title: The urine microRNA profile may help monitor post-transplant renal graft function.
abstract: Noninvasive, cost-effective biomarkers that allow accurate monitoring of graft function are needed in kidney transplantation. Since microRNAs (miRNAs) have emerged as promising disease biomarkers, we sought to establish an miRNA signature in urinary cell pellets comparing kidney transplant patients diagnosed with chronic allograft dysfunction (CAD) with interstitial fibrosis and tubular atrophy and those recipients with normal graft function. Overall, we evaluated 191 samples from 125 deceased donor primary kidney transplant recipients in the discovery, initial validation, and the longitudinal validation studies for noninvasive monitoring of graft function. Of 1733 mature miRNAs studied using microarrays, 22 were found to be differentially expressed between groups. Ontology and pathway analyses showed inflammation as the principal biological function associated with these miRNAs. Twelve selected miRNAs were longitudinally evaluated in urine samples of an independent set of 66 patients, at two time points after kidney transplant. A subset of these miRNAs was found to be differentially expressed between groups early after kidney transplant before histological allograft injury was evident. Thus, a panel of urine miRNAs was identified as potential biomarkers for monitoring graft function and anticipating progression to CAD in kidney transplant patients.
authors.affiliation: Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Maluf
authors.affiliation: Department of Pathology, Virginia Commonwealth University, Charlottesville, Virginia, USA.
authors.forename: Catherine I
authors.initials: CI
authors.lastname: Dumur
authors.affiliation: Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Jihee L
authors.initials: JL
authors.lastname: Suh
authors.affiliation: Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Mariano J
authors.initials: MJ
authors.lastname: Scian
authors.affiliation: Division of Transplant, Virginia Commonwealth University, Charlottesville, Virginia, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: King
authors.affiliation: Department of Pathology, Virginia Commonwealth University, Charlottesville, Virginia, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Cathro
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Gehrau
authors.affiliation: Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Brayman
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Comprehensive Transplant Center, Northwestern University, Chicago, Illinois, USA.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Gallon
authors.affiliation: Translational Genomics Transplant Laboratory, Transplant Division, Department of Surgery, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Valeria R
authors.initials: VR
authors.lastname: Mas
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis; D020869:Gene Expression Profiling; D005819:Genetic Markers; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D016030:Kidney Transplantation / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011507:Proteinuria / Q000175:diagnosis / Q000235:genetics / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D016482:Urinalysis; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs
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