Urinary MicroRNA as Biomarker in Renal Transplantation

Abstract

Urine represents a noninvasive source in which proteins and nucleic acids can be assessed. Such analytes may function as biomarkers to monitor kidney graft pathology at every desired frequency, thereby providing a time window to prevent graft damage by therapeutic intervention. Recently, several proteins have been measured in urine as markers of graft injury. However, the specificity is limited, and measuring urinary proteins generally lacks the potential to predict early kidney graft damage. Currently, urinary mRNA and microRNA are being investigated to evaluate the prognostic value of changes in gene expression during the initial stages of graft damage. At such time point, a change in treatment regimen and dosage is expected to have maximum potency to minimize future decline in graft function. Both mRNA and microRNAs have shown promising results in both detection and prediction of graft injury. An advantage of microRNAs compared to mRNA molecules is their stability, a characteristic that is beneficial when working with urine samples. In this review, we provide the current state of urinary biomarkers in renal transplantation, with a focus on urinary microRNA. In addition, we discuss the methods used to study urinary microRNA expression.

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

“…This finding highlighted the impact of "background noise" from uromodulin and proteinuria, suggesting that urinary EVs are a more selective source of biomarkers. Despite this, little evidence has been produced on urinary EV RNAs so far, as most papers have focused on total, cell-derived, or cell-free urinary transcripts (222).…”

Cell‐free microRNA‐148a is associated with renal allograft dysfunction: Implication for biomarker discovery

“…CAD is a phenomenon with different molecular and cellular game players, as well as a mixed histology and pathophysiology. [7][8][9] The epigenetic mechanisms in CAD and the contribution of miRNAs have paved new ways into research where the miRNAs expression patterns can act as a novel diagnostic tool and an alternative to renal biopsy. [1][2][3] Yet, the exact mechanism(s) leading to its emergence is not fully discovered.…”

“…Numerous immunological and nonimmunological factors along with donor and recipient-related factors may associate with tubulointerstitial damage and graft outcome. [14][15][16][17] The aberrant expression of miRNAs involved in immunity, epithelialmesenchymal transition (EMT), and extracellular matrix (ECM) accumulation has been reported in the biopsy, 18,19 urine, 5,9,20 and serum/plasma [21][22][23] samples of the renal transplant recipients with IFTA. 5,6 However, molecular pathways related to the progression of CAD act at an earlier step and their dysregulations may not be detected by the clinical methods.…”

“…Three pathways that are enriched among target genes of miRNA-148a and IFTA miRNAs reviewed by van de Vrie et al9 …”

MicroRNAs: the future of genomic science?

“…These are exemplified by work in areas such as cardiology, respiratory medicine and transplantation. [1][2][3][4] However, bearing in mind the potential for base-pair mismatching between mRNAs and miRNAs, various roles as biomarkers in cancer hold considerable promise, as demonstrated, for example, in tumours of the liver, [5] cervix [6] and prostate. [7] The focus on miRNAs and cancer continues in this issue of BJBS, with work reported on the role of miRNA-124 in pancreatic adenocarcinoma, [8] miRNA-21 in osteosarcoma, [9] and miRNA-146a in gastric cancer.…”