A urinary Common Rejection Module (uCRM) score for non-invasive kidney transplant monitoring

• DOI: 10.1371/journal.pone.0220052
• Publication Date: 2019-07-31T17:32:26Z
• Authors: Tara K. Sigdel; Joshua Y. C. Yang; Oriol Bestard; Andrew Schroeder; Szu-Chuan Hsieh; Juliane M. Liberto; Izabella Damm; Anna C. M. Geraedts; Minnie M. Sarwal
• Keywords: Homologous; Adult; Graft Rejection; Kidney Disease; Adolescent; General Science & Technology; Science; Clinical Sciences; Renal and urogenital; Trasplantament renal; 610; Gene Expression; Urine; Kidney; Sensitivity and Specificity; Kidney transplantation; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Humans; Transplantation, Homologous; Preschool; Child; Aged; Transplantation; screening and diagnosis; Biomedical and Clinical Sciences; Q; R; Infant; Organ Transplantation; Middle Aged; Orina; Expressió gènica; Kidney Transplantation; 4.1 Discovery and preclinical testing of markers and technologies; 3. Good health; Chemokine CXCL10; Detection; Cysteine Endopeptidases; ROC Curve; Area Under Curve; Child, Preschool; Medicine; Gene expression; Biomarkers; Biotechnology; Research Article

A Common Rejection Module (CRM) consisting of 11 genes expressed in allograft biopsies was previously reported to serve as a biomarker for acute rejection (AR), correlate with the extent of graft injury, and predict future allograft damage. We investigated the use of this gene panel on the urine cell pellet of kidney transplant patients. Urinary cell sediments collected from patients with biopsy-confirmed acute rejection, borderline AR (bAR), BK virus nephropathy (BKVN), and stable kidney grafts with normal protocol biopsies (STA) were analyzed for expression of these 11 genes using quantitative polymerase chain reaction (qPCR). We assessed these 11 CRM genes for their abundance, autocorrelation, and individual expression levels. Expression of 10/11 genes were elevated in AR when compared to STA. Psmb9 and Cxcl10could classify AR versus STA as accurately as the 11-gene model (sensitivity = 93.6%, specificity = 97.6%). A uCRM score, based on the geometric mean of the expression levels, could distinguish AR from STA with high accuracy (AUC = 0.9886) and correlated specifically with histologic measures of tubulitis and interstitial inflammation rather than tubular atrophy, glomerulosclerosis, intimal proliferation, tubular vacuolization or acute glomerulitis. This urine gene expression-based score may enable the non-invasive and quantitative monitoring of AR.