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

Transplantation
Julie HoPeter W Nickerson

Abstract

The urinary CXC chemokine ligand (CXCL)10 detects renal transplant inflammation noninvasively, 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. In preliminary studies, adult renal transplant patients with normal histology (n = 5), interstitial fibrosis and tubular atrophy (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) were 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 and integrated discrimination improvement indices, to determine whether it was better than CXCL10 alone. Urinary MMP7:creatinine (Cr) was lower in normal transpl...Continue Reading

Associated Clinical Trials

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Citations

Nov 20, 2016·European Journal of Immunology·Richard DangerSophie Brouard
Feb 22, 2017·Current Opinion in Nephrology and Hypertension·Julie HoJohn A Wilkins
Nov 7, 2017·Expert Review of Proteomics·Arjun Chakraborty, Minnie Sarwal
Apr 16, 2019·Transplantation·Mario NavarreteJulie Ho
Sep 24, 2020·International Journal of Molecular Sciences·Francesco GuzziPaola Romagnani
Feb 27, 2018·Canadian Journal of Kidney Health and Disease·Julie LeblancHéloïse Cardinal
Aug 17, 2016·Clinical Proteomics·Ravi C DwivediJohn A Wilkins

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