Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients

Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. The hallmarks of progressive CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs are small, regulatory RNAs involved in many immunological processes. In particular, microRNA-21-5p (miR-2...

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Main Authors: Michal S. Gniewkiewicz, Izabela Paszkowska, Jolanta Gozdowska, Katarzyna Czerwinska, Anna Sadowska-Jakubowicz, Dominika Deborska-Materkowska, Agnieszka Perkowska-Ptasinska, Maciej Kosieradzki, Magdalena Durlik
Format: Article
Language:English
Published: MDPI AG 2020-02-01
Series:Diagnostics
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Online Access:https://www.mdpi.com/2075-4418/10/2/113
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author Michal S. Gniewkiewicz
Izabela Paszkowska
Jolanta Gozdowska
Katarzyna Czerwinska
Anna Sadowska-Jakubowicz
Dominika Deborska-Materkowska
Agnieszka Perkowska-Ptasinska
Maciej Kosieradzki
Magdalena Durlik
author_facet Michal S. Gniewkiewicz
Izabela Paszkowska
Jolanta Gozdowska
Katarzyna Czerwinska
Anna Sadowska-Jakubowicz
Dominika Deborska-Materkowska
Agnieszka Perkowska-Ptasinska
Maciej Kosieradzki
Magdalena Durlik
author_sort Michal S. Gniewkiewicz
collection DOAJ
description Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. The hallmarks of progressive CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs are small, regulatory RNAs involved in many immunological processes. In particular, microRNA-21-5p (miR-21) is considered to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to assess urinary miR-21 expression levels in the kidney transplant recipients and determine their application in the evaluation of IFTA and kidney allograft function. The expression levels of miR-21 were quantified in the urine of 31 kidney transplant recipients with biopsy-assessed IFTA (IFTA 0 + I: <i>n</i> = 17; IFTA II + III: <i>n</i> = 14) by real-time quantitative PCR. Urine samples were collected at the time of protocolar biopsies performed 1 or 2 years after kidney transplantation. MicroRNA-191-5p was used as reference gene. MiR-21 was significantly up-regulated in IFTA II + III group compared to IFTA 0 + I group (<i>p</i> = 0.003). MiR-21 correlated significantly with serum concentration of creatinine (r = 0.52, <i>p</i> = 0.003) and eGFR (r = &#8722;0.45; <i>p</i> = 0.01). ROC analysis determined the diagnostic value of miR-21 with an area under curve (AUC) of 0.80 (<i>p</i> = 0.0002), sensitivity of 0.86 and specificity of 0.71. miR-21 is associated with renal allograft dysfunction and IFTA. Therefore, it could be considered as a potential diagnostic, non-invasive biomarker for monitoring renal graft function.
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spelling doaj.art-16c073ff9570490381904c66240d05b52022-12-22T04:00:34ZengMDPI AGDiagnostics2075-44182020-02-0110211310.3390/diagnostics10020113diagnostics10020113Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant RecipientsMichal S. Gniewkiewicz0Izabela Paszkowska1Jolanta Gozdowska2Katarzyna Czerwinska3Anna Sadowska-Jakubowicz4Dominika Deborska-Materkowska5Agnieszka Perkowska-Ptasinska6Maciej Kosieradzki7Magdalena Durlik8Department of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of General and Transplantation Surgery, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandDepartment of Transplantation Medicine, Nephrology and Internal Medicine, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, PolandChronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. The hallmarks of progressive CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs are small, regulatory RNAs involved in many immunological processes. In particular, microRNA-21-5p (miR-21) is considered to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to assess urinary miR-21 expression levels in the kidney transplant recipients and determine their application in the evaluation of IFTA and kidney allograft function. The expression levels of miR-21 were quantified in the urine of 31 kidney transplant recipients with biopsy-assessed IFTA (IFTA 0 + I: <i>n</i> = 17; IFTA II + III: <i>n</i> = 14) by real-time quantitative PCR. Urine samples were collected at the time of protocolar biopsies performed 1 or 2 years after kidney transplantation. MicroRNA-191-5p was used as reference gene. MiR-21 was significantly up-regulated in IFTA II + III group compared to IFTA 0 + I group (<i>p</i> = 0.003). MiR-21 correlated significantly with serum concentration of creatinine (r = 0.52, <i>p</i> = 0.003) and eGFR (r = &#8722;0.45; <i>p</i> = 0.01). ROC analysis determined the diagnostic value of miR-21 with an area under curve (AUC) of 0.80 (<i>p</i> = 0.0002), sensitivity of 0.86 and specificity of 0.71. miR-21 is associated with renal allograft dysfunction and IFTA. Therefore, it could be considered as a potential diagnostic, non-invasive biomarker for monitoring renal graft function.https://www.mdpi.com/2075-4418/10/2/113iftakidney transplantationmicrornamir-21
spellingShingle Michal S. Gniewkiewicz
Izabela Paszkowska
Jolanta Gozdowska
Katarzyna Czerwinska
Anna Sadowska-Jakubowicz
Dominika Deborska-Materkowska
Agnieszka Perkowska-Ptasinska
Maciej Kosieradzki
Magdalena Durlik
Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients
Diagnostics
ifta
kidney transplantation
microrna
mir-21
title Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients
title_full Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients
title_fullStr Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients
title_full_unstemmed Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients
title_short Urinary MicroRNA-21-5p as Potential Biomarker of Interstitial Fibrosis and Tubular Atrophy (IFTA) in Kidney Transplant Recipients
title_sort urinary microrna 21 5p as potential biomarker of interstitial fibrosis and tubular atrophy ifta in kidney transplant recipients
topic ifta
kidney transplantation
microrna
mir-21
url https://www.mdpi.com/2075-4418/10/2/113
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