Abstract
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.
Highlights
Kidney transplantation (KTx) is the preferred modality for treatment of end-stage renal disease (ESRD) by any cause [1]
There is an urgent need in transplant medicine for developing reliable and non-invasive monitoring tools that may help transplant clinicians predict the risk of allograft injury, preferentially before allograft damage has already been established
While a number of transcriptional biomarkers have been associated to acute rejection (AR), most of the studies have basically focused on a unique or single transcriptional factor and do not reflect the entire molecular complexity of the biological process of allograft rejection [11, 38]
Summary
Kidney transplantation (KTx) is the preferred modality for treatment of end-stage renal disease (ESRD) by any cause [1]. While this therapeutic approach has become a routine practice worldwide, significantly improving patient quality of life and survival [2], long-term kidney allograft outcomes have not improved as expected despite a better understanding of the immune biology of allograft rejection and the advent of novel and more potent immunosuppressive agents [3]. The research conducted in this manuscript is unrelated to the commercial activities of this company This does not alter our adherence to PLOS ONE policies on sharing data and materials
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