Abstract 12855: Circulating miRNA-30a, -30e, -188 as Early Biomarkers for CI-AKI diagnosis

Abstract

Background: Contrast-induced acute kidney injury (CI-AKI) is typically defined as an increase in serum creatinine (SCr) within 3 days after intravascular administration of contrast medium. However, creatinine is an unreliable indicator for acute changes in kidney function. A reliable and early biomarker for CI-AKI diagnosis is needed.

Hypothesis: Circulating miRNAs can serve as early diagnostic biomarkers for CI-AKI.

Methods and Results: We utilized a previously described rat model of CI-AKI. The microRNA profiles of plasma and kidney tissue were determined using Agilent microarray platforms. Three individual miRNA species with >1.5-fold increases in plasma expression in CI-AKI rats as compared to wild-type rats were identified: miRNA-30a, miRNA-30e, and miRNA-188. These miRNAs were selected as potential candidate miRNA biomarkers for CI-AKI (Figure 1). TaqMan quantitative RT-PCR demonstrated that the plasma expression of these miRNAs peaked around 4h after contrast medium exposure. We screened for these candidate biomarkers in the peripheral circulation of 580 consecutive patients undergoing coronary angiography or percutaneous coronary intervention in Cardiovascular Center at Renji Hospital from July 2013 to June 2014. When compared with matched control patients without CI-AKI, the plasma levels of the three candidate miRNAs were significantly elevated post procedure in 71 patients diagnosed with CI-AKI (fold changes: miR-30a, 3.26±0.05 vs. 0.68±0.01, p<0.01; miR-30e, 3.03±0.04 vs. 0.74±0.01, p<0.01; miR-188, 2.36±0.03 vs. 0.77±0.01, p<0.01). Maximal sensitivity and specificity were found to be 71.83% and 88.73% respectively in this study, suggesting a limit of assay efficacy.

Conclusions: Plasma expression levels of miRNA-30a, miRNA-30e, and miRNA-188 significantly differentiate patients with CI-AKI from those without CI-AKI. These miRNAs are potential biomarkers for the early detection of CI-AKI.