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

PLoS One. 2019 Jul 31;14(7):e0220052. doi: 10.1371/journal.pone.0220052. eCollection 2019.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers / metabolism
  • Biomarkers / urine*
  • Chemokine CXCL10 / genetics
  • Child
  • Child, Preschool
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • Gene Expression
  • Graft Rejection / diagnosis
  • Graft Rejection / genetics*
  • Humans
  • Infant
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Transplantation*
  • Middle Aged
  • ROC Curve
  • Sensitivity and Specificity
  • Transplantation, Homologous
  • Young Adult

Substances

  • Biomarkers
  • Chemokine CXCL10
  • LMP-2 protein
  • Cysteine Endopeptidases