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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Selection of candidate circulating miRNAs as early biomarkers for CI‐AKI in rats. A, Global miRNA expression profiles of kidney and plasma in CI‐AKI and control rats by miRNA microarrays. Principal component analysis (PCA) revealed that the hybridization results of 2 plasma samples (1 from the CI‐AKI group and 1 from the control group) were significantly different from the other plasma samples. These 2 components explained 81.19% of the variability. B, Hierarchical clustering analysis of dysregulated miRNAs (with a fold change >1.5) in plasma and kidney samples. The relative miRNA expression is depicted according to the color scale shown on the right. Red indicates upregulation and blue, downregulation. C, Diagram of the strategy for identifying candidate miRNAs. See Results for details. CI‐AKI indicates contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; NS, normal saline; PCA, principal component analysis.
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jah31704-fig-0001: Selection of candidate circulating miRNAs as early biomarkers for CI‐AKI in rats. A, Global miRNA expression profiles of kidney and plasma in CI‐AKI and control rats by miRNA microarrays. Principal component analysis (PCA) revealed that the hybridization results of 2 plasma samples (1 from the CI‐AKI group and 1 from the control group) were significantly different from the other plasma samples. These 2 components explained 81.19% of the variability. B, Hierarchical clustering analysis of dysregulated miRNAs (with a fold change >1.5) in plasma and kidney samples. The relative miRNA expression is depicted according to the color scale shown on the right. Red indicates upregulation and blue, downregulation. C, Diagram of the strategy for identifying candidate miRNAs. See Results for details. CI‐AKI indicates contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; NS, normal saline; PCA, principal component analysis.

Mentions: As shown in Figure 1A, 24 rats were randomly divided into 2 groups (a CI‐AKI group and a control group). In each group, 12 rats were further divided into 4 subgroups, namely, CI‐AKI subgroups 1 to 4 and control subgroups 1 to 4 (n=3 for each subgroup). Peripheral blood and kidney samples were harvested at 8 hours after CM/NS administration. The plasma or renal RNA samples extracted from rats in same subgroup were pooled and then measured with a single microarray.20 The Agilent microarray platform was adapted to profile the miRNA spectra. Principal component analysis was performed to test the consistency of hybridization results of each microarray. Principal component analysis revealed that the hybridization results of 2 pooled plasma samples (1 from the CI‐AKI subgroup and 1 from the control subgroup) significantly deviated from the results of the other plasma samples; data from these 2 arrays were excluded from further analysis (Figure 1A). The correlation coefficient of hybridization results among the remaining 6 pooled plasma samples ranged from 0.89 to 0.98 and from 0.95 to 0.99 among the 8 pooled kidney samples. The complete data set of miRNA microarray results can be accessed through Gene Expression Omnibus (Series accession number GSE81400).


Circulating Micro RNA ‐ 188, ‐ 30a, and ‐ 30e as Early Biomarkers for Contrast ‐ Induced Acute Kidney Injury
Selection of candidate circulating miRNAs as early biomarkers for CI‐AKI in rats. A, Global miRNA expression profiles of kidney and plasma in CI‐AKI and control rats by miRNA microarrays. Principal component analysis (PCA) revealed that the hybridization results of 2 plasma samples (1 from the CI‐AKI group and 1 from the control group) were significantly different from the other plasma samples. These 2 components explained 81.19% of the variability. B, Hierarchical clustering analysis of dysregulated miRNAs (with a fold change >1.5) in plasma and kidney samples. The relative miRNA expression is depicted according to the color scale shown on the right. Red indicates upregulation and blue, downregulation. C, Diagram of the strategy for identifying candidate miRNAs. See Results for details. CI‐AKI indicates contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; NS, normal saline; PCA, principal component analysis.
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jah31704-fig-0001: Selection of candidate circulating miRNAs as early biomarkers for CI‐AKI in rats. A, Global miRNA expression profiles of kidney and plasma in CI‐AKI and control rats by miRNA microarrays. Principal component analysis (PCA) revealed that the hybridization results of 2 plasma samples (1 from the CI‐AKI group and 1 from the control group) were significantly different from the other plasma samples. These 2 components explained 81.19% of the variability. B, Hierarchical clustering analysis of dysregulated miRNAs (with a fold change >1.5) in plasma and kidney samples. The relative miRNA expression is depicted according to the color scale shown on the right. Red indicates upregulation and blue, downregulation. C, Diagram of the strategy for identifying candidate miRNAs. See Results for details. CI‐AKI indicates contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; NS, normal saline; PCA, principal component analysis.
Mentions: As shown in Figure 1A, 24 rats were randomly divided into 2 groups (a CI‐AKI group and a control group). In each group, 12 rats were further divided into 4 subgroups, namely, CI‐AKI subgroups 1 to 4 and control subgroups 1 to 4 (n=3 for each subgroup). Peripheral blood and kidney samples were harvested at 8 hours after CM/NS administration. The plasma or renal RNA samples extracted from rats in same subgroup were pooled and then measured with a single microarray.20 The Agilent microarray platform was adapted to profile the miRNA spectra. Principal component analysis was performed to test the consistency of hybridization results of each microarray. Principal component analysis revealed that the hybridization results of 2 pooled plasma samples (1 from the CI‐AKI subgroup and 1 from the control subgroup) significantly deviated from the results of the other plasma samples; data from these 2 arrays were excluded from further analysis (Figure 1A). The correlation coefficient of hybridization results among the remaining 6 pooled plasma samples ranged from 0.89 to 0.98 and from 0.95 to 0.99 among the 8 pooled kidney samples. The complete data set of miRNA microarray results can be accessed through Gene Expression Omnibus (Series accession number GSE81400).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus