Elevated Urinary Matrix Metalloproteinase-7 Detects Underlying Renal Allograft Inflammation and Injury

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dc.contributor.authorHo, Julie
dc.contributor.authorRush, David
dc.contributor.authorKrokhin, Oleg
dc.contributor.authorAntonovici, Mihaela
dc.contributor.authorGao, Ang
dc.contributor.authorBestland, Jennifer
dc.contributor.authorWiebe, Chris
dc.contributor.authorHiebert, Brett
dc.contributor.authorRigatto, Claudio
dc.contributor.authorGibson, Ian
dc.contributor.authorWilkins, John
dc.contributor.authorNickerson, Peter
dc.date.accessioned2020-09-11T22:09:23Z
dc.date.available2020-09-11T22:09:23Z
dc.date.issued2016-03
dc.date.submitted2020-09-11T17:03:00Zen_US
dc.description.abstractBackground. The urinary chemokine CXCL10 detects renal transplant inflammation non-invasively, but has limited sensitivity and specificity. In this study we performed urinary proteomic analysis to identify novel biomarkers that may improve the diagnostic performance of urinary CXCL10 for detecting alloimmune inflammation in renal transplant patients. Methods. In preliminary studies, adult renal transplant patients with normal histology (n=5); interstitial fibrosis and tubular atrophy (IFTA, n=6); subclinical (n=6) and clinical rejection (n=6), underwent in-depth urine protein compositional analysis with LC-MS/MS, and matrix metalloproteinase-7 (MMP7) was identified as a potential candidate for the diagnosis of renal allograft inflammation. Urine MMP7 performance was then studied in a larger, prospective adult renal transplant population (n=148 urines from n=133 patients) with matched surveillance/indication biopsies. The diagnostic performance of urinary MMP7 and CXCL10 in combination was next evaluated using concordance (C-) statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices, to determine whether it was better than CXCL10 alone. Results. Urinary MMP7:Cr was lower in normal transplants compared to those with inflammation: glomerulonephritis (p=0.009), viral nephropathies (p=0.002), IFTA and inflammation (p=0.04), borderline (p=0.08), subclinical (p=0.01) and clinical rejection (p=0.0006), and ATN (p<0.0001). Urinary MMP7:Cr and CXCL10:Cr significantly distinguished non-inflamed from inflamed biopsies (AUC 0.74 and 0.70, respectively). The addition of urinary MMP7:Cr to CXCL10:Cr improved the diagnostic performance for subclinical and clinical inflammation/injury by IDI (p=0.002) and NRI (p=0.006) analyses. Conclusions. Urinary MMP7:Cr improves the overall diagnostic performance of urinary CXCL10:Cr for distinguishing normal histology from subclinical and clinical inflammation/injury, but not subclinical inflammation alone.en_US
dc.description.sponsorshipCanadian Institutes of Health Research (CIHR) Norman S Coplon Satellite Healthcare Extramural Grant program. Manitoba Medical Services Foundation Dr. F.W. Du Val Clinical Research Professorship. Flynn Family Chair in Renal Transplantation, University of Manitobaen_US
dc.identifier.citationTransplantation 100(3): 648-654, 2016en_US
dc.identifier.doi10.1097/TP.0000000000000867
dc.identifier.issn0041-1337/16/10003–648
dc.identifier.urihttp://hdl.handle.net/1993/35056
dc.language.isoengen_US
dc.publisherWolters Kluwer Healthen_US
dc.rightsopen accessen_US
dc.subjectProteomicsen_US
dc.subjectmass spectrometryen_US
dc.subjecturinary biomarkeren_US
dc.subjectCXCL10en_US
dc.titleElevated Urinary Matrix Metalloproteinase-7 Detects Underlying Renal Allograft Inflammation and Injuryen_US
dc.typeresearch articleen_US
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