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The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study.

Abstract：

BACKGROUND:Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR. METHODS AND FINDINGS:We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set--the Kidney Solid Organ Response Test (kSORT)--was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91-0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88-1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86-0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials. CONCLUSIONS:The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary.

journal_name

PLoS Med

journal_title

PLoS medicine

authors

Roedder S,Sigdel T,Salomonis N,Hsieh S,Dai H,Bestard O,Metes D,Zeevi A,Gritsch A,Cheeseman J,Macedo C,Peddy R,Medeiros M,Vincenti F,Asher N,Salvatierra O,Shapiro R,Kirk A,Reed EF,Sarwal MM

doi

10.1371/journal.pmed.1001759

subject

Has Abstract

pub_date

2014-11-11 00:00:00

pages

e1001759

issue

eissn

1549-1277

issn

1549-1676

pii

PMEDICINE-D-14-00316

journal_volume

pub_type

杂志文章,多中心研究

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The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study.