Circulating MicroRNA-188, -30a, and -30e as Early Biomarkers for Contrast-Induced Acute Kidney Injury

Abstract

Background: Contrast-induced acute kidney injury (CI-AKI) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating microRNAs (miRNAs) could serve as biomarkers for early detection of CI-AKI. Methods and Results: Using a rat model of CI-AKI, we first evaluated the miRNA profile of rat plasma and kidney. Three miRNA species with >1.5-fold increase in plasma samples of CI-AKI rats, including miRNA-188, miRNA-30a, and miRNA-30e, were selected as candidate miRNAs. Quantitative real-time polymerase chain reaction showed that these candidate miRNAs peaked in concentration around 4 hours after contrast medium exposure and were relatively renal-specific. We compared the plasma levels of these candidate miRNAs in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed CI-AKI with those of 71 matched controls. The plasma levels of the 3 candidate miRNAs were significantly elevated in the CI-AKI group as compared to the control group. Receiver operating characteristic analysis showed that these miRNAs significantly distinguished patients with CI-AKI from those without CI-AKI. MiRNA composites were highly accurate for CI-AKI prediction, as shown in maximized specificity by treble-positive miRNA composite or maximized Youden index by any-positive miRNA composite. Moreover, the selected miRNAs changes were associated with Mehran Risk Scores. Conclusions: Plasma levels of candidate miRNAs significantly distinguished patients with CI-AKI from those without CI-AKI. Thus, miRNAs are potential biomarkers for early detection of CI-AKI.