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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

Evaluation of candidate circulating miRNAs in CI‐AKI patients. A, The plasma levels of the three candidate miRNAs in 71 CI‐AKI patients and 71 matched controls without CI‐AKI by RT‐qPCR. Blood samples were obtained at baseline and 4 to 6 hours post CM exposure. Individual value plots represent the relative change of miRNA levels compared with baseline in each CI‐AKI patient (left) and non‐CI‐AKI patient (right). A crossbar on each plot indicates the mean expression level for each group. ***P<0.001. B, Discrimination potential of candidate circulating miRNAs. Receiver operating characteristics (ROC) curves were drawn with the data of fold change of plasma microRNAs from 71 CI‐AKI patients and 71 matched controls. The dashed line indicates “random guess” diagonal line. AUC indicates area under the curve; CI‐AKI, contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; RT‐qPCR, reverse transcription quantitative real‐time polymerase chain reaction.
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jah31704-fig-0003: Evaluation of candidate circulating miRNAs in CI‐AKI patients. A, The plasma levels of the three candidate miRNAs in 71 CI‐AKI patients and 71 matched controls without CI‐AKI by RT‐qPCR. Blood samples were obtained at baseline and 4 to 6 hours post CM exposure. Individual value plots represent the relative change of miRNA levels compared with baseline in each CI‐AKI patient (left) and non‐CI‐AKI patient (right). A crossbar on each plot indicates the mean expression level for each group. ***P<0.001. B, Discrimination potential of candidate circulating miRNAs. Receiver operating characteristics (ROC) curves were drawn with the data of fold change of plasma microRNAs from 71 CI‐AKI patients and 71 matched controls. The dashed line indicates “random guess” diagonal line. AUC indicates area under the curve; CI‐AKI, contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; RT‐qPCR, reverse transcription quantitative real‐time polymerase chain reaction.

Mentions: After inclusion of the case controls, the study consisted of 71 CI‐AKI cases and 71 controls. Baseline characteristics of these 2 groups of patients are displayed in Table 2. None of these patients required temporary dialysis during hospitalization as a result of AKI. The plasma level of the 3 candidate miRNAs before and post CM exposure were screened by using RT‐qPCR. The baseline plasma levels of the 3 candidate miRNAs were low (the average quantification cycle value: miRNA‐188 33.68; miRNA‐30a 29.05; miRNA‐30e 28.64) and without significant difference across subgroups, including baseline stages of chronic kidney disease (Table S3). The plasma levels of the 3 candidate miRNAs were significantly elevated at 4 to 6 hours postprocedure from baseline in patients with CI‐AKI as compared with the control group (mean difference in fold change of miRNAs: miRNA‐188, 1.594 [1.087–2.158], P<0.001; miRNA‐30a, 2.579 [1.756–3.508], P<0.001; miRNA‐30e, 2.283 [1.612–3.038], P<0.001; Figure 3A). The changes in these miRNAs levels in the subgroups categorized by the different CI‐AKI diagnostic criteria (SCr or CyC) are presented in Table S4. Logistic regression adjusting for age and eGFR showed significant association of the changes in these miRNAs levels with CI‐AKI (Table S5). Correlation analysis indicated that the increases in the 3 candidate miRNAs plasma levels postprocedure were related to the change of SCr or CyC (Figure S1A).


Circulating Micro RNA ‐ 188, ‐ 30a, and ‐ 30e as Early Biomarkers for Contrast ‐ Induced Acute Kidney Injury
Evaluation of candidate circulating miRNAs in CI‐AKI patients. A, The plasma levels of the three candidate miRNAs in 71 CI‐AKI patients and 71 matched controls without CI‐AKI by RT‐qPCR. Blood samples were obtained at baseline and 4 to 6 hours post CM exposure. Individual value plots represent the relative change of miRNA levels compared with baseline in each CI‐AKI patient (left) and non‐CI‐AKI patient (right). A crossbar on each plot indicates the mean expression level for each group. ***P<0.001. B, Discrimination potential of candidate circulating miRNAs. Receiver operating characteristics (ROC) curves were drawn with the data of fold change of plasma microRNAs from 71 CI‐AKI patients and 71 matched controls. The dashed line indicates “random guess” diagonal line. AUC indicates area under the curve; CI‐AKI, contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; RT‐qPCR, reverse transcription quantitative real‐time polymerase chain reaction.
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jah31704-fig-0003: Evaluation of candidate circulating miRNAs in CI‐AKI patients. A, The plasma levels of the three candidate miRNAs in 71 CI‐AKI patients and 71 matched controls without CI‐AKI by RT‐qPCR. Blood samples were obtained at baseline and 4 to 6 hours post CM exposure. Individual value plots represent the relative change of miRNA levels compared with baseline in each CI‐AKI patient (left) and non‐CI‐AKI patient (right). A crossbar on each plot indicates the mean expression level for each group. ***P<0.001. B, Discrimination potential of candidate circulating miRNAs. Receiver operating characteristics (ROC) curves were drawn with the data of fold change of plasma microRNAs from 71 CI‐AKI patients and 71 matched controls. The dashed line indicates “random guess” diagonal line. AUC indicates area under the curve; CI‐AKI, contrast‐induced acute kidney injury; CM, contrast medium; miRNA, microRNA; RT‐qPCR, reverse transcription quantitative real‐time polymerase chain reaction.
Mentions: After inclusion of the case controls, the study consisted of 71 CI‐AKI cases and 71 controls. Baseline characteristics of these 2 groups of patients are displayed in Table 2. None of these patients required temporary dialysis during hospitalization as a result of AKI. The plasma level of the 3 candidate miRNAs before and post CM exposure were screened by using RT‐qPCR. The baseline plasma levels of the 3 candidate miRNAs were low (the average quantification cycle value: miRNA‐188 33.68; miRNA‐30a 29.05; miRNA‐30e 28.64) and without significant difference across subgroups, including baseline stages of chronic kidney disease (Table S3). The plasma levels of the 3 candidate miRNAs were significantly elevated at 4 to 6 hours postprocedure from baseline in patients with CI‐AKI as compared with the control group (mean difference in fold change of miRNAs: miRNA‐188, 1.594 [1.087–2.158], P<0.001; miRNA‐30a, 2.579 [1.756–3.508], P<0.001; miRNA‐30e, 2.283 [1.612–3.038], P<0.001; Figure 3A). The changes in these miRNAs levels in the subgroups categorized by the different CI‐AKI diagnostic criteria (SCr or CyC) are presented in Table S4. Logistic regression adjusting for age and eGFR showed significant association of the changes in these miRNAs levels with CI‐AKI (Table S5). Correlation analysis indicated that the increases in the 3 candidate miRNAs plasma levels postprocedure were related to the change of SCr or CyC (Figure S1A).

View Article: PubMed Central - PubMed

ABSTRACT

Background: Contrast&#8208;induced acute kidney injury (CI&#8208;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&#8208;AKI.

Methods and results: Using a rat model of CI&#8208;AKI, we first evaluated the miRNA profile of rat plasma and kidney. Three miRNA species with &gt;1.5&#8208;fold increase in plasma samples of CI&#8208;AKI rats, including miRNA&#8208;188, miRNA&#8208;30a, and miRNA&#8208;30e, were selected as candidate miRNAs. Quantitative real&#8208;time polymerase chain reaction showed that these candidate miRNAs peaked in concentration around 4&nbsp;hours after contrast medium exposure and were relatively renal&#8208;specific. We compared the plasma levels of these candidate miRNAs in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed CI&#8208;AKI with those of 71 matched controls. The plasma levels of the 3 candidate miRNAs were significantly elevated in the CI&#8208;AKI group as compared to the control group. Receiver operating characteristic analysis showed that these miRNAs significantly distinguished patients with CI&#8208;AKI from those without CI&#8208;AKI. MiRNA composites were highly accurate for CI&#8208;AKI prediction, as shown in maximized specificity by treble&#8208;positive miRNA composite or maximized Youden index by any&#8208;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&#8208;AKI from those without CI&#8208;AKI. Thus, miRNAs are potential biomarkers for early detection of CI&#8208;AKI.

No MeSH data available.


Related in: MedlinePlus