A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury

Abstract

In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRNAs useful for AKI diagnosis and management. Using qRT-PCR arrays in serum samples, we determined miRNAs differentially expressed between AKI patients and healthy controls. Statistical and target prediction analysis allowed us to identify a panel of 10 serum miRNAs. This set was further validated, by qRT-PCR, in two independent cohorts of patients with relevant morbi-mortality related to AKI: Intensive Care Units (ICU) and Cardiac Surgery (CS). Statistical correlations with patient clinical parameter were performed. Our results demonstrated that the 10 selected miRNAs (miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p and miR-10a-5p) were diagnostic biomarkers of AKI in ICU patients, exhibiting areas under the curve close to 1 in ROC analysis. Outstandingly, serum miRNAs estimated before CS predicted AKI development later on, thus becoming biomarkers to predict AKI predisposition. Moreover, after surgery, the expression of the miRNAs was modulated days before serum creatinine increased, demonstrating early diagnostic value. In summary, we have identified a set of serum miRNAs as AKI biomarkers useful in clinical practice, since they demonstrate early detection and high diagnostic value and they recognize patients at risk.

Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome

“…miRNAs are already being used commercially as disease biomarkers in oncology [17]. There is evidence for the use miRNAs as biomarkers in a wide range of diseases including prostate cancer [36], cardiac disease [37], acute kidney injury [38], and Alzheimer's disease [39]. If we could identify miRNAs that could be used as biomarkers for PCOS, the diagnosis and treatment of PCOS would be revolutionized.…”

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…In addition, urine and plasma miR-21 can predict AKI progression, with an AUC of 0.81 and 0.83, respectively [47]. Moreover, a recent pilot study showed that other sets of microRNAs, including miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p, and miR-10a-5p, were altered several days prior to the increase in SCr, indicating their potential as prognostic AKI biomarkers among ICU patients [48]. Lorenzen et al recently demonstrated that elevated levels of plasma miR-210, a microRNA upregulated by hypoxia-inducible factor, was an independent predictor of mortality, with a hazard ratio (HR) 1.69 in patients with AKI requiring RRT [56].…”

The potential use of biomarkers in predicting contrast-induced acute kidney injury

“…170 Another study utilized serum samples from normal subjects and patients with AKI; miRNA molecules could be considered as markers of AKI. 171 Notably, several of the miRNA molecules had already been associated with kidney injury: in proximal tubule adhesion and trafficking during IRI (miR-127), in an in vivo mouse model of IRI and in patients with immunoglobulin A nephropathy (miR-146a), and in progression of chronic kidney disease (miR-29a). In addition, several of the miRNA molecules could also be correlated with AKI severity according to the Acute Kidney Injury Network classification.…”

“…In addition, several of the miRNA molecules could also be correlated with AKI severity according to the Acute Kidney Injury Network classification. 171 Two groups have found several miRNAs whose serum levels were increased in patients with CI-AKI. 172,173 Future aims could be directed toward identifying miRNAs that are expressed specifically in the kidney 174 and to correlate their changes with kidney injury due to use of CM.…”