MicroRNA Expression Changes in Kidney Transplant: Diagnostic Efficacy of miR-150-5p as Potential Rejection Biomarker, Pilot Study

Abstract

Background: The kidney allograft biopsy is considered the gold standard for rejection diagnosis but is invasive and could be indeterminate. Several publications point to the role of miRNA expression in suggesting its involvement in the acceptance or rejection of organ transplantation. This study aimed to analyze microRNAs involved in the differentiation and activation of B and T lymphocytes from kidney transplant (KT) patients’ peripheral blood leukocytes to be used as biomarkers of acute renal rejection (AR). Methods: A total of 15 KT patients with and without acute rejection (AR/NAR) were analyzed and quantified by miRNA PCR array. A total of 84 miRNAs related to lymphocyte differentiation and activation B and T were studied. The functions and biological pathways were analyzed to predict the potential targets of differential expressed miRNAs. Results: Six miRNA were increased in the AR group (miR-191-5p, miR-223-3p, miR-346, miR-423-5p, miR-574-3p, and miR-181d) and miR-150-5p was increased in the NAR group. In silico studies showed a total of 2603 target genes for the increased miRNAs in AR, while for the decrease miRNA, a total of 1107 target-potential genes were found. Conclusions: Our results show that KT with AR shows a decrease in miR-150-5p expression compared to NAR, suggesting that the decrease in miR-150-5p could be related to an increased MBD6 whose deregulation could have clinical consequences.

Gender Differences in microRNA Expressions as Related to Long-Term Graft Function in Kidney Transplant Patients

“…In transplant patients, immune suppression status is especially important for preventing graft rejections. This could explain why female patients with a worse long-term graft function have shown a significantly lower expression of miR-150 in our study [ 9 ].…”

“…MiRNAs are groups of non-coding RNAs possessing essential cellular functions such as cell proliferation, cell differentiation, organ development and immuno-regulation [ 7 ]. Their various functions make them ideal non-invasive markers during certain evaluations or follow ups [ 8 , 9 ]. Renal graft biopsies are the current gold standard for the examination of entities involving renal graft dysfunction.…”

Computational Prediction of Biomarkers, Pathways, and New Target Drugs in the Pathogenesis of Immune-Based Diseases Regarding Kidney Transplantation Rejection

“…The Kruskal Wallis test and Dunn’s post hoc test with Bonferroni correction for multiple comparisons compared three or more groups. Correlation analyzes were carried out using the Spearman index, as previously published ( 5 , 21 , 22 ). For the longitudinal comparison of two related groups, the Wilcoxon non-parametric test for related samples was used.…”

Epigenetic Regulation in Kidney Transplantation

“…Similarly, another study using logistic regression analysis showed that urinary miR-155-5p could identify patients with potential high risk of rejection at early stage of post-transplantation (95). Alfaro et al showed that miR-150-5p was decreased in acute rejection kidney transplantation patients, the decrease could be related to activation and proliferation of the immune system's cells (96). A pilot study showed that in the first 3 months post transplantation with tacrolimus therapy, urinary exosome derived miR-155-5p and miR-223-3p correlated with tacrolimus dose, miR-223-3p with serum creatinine, and miR-223-3p and miR-1228-3p with blood leukocytes, indicating that differentially expressed urinary exosome miRNAs might monitor tacrolimus therapy and renal graft function (97).…”