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Circulating miR-150, miR-192, miR-200b, and miR-423-3p as Non-invasive Biomarkers of Chronic Allograft Dysfunction
Sepideh Zununi Vahed1, Ahmad Poursadegh Zonouzi2, Fariba Mahmoodpoor3
1Chronic Kidney Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Background And Aims:
Chronic allograft dysfunction (CAD) is the major cause of renal allograft loss and can only be diagnosed by invasive histological examinations. The current study aimed to determine whether or not the circulating miR-125a, miR-150, miR-192, miR-200b, miR-423-3p and miR-433 could serve as predictors of graft outcome in the renal transplant recipients with CAD.
Methods:
To evaluate the expression levels of miRNAs, we used quantitative real-time PCR (qPCR) and analyzed the plasma samples of 53 renal transplant recipients, including: 27 recipients with stable graft function (SGF), 26 recipients with biopsy-proven interstitial fibrosis and tubular atrophy (IFTA) and 15 healthy controls. Possible correlation between the clinicopathological parameters and the studied circulating miRNAs was also evaluated.
Results:
miR-150 (p <0.001), miR-192 (p = 0.003), miR-200b (p = 0.048) and miR-423-3p (p <0.001) were differentially expressed between IFTA and SGF plasma samples. Creatinine correlated with miR-192 (r = 0.414, p = 0.036) and miR-423-3p (r = -0.431, p = 0.028). Moreover, the estimated glomerular filtration rate (eGFR) significantly correlated with the circulating miR-192 (r = -0.390, p = 0.049) and miR-423 (r = 0.432, p = 0.028). Receiver operating characteristic (ROC) analysis indicated that four miRNAs possessed the best diagnostic value for discriminating IFTA from SGF recipients with the areas under the curve (AUC) of 0.87 and high sensitivity and specificity values of 78% and 91%, respectively.
Conclusions:
The results suggest that aberrant plasma levels of these miRNAs are associated with the renal allograft dysfunction. Therefore, they are proposed to be considered as potential diagnostic biomarkers for monitoring of renal graft function.
