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Suhre, K. ; Schwartz, J.E.* ; Sharma, V.K.* ; Chen, Q.* ; Lee, J.R.* ; Muthukumar, T.* ; Dadhania, D.M.* ; Ding, R.* ; Ikle, D.N.* ; Bridges, N.D.* ; Williams, N.M.* ; Kastenmüller, G. ; Karoly, E.D.* ; Mohney, R.P.* ; Abecassis, M.* ; Friedewald, J.* ; Knechtle, S.J.* ; Becker, Y.T.* ; Samstein, B.* ; Shaked, A.* ; Gross, S.S.* ; Suthanthiran, M.*

Urine metabolite profiles predictive of human kidney allograft status.

J. Am. Soc. Nephrol. 27, 626-636 (2015)
DOI PMC
Open Access Gold möglich sobald Verlagsversion bei der ZB eingereicht worden ist.
Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acute Rejection ; Kidney Biopsy ; Renal Transplantation ; Transplant Outcomes; General-population; Metabolomics; Rejection; Transplantation; Inhibition; Biomarker
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1046-6673
e-ISSN 1533-3450
Zeitschrift Journal of the American Society of Nephrology
Quellenangaben Band: 27, Heft: 2, Seiten: 626-636 Artikelnummer: , Supplement: ,
Verlag American Society of Nephrology
Verlagsort Washington
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Bioinformatics and Systems Biology (IBIS)
POF Topic(s) 30505 - New Technologies for Biomedical Discoveries
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503700-001
PubMed ID 26047788
DOI 10.1681/ASN.2015010107
WOS ID WOS:000368957600031
Scopus ID 84970922503
Erfassungsdatum 2015-06-08
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