Sepideh Zununi Vahed1, Yadollah Omidi2, Mohammadreza Ardalan3, Nasser Samadi4. 1. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: drnsamadi@yahoo.com.
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.
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 IFTApatients 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.