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

PloS One
Tara K SigdelMinnie M Sarwal

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 vacuoli...Continue Reading

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Citations

Apr 7, 2020·The Journal of Clinical Investigation·Hamid Rabb
Sep 24, 2020·International Journal of Molecular Sciences·Francesco GuzziPaola Romagnani
Sep 6, 2020·Current Opinion in Nephrology and Hypertension·Sook Hyeon Park, John J Friedewald
Mar 20, 2020·Science Translational Medicine·Joshua Y C YangMinnie M Sarwal
Sep 13, 2019·International Journal of Molecular Sciences·Joshua Y C YangRichard A Lafayette
Oct 1, 2020·World Journal of Transplantation·Kurtis J SwansonSandesh Parajuli
Apr 30, 2021·Néphrologie & thérapeutique·Claire Tinel, Dany Anglicheau

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Methods Mentioned

BETA
biopsies
biopsy
urine collection
PCR
chip

Software Mentioned

Prism
Random Forest
Mathematica
Morpheus
JMP
GeneMANIA

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