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

Abstract

BackgroundContrast‐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 ResultsUsing 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.ConclusionsPlasma 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.

Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes

“…From our small-RNAseq results, we identified miRNAs that showed significant concentration changes in patients when compared with non-DN controls (for patients with overt DN) or when compared with their previous non-MA urine collection cycle (for patients with IMA or PMA). Many of these miRNAs have been previously associated with kidney function, and have roles in the pathophysiology of diabetes 23 , 24 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , ...…”

Comparison of Effects of Different Statins on Contrast‐Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings

“…Our results indicate that statins exhibit differential effects in CI-AKI prevention when given at equivalent lipid-lowering doses. These results must be confirmed by randomized controlled trials with larger sample sizes using more sensitive markers of renal parenchymal injury, such as neutrophil gelatinase-associated lipocalin or microRNAs [ 29 , 30 ].…”

miR-21 attenuates contrast-induced renal cell apoptosis by targeting PDCD4

“…miR-21 levels have been observed to increase continuously in proliferating cells ( 12 , 25 ), starting at 24 h post injury ( 29 ). Therefore, its expression did not increase within 24 h reperfusion subsequent to 20 min of ischemia, or within 8 h of CM administration ( 13 , 30 ). It has been demonstrated that one-half of the amount of CM in the bloodstream may be eliminated quickly, in ~2 h ( 31 ).…”