidney transplantation, Rejection, Urinalysis
Session Information
Session Name: Poster Session C: Translational Biomarkers and Immune Monitoring
Session Type: Poster Session
Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
A common rejection module (CRM) consisting of 11 genes expressed on allograft biopsies was recently shown to be highly accurate to discriminate patients undergoing acute rejection (AR), correlate with the extent of graft injury and even predict future allograft damage. Here we sought to investigate the CRM score in urine samples (uCRM) as a non-invasive biomarker to accurately identify kidney transplant patients at risk of AR.
Methods.
136 urine specimens matching with a kidney allograft biopsy from 2 independent cohort of kidney transplant patients were evaluated for the expression of the 11 CRM genes using RT-PCR. All allograft biopsies were blindly graded according to the Banff'09 score. Histological phenotypes were classified as AR (n=46), normal biopsies (STA, n=42), Polyoma virus associated Nephropathy (PVAN, n=9) and unspecific severe chronic injury (IFTA, n=11). 28 additional samples were also analyzed prior (n=16) and after (n=12) conducting the allograft biopsies in AR patients (2-4 months).
Results.
Out of the 11 genes, 5 were significantly higher expressed in AR patients as compared to STA transplant recipients. Using discriminant analysis in 41 samples for AR classification, the 11-gene uCRM was revealed to be the most accurate score distinguishing AR from STA (AUC=0.961; 95% CI 0.911-1), and was further validated in 47 independent serial samples (AUC=0.925; 95% CI 0.851-1). Taking into account the most sensitive and specific 11-gene uCRM cut-off score in order to use the test as a binary variable (High Risk or Low Risk), a high specificity (94.1%) and PPV (95,4) for predicting AR was obtained. Interestingly, uCRM scores assessed in 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 were significantly lower (p=0.04). Furthermore, the 11-gene uCRM score was not different between AR patients and patients showing severe IFTA and BKVN.
Summary:
The assessment of an 11-gene uCRM score in urine samples is able to non-invasively detect kidney transplant patients at high risk of AR.
To cite this abstract in AMA style:
Bestard O, Sigdel T, Ng Y, Hsieh S-C, Roedder S, Dvorak N, Tran T, Sarwal M. A Non-Invasive Urinary Common Rejection Module (uCRM) Gene Expression Score Enables Accurate Discrimination of Acute Rejection in Kidney Transplant Patients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/a-non-invasive-urinary-common-rejection-module-ucrm-gene-expression-score-enables-accurate-discrimination-of-acute-rejection-in-kidney-transplant-patients/. Accessed May 9, 2025.« Back to 2015 American Transplant Congress