Dysregulation of urinary miR-21 and miR-200b associated with interstitial fibrosis and tubular atrophy (IFTA) in renal transplant recipients

Abstract

Objective: microRNAs (miRNAs) are endogenous gene expression regulators that are involved in renal function and physiopathology, making them potential biomarkers in the realm of transplantation. Here, we aimed to evaluate urinary miRNA expression levels and assess their possible values in the prospective evaluation of renal allograft function. Design and methods: The expression levels of four miRNAs involved in renal fibrosis were quantified in urine cell pellets of 47 kidney recipients (with stable allograft function (SGF) and biopsy proven interstitial fibrosis and tubular atrophy; IFTA) and 15 healthy controls by real-time quantitative-PCR (RT-qPCR). The hierarchical clustering and receiver operating characteristic (ROC) analysis of miRNAs were performed in the study groups. Results: Significant differences were observed in the urinary expression of miR-21 (P < 0.001), miR-142-3p (P < 0.001), and miR-200b (P = 0.021) between IFTA and controls. The hierarchical clustering of miRNA expression clustered most of the SGF and IFTA patients in separated groups. Estimated GFR was significantly correlated with urinary levels of miR-21 (r = 0.585, P = 0.003) and miR-200 (r = -0.447, P = 0.033). ROC analysis confirmed the ability of urinary miR-21 and miR-200b to discriminate the IFTA recipients with an area under the ROC curve of 0.81 (P < 0.001) and high sensitivity and specificity. Conclusion: Taken together, our findings indicated that the aberrant urinary miR-21 and miR-200b expression levels were accompanied with renal allograft dysfunction and IFTA. Therefore, they can be considered as potential diagnostic biomarkers for renal allograft monitoring. (C) 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.